What changed in this filing

/stocks — the workspaceLOADING

Item 1A. Risk Factors

2021-07-29 compared with 2021-04-29 · 101 added, 123 removed, 714 unchanged (24% of the section changed)

15 unchanged sentences

• The amount of contingent consideration we will receive from the sale of our oncology business to Servier is subject to various risks and uncertainties.

• We may not be able to realize the anticipated benefits of the recent sale of our oncology business to Servier and we may face new challenges as a smaller, less diversified company.

• If we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

• We may not be able to realize the anticipated benefits of the recent sale of our oncology business to Servier, including deploying the proceeds to expand our GDD business, and we may face new challenges as a smaller, less diversified company.

• If our existing capital is insufficient to fund our operations through major catalysts and until such time when we can generate positive cash flow, we will need to raise capital, and if we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

• We have historically incurred operating losses.

We expect to incur losses in the future and may never achieve or maintain profitability.

Our net income for the three months ended March 31, 2021 was $1.9 billion and our net loss for the three months ended March 31, 2020 was $40.3 million.

The net income we generated in the three months ended March 31, 2021 was primarily due to the sale of our oncology business to Servier, which was consummated on March 31, 2021.

As of March 31, 2021, we had retained earnings of $30.9 million.

Our net income for the six months ended June 30, 2021 was $1,788.1 million and our net loss for the six months ended June 30, 2020 was $130.7 million.

The net income we generated in the six months ended June 30, 2021 was primarily due to the sale of our oncology business to Servier, which was consummated on March 31, 2021.

As of June 30, 2021, we had an accumulated deficit of $55.4 million.

• We depend heavily on the success of our clinical product candidates, including our lead product candidate mitapivat.

6 unchanged sentences

• We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.

There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of the disease indications for which we are developing our product candidates.

There are a number of large pharmaceutical and biotechnology companies that

currently market and sell products or are pursuing the development of products for the treatment of the disease indications for which we are developing our product candidates.

• We currently rely, and expect to continue to rely, on third-party manufacturers for the materials and manufacture of our product candidates for preclinical and clinical testing and we expect to rely on third-party manufacturers for commercial supply of any product candidate for which we or our collaborators obtain marketing approval.

7 unchanged sentences

In addition, Servier will pay to us:

• $200 million in cash if, prior to January 1, 2027, vorasidenib is granted approval for an NDA from the FDA with an approved label that permits vorasidenib’s use as a single agent for the adjuvant treatment of patients with Grade 2 glioma that have an IDH1 or IDH2 mutation (and, to the extent required by such approval, the vorasidenib companion diagnostic test is granted an FDA premarket approval);

• $200 million in cash if, prior to January 1, 2027, vorasidenib is granted approval for a new drug application, or NDA, from the FDA with an approved label that permits vorasidenib’s use as a single agent for the adjuvant treatment of patients with Grade 2 glioma that have an IDH1 or IDH2 mutation (and, to the extent required by such approval, the vorasidenib companion diagnostic test is granted an FDA premarket approval);

• a royalty payment of 5% of the U.S.

net sales (as defined in the Purchase Agreement) of TIBSOVO® from the completion of the transaction through loss of exclusivity of TIBSOVO®;

net sales (as defined in the purchase agreement with Servier) of TIBSOVO® from the completion of the transaction through loss of exclusivity of TIBSOVO®;

• a royalty payment of 15% of the U.S.

net sales (as defined in the Purchase Agreement) of vorasidenib from its first commercial sale through loss of exclusivity of vorasidenib.

net sales (as defined in the purchase agreement with Servier) of vorasidenib from its first commercial sale through loss of exclusivity of vorasidenib.

The contingent consideration described above is subject to various risks and uncertainties.

Whether the regulatory approval milestone will be achieved prior to January 1, 2027 is subject to various risks and uncertainties, many of which are outside of the control of the parties, including adverse clinical developments with respect to vorasidenib.

In addition, the parties cannot predict what success, if any, Servier may have in the United States with respect to sales of TIBSOVO® and vorasidenib and, therefore, the amount of royalty payments that we can expect to receive from Servier under the terms of the Purchase Agreement prior to the loss of exclusivity of these products.

In addition, we cannot predict what success, if any, Servier may have in the United States with respect to sales of TIBSOVO® and vorasidenib, if approved, and, therefore, the amount of royalty payments that we can expect to receive from Servier under the terms of the purchase agreement prior to the loss of exclusivity of these products.

The royalty payments are also subject to deductions and other adjustments under the terms of the purchase agreement, the amounts of which are uncertain as of the date of this Quarterly Report on Form 10-Q.

We may not be able to realize the anticipated benefits of the recent sale of our oncology business to Servier and we may face new challenges as a smaller, less diversified company.

We may not be able to realize the anticipated benefits from the recent sale of our oncology business to Servier, including potentially deploying the proceeds from the transaction to expand our GDD business.

Our ability to realize the anticipated benefits of the transaction and the success of the remaining company is subject to various risks and uncertainties, including the possibility of adverse clinical and other developments in respect of mitapivat or other pipeline products of the GDD business, the possibility that we may not be able to successfully develop and commercialize products based on PK activation and cellular metabolism and unanticipated changes in applicable laws and regulations that may adversely affect the GDD business.

We may not be able to realize the anticipated benefits from the recent sale of our oncology business to Servier, including deploying the proceeds from the transaction to expand our GDD business.

Our ability to realize the anticipated benefits of the transaction and the success of the GDD business is subject to various risks and uncertainties, including the possibility of adverse clinical and other developments in respect of mitapivat or other pipeline products of the GDD business, the possibility that we may not be able to successfully develop and commercialize products based on PK activation and cellular metabolism and unanticipated changes in applicable laws and regulations that may adversely affect the GDD business.

We developed most of our initial products and product candidates for the treatment of various types of cancer.

The sale of our oncology business to Servier resulted in us being a smaller, less diversified company with a more limited business concentrated on GDDs.

The sale of our oncology business to Servier, including all of our approved products, resulted in us being a smaller, less diversified company with a more limited business concentrated on product candidates for the treatment of GDDs.

As a result, we may be more susceptible to changing market conditions, including fluctuations and risks particular to the markets for patients with GDDs, than a more diversified company, which could adversely affect our business, financial condition and results of operations.

In addition, the diversification of our revenues, costs and cash flows will diminish following the transaction, such that our results of operations, cash flows, working capital and financing requirements may be subject to increased volatility and our ability to fund capital expenditures and investments or satisfy other financial commitments may be diminished.

In addition, the diversification of our revenues, costs and cash flows will diminish following the transaction, such that our results

of operations, cash flows, working capital and financing requirements may be subject to increased volatility and our ability to fund capital expenditures and investments or satisfy other financial commitments may be diminished.

We may also face new challenges with maintaining employee morale, retaining key management and other employees and attracting new employees and retaining existing business and operational relationships, including with third parties, employees and other counterparties that otherwise prefer to transact with larger companies (or will only transact with smaller companies on less favorable terms).

We will have broad discretion as to the use of the proceeds from the sale of our oncology business to Servier, and may not use the proceeds effectively.

We will have broad discretion with respect to the use of proceeds of the sale of our oncology business to Servier.

The results and effectiveness of the use of proceeds, including the repurchase of up to $1.2 billion of our outstanding share of common stock, are uncertain, and we could spend the proceeds in ways that do not improve our remaining business, financial condition or results of operations.

We have broad discretion as to the use of the proceeds from the sale of our oncology business to Servier, and we may not use the proceeds effectively.

We have broad discretion with respect to the use of proceeds of the sale of our oncology business to Servier.

The results and effectiveness of the use of proceeds, including the repurchase of up to $1.2 billion of our outstanding shares of common stock, are uncertain, and we could spend the proceeds in ways that do not improve our remaining business, financial condition or results of operations.

Our failure to apply these funds effectively could have an adverse effect on its business, financial condition and results of operations.

Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs primarily through cash on hand and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs primarily through cash on hand, royalty payments from Servier with respect to U.S.

net sales of TIBSOVO®, a potential milestone payment from Servier if vorasidenib is approved by the FDA and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions.

In addition, in connection with potential future strategic transactions, we may pursue opportunistic debt offerings, and equity or equity-linked offerings.

4 unchanged sentences

If we raise funds through collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.

If we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

If our existing capital is insufficient to execute our operating plan through major catalysts and to cash-flow positivity, we will need to raise capital, and if we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

We expect to incur significant expenses as we continue to advance our ongoing activities.

Following the completion of the the share repurchase from subsidiaries of BMS and the other anticipated repurchases from our stockholders, we expect to have sufficient capital to fund operations through major catalysts and to cash-flow positivity without the need to raise additional equity.

We expect to execute our operating plan through major catalysts and to cash-flow positivity without the need to raise additional equity.

Our estimate as to how long we expect our existing cash, cash equivalents, and marketable securities to be available to fund our operations is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect.

14 unchanged sentences

We have historically incurred operating losses.

Our net income for the three months ended March 31, 2021 was $1.9 billion and our net loss for the three months ended March 31, 2020 was $40.3 million.

The net income we generated in the three months ended March 31, 2021 was primarily due to the sale of our oncology business to Servier, which was consummated on March 31, 2021.

As of March 31, 2021, we had retained earnings of $30.9 million.

Our net income for the six months ended June 30, 2021 was $1.8 billion and our net loss for the six months ended June 30, 2020 was $130.7 million.

The net income we generated in the six months ended June 30, 2021 was primarily due to the sale of our oncology business to Servier, which was consummated on March 31, 2021.

As of June 30, 2021, we had an accumulated deficit of $55.4 million.

Prior to the sale of our oncology business to Servier, we had generated only modest revenue from sales of TIBSOVO® and, prior to our sale to Royalty Pharma, or RPI, of our royalty rights to IDHIFA®, royalties on sales of IDHIFA®.

1 unchanged sentence

We have financed our operations primarily through public offerings of our common stock and our collaboration agreements with Celgene and have devoted substantially all of our efforts to research and development.

Following the sale of our oncology business to Servier on March 31, 2021, we expect to finance our operations primarily through cash on hand.

Following the sale of our oncology business to Servier on March 31, 2021, we expect to finance our operations primarily through cash on hand, royalty payments from Servier with respect to U.S.

net sales of TIBSOVO®, a potential milestone payment from Servier if vorasidenib is approved by the FDA, future potential sales of mitapivat, if approved for marketing by regulatory authorities and successfully launched by us and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions.

We expect to continue to incur significant expenses and net losses until such time as we are able to report profitable results.

1 unchanged sentence

We anticipate that we will incur significant expenses if and as we:

• initiate and continue clinical trials for our products and product candidates;

• initiate and continue clinical trials for our product candidates;

continue our research and preclinical development of our product candidates and seek to identify additional product candidates;

21 unchanged sentences

Regulatory guidance under the Tax Act, the FFCR Act, the CARES Act, and the CAA is and continues to be forthcoming, and such guidance could ultimately increase or lessen impact of these laws on our business and financial condition.

It is also possible that Congress will enact additional legislation in

connection with the COVID-19 pandemic, some of which could have an impact on our company.

It is also possible that Congress will enact additional legislation in connection with the COVID-19 pandemic, some of which could have an impact on our company.

In addition, it is uncertain if and to what extent various states will conform to the Tax Act, the FFCR Act, the CARES Act, or the CAA.

4 unchanged sentences

Our ability to generate product revenue will depend heavily on the successful clinical development and eventual commercialization of our current and any future product candidates, including our lead product candidate mitapivat.

We have invested a significant portion of our efforts and financial resources in the identification of our product candidates and development of our most advanced programs, including mitapivat, In June 2021, we submitted an NDA to the FDA for mitapivat for the treatment of adults with PK deficiency and a MAA, for mitapivat in adults with PK deficiency to the EMA.

We, and any collaborators, are not permitted to commercialize, market, promote or sell any product candidate in the United States without obtaining marketing approval from the FDA.

15 unchanged sentences

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

enrollment in these clinical trials, which may be particularly challenging for some of the orphan diseases we target in our GDD programs, may be slower than we anticipate;

enrollment in these clinical trials, which may be particularly challenging for some of the orphan diseases we target in our GDD

programs, may be slower than we anticipate;

or participants may drop out of these clinical trials at a higher rate than we anticipate;

19 unchanged sentences

In response to the COVID-19 pandemic, we were required to close our facilities except for a limited number of essential facilities and laboratory staff.

We recently opened our Cambridge office to an additional, limited number of employees who prefer to work onsite, and our field-based employees engage with healthcare providers and other third parties remotely and, where local regulations allow, on a limited in-person basis.

We recently opened our Cambridge office to employees who prefer to work onsite all or some of the time, and our field-based employees engage with healthcare providers and other third parties remotely and, where local regulations allow, on a limited in-person basis.

We may face disruptions that may affect our ability to initiate and complete clinical trials including disruptions in procuring items that are essential for our research and development activities, including, for example, raw materials used in the manufacturing of our product candidates and laboratory supplies for planned and ongoing clinical trials, in each case, for which there may be shortages because of ongoing efforts to address the outbreak.

We have enrolled, and seek to enroll, patients in our clinical trials at sites located both in the United States and internationally.

Site initiation, participant recruitment and enrollment, participant dosing, distribution of clinical trial materials, study monitoring and data analysis has been and may continue to be paused or delayed due to changes in hospital or university policies, federal, state or local regulations, prioritization of hospital resources toward pandemic efforts, or other reasons related to the pandemic.

Site initiation, participant recruitment and enrollment, participant dosing, distribution of clinical trial materials, study monitoring and data analysis has been and may continue to be

paused or delayed due to changes in hospital or university policies, federal, state or local regulations, prioritization of hospital resources toward pandemic efforts, or other reasons related to the pandemic.

We have faced and expect to continue to face difficulties recruiting or retaining patients in our ongoing clinical trials because of the pandemic.

2 unchanged sentences

Additionally, the potential suspension of clinical trial activity at clinical trial sites may have an adverse impact on our clinical trial plans and timelines.

We have faced and may continue to face disruptions in our ability to prepare and submit applications to regulatory authorities for drug approvals and to build and maintain a commercial infrastructure for our products and product candidates.

We may face manufacturing disruptions or disruptions related to the ability to obtain necessary institutional review board or other necessary site approvals, as well as other delays at clinical trial sites.

21 unchanged sentences

Imara Inc., or Imara, is developing molecules for the treatment of beta thalassemia and SCD;

and Forma Therapeutics Holdings, LLC, or Forma, is developing a PKR activator for the treatment of hemolytic anemias, including PK deficiency and SCD.

and Forma Therapeutics Holdings, Inc., or Forma, is developing a PKR activator for the treatment of hemolytic anemias, including PK deficiency and SCD.

Competition for eligible patients may make it particularly difficult for us to enroll enough patients to complete our clinical trials for our product candidates in a timely and cost-effective manner.

We rely on contract research organization, or CROs, and clinical trial sites to ensure the proper and timely conduct of our clinical trials and while we have agreements governing their committed activities, we have limited influence over their actual performance.

Our or our collaborators’ inability to enroll a sufficient number of patients for our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether.

Our or our collaborators’ inability to enroll a sufficient number of patients for our clinical trials would result in

significant delays or may require us to abandon one or more clinical trials altogether.

Enrollment delays in our clinical trials may result in increased development costs for our product candidates, which would cause the value of our company to decline and limit our ability to obtain additional financing.

2 unchanged sentences

Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials after achieving positive results in earlier development, and we could face similar setbacks.

The design of a clinical trial can determine whether its results will support approval of a product and flaws in the design of a clinical trial may not become apparent until the clinical trial is well

We have limited experience in designing clinical trials and may be unable to design and execute a clinical trial to support marketing approval.

17 unchanged sentences

Given our limited experience in developing diagnostics, we rely and expect to continue to rely in part or in whole on third parties for their design and manufacture.

We also may in the future depend on other third parties for the development of other companion diagnostics for our therapeutic product candidates.

We also may in the future depend on other third parties for the development of other companion diagnostics for

our therapeutic product candidates.

If we or our collaborators are unable to successfully develop companion diagnostics for our therapeutic product candidates, or experience delays in doing so:

31 unchanged sentences

To achieve commercial success for approved medicines for which we retain sales and marketing responsibilities, we must either develop a sales and marketing organization or outsource these functions to other third parties.

Although we had established sales and marketing capabilities to support our co-promotion efforts for IDHIFA® and our sales of TIBSOVO® prior to the sale of our oncology business to Servier, we will need to further build our sales and marketing infrastructure to sell, or participate in sales activities with any collaborators for, our other product candidates if and when they are approved.

Although we had established sales and marketing capabilities to support our co-promotion efforts for IDHIFA® and our sales of TIBSOVO® prior to the sale of our oncology business to

Servier, we are in the process of building our sales and marketing infrastructure to sell, or participate in sales activities with any collaborators for, our other product candidates if and when they are approved.

There are risks involved with both establishing our own sales and marketing capabilities and entering into arrangements with third parties to perform these services.

12 unchanged sentences

We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.

We face competition with respect to our current products and product candidates, and we and our collaborators will face competition with respect to any product candidates that we or they may seek to develop or commercialize in the future.

We face competition with respect to our current product candidates, and we and our collaborators will face competition with respect to any product candidates that we or they may seek to develop or commercialize in the future.

Potential competitors include major pharmaceutical companies, specialty pharmaceutical companies, biotechnology companies, academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.

2 unchanged sentences

and bluebird bio, Inc., or bluebird, are each marketing therapies to treat beta thalassemia, Novartis International AG and Global Blood Therapeutics are each marketing therapies to treat SCD, Rocket Pharma is conducting a clinical trial of a gene therapy targeting PK deficiency, and a number of other biotechnology companies have product candidates in clinical development in similar indications as ours.

Some competitive products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely different approaches, for example, in the area of GDDs.

We are developing product candidates to treat patients with GDDs.

9 unchanged sentences

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.

Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.

Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources

being concentrated among a smaller number of our competitors.

Smaller and other clinical stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

If the FDA does not grant our products appropriate periods of data exclusivity before approving generic versions of our products, the sales of our products could be adversely affected.

If the FDA does not grant our products, if and when approved, appropriate periods of data exclusivity before approving generic versions of our products, the sales of our products could be adversely affected.

With FDA approval of an NDA, the product covered by the application is specified as a “reference-listed drug” in the FDA’s publication, “Approved Drug Products with Therapeutic Equivalence Evaluations,” or the Orange Book.

2 unchanged sentences

Rather, the applicant generally must show that its product has the same active ingredient(s), dosage form, strength, route of administration and conditions of use or labeling as the reference-listed drug and that the generic version is bioequivalent to the reference-listed drug, meaning it is absorbed in the body at the same rate and to the same extent.

Generic products may be significantly less costly to bring to market than the reference-listed drug and companies that produce generic products are generally able to offer

them at lower prices.

Generic products may be significantly less costly to bring to market than the reference-listed drug and companies that produce generic products are generally able to offer them at lower prices.

Thus, following the introduction of a generic drug, a significant percentage of the sales of any reference-listed drug may be typically lost to the generic product.

16 unchanged sentences

We could be subject to risks caused by misappropriation, misuse, leakage, falsification or intentional or accidental release or loss of information maintained in the information systems and networks of our company, including personal information of our employees.

System failures, accidents, cyber incidents or security breaches could cause interruptions in our operations, and could result in a material disruption of our clinical and commercialization activities and business operations, whether due to a loss of our trade secrets or other proprietary information or other similar disruptions, in addition to possibly requiring substantial expenditures of resources to remedy.

secrets or other proprietary information or other similar disruptions, in addition to possibly requiring substantial expenditures of resources to remedy.

For example, the loss of clinical trial data from completed or future trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.

54 unchanged sentences

For example, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable protocol and legal, regulatory and scientific standards, and our reliance on third parties does not relieve us of our responsibility to comply with any such standards.

We and these third parties are required to comply with current good clinical practices, or cGCP, which are regulations and guidelines enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area and comparable foreign regulatory authorities for all of our products in clinical development.

Regulatory authorities enforce these cGCPs through periodic inspections of trial sponsors, principal investigators and trial sites.

2 unchanged sentences

We also are required to register ongoing clinical trials and post the results of completed clinical trials on a U.S.

government-sponsored database, clinicaltrials.gov, within certain timeframes.

government-sponsored database,

clinicaltrials.gov, within certain timeframes.

Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.

7 unchanged sentences

We currently rely, and expect to continue to rely, on third-party manufacturers for the materials and manufacture of our product candidates for preclinical and clinical testing and expect to rely on third-party manufacturers for commercial supply of any product candidate for which we or our collaborators obtain marketing approval.

Although we had long-term supply agreements in place for commercial supply of TIBSOVO® with third-party manufacturers prior to the sale of our oncology business to Servier, we may be unable to establish similar long-term supply agreements with respect to our GDD product candidates with third-party manufacturers or to do so on acceptable terms.

Although we had long-term supply agreements in place for commercial supply of TIBSOVO® with third-party manufacturers prior to the sale of our oncology business to Servier, we may be unable to establish similar long-term supply agreements with third-party manufacturers with respect to our GDD product candidates or to do so on acceptable terms.

Even if we are able to establish agreements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including:

2 unchanged sentences

• the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.

Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements on a global basis.

Third-party manufacturers may not be able to comply with current good manufacturing practices, or cGMP.

regulations or similar regulatory requirements on a global basis.

Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or medicines, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our medicines and harm our business and results of operations.

8 unchanged sentences

Risks Related to Our Intellectual Property

If we are unable to obtain and maintain patent or trade secret protection for our medicines and technology, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize medicines and technology similar or identical to ours, and our ability to successfully commercialize our medicines and technology may be adversely affected.

technology similar or identical to ours, and our ability to successfully commercialize our medicines and technology may be adversely affected.

Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary medicines and technology.

3 unchanged sentences

It is also possible that we will fail to identify and/or file patent applications on every aspect of our research and development output that is or may be eligible for patent protection.

Although we enter into non-disclosure and confidentiality agreements with parties who may have access to patentable aspects of our research and development output, such as our employees, corporate collaborators, outside scientific collaborators, contract research organizations, contract manufacturers, consultants, advisors and other third parties, any of these parties may breach the agreements and disclose such output before a patent application is filed, thereby jeopardizing our ability to seek

patent protection.

There is also the possibility that loss or theft of data or records may jeopardize the ability to seek patent protection or impede the progress or drafting of patent applications.

21 unchanged sentences

Such challenges may result in loss of the patent or in one or more patent claims being narrowed or invalidated, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and medicines.

Given the significant amount of time required for the discovery, development, preclinical and clinical testing and regulatory review and approval of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.

Given the significant amount of time required for the discovery, development, preclinical and clinical testing

and regulatory review and approval of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.

As a result, our intellectual property may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

5 unchanged sentences

An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly.

because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation.

Third parties may initiate legal proceedings alleging that we or our collaborators are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

23 unchanged sentences

In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.

Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities.

Such litigation or proceedings could substantially increase our operating losses and reduce the resources

available for development activities or any future sales, marketing or distribution activities.

We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings.

20 unchanged sentences

The FDA, EMA and other foreign regulatory authorities have substantial discretion in the approval process.

Accordingly, it is possible that the FDA or EMA may refuse to accept for substantive review any NDA, sNDA or MAA that we submit for our product candidates, or may conclude after review of our data that our marketing application is insufficient to obtain marketing approval of our product candidates.

If the FDA or EMA does not accept or approve our applications for any of our product candidates, the applicable regulator may require that we conduct additional clinical trials, preclinical studies or manufacturing validation studies and submit that data before reconsidering our applications.

2 unchanged sentences

We may not be successful in obtaining FDA or EMA approval of our product candidates on a timely basis, or ever.

We have limited experience in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third-party contract research organizations to assist us in this process, and failure to obtain marketing approval for our products or product candidates will prevent us from commercializing the product or product candidate in the applicable jurisdictions.

We have limited experience in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third-party contract

research organizations to assist us in this process, and failure to obtain marketing approval for our product candidates will prevent us from commercializing the product candidate in the applicable jurisdictions.

Further, the process of obtaining marketing approvals, both in the United States and abroad, is expensive, may take many years if additional clinical trials are required, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved.

4 unchanged sentences

and international healthcare and regulatory systems.

These disruptions could materially delay the review of, and/or decision making with respect to, marketing approvals for our

product candidates.

These disruptions could materially delay the review of, and/or decision making with respect to, marketing approvals for our product candidates.

Any delay in regulatory review or decision making resulting from such disruptions could materially affect the development of our product candidates.

3 unchanged sentences

If a prolonged government shutdown were to occur, 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.

The Trump Administration also took several executive actions that could impose significant burdens on, or otherwise materially delay, the FDA’s ability to engage in routine regulatory and oversight activities.

If we or our collaborators experience delays in obtaining approval or if we or they fail to obtain approval of our product candidates, the commercial prospects for our product candidates may be harmed and our ability to generate revenue will be materially impaired.

24 unchanged sentences

Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs and biologics for relatively small patient populations as orphan drugs.

Under the Orphan Drug Act, the FDA may designate a product as an

orphan drug if it is a drug or biologic intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States.

Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is a drug or biologic intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States.

Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the EMA or the FDA from approving another marketing application for the same product for that time period.

15 unchanged sentences

Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval.

Our future arrangements with healthcare providers, physicians and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute any medicines for which we obtain marketing approval.

Our future arrangements with healthcare providers, physicians and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may

constrain the business or financial arrangements and relationships through which we market, sell and distribute any medicines for which we obtain marketing approval.

Restrictions under applicable federal and state healthcare laws and regulations include the following:

• the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;

of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties;

• the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties;

• the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

19 unchanged sentences

If coverage and reimbursement is not available, or reimbursement is available only to limited levels, we, or any collaborators, may not be able to successfully commercialize our product candidates.

Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us, or any future collaborators, to establish or maintain pricing sufficient to realize a sufficient return on our or their investments.

Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us, or any future collaborators, to

establish or maintain pricing sufficient to realize a sufficient return on our or their investments.

In the United States, no uniform policy of coverage and reimbursement for products exists among third-party payors and coverage and reimbursement for products can differ significantly from payor to payor.

5 unchanged sentences

In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted.

In these countries, pricing negotiations with

governmental authorities can take considerable time after the receipt of marketing approval for a product.

In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product.

To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost effectiveness of our product candidates to other available therapies.

20 unchanged sentences

In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.

This legislation resulted in aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which will remain in effect through 2030 under the CARES Act.

This legislation resulted in aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which will remain in effect through 2030 under the

The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

2 unchanged sentences

For example, in 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.

On November 10, 2020, the Supreme Court heard oral arguments as to whether 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 February 10, 2021, the Biden Administration withdrew the federal government’s support for overturning the ACA.

A ruling by the Supreme Court is expected sometime this year.

On June 17, 2021, the Supreme Court struck down the lower court rulings, finding that the plaintiffs did not have standing to challenge the ACA’s minimum essential coverage provision at issue in the case.

The Trump Administration also took executive actions to undermine or delay implementation of the ACA, including directing federal agencies with authorities and responsibilities under the ACA to waive, defer, grant exemptions from, or delay the implementation of any provision of the ACA that would impose a fiscal or regulatory burden on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices.

On January 28, 2021, however, President Biden issued a new Executive Order which directs federal agencies to reconsider rules and other policies that limit Americans’ access to health care, and consider actions that will protect and strengthen that access.

On January 28, 2021, however, President Biden revoked these Orders and issued a new Executive Order which directs federal agencies to reconsider rules and other policies that limit Americans’ access to health care, and consider actions that will protect and strengthen that access.

This Executive Order also directs the U.S.

1 unchanged sentence

We cannot predict how federal agencies will respond to such Executive Orders.

The costs of prescription pharmaceuticals in the United States and foreign jurisdictions is subject to considerable legislative and executive actions and could impact the prices we obtain for our drug products, if and when approved.

The costs of prescription pharmaceuticals in the United States and foreign jurisdictions are subject to considerable legislative and executive actions and could impact the prices we obtain for our drug products, if and when approved.

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

18 unchanged sentences

Travel Act, the USA PATRIOT Act, and other state and national anti-bribery and anti-money laundering laws in countries in which we conduct activities.

Anti-corruption laws are interpreted broadly and prohibit companies and their employees, agents, third-party intermediaries, joint venture partners and collaborators from authorizing, promising, offering, or providing, directly or indirectly, improper payments or benefits to recipients in the public or private sector.

providing, directly or indirectly, improper payments or benefits to recipients in the public or private sector.

We may have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations.

3 unchanged sentences

If any subpoenas, investigations, or other enforcement actions are launched, or governmental or other sanctions are imposed, or if we do not prevail in any possible civil or criminal litigation, our business, results of operations and financial condition could be materially harmed.

In addition, responding to any action will likely result in a materially significant diversion of management’s attention

and resources and significant defense and compliance costs and other professional fees.

In addition, responding to any action will likely result in a materially significant diversion of management’s attention and resources and significant defense and compliance costs and other professional fees.

In certain cases, enforcement authorities may even cause us to appoint an independent compliance monitor which can result in added costs and administrative burdens.

23 unchanged sentences

Our current and prospective employees may feel uncertain about their roles with us now that we are a smaller company focused on GDDs, which may have an adverse effect on our ability to attract or retain key management personnel or other key employees.

Furthermore, the ongoing COVID-19 pandemic and our associated work from home policy may make it difficult for us to maintain our corporate culture.

Furthermore, the ongoing COVID-19 pandemic and our flexible workplace policy allowing employees to work from home may make it difficult for us to maintain our corporate culture.

We expect to continue to experience growth in the number of our employees as we expand our development, regulatory and future sales and marketing capabilities.

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

To manage our anticipated future growth, we must continue to implement and improve

our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel.

Any inability to manage growth could delay the execution of our business plans or disrupt our operations.

3 unchanged sentences

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

We have adopted a Code of Business Conduct and Ethics, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental

investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions.

27 unchanged sentences

For example, since January 1, 2015 the price of our common stock on the Nasdaq Global Select Market has ranged from $27.77 per share to $138.85 per share.

The stock market in general and the market for biopharmaceutical companies in particular have experienced extreme volatility that has often been unrelated

to the operating performance of particular companies.

The stock market in general and the market for biopharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.

While the full extent of the economic impact and the duration of the COVID-19 pandemic may be difficult to assess or predict, it has already caused, and is likely to result in further, significant disruption of global financial markets, which may reduce our ability to access capital either at all or on favorable terms.

11 unchanged sentences

• the level of expenses related to any of our product candidates or clinical development programs;

• the results of our efforts to develop additional product candidates or products;

• the results of our efforts to develop additional product candidates;

• actual or anticipated changes in estimates as to financial results or development timelines;

16 unchanged sentences

Our executive officers, directors and principal stockholders maintain the ability to significantly influence all matters submitted to stockholders for approval.

As of March 31, 2021, our executive officers, directors and principal stockholders, in the aggregate, beneficially owned shares representing a significant percentage of our capital stock.

As of June 30, 2021, our executive officers, directors and principal stockholders, in the aggregate, beneficially owned shares representing a significant percentage of our capital stock.

As a result, if these stockholders were to choose to act together, they would be able to significantly influence all matters submitted to our stockholders for approval, as well as our management and affairs.

25 unchanged sentences

There can be no assurance that we will repurchase shares of our common stock or that we will repurchase shares at favorable prices.

In March 2021, our board of directors authorized a share repurchase program to purchase up to $1.2 billion of our common stock.

Following our repurchase of approximately $344.5 million of shares of our common stock from affiliated of BMS in April 2021, we had remaining available approximately $855.5 million to repurchase additional shares pursuant to this program, of which we committed up to $600 million in the form of a Rule 10b5-1 repurchase plan.

The amount and timing of share repurchases are subject to capital availability, our cash balances and future capital requirements and our determination that share repurchases are in the best interest of our shareholders and are in compliance with all respective laws and our applicable agreements.

A reduction in repurchases under, or the completion of, our share repurchase programs could have a negative effect on our stock price.

On March 25, 2021, we announced that our board of directors authorized the Repurchase Program for the repurchase of up to $1.2 billion of our outstanding shares of common stock.

On March 31, 2021, in connection with the Repurchase Program, we

entered into a definitive share repurchase agreement with BMS to repurchase 7,121,658 shares of our common stock held by certain subsidiaries of BMS for an aggregate purchase price of $344.5 million, or $48.3785 per share.

This repurchase was completed on April 5, 2021.

Further, on April 2, 2021, in connection with the Repurchase Program, we entered into a Rule 10b5-1 repurchase plan to which we may repurchase up to $600 million of shares of our common stock.

As of June 30, 2021, we have repurchased approximately 3.4 million shares of common stock for $184.5 million, or $54.71 per share, under the plan with approximately $415.5 million remaining under the plan for additional repurchases.

In total, as of June 30, 2021, we have repurchased 10.5 million common shares for $529.0 million under the Repurchase Program.

The amount and timing of share repurchases are subject to capital availability, our cash balances and future capital requirements and our determination that share repurchases are in the best interest of our stockholders and are in compliance with all respective laws and our applicable agreements.

A reduction in repurchases under, or the completion of, our share Repurchase Program could have a negative effect on our stock price.

We can provide no assurance that we will repurchase shares at favorable prices, if at all.

3 unchanged sentences

As a result, capital appreciation, if any, of our common stock will be the sole source of gain for our stockholders for the foreseeable future.

Incorporated by Reference

Description of Exhibit

Date of Filing

3.1 Restated Certificate of Incorporation

July 30, 2013 3.1

3.2 Second Amended and Restated By-Laws

December 19, 2018 3.1

10.1 Share Repurchase Agreement, dated as of March 31, 2021, by and between Agios Pharmaceuticals, Inc.

and Bristol-Myers Squibb Company

April 2, 2021 10.1

31.1 Certification of principal executive officer pursuant to Rule 13a 14(a)/15d 14(a) of the Securities Exchange Act of 1934, as amended

31.2 Certification of principal financial officer pursuant to Rule 13a-14(a)/15d-14(a) of the Securities Exchange Act of 1934, as amended.

32.1* Certification of principal executive officer pursuant to 18 U.S.C.

§1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.

32.2* Certification of principal financial officer pursuant to 18 U.S.C.

§1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.

XBRL Instance Document - the instance document does not appear in the Interactive Data File because its XBRL tags are not embedded within the Inline XBRL document

XBRL Taxonomy Extension Schema Document

XBRL Taxonomy Calculation Linkbase Document

XBRL Taxonomy Extension Definition Linkbase Document

XBRL Taxonomy Label Linkbase Document

XBRL Taxonomy Presentation Linkbase Document

104 Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101.INS) X

* This certification will not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, or otherwise subject to the liability of that section.

Such certification will not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except to the extent specifically incorporated by reference into such filing.

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

AGIOS PHARMACEUTICALS, INC.

April 29, 2021 By:

/s/ Jacqualyn A.

Chief Executive Officer

(principal executive officer)

April 29, 2021 By:

/s/ Jonathan Biller

Jonathan Biller

Chief Financial Officer and Head of Legal and Corporate Affairs

(principal financial officer)

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