What changed in this filing

/stocks — the workspaceLOADING

Item 1A. Risk Factors

2021-08-05 compared with 2021-05-10 · 154 added, 164 removed, 1336 unchanged (19% of the section changed)

9 unchanged sentences

Prior to the Merger, 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 have incurred net losses each year since our inception, including net losses of $69.6 million for the three months ended March 31, 2021.

As of March 31, 2021, we had an accumulated deficit of $1.2 billion.

We are not currently profitable and have incurred net losses each year since our inception, including net losses of $152.6 million for the six months ended June 30, 2021.

As of June 30, 2021,

we had an accumulated deficit of $1.3 billion.

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

20 unchanged sentences

• adapt to any changes in reimbursement practices by third party payors;

• continue our Merger-related integration activities;

• enroll patients in our clinical trials;

16 unchanged sentences

Our expenses could increase beyond expectations if we are required by the U.S.

Food and Drug Administration, or 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 repeat any of our clinical trials, to perform studies in addition to, different from or larger than those currently expected, if there are any delays in completing our clinical trials or if there are delays to or issues with obtaining marketing approval for vadadustat in the United States, the EU or other jurisdictions.

Food and Drug Administration, or 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 repeat any of our clinical trials, to perform studies in addition to, different from or larger than those currently expected, if there are any delays in completing our clinical trials or if there are delays to or issues with obtaining marketing approval for vadadustat in the United States, the EU or other jurisdictions.

Even if vadadustat and any other product candidate, including those that may be in-licensed or acquired, are approved for commercial sale, we anticipate incurring significant costs associated with commercialization.

3 unchanged sentences

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

As of March 31, 2021, our cash and cash equivalents and available for sale securities were $272.8 million.

As of June 30, 2021, our cash and cash equivalents and available for sale securities were $247.0 million.

We expect to continue to expend substantial amounts of cash for the foreseeable future as we continue to commercialize Auryxia and develop and commercialize vadadustat, if approved, and any other product or product candidate, including those that may be in-licensed or acquired.

6 unchanged sentences

• the results of our meetings with the FDA, the EMA and other regulatory authorities and any consequential effects, including on timing of and ability to obtain and maintain marketing approval, study design, study size and resulting operating costs;

• Merger-related integration costs;

• difficulties or delays in enrolling patients in our clinical trials;

79 unchanged sentences

If we are unable to successfully manage any transaction in which we may engage, our ability to develop new products and continue to expand and diversify our portfolio may be limited.

Risks Related to our Merger with Keryx

Risks Related to the Merger

We may fail to realize the anticipated benefits of our merger with Keryx, those benefits may take longer to realize than expected, and we may encounter significant integration difficulties and liabilities, which may have a material adverse effect on our business and financial position.

11 unchanged sentences

Any monetary damages, or other adverse judgment could have a material adverse effect on us.

There is an ongoing appeal of a putative class action lawsuit filed by purported Keryx shareholders challenging the disclosures made in connection with the Merger.

In addition, a stockholder of Keryx filed a complaint against Keryx pursuant to Section 220 of the Delaware General Corporation Law, which sought inspection of various Keryx books and records, purportedly to investigate “possible wrongdoing,” in connection with Keryx’s negotiation and approval of the Merger, as well as the independence of former members of Keryx’s Board of Directors (some of whom are current members of our Board of Directors).

There is an ongoing appeal of a putative class action lawsuit filed in federal court, and an ongoing putative class action lawsuit in state court, each filed by purported Keryx shareholders challenging the disclosures made in connection with the Merger.

See Part II, Item 1.

7 unchanged sentences

Any potential future impairment of goodwill or intangible assets may significantly impact our results of operations and financial condition.

As of March 31, 2021, we had approximately $190.2 million of goodwill and a definite lived intangible asset from the Merger.

In accordance with generally accepted accounting principles, or GAAP, we are required annually, or more frequently upon

certain indicators of impairment, to review our estimates and assumptions underlying the fair value of our goodwill and our definite lived intangible assets when indicators of impairment are present.

As of June 30, 2021, we had approximately $181.2 million of goodwill and a definite lived intangible asset from the Merger.

In accordance with generally accepted accounting principles, or GAAP, we are required annually, or more frequently upon certain indicators of impairment, to review our estimates and assumptions underlying the fair value of our goodwill and our definite lived intangible assets when indicators of impairment are present.

Events giving rise to impairment of goodwill or intangible 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, and 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 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, and 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 that goodwill and/or definite lived intangible 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.

3 unchanged sentences

As a result, we recorded an impairment charge of $115.5 million during the three months ended June 30, 2020, which was entirely allocated to our only intangible asset, the developed product rights for Auryxia, and made a corresponding adjustment to the estimated useful life of the developed product rights for Auryxia, which we again adjusted during the three months ended December 31, 2020.

The estimates, judgments and assumptions used in our impairment testing, and the results of our testing, are discussed in Note 9 to our unaudited condensed consolidated financial statements in Part I, Item 1.

Financial Statements (unaudited).

The estimates, judgments and assumptions used in our impairment testing, and the results of our testing, are discussed in Note 9 to the consolidated financial statements in the Company’s 2020 Annual Report on Form 10-K.

If these estimates, judgments and assumptions change in the future, including if the Auryxia asset group does not meet its current forecasted projections, additional impairment charges 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.

3 unchanged sentences

The full extent to which the COVID-19 pandemic will directly or indirectly impact our business, results of operations and financial condition continues to depend on future developments that are highly uncertain and cannot be accurately predicted, including new information that may emerge concerning COVID-19, any resurgences or mutations of COVID-19, the actions taken to contain it or treat its impact and the economic impact on local, regional, national and international markets where the healthcare providers with whom we interact, our partners, our CROs, our CMOs, and our other vendors operate.

We believe our revenue growth was negatively impacted in the first quarter of 2021 primarily as the kidney patient populations that we serve continue to experience both higher hospitalization and mortality rates due to COVID-19.

We believe our revenue growth was negatively impacted in the first half of 2021 primarily as the kidney patient populations that we serve continue to experience both higher hospitalization and mortality rates due to COVID-19.

While we are unable to quantify the impact of the COVID-19 pandemic on future revenues and revenue growth, COVID-19 continues to adversely and disproportionately impact our patient population;

3 unchanged sentences

For example, DaVita, Inc., or DaVita, and Fresenius Medical Care, or Fresenius, which account for a vast majority of the dialysis population in the United States, have restricted access to their clinics.

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

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 could negatively impact our access to healthcare providers and, ultimately, our sales.

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

Nevertheless, 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 COVID-19 pandemic on CKD patients, we are actively monitoring the demand for Auryxia, 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.

While most of our office-based operations can be performed remotely, there is no guarantee that we will be as effective while working remotely because our team is dispersed, many employees may have additional personal needs to attend to (such as looking after children as a result of school closures or family members who may become sick), and employees may become

sick themselves and be unable to work.

While most of our office-based operations can be performed remotely, there is no guarantee that we will continue to be as effective while working remotely because our team is dispersed, many employees may have additional personal needs to attend to (such as looking after children as a result of school closures or family members who may become sick), and employees may become sick themselves and be unable to work.

Further, our increased reliance on remote access to our information systems increases our exposure to potential cybersecurity breaches.

3 unchanged sentences

In addition, the pandemic or the response efforts to the pandemic may cause disruptions to, closures of or other impacts on our CMOs and other vendors in our supply chain on which we rely for the supply of our products and product candidates.

These impacts could lead to delays or disruptions in supply of our products and product candidates and have a negative effect on our inventory reserves, which could result in an increase in inventory write-offs due to expiry.

These impacts could lead to delays, increased costs or disruptions in supply of our products and product candidates and have a negative effect on our inventory reserves, which could result in an increase in inventory write-offs due to expiry.

The pandemic has resulted in closures of and may continue to impact clinical trial sites on which we rely and will rely for the completion of certain clinical trials and COVID-19 pandemic precautions have caused moderate delays in enrolling new clinical trials and may cause delays in enrolling other new clinical trials.

11 unchanged sentences

The global impact of COVID-19 continues to rapidly evolve, and we will continue to monitor the situation closely.

In particular, areas we are monitoring include possible COVID-related changes in our commercial revenue payer mix, overall product sales, and reserves and allowances, as well as negative trends that could potentially have a further significant impact on product demand and, ultimately, product revenue, or could indicate goodwill, intangible assets, and other assets to be impaired.

In particular, areas we are monitoring include possible COVID-related changes in our commercial revenue payor mix, overall product sales, and reserves and allowances, as well as negative trends that could potentially have a further significant impact on product demand and, ultimately, product revenue, or could indicate goodwill, intangible assets, and other assets to be impaired.

This uncertain COVID-19 pandemic environment has presented new risks to our business.

3 unchanged sentences

Our ability to successfully commercialize any approved product, including our ability to achieve widespread market acceptance, is critical to the success of our business.

Our ability to generate significant product revenue will depend almost entirely on our ability to execute on our commercialization plans, the level of market adoption for, and the availability of and continued use of any approved product by physicians, hospitals, dialysis clinics, wholesalers, patients, and/or healthcare payors, including government payors, consumers,

managed care organizations, pharmacy benefit managers, or PBMs, and pharmacies.

If we are not successful in commercializing any approved product, including achieving and maintaining an adequate level of market adoption, our profitability and our future business prospects will be adversely impacted.

If we are not successful in commercializing any approved product, including achieving and maintaining an adequate level of market adoption, our

profitability and our future business prospects will be adversely impacted.

Market acceptance of any approved product depends on a number of other factors, including:

28 unchanged sentences

In addition, litigation to enforce or defend intellectual property rights is complex, costly and involves significant management time.

If our Orange Book-listed patents are successfully challenged by a third party and a generic version of Auryxia is

approved and launched, revenue from Auryxia could decline significantly, which would have a material adverse effect on our sales, results of operations and financial condition.

If our Orange Book-listed patents are successfully challenged by a third party and a generic version of Auryxia is approved and launched, revenue from Auryxia could decline significantly, which would have a material adverse effect on our sales, results of operations and financial condition.

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

26 unchanged sentences

Department of Health and Human Services challenging CMS’s decision that Auryxia would no longer be covered by Medicare for the IDA Indication and imposing a prior authorization requirement for Auryxia in the Hyperphosphatemia Indication, or the CMS Decision.

While we believe that the

vast majority of the Medicare prescriptions written for Auryxia today are for the Hyperphosphatemia Indication and therefore will continue to be covered by Medicare with prior authorization, the CMS Decision has had and will continue to have an adverse impact on the sales and future growth of Auryxia for the Hyperphosphatemia Indication and the IDA Indication.

For example, in the second quarter of 2020, we reduced our short-term and long-term Auryxia revenue forecast, primarily driven by the compounding impact of the CMS Decision.

While we believe that the vast majority of the Medicare prescriptions written for Auryxia today are for the Hyperphosphatemia Indication and therefore will continue to be covered by Medicare with prior authorization, the CMS Decision has had and will continue to have an adverse impact on the sales and future growth of Auryxia for the Hyperphosphatemia Indication and the IDA Indication.

For example, in the second quarter of 2020, we reduced our short-term and long-term Auryxia revenue forecast, primarily driven by

the compounding impact of the CMS Decision.

As a result, we recorded an impairment charge of $115.5 million to the Auryxia intangible asset associated with the developed product rights for Auryxia during the three months ended June 30, 2020.

13 unchanged sentences

We have four distributors, Fresenius Medical Care Rx, McKesson Corporation, Cardinal Health, Inc.

and Amerisource Bergen Drug Corporation, that, in the aggregate, accounted for a significant percentage of our gross accounts receivable as of March 31, 2021.

and Amerisource Bergen Drug Corporation, that, in the aggregate, accounted for a significant percentage of our gross accounts receivable as of June 30, 2021.

If we are not able to maintain our contracts 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, or such distributors’ end users’ prescribing practices or clinical protocols, it would adversely impact the market opportunity for Auryxia, our product revenues and operating results.

11 unchanged sentences

If vadadustat is approved and we are not able to maintain the Vifor Agreement or enter into a supply agreement with DaVita, our business may be materially harmed.

reimbursement model, then the Vifor Agreement will not become effective, and patients would access vadadustat through contracts we negotiate with third party payors for reimbursement of vadadustat, which would be subject to the risks and uncertainties described above.

Additionally, applying for and obtaining reimbursement under the TDAPA may take several months following approval, which would affect adoption, uptake and product revenue for vadadustat, and if there are updates to the TDAPA rule that decrease the basis for reimbursement or eligibility criteria during the transition period or if the TDAPA is eliminated, then our profitability may be adversely affected .

Although we currently believe it is likely that vadadustat, if approved, will be reimbursed using the TDAPA followed by reimbursement via the bundled reimbursement model, if vadadustat is neither reimbursed under the TDAPA nor the bundled reimbursement model, then the Vifor Agreement will not become effective, and patients would access vadadustat through contracts we negotiate with third party payors for reimbursement of vadadustat, which would be subject to the risks and uncertainties described above.

the TDAPA rule that decrease the basis for reimbursement or eligibility criteria during the transition period or if the TDAPA is eliminated, then our profitability may be adversely affected .

For example, the Medicare Payment Advisory Commission, or MedPAC, 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.

25 unchanged sentences

The development and commercialization of new drugs is highly competitive and subject to rapid and significant technological change.

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

may be in-licensed or acquired.

Our objective is to continue to commercialize Auryxia and develop and commercialize new products with superior efficacy, convenience, tolerability and/or safety.

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

Auryxia is competing in the hyperphosphatemia market in the United States with other FDA-approved phosphate binders such as Renagel ® (sevelamer hydrochloride) and Renvela ® (sevelamer carbonate), both marketed by Genzyme Corporation (a wholly-owned subsidiary of Sanofi), PhosLo ® and Phoslyra ® (calcium acetate), marketed by Fresenius Medical Care North America, Fosrenol ® (lanthanum carbonate), marketed by Shire Pharmaceuticals Group plc, and Velphoro ® (sucroferric oxyhydroxide), marketed by Fresenius Medical Care North America, as well as over-the-counter calcium carbonate products such as TUMS ® and metal-based options such as aluminum, lanthanum and magnesium.

Auryxia is competing in the hyperphosphatemia market in the United States with other FDA-approved phosphate binders such as Renagel ® (sevelamer hydrochloride) and Renvela ® (sevelamer carbonate), both marketed by Sanofi, PhosLo ® and Phoslyra ® (calcium acetate), marketed by Fresenius Medical Care North America, Fosrenol ® (lanthanum carbonate), marketed by Shire Pharmaceuticals Group plc, and Velphoro ® (sucroferric oxyhydroxide), marketed by Fresenius Medical Care North America, as well as over-the-counter calcium carbonate products such as TUMS ® and metal-based options such as aluminum, lanthanum and magnesium.

Most of the phosphate binders listed above are now also available in generic forms.

In addition, other agents are in development, including Ardelyx, Inc.’s tenapanor (for which an NDA has been submitted to the FDA) and OPKO Health Inc.’s Alpharen ™ Tablets (fermagate tablets), that may impact the market for Auryxia.

In addition, other agents are in development, including OPKO Health Inc.’s Alpharen ™ Tablets (fermagate tablets), that may impact the market for Auryxia.

Auryxia is competing in the IDA market in the United States 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).

In addition, other new therapies for the treatment of IDA may impact the market for Auryxia, such as Shield Therapeutics’ Feraccru ® (ferric maltol), which is available in Europe for the treatment of IDA and Accrufer ® (ferric maltol), which is approved in the United States for the treatment of IDA.

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

In addition, other new therapies for the treatment of IDA may impact the market for Auryxia, such as Shield Therapeutics plc's Feraccru ® (ferric maltol), which is available in Europe for the treatment of IDA and Accrufer ® (ferric maltol), which was launched in the United States for the treatment of IDA on July 1, 2021.

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

3 unchanged sentences

There are several other HIF-PHI product candidates in various stages of development for anemia indications that may be in direct competition with vadadustat if and when they are approved and launched commercially.

These candidates are being developed by such companies as FibroGen Inc., Japan Tobacco International, GlaxoSmithKline plc and Bayer HealthCare AG.

FibroGen, together with its collaboration partners, Astellas Pharma Inc.

and AstraZeneca PLC, is currently in global Phase 3 clinical development of its product candidate, roxadustat.

In Japan, roxadustat has launched for the treatment of anemia due to CKD in patients on dialysis, or DD-CKD.

In November 2020, Astellas and Fibrogen announced the approval of roxadustat for NDD-CKD patients in Japan.

In China, roxadustat has launched for the treatment of anemia of DD-CKD and for the treatment of anemia due to CKD in patients not on dialysis, or NDD-CKD.

FibroGen announced that the FDA set an initial Prescription Drug User Fee Act, or PDUFA, date of December 20, 2020;

however, on December 18, 2020, FibroGen disclosed a new PDUFA date of March 20, 2021 for its NDA for roxadustat for both DD-CKD and NDD-CKD and on March 1, 2021 announced that the Cardiovascular and Renal Drugs Advisory Committee of the FDA will hold an Advisory Committee meeting to review the NDA for roxadustat in the U.S., which FibroGen subsequently indicated has been tentatively scheduled for July 15, 2021.

In Japan, roxadustat, daprodustat and enarodustat are approved for treatment of anemia due to CKD.

These candidates are being developed by companies such as FibroGen Inc., together with its collaboration partners, Astellas Pharma Inc.

and AstraZeneca PLC, Japan Tobacco International, or JT, GlaxoSmithKline plc, or GSK, and Bayer HealthCare AG, or Bayer.

In the United States, FibroGen Inc., or FibroGen, has filed an NDA for its product candidate, roxadustat, with the FDA.

In Europe, the EMA Committee for Medical Products for Human Use recently recommended that roxadustat be approved for the treatment of anemia in patients with CKD.

In Japan, roxadustat is approved for the treatment of anemia due to CKD in patients on dialysis, or DD-CKD, and patients not on dialysis, or NDD-CKD.

In addition, daprodustat, GSK’s product candidate, and enarodustat, JT’s product candidate, are approved in Japan for the treatment of anemia due to CKD.

Bayer HealthCare AG has submitted an NDA for its product candidate for the treatment of renal anemia in Japan.

In China, roxadustat has launched for the treatment of anemia of DD-CKD and for the treatment of anemia due to CKD in NDD-CKD patients.

Recently, GSK announced that its Phase 3 ASCEND program, evaluating the efficacy and safety profile of daprodustat for patients with anemia due to CKD, met its primary endpoints and across the ASCEND program, daprodustat was generally well tolerated in both non-dialysis and dialysis patients.

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

3 unchanged sentences

In addition, an application for a biosimilar product cannot be approved by the FDA until 12 years after the existing, branded product was approved under a Biologics License Application, or BLA.

The patents for epoetin alfa, an injectable ESA, expired in 2004 in the EU, and the remaining

patents expired between 2012 and 2016 in the United States.

The patents for epoetin alfa, an injectable ESA, expired in 2004 in the EU, and the remaining patents expired between 2012 and 2016 in the United States.

Because injectable ESAs are biologic products, the introduction of biosimilars into the injectable ESA market in the United States will constitute additional competition for vadadustat if we are able to obtain approval for and commercially launch our product.

Several biosimilar versions of injectable ESAs are available for sale in the EU.

Several biosimilar versions of injectable ESAs are available

for sale in the EU.

In the United States, Pfizer’s biosimilar version of injectable ESAs, Retacrit ® (epoetin alfa-epbx), was approved by the FDA in May 2018 and launched in November 2018.

40 unchanged sentences

Risks Related to Clinical Development

In addition to Auryxia, we will continue to depend heavily on the success of our product candidate, vadadustat, for which we completed Phase 3 clinical development in 2020 and submitted an NDA to the FDA in March 2021.

In addition to Auryxia, we will continue to depend heavily on the success of our product candidate, vadadustat, for which we submitted an NDA to the FDA, which was accepted for filing in May 2021.

Clinical drug development involves a lengthy and expensive process with an uncertain outcome.

101 unchanged sentences

• a product candidate may not be accepted as safe and effective by patients, the medical community, or third party payors, if applicable.

If any of these events occurs, we may be forced to abandon our research and development efforts for one or more of our programs, or we may not be able to identify, discover, develop or commercialize additional product candidates, which would have a material adverse effect on our business.

If any of these events occur, we may be forced to abandon our research and development efforts for one or more of our programs, or we may not be able to identify, discover, develop or commercialize additional product candidates, which would have a material adverse effect on our business.

Because we have limited financial and managerial resources, we focus on research programs and product candidates for specific indications.

75 unchanged sentences

We submitted an NDA to the FDA for vadadustat for the treatment of anemia due to CKD in adult dialysis-dependent and non-dialysis dependent patients in March 2021.

Our NDA submission did not include a Priority Review Voucher.

Based on standard FDA review timelines, the FDA has a 60-day period to determine whether the NDA is complete and acceptable for review.

As vadadustat did not meet the primary safety endpoint of the PRO 2 TECT program, we are remaining cautious in our outlook for potential approval of vadadustat for the treatment of anemia due to CKD in adult non-dialysis dependent patients.

Our NDA submission was accepted for filing by the FDA in May 2021.

The FDA assigned the application standard review and a Prescription Drug User Fee Act (PDUFA) target action date of March 29, 2022 .

At the time of filing, the FDA also indicated that they were not currently planning to hold an Advisory Committee meeting to discuss the application for vadadustat .

While we remain cautious in our outlook for potential approval of vadadustat for the treatment of anemia due to CKD in adult non-dialysis dependent patients as vadadustat did not meet the primary safety endpoint of the PRO 2 TECT program, we look forward to working with the FDA in their review of all of the data.

Further, vadadustat may not receive marketing approval even if it is approved in other countries.

2 unchanged sentences

Furthermore, approval of a drug does not ensure successful commercialization.

For example, on September 23, 2015, the European Commission, or EC, approved Fexeric for the control of hyperphosphatemia, in adult patients with CKD.

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;

For example, on September 23, 2015, the

European Commission, or EC, approved Fexeric for the control of hyperphosphatemia in adult patients with CKD.

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

5 unchanged sentences

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

• the FDA may determine during its 60-day preliminary review period following submission of our NDA that the vadadustat NDA is not sufficiently complete to permit substantive review;

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

11 unchanged sentences

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

• 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;

• although at the time of filing the NDA, the FDA indicated that they were not currently planning to hold an Advisory Committee meeting to discuss the NDA, 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;

• the FDA may require development of a REMS as a condition of approval or post-approval;

14 unchanged sentences

Also, favorable pricing in certain countries depends on a number of factors, some of which are outside of our control.

Additionally, we could face heightened risks with respect to seeking marketing approval in the United Kingdom as a result of the recent withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit.

Pursuant to the formal withdrawal arrangements agreed between the United Kingdom and the European Union, the United Kingdom withdrew from the European Union, effective December 31, 2020.

Additionally, we could face heightened risks with respect to seeking marketing approval in the United Kingdom, or UK, as a result of the recent withdrawal of the UK from the EU, commonly referred to as Brexit.

Pursuant to the formal withdrawal arrangements agreed between the UK and the EU, the United Kingdom withdrew from the EU, effective December 31, 2020.

On December 24, 2020, the United Kingdom and European Union entered into a Trade and Cooperation Agreement.

The agreement sets out certain procedures for approval and recognition of medical products in each jurisdiction.

Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of the Trade and Cooperation Agreement would prevent us from commercializing vadadustat or any other product candidate, including those that may be in-licensed or acquired, in the United Kingdom and/or the European Union and restrict our ability to generate revenue and achieve and sustain profitability.

If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the United Kingdom and/or the European Union for vadadustat or any other product candidate, which could significantly and materially harm our business.

Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of the Trade and Cooperation Agreement would prevent us from commercializing vadadustat or any other product candidate, including those that may be in-licensed or acquired, in the UK and/or the EU and restrict our ability to generate revenue and achieve and sustain profitability.

If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the UK and/or the EU for vadadustat or any other product candidate, which could significantly and materially harm our business.

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

6 unchanged sentences

Our request to extend this deadline was denied, and the study is considered delayed.

With regard to the IDA Indication, we did not meet a milestone relating to the post-approval pediatric study of Auryxia in a

timely manner and received a notification from the FDA.

Subsequently, the FDA agreed to extend the pediatric clinical study timelines for the IDA Indication.

With regard to the IDA Indication, we did not meet a milestone relating to the post-approval pediatric study of Auryxia in a timely manner and received a notification from the FDA.

Subsequently, the FDA agreed to extend the pediatric clinical study

timelines for the IDA Indication.

If we are unable to complete these studies successfully, we will need to inform the FDA, have further discussions, and if the FDA finds that we failed to comply with pediatric study requirements, it could initiate proceedings to seize or enjoin the sale of Auryxia, which would have a material adverse impact on our ability to commercialize Auryxia and our ability to generate revenues from Auryxia.

24 unchanged sentences

Failure to comply with applicable laws could subject us to government scrutiny or government enforcement, potentially resulting in costly investigations and/or fines or sanctions, or impacting our relationships with key regulatory agencies such as the FDA, the U.S.

Securities and Exchange Commission or the EMA.

Securities and Exchange Commission, or the SEC, or the EMA.

A variety of laws apply to us or may otherwise restrict our activities, including the following:

19 unchanged sentences

The FDA, the Department of Justice and other regulatory and enforcement authorities enforce laws and regulations prohibiting promotion of off-label uses and the promotion of products for which marketing approval has not been obtained, as well as the false advertising or misleading promotion of drugs.

In addition, laws and regulations govern the distribution and tracing of prescription drugs and prescription drug samples, including the Prescription Drug Marketing Act of 1976 and the Drug Supply Chain Security Act, which regulate the distribution and tracing of prescription drugs and prescription drug samples at the U.S.

federal level and set minimum standards for the

regulation of drug distributors by the states.

A company that is found to have improperly promoted off-label uses or to have otherwise engaged in false or misleading promotion or improper distribution of drugs will be subject to significant liability, potentially including civil and administrative remedies as well as criminal sanctions.

A company that is found to have improperly promoted off-label uses or to have otherwise

engaged in false or misleading promotion or improper distribution of drugs will be subject to significant liability, potentially including civil and administrative remedies as well as criminal sanctions.

It may also be subject to exclusion and debarment from federal healthcare reimbursement programs.

12 unchanged sentences

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

For example, over the last several years, including for 35 days beginning on December 22, 2018, the U.S.

government has shut down.

For example, over the last several years, including for 35 days beginning on December 22, 2018, the United States government has shut down.

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

1 unchanged sentence

Subsequently, on July 10, 2020, the FDA announced its intention to resume certain on-site inspections of domestic manufacturing facilities subject to a risk-based prioritization system.

The FDA intends to use this risk-based assessment system to identify the categories of regulatory activity that can occur within a given geographic area, ranging from mission critical inspections to resumption of all regulatory activities.

Regulatory authorities outside the U.S.

may also impose similar restrictions or other policy measures in response to the COVID-19 pandemic.

This risk-based assessment system identifies the categories of regulatory activity that can occur within a given geographic area, ranging from mission critical inspections to resumption of all regulatory activities.

In May 2021, the FDA issued a new report “Resiliency Roadmap for FDA Inspectional Oversight” which include its detailed plan to move towards a more consistent state of operations;

best-case, base-case and worst-case scenarios are identified, as well as the drivers that determine these scenarios and the impact these will have on inspection activities.

Regulatory authorities outside the United States may also impose similar restrictions or other policy measures in response to the COVID-19 pandemic.

If a prolonged government shutdown occurs, or if global health concerns continue to 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.

91 unchanged sentences

In addition, CMS has proposed regulations that would give states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

Further, on December 14, 2018, a U.S.

District Court judge in the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature of the ACA and, therefore, because the mandate was repealed as part of the Tax Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well.

On November 10, 2020, the U.S.

Supreme Court heard this case and a decision is expected sometime this year.

Pending resolution of the litigation, all of the provisions in the ACA but the individual mandate to buy health insurance remains in effect.

Further, on December 14, 2018, a United States District Court judge in the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature of the ACA and, therefore, because the mandate was repealed as part of the Tax Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well.

On November 10, 2020, the United States Supreme Court heard this case.

On June 17, 2021, the Supreme Court dismissed this case after finding that the plaintiffs do not have standing to challenge the constitutionality of the ACA.

Accordingly, all of the provisions in the ACA but the individual mandate to buy health insurance remain in effect.

It is unclear how such litigation and other efforts to repeal and replace the ACA will impact the ACA and our business.

The costs and prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.

To date, there have been several recent U.S.

congressional inquiries and proposed and enacted state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

Specifically, there have been several recent U.S.

congressional inquiries and proposed federal and proposed and enacted state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

To date, there have been several recent United States congressional inquiries and proposed and enacted state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

Specifically, there have been several recent United States congressional inquiries and proposed federal and proposed and enacted state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

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.

88 unchanged sentences

The facilities and processes used by our third party manufacturers to manufacture Auryxia may be inspected by the FDA and other regulatory authorities at any time, and the facilities and processes used by our third party manufacturers to manufacture vadadustat will be inspected by the FDA, the EMA and other regulatory authorities prior to or after we submit our marketing applications.

We do not control the manufacturing processes of, and have little control over, our third party manufacturers, including, without

limitation, their compliance with cGMP requirements and guidance for the manufacture of certain starting materials, drug substance and finished drug product.

In addition, we have little control over the ability of our third party manufacturers to maintain adequate quality control, quality assurance and qualified personnel.

Although we have general visibility into the manufacturing processes of our third party manufacturers, we do not ultimately

control such manufacturing processes of, and have little control over, our third party manufacturers, including, without limitation, their compliance with cGMP requirements and guidance for the manufacture of certain starting materials, drug substance and finished drug product.

Similarly, although we review final production, we have little control over the ability of our third party manufacturers to maintain adequate quality control, quality assurance and qualified personnel.

Our third party manufacturers may experience problems with their manufacturing and distribution operations and processes, including, for example, quality issues, such as product specification and stability failures, procedural deviations, improper equipment installation or operation, utility failures, contamination, natural disasters and public health epidemics.

17 unchanged sentences

This supply interruption negatively impacted Keryx’s revenues in 2016.

Although this supply interruption was resolved and actions designed to prevent future interruptions in the supply of Auryxia are ongoing, any future supply interruptions, whether quality or quantity based, for Auryxia and vadadustat, if and where approved, would negatively and materially impact our reputation and financial condition.

Although this supply interruption was resolved and actions designed to prevent future interruptions in the supply of Auryxia are ongoing, any future supply

interruptions, whether quality or quantity based, for Auryxia and vadadustat, if and where approved, would negatively and materially impact our reputation and financial condition.

In addition, in order to complete our development of and commercialize vadadustat, if approved in regions beyond Japan, we will need to work with third party manufacturers to manufacture vadadustat in large quantities, including to prepare for launch demand.

21 unchanged sentences

• collaborations may not lead to development or commercialization of products and product candidates, if approved, in the most efficient manner or at all;

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;

• 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 requirements.

23 unchanged sentences

Our commercial success will depend in part on our ability, and the ability of our licensors, to obtain and maintain patent protection on our drug product and technologies, and to successfully defend these patents against third party challenges.

seek to protect our proprietary products and technology by filing patent applications in the United States and certain foreign jurisdictions.

We seek to protect our proprietary products and technology by filing patent applications in the United States and certain foreign jurisdictions.

The process for obtaining patent protection is expensive and time consuming, and we may not be able to file and prosecute all necessary or desirable patent applications in a cost effective or timely manner.

31 unchanged sentences

On February 27, 2018, we withdrew the ’005 EP Patent from appeal and filed a divisional patent application to pursue a focused claim set that includes claims for vadadustat, as well as pharmaceutical compositions and methods of treating anemia.

We cannot be assured that such claims in the divisional application will be granted by the European Patent Office.

If such claims are not granted, or the scope of the

claims is significantly narrowed, we may not be able to adequately protect our rights, provide sufficient exclusivity, or preserve our competitive advantage.

We cannot be assured that such claims in

the divisional application will be granted by the European Patent Office.

If such claims are not granted, or the scope of the claims is significantly narrowed, we may not be able to adequately protect our rights, provide sufficient exclusivity, or preserve our competitive advantage.

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 United States or elsewhere, challenging our patent rights or the patent rights of others.

25 unchanged sentences

In the United States, 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 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 to patent protection, we may utilize, if granted by the FDA, pediatric exclusivity or other provisions of the FDCA such as new chemical entity, or NCE, exclusivity, or exclusivity for a new use or new formulation, to provide non-patent exclusivity for a drug product.

9 unchanged sentences

however, an applicant submitting a full NDA would be required to conduct all of its own studies needed to independently support a finding of safety and effectiveness for the proposed product, or have a full right of reference to all studies not conducted by the applicant.

On August 23, 2018, Keryx submitted a Citizen Petition requesting, inter alia, that FDA recognize that Auryxia is eligible for five years of new chemical entity, or NCE, exclusivity based on its novel active ingredient and for three years exclusivity for the IDA Indication.

On January 19, 2019, FDA responded that Auryxia is eligible for a three-year exclusivity period for the IDA Indication, which expired on November 6, 2020.

On August 23, 2018, Keryx submitted a Citizen Petition requesting, inter alia, that the FDA recognize that Auryxia is eligible for five years of new chemical entity, or NCE, exclusivity based on its novel active ingredient and for three years exclusivity for the IDA Indication.

On January 19, 2019, the FDA responded that Auryxia is eligible for a three-year exclusivity period for the IDA Indication, which expired on November 6, 2020.

FDA, however, denied the NCE exclusivity based on its determination that Auryxia contains a previously-approved active moiety (ferric cation).

FDA’s decision on the Citizen Petition is subject to further review both within FDA and in the courts.

On February 21, 2019, we filed a Petition for Reconsideration of FDA’s decision on the NCE determination for Auryxia.

The FDA’s determination as to whether to grant NCE exclusivity to Auryxia may also affect the timing of the 30 month stay barring FDA from granting final approval to generic versions of Auryxia.

FDA’s decision on the Citizen Petition is subject to further review both within the FDA and in the courts.

On February 21, 2019, we filed a Petition for Reconsideration of the FDA’s decision on the NCE determination for Auryxia.

The FDA’s determination as to whether to grant NCE exclusivity to Auryxia may also affect the timing of the 30-month stay barring the FDA from granting final approval to generic versions of Auryxia.

When an ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA.

10 unchanged sentences

Because we rely on third parties to assist with research, development and manufacture of our product candidates, we must, at times, share trade secrets with them.

We seek to protect our proprietary technology in part by entering into confidentiality

agreements and, if applicable, services agreements, material transfer agreements, consulting agreements, research agreements or other similar agreements with our advisors, employees, third party contractors, collaborators and consultants prior to beginning research or disclosing proprietary information.

We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if applicable, services agreements, material transfer agreements, consulting agreements, research agreements or other similar agreements with our advisors, employees, third party contractors, collaborators and consultants prior to beginning research or disclosing proprietary information.

These agreements typically limit the rights of the third parties to use or disclose our confidential information, including our trade secrets.

24 unchanged sentences

Third parties may hold or obtain patents or other intellectual property rights and allege in the future that the use of our product or product candidate infringes these patents or intellectual property rights, or that we are employing their proprietary technology without authorization.

We do not believe that there are any currently issued U.S.

patents that will prevent us from commercializing Auryxia or vadadustat;

We do not believe that there are any currently issued United States patents that will prevent us from commercializing Auryxia or vadadustat;

nor do we make any admission that any of such patents are valid, enforceable or infringed.

law, a party may be able to patent a discovery of a new way to use a previously known compound, even

if such compound itself is patented, provided the newly discovered use is novel and nonobvious.

Under United States law, a party may be able to patent a discovery of a new way to use a previously known compound, even if such compound itself is patented, provided the newly discovered use is novel and nonobvious.

Such a method-of-use patent, however, if valid, only protects the use of a claimed compound for the specified methods claimed in the patent.

1 unchanged sentence

Further, this type of patent does not prevent persons from making and marketing the compound for an indication that is outside the scope of the patented method.

We are not aware of any valid U.S.

patents issued to FibroGen, or any other person, that claim methods of using any of our product candidates for purposes of inhibiting hypoxia-inducible factor prolyl hydroxylases, or HIF-PHs, for the treatment of anemia due to CKD.

We are not aware of any valid United States patents issued to FibroGen, or any other person, that claim methods of using any of our product candidates for purposes of inhibiting hypoxia-inducible factor prolyl hydroxylases, or HIF-PHs, for the treatment of anemia due to CKD.

For example, we are aware of certain patents that have been acquired by FibroGen directed to certain heterocyclic carboxamide compounds that are described as inhibitors of prolyl-4-hydroxylase.

16 unchanged sentences

In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties or redesign our products, which may be impossible or require substantial time and monetary expenditure.

We are currently involved in a patent infringement lawsuit and opposition and invalidity proceedings and may in the future be involved in additional lawsuits or administrative proceedings to challenge the patents of our competitors or to protect or enforce our patents, which could be expensive, time consuming, and unsuccessful.

We are currently involved in a patent infringement lawsuit, a declaratory judgment of non-infringement and invalidity lawsuit, opposition and invalidation proceedings, and may in the future be involved in additional lawsuits or administrative proceedings to challenge the patents of our competitors or to protect or enforce our patents, which could be expensive, time consuming, and unsuccessful.

Competitors may infringe our patents or misappropriate our trade secrets or confidential information.

To counter infringement or unauthorized use, we may be required to file infringement or misappropriation claims, which can be expensive and time-consuming.

To counter infringement or unauthorized use, we may be required to file infringement or misappropriation claims, which can be expensive and time-

We may not be able to prevent infringement of our patents or misappropriation of our trade secrets or confidential information, particularly in countries where the laws may not protect those rights as fully as in the United States.

9 unchanged sentences

For example, we are currently involved in a patent infringement lawsuit against a generic company in the federal district courts.

In addition, we are currently involved in opposition or invalidation proceedings in the European Patent Office, the Japan Patent Office, the Canadian Federal Court and the United Kingdom Patents Court.

We are also involved in an action against our competitors in the federal district court to obtain a declaratory judgment of non-infringement and invalidity of certain patents of the competitors.

In addition, we are currently involved in opposition and invalidation proceedings in the European Patent Office, the Japan Patent Office, and the Patents Court of the UK.

These proceedings may be ongoing for a number of years and may involve substantial expense and diversion of employee resources from our business.

15 unchanged sentences

We may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed confidential information of these third parties or our employees’ former employers.

We may also be subject to claims that former employees, collaborators or other third parties have an ownership interest in our patents or other intellectual property.

We may also be subject to claims that former employees, collaborators or other third parties have an ownership interest in our patents or other

intellectual property.

We may be subject to ownership disputes in the future arising, for example, from conflicting obligations of consultants or others who are involved in developing our product candidates.

34 unchanged sentences

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

do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.

If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.

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 studies, 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.

18 unchanged sentences

Outside parties may also subject us to distributed denial of services attacks or introduce viruses or other malware through “trojan horse” programs to our users’ computers in order to gain access to our systems and the data stored therein.

In the recent past, cyber-attacks have become more prevalent and much harder to detect and defend against and, because the techniques used to obtain unauthorized access, disable or degrade service, or sabotage systems change frequently and continuously become more sophisticated, often are not recognized until launched against a target and may be difficult to detect for a long time, we may be unable to anticipate these techniques or to implement adequate preventive or detective measures, and we might not immediately detect such incidents and the damage caused by such incidents.

damages or fines, or taking other remedial steps with respect to third parties, inadvertent diversion of cash, divert the attention of our management and key information technology resources, disrupt key business operations, harm our reputation and deter business partners from working with us.

the recent past, cyber-attacks have become more prevalent and much harder to detect and defend against and, because the techniques used to obtain unauthorized access, disable or degrade service, or sabotage systems change frequently and continuously become more sophisticated, often are not recognized until launched against a target and may be difficult to detect for a long time, we may be unable to anticipate these techniques or to implement adequate preventive or detective measures, and we might not immediately detect such incidents and the damage caused by such incidents.

Such attacks, whether successful or unsuccessful, or other compromises with respect to our information security and the measures we implement to prevent, detect and respond to them, could result in our incurring significant costs related to, for example, rebuilding internal systems, defending against litigation, responding to regulatory inquiries or actions, paying damages or fines, or taking other remedial steps with respect to third parties, inadvertent diversion of cash, divert the attention of our management and key information technology resources, disrupt key business operations, harm our reputation and deter business partners from working with us.

A compromise with respect to our information security could lead to public exposure of personal information of our clinical trial patients, Auryxia patients and others, and negative publicity.

14 unchanged sentences

• laws that require the reporting of true and accurate financial information and data;

state and federal securities laws and regulations and their non-U.S.

• United States state and federal securities laws and regulations and their non-U.S.

We are currently closing out global clinical 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.

These laws include the FCPA, which prohibits U.S.

companies and their intermediaries, such as CROs or CMOs, from making improper payments to foreign government officials for the purposes of obtaining or keeping business or to obtain any kind of advantage for the company.

These laws include the FCPA, which prohibits United States companies and their intermediaries, such as CROs or CMOs, from making improper payments to foreign government officials for the purposes of obtaining or keeping business or to obtain any kind of advantage for the company.

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 U.S.

Securities and Exchange Commission have focused on the life sciences sector.

Securities and Exchange Commission, or the SEC, have focused on the life sciences sector.

Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem.

8 unchanged sentences

Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation.

This could include violations of HIPAA, other U.S.

federal and state law, and requirements of non-U.S.

This could include violations of HIPAA, other United States federal and state law, and requirements of non-U.S.

jurisdictions, including the European Union Data Protection Directive.

6 unchanged sentences

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.

If any of our service providers are later legally deemed to be employees, we could be subject to employment and tax withholding liabilities and other additional costs as well as other multiple damages and attorneys’ fees.

We rely on independent third parties to provide certain services to us.

We structure our relationships with these outside service providers in a manner that we believe results in an independent contractor relationship, not an employee relationship.

An independent contractor is generally distinguished from an employee by his or her degree of autonomy and independence in providing services.

A high degree of autonomy and independence is generally indicative of an independent contractor relationship, while a high degree of control is generally indicative of an employment relationship.

Tax or other regulatory authorities may challenge our characterization of services providers as independent contractors both under existing laws and regulations and under laws and regulations adopted in the future.

If such regulatory authorities or state, federal or foreign courts were to determine that our service providers are employees and not independent contractors, we would, among other things, may be required to withhold income taxes, to withhold and pay Social Security, Medicare and similar taxes, to pay unemployment and other related payroll taxes, and to provide certain employee benefits.

We could also be liable for unpaid past taxes, interest and other costs and subject to penalties.

Likewise, our service providers themselves may later successfully challenge their classification as independent contractors, which may result in additional damages, including back wages,

penalties, interest and attorneys’ fees.

As a result, any legally binding determination that the service providers we characterize as independent contractors are actually our employees could have a material adverse effect on our business, financial condition and results of operations.

We may encounter difficulties in managing our growth and expanding our operations successfully.

8 unchanged sentences

Our future financial performance and our ability to commercialize Auryxia and vadadustat, if and where approved, and to compete effectively will depend, in part, on our ability to manage any future growth effectively.

To manage our recent and

anticipated future growth, we must continue to implement and improve our managerial, operational and financial systems, procedures and processes, expand our facilities and continue to recruit, train, and retain additional qualified personnel.

To manage our recent and anticipated future growth, we must continue to implement and improve our managerial, operational and financial systems, procedures and processes, expand our facilities and continue to recruit, train, and retain additional qualified personnel.

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.

39 unchanged sentences

Since our initial public offering in March 2014, the price of our common stock as reported on The Nasdaq Global Market has ranged from a low of $2.09 on October 30, 2020 to a high of $31.00 on June 20, 2014.

The daily closing market price for our common stock has varied between a high price of $13.58 on June 30, 2020 and a low price of $2.09 on October 30, 2020 in the twelve-month period ending on March 31, 2021.

The daily closing market price for our common stock has varied between a high price of $13.08 on July 2, 2020 and a low price of $2.22 on October 30, 2020 in the twelve-month period ending on June 30, 2021.

During this time, the price of our common stock has ranged from an intra-day low of $2.09 per share to an intra-day high of $13.71 per share.

10 unchanged sentences

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, 2021 and based on the amounts reported in the most recent filings made under Section 13(d) and 13(g) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, BlackRock, Inc., or BlackRock, beneficially owned approximately 7.2% of our outstanding shares of common stock, State Street Corporation, or State Street, beneficially owned approximately 14.2% of our outstanding shares of common stock, Wellington Management Group LLP, or Wellington, beneficially owned approximately 7.9% of our outstanding common stock.

In addition, as of March 31, 2021, our former director, Muneer Satter, beneficially owned approximately 1.9% of our outstanding common stock.

Subject to certain restrictions, Mr.

Satter is able to sell his shares of common stock in the public market from time to time without registering them, subject to certain limitations on the timing, amount and method of those sales imposed by Rule 144 under the Securities Act of 1933, as amended.

As of June 30, 2021 and based on the amounts reported in the most recent filings made under Section 13(d) and 13(g) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, State Street Corporation, or State Street, beneficially owned approximately 8.8% of our outstanding shares of common stock, Wellington Management Group LLP, or Wellington, beneficially owned approximately 7.9% of our outstanding common stock, and BlackRock, Inc., or BlackRock, beneficially owned approximately 7.2% of our outstanding shares of common stock.

In addition, as of June 30, 2021, our former director, Muneer Satter, beneficially owned approximately 1.9% of our outstanding common stock.

In addition, pursuant to our Fourth Amended and Restated Investors’ Rights Agreement, as amended, with Mr.

6 unchanged sentences

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.

Also, the Merger was financed by the issuance of shares of our common stock to shareholders of Keryx, comprising approximately 50.6% of our issued and outstanding shares of common stock, calculated based on our fully diluted market capitalization as of the date of

signing the Agreement and Plan of Merger relating to the Merger.

Keryx shareholders may decide not to hold the shares of our common stock they received in the Merger.

1 unchanged sentence

Such sales of our common stock could result in higher than average trading volume and may cause the market price for our common stock to decline.

In addition, we currently have on file with the U.S.

Securities and Exchange Commission a shelf registration statement, which allows us to offer and sell certain registered securities, such as common stock, preferred stock, debt securities, warrants and units, from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale.

In addition, we currently have on file with the SEC a shelf registration statement, which allows us to offer and sell certain registered securities, such as common stock, preferred stock, debt securities, warrants and units, from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale.

Sales of substantial amounts of shares of our common stock or other securities by our employees or our other shareholders or by us under our shelf registration statement, pursuant to at-the-market offerings or otherwise, could dilute our stockholders, lower the market price of our common stock and impair our ability to raise capital through the sale of equity securities.

Insiders and significant stockholders could cause us to take actions that may not be, or refrain from taking actions that may be, in our best interest or in the best interest of all of our stockholders.

As of March 31, 2021, we believe that our directors and executive officers, together with their affiliates, owned, in the aggregate, approximately 1.8% of our outstanding common stock.

In addition, we have certain significant stockholders, including BlackRock, which beneficially owned approximately 7.2% of our outstanding shares of common stock, State Street, which beneficially owned approximately 14.2% of our outstanding shares of common stock, Wellington, which beneficially owned approximately 7.9% of our outstanding common stock,according to the most recent filings made under Section 13(d) and 13(g) of the Exchange Act.

As of June 30, 2021, we believe that our directors and executive officers, together with their affiliates, owned, in the aggregate, approximately 1.8% of our outstanding common stock.

In addition, we have certain significant stockholders, including Wellington, which beneficially owned approximately 7.9% of our outstanding common stock, State Street, which beneficially owned approximately 8.8% of our outstanding shares of common stock, and BlackRock, which beneficially owned approximately 7.2% of our outstanding shares of common stock based on the amounts reported in the most recent filings made by such significant stockholders under Section 13(d) and 13(g) of the Exchange Act.

If they were to choose to act together, they would have significant influence on all matters submitted to our stockholders for approval, as well as our management and affairs, such as:

• the composition of our Board of Directors;

• the adoption of amendments to our Ninth Amended and Restated Certificate of Incorporation, or Charter, and Amended and Restated By-Laws;

• the adoption of amendments to our Ninth Amended and Restated Certificate of Incorporation, as amended, or Charter, and our Amended and Restated By-Laws, or Bylaws;

• the approval of mergers or sales of substantially all of our assets;

12 unchanged sentences

We cannot predict or estimate the amount of additional costs we may incur to continue to operate as a public company, nor can we predict the timing of such costs.

regulatory and governing bodies, which could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies, which could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.

We have identified a material weakness in our internal control over financial reporting relating to our inventory process.

9 unchanged sentences

Controls and Procedures of this Quarterly Report on Form 10-Q and Part II, Item 9A.

Controls and Procedures of our 2020 Annual Report on Form 10-K.

Additionally, as revised and enhanced controls need to be in operation for a sufficient period of time and be tested to ensure that the controls are operating as designed, management has concluded that the material weakness cannot be considered remediated as of March 31, 2021.

Controls and Procedures of our Annual Report on Form 10-K for the year ended December 31, 2020.

Although we have initiated remediation measures to address the material weakness, 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 controls will be effective in the future.

1 unchanged sentence

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 inventory process 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 reporting.

Securities and Exchange Commission, the Nasdaq Stock Market or other regulatory authorities as well as shareholder litigation which 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 SEC, the Nasdaq Stock Market or other regulatory authorities as well as shareholder litigation which would require additional financial and management resources and could adversely affect the market price of our common stock.

Furthermore, if we cannot provide reliable financial reports or prevent fraud, our business and results of operations could be harmed.

1 unchanged sentence

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 Charter and Amended and Restated Bylaws 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.

Our Charter and our Amended and Restated 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.

In addition, as permitted by Section 145 of the DGCL our Amended and Restated Bylaws and our indemnification agreements that we have entered into with our directors and executive officers provide that:

• We will indemnify our directors and officers, as defined in our Amended and Restated Bylaws, for serving us in those capacities or for serving other related business enterprises at our request, to the fullest extent permitted by Delaware law.

Delaware law provides that a corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of the registrant and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful.

Our Charter and our Bylaws 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.

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.

In addition, as permitted by Section 145 of the DGCL our Bylaws and our indemnification agreements that we have entered into with our directors and executive officers provide that:

• We will indemnify our directors and officers, as defined in our Bylaws, for serving us in those capacities or for serving other related business enterprises at our request, to the fullest extent permitted by Delaware law.

Delaware law provides that a corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of Akebia and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful.

• We may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law.

• We are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such directors or officers shall undertake to repay such advances if it is ultimately determined that such person is not entitled to indemnification.

• The rights conferred in our Amended and Restated Bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons.

• The rights conferred in our Bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to indemnify such persons.

Any claims for indemnification made by our directors or officers could impact our cash resources and our ability to fund the business.

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.

Provisions in our Charter and our Amended and Restated By-Laws contain provisions that may have the effect of discouraging, delaying or preventing a change in control of us or changes in our management.

Provisions in our Charter and our Bylaws contain provisions that may have the effect of discouraging, delaying or preventing a change in control of us or changes in our management.

These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock.

8 unchanged sentences

• 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;

• require a supermajority vote of 75% of the holders of our capital stock entitled to vote or the majority vote of our Board of Directors to amend our Amended and Restated By-Laws;

• require a supermajority vote of 75% of the holders of our capital stock entitled to vote or the majority vote of our Board of Directors to amend our Bylaws;

• require a supermajority vote of 85% of the holders of our capital stock entitled to vote to amend the classification of our Board of Directors and to amend certain other provisions of our Charter.

1 unchanged sentence

In addition, Section 203 of the DGCL prohibits a publicly-held Delaware corporation from engaging in a business combination with an interested stockholder, generally a person which together with its affiliates owns, or within the last three years has owned, 15% of our voting stock, for a period of three years after the date of the transaction in which the person became an interested stockholder, unless the business combination is approved in a prescribed manner.

Any provision of our Charter, our Amended and Restated By-Laws or Delaware law that has the effect of delaying or deterring a change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.

Any provision of our Charter, our Bylaws or Delaware law that has the effect of delaying or deterring a change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.

Our ability to use net operating losses to offset future taxable income may be subject to certain limitations.

1 unchanged sentence

On December 12, 2018, we completed the Merger, which we believe has resulted in an ownership change under Section 382.

In addition, the Tax Cuts and Jobs Act, including amendments made by the CARES Act, includes changes to U.S.

federal tax rates and the rules governing net operating loss carryforwards that may significantly impact our ability to utilize our net operating losses to fully offset taxable income in the future.

In addition, the Tax Cuts and Jobs Act, including amendments made by the CARES Act, includes changes to United States federal tax rates and the rules governing net operating loss carryforwards that may significantly impact our ability to utilize our net operating losses to fully offset taxable income in the future.

Future changes in our stock ownership, many of which are outside of our control, could result in an additional ownership change under Section 382.

1 unchanged sentence

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.

Furthermore, our ability to utilize our NOLs is conditioned upon our attaining profitability and generating U.S.

taxable income.

Furthermore, our ability to utilize our NOLs is conditioned upon our attaining profitability and generating United States taxable income.

As described above under “—Risks Related to our Financial Position and Need for Additional Capital,” we have incurred significant net losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future;

thus, we do not know whether or when we will generate the U.S.

taxable income necessary to utilize our NOLs.

thus, we do not know whether or when we will generate the United States taxable income necessary to utilize our NOLs.

A valuation allowance has been provided for the entire amount of our NOLs.

Our Charter designates the Court of Chancery of the State of Delaware as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

Our Charter provides that, subject to limited exceptions, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or other employees to us or our stockholders, (3) any action asserting a claim against us arising pursuant to any provision of the DGCL our Charter or our Amended and Restated By-Laws, or (4) any other action asserting a claim against us, our directors, officers or other employees that is governed by the internal affairs doctrine.

Our Charter provides that, subject to limited exceptions, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or other employees to us or our stockholders, (3) any action asserting a claim against us arising pursuant to any provision of the DGCL our Charter or our Bylaws, or (4) any other action asserting a claim against us, our directors, officers or other employees that is governed by the internal affairs doctrine.

Under our Charter, this exclusive forum provision will not apply to claims that are vested in the exclusive jurisdiction of a court or forum other than the Court of Chancery of the State of Delaware, or for which the Court of Chancery of the State of Delaware does not have subject matter jurisdiction.

1 unchanged sentence

Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our Charter described above.

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.

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.

8 unchanged sentences

We have never declared or paid cash dividends on our capital stock.

Any payment of cash dividends in the future would be at the discretion of our Board of Directors and would depend on, among other things, our earnings, financial condition, capital

requirements, level of indebtedness, statutory and contractual restrictions applying to the payment of dividends and other considerations that the Board of Directors deems relevant.

Any payment of cash dividends in the future would be at the discretion of our Board of Directors and would depend on, among other things, our earnings, financial condition, capital requirements, level of indebtedness, statutory and contractual restrictions applying to the payment of dividends and other considerations that the Board of Directors deems relevant.

We currently intend to retain all of our future earnings, if any, to finance the development and growth of our business.

3 unchanged sentences

Sales of Unregistered Securities

During the quarter ended March 31, 2021, we did not have any sales of unregistered securities.

During the quarter ended June 30, 2021, we did not have any sales of unregistered securities.

Defaults Upon Senior Securities.

3 unchanged sentences

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