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Item 1A. Risk Factors

2025-05-07 compared with 2024-11-07 · 515 added, 405 removed, 848 unchanged (52% of the section changed)

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Consequently, you should not consider this summary to be a complete discussion of all potential risks or uncertainties that may substantially impact our business.

Additional discussion of the risks and uncertainties summarized in this risk factor summary, as well as other risks and uncertainties that we face, are described under the heading “Risk Factors” below, and this summary is qualified in its entirety by that discussion.

Additional discussion of the risks and uncertainties summarized in this risk factor summary, as well as other risks and uncertainties that we face, are described under the heading “Risk Factors”below, and this summary is qualified in its entirety by that more complete discussion of such risks and uncertainties.

Moreover, we operate in a competitive and rapidly changing environment.

New factors emerge from time to time and it is not possible to predict the impact of all of these factors on our business, financial condition or results of operations.

You should consider carefully the risks and uncertainties described under the heading “Risk Factors” below.

Risks Related to the Commercialization of RYTELO TM (Imetelstat)

You should consider carefully the risks and uncertainties described under the heading “Risk Factors” below as part of your evaluation of an investment in our common stock.

Risks Related to the Commercialization of RYTELO ® (Imetelstat)

• Our near-term prospects are wholly dependent on RYTELO.

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• If we are unable to continue to execute on our sales, marketing and distribution plans to commercialize RYTELO, we may be unable to generate meaningful product revenue.

• If we do not obtain acceptable prices or adequate reimbursement for RYTELO, the use of RYTELO could be severely limited.

• If we do not maintain acceptable prices or adequate reimbursement for RYTELO, the use of RYTELO could be severely limited.

• To be commercially successful, RYTELO must be accepted by the healthcare community, which can be slow to adopt or unreceptive to new technologies and products.

• If the market opportunities for RYTELO are smaller than we believe, our revenue may be adversely affected and our business may suffer.

• If competitors develop products, product candidates or technologies that are superior to or more cost-effective than RYTELO, it would significantly impact the development and commercial viability of RYTELO, which would severely and adversely affect our financial results, business and business prospects, and the future of RYTELO, and might cause us to cease operations.

• We rely on a select network of third party distributors, specialty pharmacies and other vendors to distribute RYTELO, and any failure by such distributors, specialty pharmacies and vendors could adversely affect our revenues, financial condition, or results of operations.

• We are seeking regulatory approval to commercialize RYTELO in the EU, and any such approval, if received, will be subject to pricing, drug marketing and reimbursement regulations in the EU, which may materially affect our ability to commercialize and receive reimbursement coverage for RYTELO in the EU.

• We will be subject to pricing, drug marketing and reimbursement regulations in the European Union, or EU, which may materially affect our ability to commercialize and receive reimbursement coverage for RYTELO in the EU.

Risks Related to Regulatory Approval of RYTELO

• We may be unable to maintain regulatory approval from the FDA for RYTELO in the U.S.

for lower-risk MDS, which would severely and adversely affect our business and business prospects, and might cause us to cease operations.

• Our regulatory approval for RYTELO in the U.S.

for lower-risk MDS is subject to certain post-marketing requirements and commitments, and we may be subject to penalties or product withdrawal if we fail to comply with such regulatory requirements or commitments, or if we experience unanticipated problems with RYTELO.

• We may be unable to obtain regulatory approval to commercialize RYTELO in any other jurisdictions or for any new indications, or may experience significant delays in doing so, any of which could severely and adversely affect our business and business prospects, and might cause us to cease operations.

• Although orphan drug designation has been granted to RYTELO for the treatment of MDS and MF in the U.S.

and in the EU, these designations may not be maintained, which would eliminate the benefits associated with orphan drug

designation, including market exclusivity, which could limit the period of exclusivity we are able to maintain for the commercialization of RYTELO, and would likely harm our business and business prospects.

• We may be unable to maintain regulatory approvals for RYTELO in the U.S.

and the EU for lower-risk MDS, which would severely and adversely affect our business and business prospects, and might cause us to cease operations.

• Our regulatory approvals for RYTELO for lower-risk MDS are subject to certain post-marketing requirements and commitments, and we may be subject to penalties or product withdrawal if we fail to comply with such regulatory requirements or commitments, or if we experience unanticipated problems with RYTELO.

• We may be unable to obtain regulatory approval to commercialize RYTELO in other jurisdictions or for any new indications, or may experience significant delays in doing so, any of which could severely and adversely affect our business and business prospects, and might cause us to cease operations.

Risks Related to Compliance with Healthcare Laws

• The FDA, the Department of Justice, or DOJ, and other regulatory authorities actively enforce regulations related to the promotion and advertisement of pharmaceutical products, and if we were found to have violated the Food, Drug and Cosmetic Act, we could be subject to significant penalties, including civil, criminal and administrative penalties.

• If our business activities become subject to challenge under supranational, national, federal, state or international healthcare laws, including fraud and abuse, transparency, and health information privacy and security laws, we could face substantial penalties and our business, results of operations, financial condition and prospects could be adversely affected.

• The adoption of health policy changes and healthcare reform both in the U.S.

and outside the U.S.

may adversely affect our business and financial results.

Risks Related to the Further Development of RYTELO (Imetelstat)

• We cannot be certain that we will be able to continue to develop RYTELO (imetelstat) or advance it in clinical trials, or that we will be able to receive regulatory approval for RYTELO in any other indications in the U.S., the EU or any other region, on a timely basis or at all.

• RYTELO (imetelstat) may cause, or have attributed to it, undesirable or unintended side effects or other adverse events that could halt or limit its commercialization, delay or prevent its regulatory approval in any other jurisdiction or indication, or cause us to delay or terminate our clinical trials.

Risks Related to the Further Development of Imetelstat

• We cannot be certain that we will be able to continue to develop imetelstat or advance it in clinical trials, or that we will be able to receive regulatory approval for imetelstat in any other indications in the U.S., the EU, or any other region, on a timely basis or at all.

• RYTELO may cause, or have attributed to it, undesirable or unintended side effects or other adverse events that could halt or limit its further commercialization, delay or prevent its regulatory approval in any other jurisdiction or indication, or cause us to delay or terminate our clinical trials.

• Results and data we disclosed from prior non-clinical studies and clinical trials may not predict success in later clinical trials, and we cannot assure you that any ongoing or future clinical trials of imetelstat, including IMpactMF, will lead to similar results and data that could potentially enable us to obtain any further regulatory approvals.

• We rely on third parties to conduct our current and potential future clinical trials of imetelstat.

If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may be unable to continue the development of imetelstat.

• We do not control the conduct of current or any potential future investigator-led clinical trials, and data from such trials could show marginal efficacy and/or clinically relevant safety concerns related to imetelstat resulting in an unfavorable benefit-risk assessment that could materially and adversely impact our ongoing clinical trials, or our imetelstat development program as a whole.

Risks Related to Manufacturing RYTELO

• Failure by us to maintain a manufacturing supply chain to appropriately and adequately supply RYTELO for commercial and future clinical uses would adversely affect our ability to commercialize RYTELO and result in a further delay in or cessation of clinical trials, and our business and business prospects could be severely harmed.

• If third parties that manufacture RYTELO fail to perform as needed, the commercial and clinical supply of RYTELO will be limited, and we may be unable to successfully commercialize RYTELO or conduct or complete current or potential future clinical trials.

Risks Related to Our Operating Results, Financial Position and Need for Additional Capital

• We have a history of net losses.

We expect to continue to incur net losses in the near term and may not achieve consistent future profitability for some time, if ever.

• If third parties that manufacture RYTELO fail to perform as needed, the commercial and clinical supply of RYTELO could be interrupted or limited, and we may be unable to successfully commercialize RYTELO or conduct or complete current or potential future clinical trials.

Ris ks Related to Our Operating Results, Financial Position and Need for Additional Capital

• We have a history of net losses and may not achieve consistent future profitability for some time, if ever.

• Our operating results are unpredictable and may fluctuate.

If our operating results are below the expectations of securities analysts or investors, the trading price of our common stock could decline.

• Our failure to obtain additional capital when needed would force us to further delay, reduce or eliminate the further development of imetelstat, or to halt the commercialization of RYTELO, any of which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

If our operating results are below the expect ations of securities analysts or investors, the trading price of our common stock could decline.

• Our failure to obtain additional capital if and when needed would force us to further delay, reduce or eliminate the further development of imetelstat, or to halt the commercialization of RYTELO, any of which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

Risks Related to Our Indebtedness and Liabilities

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Risks Related to Protecting Our Intellectual Property

• If we are unable to obtain and maintain sufficient intellectual property protection for RYTELO, our competitors could develop and commercialize products similar or identical to RYTELO, and our ability to successfully commercialize RYTELO may be adversely affected.

• Obtaining and maintaining our patent rights depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for noncompliance with these requirements.

• Patent terms may be inadequate to protect our competitive position on RYTELO for an adequate amount of time.

• The validity, scope and enforceability of any patents listed in the Orange Book that cover RYTELO or its methods of use can be challenged by third parties and may not protect us from generic or innovator competition.

Risks Related to Information Technology Systems, Data Security and Data Privacy

• If our information technology systems or data, or those of third parties upon which we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including regulatory investigations or actions;

fines and penalties;

a disruption of our business operations, including our clinical trials;

reputational harm;

loss of revenue and profits;

and other adverse consequences.

• If we are unable to obtain and maintain sufficient intellectual property protection and relevant regulatory exclusivities for RYTELO, our competitors could develop and commercialize products similar or identical to RYTELO, and our ability to successfully commercialize RYTELO may be adversely affected.

Risks Related to Our Common Stock and Financial Reporting

• Historically, our stock price has been extremely volatile, and your investment may suffer a decline in value.

Risks Related to Managing Our Growth and Other Business Operations

• We and certain of our current and former officers have been named as defendants in securities class action lawsuits and derivative lawsuits.

These lawsuits, and potential similar or related lawsuits, could result in substantial damages, divert management’s time and attention from our business, and have a material adverse effect on our results of operations.

These lawsuits, and any other lawsuits to which we are subject, will be costly to defend or pursue and are uncertain in their outcome.

We operate in a dynamic and rapidly changing environment involving numerous risks and uncertainties that may have a material adverse effect on our business, financial condition or results of operations.

You should carefully consider the risks and uncertainties described below, together with all of the other information included in this Report.

Our business faces significant risks and uncertainties, and those described below may not be the only risks and uncertainties we face.

You should carefully consider the following risk factors, together with the information contained herein and in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission, or SEC, on February 28, 2024, including our consolidated financial statements and the related notes, and our other filings with the SEC, before deciding whether to invest in our common stock.

Additional risks and uncertainties not presently known to us or that we currently believe are immaterial may also significantly impair our business, financial condition or results of operations.

If any of these risks or uncertainties occur, our business, financial condition or results of operations could suffer, the market price of our common stock could decline and you could lose all or part of your investment in our common stock.

Risks Related to THE Commercialization of RYTELO

RISKS RELATED TO THE COMMERCIALIZATION OF RYTELO ® (IMETELSTAT)

Our near-term prospects are wholly dependent on RYTELO.

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in that indication.

RYTELO is our only product approved for marketing by the FDA, and our ability to generate revenue from product sales and achieve profitability is wholly dependent on our ability to successfully commercialize RYTELO in the U.S.

RYTELO is our only product approved for marketing by the FDA, and our ability to generate meaningful revenue from product sales and achieve profitability is wholly dependent on our ability to successfully commercialize RYTELO in the U.S.

for lower-risk MDS or to expand its indications of use.

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• our limited historical experience in marketing, selling and distributing RYTELO;

• reimbursement and coverage policies of government and private payers such as Medicare, Medicaid, insurance companies, health maintenance organizations and other plan administrators;

• reimbursement and coverage policies of government and private payors such as Medicare, Medicaid, insurance companies, health maintenance organizations and other plan administrators;

• the relative price of RYTELO as compared to alternative treatment options;

• the relatively low incidence and prevalence of patients in RYTELO’s approved indication, including the reliability of our market and sales estimates;

• the market penetration rate of RYTELO across the breadth of eligible patient segments in its approved indication may continue to be lower than our expectations;

• future competitive or other market factors may adversely affect the commercial potential of RYTELO;

• we may not be able to obtain and maintain regulatory approvals for RYTELO in any other jurisdictions or for any other indications, including in the EU for lower-risk MDS or in any other jurisdiction for relapsed/refractory MF;

• we may not be able to obtain and maintain regulatory approvals for RYTELO in any other jurisdictions for lower-risk MDS or for any other indications, including relapsed/refractory MF;

• changed or increased regulatory restrictions;

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We have limited experience as a commercial company and our sales, marketing, and distribution of RYTELO may be unsuccessful or less successful than anticipated.

As a company, we have limited prior experience in selling and marketing or commercializing an approved drug product in the U.S., and we have no experience marketing or commercializing an approved drug outside of the U.S.

As a company, we have limited prior experience in selling and marketing or commercializing an approved drug product in the U.S., and we have no experience selling, marketing or commercializing an approved drug outside of the U.S.

The success of our commercialization efforts is subject to, among other things, managing our internal sales, marketing, and distribution capabilities and our ability to navigate the significant expenses and risks involved with the management of such capabilities.

For example, our commercial launch of RYTELO in the U.S.

may not continue as planned or anticipated, which may require us to, among others, adjust or amend our commercialization plan and incur significant expenses.

For example, although we have generated approximately $115.9 million in net product revenues since our commercial launch of RYTELO in the U.S.

through March 31, 2025, as previously disclosed, weekly sales growth of RYTELO has been relatively flat since the end of the fourth quarter of 2024, which has continued in the first quarter of 2025.

Our priority is to drive new patient starts across the breadth of the eligible patient population in RYTELO’s approved indication in the U.S.

Our strategy to drive sales growth in the U.S.

is currently focused on three key areas:

investing additional resources to increase brand awareness, including increasing the size of our commercial and medical field forces;

refining our marketing and medical efforts to enhance prescribing clarity and confidence with the approved use of RYTELO;

and implementing programs to expand key opinion leader support and advocacy.

However, this strategy and our ongoing commercialization efforts may not achieve meaningful sales growth, which may require us to, among other things, further adjust or amend our commercialization strategy and plans and incur significant expenses, and there can be no assurance that we will be able to grow RYTELO net product revenues in future periods.

In particular, our strategy may be unable to drive new patient starts across the breadth of the eligible patient population in RYTELO's approved indication in a timely manner or at all, or the duration of therapy could be shorter than we expect, each of which would limit RYTELO's growth potential and could preclude or delay our ability to generate meaningful revenue from product sales and to achieve profitability.

Further, given our limited historical experience commercializing drug products, we do not have a track record of successfully executing a commercial launch.

If we are unsuccessful in accomplishing our objectives or if our commercialization efforts do not continue as planned, we may not be able to successfully commercialize RYTELO in lower-risk MDS, we may require significant additional capital and financial resources, we may not become profitable, and we may not be able to compete against more established companies in our industry, any of which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

If we are unsuccessful in accomplishing our objectives from our commercialization efforts and strategy, or they are not executed as planned, we may not be able to generate meaningful revenues from the commercialization of RYTELO in lower-risk MDS, we may require significant additional capital and financial resources, we may not become profitable, and we may not be able to compete against more established companies in our industry, any of which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

If we are unable to continue to execute on our sales, marketing and distribution plans to commercialize RYTELO, we may be unable to generate meaningful product revenue.

To successfully commercialize RYTELO in the U.S., we need to continue to execute on our sales, marketing and distribution plans.

The ongoing execution of our sales, marketing and distribution plans is, and will continue to be, expensive and time-consuming and we cannot be certain that we will be able to continue to execute on these plans successfully.

To successfully commercialize RYTELO in the U.S., we need to continue to execute on our sales, marketing and distribution plans, including on our efforts to drive new patient starts in RYTELO's approved indication.

The ongoing execution of our sales, marketing and distribution plans requires investment of capital and time, and we cannot be certain that we will be able to execute on our plans successfully in a timely manner or at all.

In addition, we compete with many companies that currently have extensive, experienced and well-funded sales, distribution and marketing operations to recruit, hire, train and retain marketing and sales personnel.

If we are unable to recruit as needed, and to retain and effectively train marketing and sales personnel and equip them with compliant and effective materials, our efforts to successfully commercialize RYTELO could be adversely affected.

We currently have no marketing or sales organization outside of the U.S.

We do not yet have any products approved for sale outside of the U.S, and we, as a company, have no experience selling and marketing approved drugs outside of the U.S.

To successfully commercialize any approved drugs outside of the U.S, we will need to develop these capabilities, either on our own or with others.

Doing so will be expensive, difficult and time-consuming.

If we receive regulatory approval to commercialize RYTELO in any other regions, such as the EU, we may seek strategic partnerships, collaborations, alliances or licensing arrangements, at an appropriate time, to assist us in the potential development and commercialization of RYTELO, or we may seek to self-commercialize and need to establish business operations in such regions.

We may be unsuccessful in our efforts to recruit, hire, train and retain personnel to support such business operations;

or we may be unable to enter into and conduct successful strategic partnerships, collaborations, alliances or licensing arrangements with third parties to commercialize RYTELO in such regions, should we seek to do so.

Any failure or delay in the development of our internal sales, marketing and distribution capabilities would adversely impact the commercialization of RYTELO outside the U.S..

Further, given our lack of prior experience in marketing and selling our product, our initial estimate of the size of the required sales force may be materially more or less than the size of the sales force actually required to effectively commercialize our product.

As such, we may be required to hire substantially more sales representatives and medical support liaisons to adequately support the commercialization of RYTELO, if approved, or we may incur excess costs as a result of hiring more sales representatives than necessary.

With respect to certain geographical markets, we may enter into arrangements with other entities to utilize their local marketing and distribution capabilities, but we may be unable to enter into such arrangements on favorable terms, if at all.

If our potential future partners do not commit sufficient resources to commercialize our future products, if any, and we are unable to develop the necessary marketing capabilities on our own, we will be unable to generate sufficient product revenue to sustain our business.

If we are unable to establish sales and marketing capabilities for RYTELO, whether on our own or through collaborations, our results of operations will be negatively impacted.

If we are unable to recruit as needed, and to retain and effectively train marketing, sales and medical personnel and equip them with compliant and effective materials, our efforts to successfully commercialize RYTELO could be adversely affected.

Although we received marketing authorization for RYTELO in the EU for the treatment of certain adult patients with transfusion-dependent anemia due to lower-risk MDS in March 2025, we currently have no marketing or sales organization outside of the U.S., and as a company, we have no experience selling and marketing approved drugs

outside of the U.S.

To successfully commercialize RYTELO in the EU or in any other regions outside the U.S.

where we might seek marketing authorization in the future, we will need to develop these capabilities, which we plan to do by working with experienced third-party contractors or commercialization partners.

Doing so will require additional investment of capital and time.

Particularly in light of our current priority to drive new patient starts across the breadth of the eligible patient population in RYTELO’s approved indication in the U.S., we currently intend to seek contractual arrangements, strategic partnerships, collaborations, alliances or licensing arrangements with third parties to assist us in the commercialization of RYTELO in the EU and in any other regions outside of the U.S.

where RYTELO may be approved for marketing in the future.

However, we may be unable to enter into and conduct successful contractual arrangements, strategic partnerships, collaborations, alliances or licensing arrangements with third parties to commercialize RYTELO in the EU or in any other regions where RYTELO may be approved for marketing in the future.

Any failure or delay in entering into and conducting such contractual arrangements, strategic partnerships, collaborations, alliances or licensing arrangements with third parties would adversely impact the commercialization of RYTELO in the EU or in any other regions outside the U.S.

where RYTELO may be approved for marketing in the future.

Further, given our limited experience in marketing and selling RYTELO, we continue to evaluate and adapt our strategy in response to experience in the marketplace and have determined to expand our field sales force and medical support liaisons to support our U.S.

commercialization efforts.

However, we may determine that we need further changes in the future that require additional hiring to further expand our field sales force and medical support liaisons to adequately support the commercialization of RYTELO in the U.S., which could further increase our costs.

With respect to the EU or any other regions outside the U.S.

where we might seek marketing authorization in the future for RYTELO, we plan to enter into arrangements with other third parties to utilize their local marketing and distribution capabilities, but we may be unable to enter into such arrangements on favorable terms, if at all.

If potential future partners do not commit sufficient resources to commercialize RYTELO, we may be unable to generate sufficient product revenue to sustain our business.

In any event, if we are unable to establish and maintain adequate sales and marketing capabilities for RYTELO, whether on our own or through contractual arrangements, collaborations or other arrangements, our results of operations may be negatively impacted.

Any of the foregoing would negatively impact our business and business prospects, severely and adversely affect our financial results, and might cause us to cease operations.

If we do not obtain acceptable prices or adequate reimbursement for RYTELO, the use of RYTELO could be severely limited.

Our ability to successfully commercialize RYTELO will depend significantly on obtaining acceptable prices and the availability of coverage and adequate reimbursement to patients from third-party payors.

If we do not maintain acceptable prices or adequate reimbursement for RYTELO, the use of RYTELO could be severely limited.

Our ability to successfully commercialize RYTELO will depend significantly on maintaining acceptable prices and the availability of coverage and adequate reimbursement to patients from third-party payors.

Government payors, such as the Medicare and Medicaid programs, and other third-party payors, such as private health insurers and health maintenance organizations, determine which medications they will cover and the reimbursement levels.

Although we have received a permanent and product-specific J-code (J0870) for RYTELO which will become effective on January 1, 2025, the resulting reimbursement payment rates may not be adequate or may require significant restrictions on use or increased co-payments from commercially insured patients that patients may find unacceptably high.

The resulting reimbursement payment rates may not be adequate or may require significant restrictions on use or increased co-payments from commercially insured patients that patients may find unacceptably high.

Patients are unlikely to use RYTELO unless coverage is provided, and reimbursement is adequate to cover all or a significant portion of its cost.

Therefore, coverage and adequate reimbursement will be critical to market acceptance of RYTELO.

Further, the status of reimbursement codes for RYTELO could also affect reimbursement.

J-Codes are reimbursement codes maintained by the Centers for Medicare and Medicaid Services, or CMS, that are a component of the Healthcare Common Procedure Coding System and are typically used to report drugs that ordinarily cannot be self-administered.

On October 3, 2024, CMS assigned a permanent and product specific J-code (J0870) for RYTELO, which will become effective on January 1, 2025.

For the remainder of 2024, and until CMS systems are updated, physicians will continue to use the non-specific miscellaneous J-Code to bill third-party payors for RYTELO.

Because miscellaneous J-Codes may be used for a wide variety of products, health plans may have more difficulty determining the actual product used and billed for the patient.

These claims increase the provider administrative burden and must often be submitted with additional information and manually processed, which can delay claims processing times as well as increase the likelihood for claim denials and claim errors.

Therefore, coverage and adequate reimbursement is critical to market acceptance of RYTELO.

In addition, government authorities and other third-party payors in the U.S.

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Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices as a condition of coverage, are using restrictive formularies and preferred drug lists to leverage greater discounts in competitive classes, and are challenging the prices charged for medical products.

The Inflation Reduction Act of 2022, or the Inflation Reduction Act, includes several provisions to lower prescription drug costs for people with Medicare and reduce drug spending by the federal government, which may ultimately have a negative effect on the pricing for RYTELO.

The Inflation Reduction Act of 2022 includes several provisions to lower prescription drug costs for people with Medicare and reduce drug spending by the federal government, which may ultimately have a negative effect on the pricing for RYTELO.

However, the Medicare Drug Pricing Negotiation Program provisions of the law are currently subject to legal challenges.

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As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of RYTELO to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

We cannot be sure that coverage and reimbursement will be available for RYTELO, and, if reimbursement is available, what the level of reimbursement will be.

Although we have received a permanent and product-specific J-code (J0870) for RYTELO which will become effective on January 1, 2025, there may also be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar international regulatory authorities.

Coverage and reimbursement may impact the demand for, or the price of RYTELO.

Although we have received a permanent and product-specific J-Code (J0870) for RYTELO which became effective on January 1, 2025, there may also be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar international regulatory authorities.

Coverage and reimbursement may impact the demand for, or the price of RYTELO, and reimbursement policies in the U.S., the EU, and other jurisdictions may evolve which may adversely impact our ability to successfully commercialize RYTELO.

Even if favorable coverage and reimbursement status is attained for one or more

products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize RYTELO, which would negatively impact our business and business prospects.

To be commercially successful, RYTELO must be accepted by the healthcare community, which can be slow to adopt or unreceptive to new technologies and products.

RYTELO may not achieve market acceptance in the U.S.

for lower-risk MDS or any other indication that might be approved in the future, or achieve the potential U.S.

or international revenue we believe may be possible if approved outside the U.S., since hospitals, physicians, patients or the medical community in general may decide not to accept and utilize RYTELO.

RYTELO competes with a number of conventional and widely accepted drugs and therapies manufactured and marketed by major pharmaceutical companies.

RYTELO may not achieve market acceptance for lower-risk MDS or any other indication that might be approved in the future, or achieve the potential U.S.

or international revenue we believe may be possible for lower-risk MDS, since hospitals, physicians, patients or the medical community in general may decide not to accept and utilize RYTELO at the rate we expect or may not use RYTELO across the breadth of eligible patient segments .

For example, new patient starts in the U.S.

through the end of the first quarter of 2025 have been primarily in the third-line setting.

While our current priority is to drive new patient starts across the breadth of eligible patient segments in RYTELO's approved indication, we may be unable to do so in a timely manner or at all, which would limit RYTELO's growth potential and which could delay or preclude our ability to generate meaningful revenue from product sales and to achieve profitability.

Furthermore, RYTELO competes with a number of conventional and widely accepted drugs and therapies manufactured and marketed by major pharmaceutical companies.

The degree of market acceptance of RYTELO depends on a number of factors, including:

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• restrictions on use of RYTELO alone or in combination with other products;

• the label and promotional claims allowed by the FDA for RYTELO, as well as any such claims allowed by similar international regulatory authorities for RYTELO, if any, including usage for only certain indications and any limitations or warnings about the prevalence or severity of any side effects;

• the label and promotional claims allowed by the FDA for RYTELO, as well as any such claims allowed by similar international regulatory authorities for RYTELO, including usage for only certain indications and any limitations or warnings about the prevalence or severity of any side effects;

• the timing of market introduction of RYTELO as well as competitive products, including sequencing of available products;

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We may be unable to demonstrate any therapeutic or economic advantage for RYTELO compared to established or standard-of-care therapies, or newly developed therapies, for myeloid hematologic malignancies.

Third-party payors may decide that any potential benefit that RYTELO may provide to clinical outcomes in myeloid hematologic malignancies is not adequate to justify the potential adverse effects or the costs of treatment with RYTELO.

If the healthcare community does not accept RYTELO for any of the foregoing reasons, or for any other reasons, our ability to commercialize RYTELO in the U.S.

for lower-risk MDS may be negatively impacted or precluded altogether, which would seriously and adversely affect our business and business prospects.

National health insurance and/or third-party payors may decide that any potential benefit that RYTELO may provide to clinical outcomes in myeloid hematologic malignancies is not adequate to justify the potential adverse effects or the costs of treatment with RYTELO.

If the healthcare community does not accept RYTELO for any of the foregoing reasons, or for

any other reasons, our ability to commercialize RYTELO in the U.S.

or the EU for lower-risk MDS or for any other indications for which RYTELO may be approved, may be negatively impacted or precluded altogether, which would seriously and adversely affect our business and business prospects.

If the market opportunities for RYTELO are smaller than we believe, our revenue may be adversely affected, and our business may suffer.

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Further, new information from us or others may change the estimated incidence or prevalence of patients with lower-risk MDS in the U.S.

Additionally, the potentially addressable patient population for RYTELO may not ultimately be amenable to treatment with RYTELO, or we may be unable to successfully identify patients and achieve a significant market share in RYTELO’s approved indication, or initial sales of RYTELO may deplete the prevalence pool of patients in the RYTELO’s approved indication more quickly than expected, which would have a negative impact on sales of RYTELO in the future.

Additionally, the potentially addressable patient population for RYTELO may not ultimately be amenable to treatment with RYTELO, we may be unable to successfully identify patients and achieve a significant market share in all eligible patient segments in RYTELO’s approved indication, or the duration of therapy for patients receiving RYTELO could be shorter than we expect, each of which would have a negative impac t on sales of RYTELO in the future and may limit its growth potential.

Our commercialization of RYTELO in the U.S.

is limited to lower-risk MDS, and any future potential commercialization will be limited to the therapeutic indications examined in our clinical trials and as determined by the FDA and similar international regulatory authorities, which would not permit us to market RYTELO for any other indications not expressly approved by those regulatory authorities.

and our planned commercialization in the EU is limited to certain patients with lower-risk MDS, and any future potential commercialization will be limited to the therapeutic indications examined in our clinical trials and as determined by the FDA and similar international regulatory authorities, which would not permit us to market RYTELO for any other indications not expressly approved by those regulatory authorities.

Future regulatory approvals for RYTELO, if any, could be conditioned upon label restrictions that materially limit the addressable patient population.

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If any of our estimates prove to be inaccurate, the market opportunities for RYTELO that we or any potential future collaborative partners develop could be significantly diminished, which would have a material adverse impact on our business and business prospects, and would adversely affect our ability to achieve profitability.

If competitors develop products, product candidates or technologies that are superior to or more cost-effective than RYTELO, it would significantly impact the development and commercial viability of RYTELO, which would severely and adversely affect our financial results, business and business prospects, and the future of RYTELO, and might cause us to cease operations.

The pharmaceutical and biotechnology industries are characterized by intense and dynamic competition with rapidly advancing technologies and a strong emphasis on proprietary products.

While we believe our proprietary oligonucleotide chemistry;

experience with the biological mechanisms related to RYTELO, telomeres and telomerase;

clinical data to date indicating potential disease-modifying activity with RYTELO treatment;

and knowledge and expertise around the development of potential treatments for myeloid hematologic malignancies provide us with competitive advantages, we face competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and private research institutions.

RYTELO competes with other products and therapies that currently exist, are being developed or will in the future be developed, some of which we may not currently be aware of.

A discussion of current and potential future competitors of RYTELO can be found in the sub‑section entitled “Competition” in Part I, Item 1, entitled “Business” included in our Annual Report on Form 10-K for the year ended December 31, 2024.

Many of our competitors, either alone or with their strategic partners, could have substantially greater financial, technical and human resources than we do and significantly greater experience in obtaining FDA and other regulatory approvals of treatments and commercializing those treatments.

We believe that the commercial success of RYTELO is subject to a number of factors, including:

product efficacy and safety;

method of product administration;

cost of manufacturing;

the timing and scope of regulatory consents;

status of coverage and reimbursement;

the level of generic competition;

and our patent and regulatory exclusivity position.

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

We anticipate increased competition in the future as new companies explore treatments for myeloid hematologic malignancies, which may significantly impact the commercial viability of RYTELO.

Academic institutions, government agencies and other public and private research organizations may also conduct research, seek patent protection and establish collaborative arrangements for research, clinical development and marketing of products similar to RYTELO.

These companies and institutions compete with us in recruiting and retaining

qualified development and management personnel as well as in acquiring technologies complementary to the RYTELO program.

As a result of the foregoing, competitors may develop more commercially desirable or affordable products than RYTELO or achieve earlier patent protection or product commercialization than we may be able to achieve with RYTELO.

Competitors have developed, or are in the process of developing, technologies that are, or in the future may be, competitive to RYTELO.

Some of these products may have an entirely different approach or means of accomplishing therapeutic effects similar or superior to those that may be demonstrated by RYTELO.

Competitors may develop products that are safer, more effective, or less costly than RYTELO, or more convenient to administer to patients and, therefore, present a serious competitive threat to RYTELO.

In addition, competitors may price their products below what we may determine to be an acceptable price for RYTELO, may receive better third-party payor coverage and/or reimbursement, or may be more cost-effective than RYTELO.

Such competitive products or activities by competitors may render RYTELO obsolete, which may cause us to cease any further development or future commercialization of RYTELO, which would severely and adversely affect our financial results, business and business prospects, and the future of RYTELO, and might cause us to cease operations.

We rely on a select network of third party distributors, specialty pharmacies and other vendors to distribute RYTELO in the U.S., and any failure by such distributors, specialty pharmacies and vendors could adversely affect our revenues, financial condition, or results of operations.

We rely on a select network of third party distributors, specialty pharmacies and other vendors to distribute RYTELO, and the financial failure of any of these parties could adversely affect our revenues, financial condition or results of operations.

We rely on a select network of third party distributors, specialty pharmacies and other vendors to distribute RYTELO in the U.S., and the financial failure of any of these parties could adversely affect our revenues, financial condition or results of operations.

We rely on such distributors and specialty pharmacies to effectively distribute RYTELO in a timely manner, provide certain patient support services, manage prescription intake, collect accurate patient and inventory data and collect payments from payors.

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In the event that such network fails to properly meet our or our patients’ needs, we may need to partner with other distributors, specialty pharmacies or vendors to replace or supplement our current network and there is no guarantee that we will be able to do so on commercially reasonable terms or at all.

We are seeking regulatory approval to commercialize RYTELO in the EU, and any such approval, if received, will be subject to pricing, drug marketing, post-market and reimbursement regulations in the EU, which may materially affect our ability to commercialize and receive reimbursement coverage for RYTELO in the EU.

We are seeking approval to market RYTELO in the EU for lower-risk MDS.

Even if we obtain approval for RYTELO in the EU, t he competent regulatory authorities may still impose significant restrictions on the indicated uses or marketing of our product or impose ongoing requirements for potentially costly post-approval studies, post-market surveillance or patient or drug restrictions.

We will also be subject to rules and regulations in the EU applicable to the manufacturing, marketing, promotion and sale of medicinal products .

We will be subject to pricing, drug marketing, post-market and reimbursement regulations in the EU, which may materially affect our ability to commercialize and receive reimbursement coverage for RYTELO in the EU.

In March 2025, we received marketing authorization for RYTELO in the EU for the treatment of adult patients with transfusion-dependent, or TD, anemia due to lower-risk MDS without an isolated deletion 5q cytogenic abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.

In connection with such approval, we are subject to post-marketing requirements to submit final results from certain ongoing non-clinical and clinical studies and the completion of certain quality-related activities and study.

We are also subject to rules and regulations in the EU applicable to the manufacturing, marketing, promotion and sale of medicinal products.

If we or a regulatory authority discovers previously unknown problems with RYTELO, such as adverse events of unanticipated severity or frequency, or problems with a facility where RYTELO is manufactured, a regulatory authority may impose restrictions relative to RYTELO or the manufacturing facility, including requiring recall or withdrawal of RYTELO from the market or suspension of manufacturing.

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In addition, the pricing of RYTELO will be subject to governmental control and other market regulations which could put pressure on the pricing and usage of RYTELO.

In the EU, pricing negotiations with governmental authorities can take considerable time after obtaining marketing approval of a product candidate.

In addition, if approved, market acceptance and sales of RYTELO will depend significantly on the availability of adequate coverage and reimbursement from third-party payors for RYTELO and may be affected by existing and future healthcare reform measures.

In the EU, pricing negotiations with governmental authorities can take considerable time after obtaining marketing approval of a product candidate and market acceptance and

sales of RYTELO will depend significantly on the availability of adequate coverage and reimbursement from third-party payors for RYTELO and may be affected by existing and future healthcare reform measures.

The requirements governing drug pricing and reimbursement vary widely from country to country.

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An EU Member State may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

If RYTELO is approved for commercialization in the EU, in some countries, we may be required to conduct a clinical study or other studies that compare the cost-effectiveness of RYTELO to other available therapies in order to obtain or maintain reimbursement or pricing approval.

There can be no assurance that any country that has price controls or reimbursement limitations for biopharmaceutical products will allow favorable reimbursement and pricing arrangements for RYTELO, if it is approved for marketing in the EU.

In some countries in the EU, we may be required to conduct a clinical study or other studies that compare the cost-effectiveness of RYTELO to other available therapies in order to obtain or maintain reimbursement or pricing approval.

There can be no assurance that any country that has price controls or reimbursement limitations for biopharmaceutical products will allow favorable reimbursement and pricing arrangements for RYTELO.

Historically, products launched in the EU do not follow price structures of the U.S.

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Interactions between pharmaceutical companies and health care professionals are governed by strict laws, such as national anti-bribery laws of European countries, national sunshine rules, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct.

Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.Infringement of related laws could result in substantial fines and imprisonment.

Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

Infringement of related laws could result in substantial fines and imprisonment.

Payments made to physicians and other healthcare professionals in certain EU Member States must be publicly disclosed.

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Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

If our competitors have existing products or develop new products, product candidates or technologies that are superior to or more cost-effective than RYTELO, this could significantly impact the commercial viability and further development of RYTELO, which would severely and adversely affect our financial results, business and business prospects.

The pharmaceutical and biotechnology industries are characterized by intense and dynamic competition with rapidly advancing technologies and a strong emphasis on proprietary products.

While we believe our proprietary oligonucleotide chemistry;

experience with the biological mechanisms related to telomeres and telomerase;

clinical data to date;

and knowledge and expertise around the

development of potential treatments for myeloid hematologic malignancies provide us with competitive advantages, we face competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and private research institutions.

RYTELO will compete with other products and therapies that currently exist, are being developed or will in the future be developed, some of which we may not currently be aware of.

For a description of the competition that RYTELO may face in our lead indications of lower-risk MDS and relapsed/refractory MF, see Item 1, “Business - Competition” in our 2023 Form 10-K.

Competitors may have or develop more commercially desirable or affordable products than RYTELO, or achieve earlier or longer patent and regulatory exclusivity protection or product commercialization than we may be able to achieve with RYTELO.

Some of these products may have an entirely different approach or means of accomplishing therapeutic effects similar or superior to those that may be demonstrated by RYTELO.

Competitors may have or develop products that are safer, more effective, or less costly than RYTELO, or more convenient to administer to patients.

In addition, competitors may price their products below our price for RYTELO, may receive better third-party payor coverage and/or reimbursement, or may be more cost-effective than RYTELO.

Such competitive products or activities by competitors may limit the commercial potential of RYTELO, which may cause us to cease commercialization and any further development of RYTELO, which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

RISKS RELATED TO REGULATORY APPROVAL OF RYTELO

We may be unable to maintain regulatory approval from the FDA for RYTELO in the U.S.

for lower-risk MDS, which would severely and adversely affect our business and business prospects, and might cause us to cease operations.

We may be unable to maintain regulatory approvals for RYTELO in the U.S.

and the EU for lower-risk MDS, which would severely and adversely affect our business and business prospects, and might cause us to cease operations.

In June 2024, we received regulatory approval from the FDA to commercialize RYTELO in the U.S.

in lower-risk MDS.

Federal, state and local governments in the U.S.

have significant regulations in place that may limit or prevent us from successfully commercializing RYTELO in the U.S.

for lower-risk MDS.

We do not currently have regulatory approval for RYTELO in any other jurisdiction or for any other indication, and governments in other jurisdictions have significant regulations that may limit or prevent us from successfully commercializing RYTELO in other jurisdictions.

in certain patients with lower-risk MDS and in March 2025, we received marketing authorization from the EC to commercialize RYTELO in the EU for certain adult patients with TD anemia due to lower-risk MDS.

Federal, state and local governments in the U.S., and regulatory authorities in the EU, have significant regulations in place that may limit or prevent us from successfully commercializing RYTELO for lower-risk MDS.

We do not currently have regulatory approval for RYTELO in any other jurisdictions or for any other indication, and governments in other jurisdictions have significant regulations that may limit or prevent us from successfully commercializing RYTELO in other jurisdictions.

Failure to maintain regulatory approval for RYTELO from the FDA in the U.S.

for lower-risk MDS, or delays in obtaining, failure to obtain, or limitations in the scope of such approvals in any other jurisdictions or for any other indications, could:

• result in a withdrawal of RYTELO from the market or could otherwise delay, limit or preclude any revenue we may receive from the commercialization of RYTELO in the U.S.

for lower-risk MDS;

and from the EC in the EU for lower-risk MDS, or delays in obtaining, failure to obtain, or limitations in the scope of such approvals in any other jurisdictions or for any other indications, could:

• result in a withdrawal of RYTELO from the market or could otherwise delay, limit or preclude any revenue we may receive from the commercialization of RYTELO for lower-risk MDS;

• significantly harm the commercial potential of RYTELO;

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• delay or preclude any revenue we may receive from the future commercialization of RYTELO in any other jurisdictions or for any other indications, if any.

In addition, approved products and their manufacturers are subject to continual review, and discovery of previously unknown problems with a product or its manufacturer may result in restrictions on the product or manufacturer, including import restrictions, seizure and withdrawal of the product from the market.

In addition, approved products and their manufacturers, together with other vendors involved in the commercialization process, are subject to continual review, and discovery of previously unknown problems with a product or its manufacturer may result in restrictions on the product or manufacturer, including import restrictions, seizure and withdrawal of the product from the market.

Commercialization and sales of RYTELO are subject to government regulations related to numerous matters, including the processes of:

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Further, if RYTELO causes serious or unexpected side effects, or if other safety risks are observed as a result of our commercialization efforts for RYTELO in the U.S.

in lower-risk MDS or in current or potential future clinical trials, a number of potential significant negative consequences could result, including:

• the FDA may withdraw its approval of RYTELO;

or the EU in lower-risk MDS or in current or potential future clinical trials, a number of potential significant negative consequences could result, including:

• regulatory authorities may withdraw approval of RYTELO;

• we may be required to recall RYTELO, seek to change the way it is administered, conduct additional clinical trials or change the labeling of the product;

• the FDA may require revisions to the labeling of RYTELO, including limitations on approved uses or the addition of further warnings, contraindications or other safety information, or may impose restrictions on distribution in the form of REMS;

• regulatory authorities may require revisions to the labeling of RYTELO, including limitations on approved uses or the addition of further warnings, contraindications or other safety information, or may impose restrictions on distribution in the form of additional requirements in a risk evaluation and management plan or risk management plan;

• we may experience manufacturing delays and supply disruptions if regulatory inspectors identify regulatory noncompliance by third-party manufacturers requiring remediation;

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• we may be exposed to potential lawsuits and associated legal expenses, including costs of resolving claims;

• the FDA or similar international regulatory authorities may refuse to approve pending applications, such as our MAA in the EU, or supplements to approved applications filed by us, or may suspend or revoke license approvals;

• regulatory authorities may refuse to approve supplements to approved applications filed by us, or may suspend or revoke license approvals;

• we may be required to change or stop ongoing clinical trials of RYTELO (imetelstat), which would negatively impact the development of RYTELO (imetelstat) for other potential indications.

Any of these events could prevent us from achieving or maintaining market acceptance for RYTELO, could substantially increase the costs and expenses of commercializing RYTELO, or could limit its commercial potential, which in turn could delay or prevent us from generating any meaningful revenues from the sale of the RYTELO.

If RYTELO is approved outside the U.S., we will be subject to similar requirements, considerations and risks in other regions.

If RYTELO is approved outside the U.S.

and EU, we will be subject to similar requirements, considerations and risks in other regions.

Our regulatory approval for RYTELO in the U.S.

for lower-risk MDS is subject to post-marketing requirements and commitments, and we may be subject to penalties or product withdrawal if we fail to comply with these regulatory requirements and commitments or if we experience unanticipated problems with RYTELO.

Our regulatory approval for RYTELO in lower-risk MDS is subject to clinical, non-clinical and manufacturing post-marketing requirements and commitments, including the requirement of continuing to assess long-term safety of RYTELO (imetelstat) in the IMerge trial and a clinical trial to evaluate alternative dosing regimens in lower-risk MDS, with timelines for completion and reporting established by the FDA.

and in the EU for certain patients with lower-risk MDS is subject to post-marketing requirements and commitments, and we may be subject to penalties or product withdrawal if we fail to comply with these regulatory requirements and commitments or if we experience unanticipated problems with RYTELO.

Our regulatory approval for RYTELO in lower-risk MDS in the U.S.

is subject to non-clinical, clinical and manufacturing post-marketing requirements and commitments, including the requirement of continuing to assess long-term safety of RYTELO (imetelstat) in the IMerge trial and a clinical trial to evaluate alternative dosing regimens in lower-risk MDS, with timelines for completion and reporting established by the FDA.

In the EU, our regulatory approval for RYTELO in certain patients with TD anemia due to lower-risk MDS is subject to our commitment to submit the results from certain ongoing non-clinical and clinical studies required by the FDA, including the assessment of the long-term safety of RYTELO in the IMerge trial, as well as results from an ongoing substudy within the IMerge trial and the completion of certain quality-related activities and study.

In addition, RYTELO and the manufacturing processes and facilities, post-approval clinical data, labeling, advertising and promotional activities related to RYTELO will be subject to continual requirements of, and review by, the FDA and comparable regulatory authorities.

These requirements include submissions of safety and other post-marketing information and reports, registration requirements, current Good Manufacturing Practice, or cGMP, requirements relating to quality control, quality assurance and corresponding maintenance of records and documents, and requirements regarding promotional interactions with healthcare professionals.

These requirements include submissions of safety and other post-marketing information and reports, compliance with good pharmacovigilance practices, registration requirements, current Good Manufacturing Practice, or cGMP, requirements relating to quality control, quality assurance and corresponding maintenance of records and documents, and requirements regarding promotional interactions with healthcare professionals.

Failure to comply with these post-marketing requirements and commitments or any other regulatory requirements, or later discovery of previously unknown problems with RYTELO, or our manufacturers, or manufacturing processes for RYTELO, may result in actions such as:

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Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity.

In addition, the FDA’s regulations, policies or guidance may change and new or additional statutes or government regulations may be enacted that could prevent or delay regulatory approval of our product candidates or further restrict or regulate post-approval activities.

In addition, the regulations, policies or guidance of the FDA, EC or any other regulatory authority may change and new or additional statutes or government regulations may be enacted that could prevent or delay regulatory approval of our product candidates or further restrict or regulate post-approval activities.

We also cannot predict the likelihood, nature, or extent of adverse government regulation that may arise from pending or future legislation or administrative action, either in the United States or abroad.

If we are unable to fulfill the post-marketing requirements and commitments established by the FDA for RYTELO in lower-risk MDS, or that may be applied to the approval and commercialization of RYTELO by any regulatory authority, or are unable to adapt to changes in existing regulatory requirements or adoption of new regulatory requirements or policies, there may be a negative impact to our business and continued regulatory approval of RYTELO.

If we are unable to fulfill the post-marketing requirements and commitments established by the FDA or the EC for RYTELO in lower-risk MDS, or that may be applied to the approval and commercialization of RYTELO by any

regulatory authority, or are unable to adapt to changes in existing regulatory requirements or adoption of new regulatory requirements or policies, there may be a negative impact to our business and continued regulatory approval of RYTELO.

Under such circumstances, we or our respective service providers may be subject to the actions listed above, including losing marketing approval for RYTELO, which would severely and adversely affect our business and business prospects, and might cause us to cease operations.

If RYTELO is approved outside the U.S., we will be subject to similar requirements, considerations and risks in other regions.

If RYTELO is approved outside the U.S.

and the EU, we will be subject to similar requirements, considerations and risks in other regions.

We may be unable to obtain regulatory approval to commercialize RYTELO in any other jurisdictions or for any new indications, or may experience significant delays in doing so, any of which could severely and adversely affect our business and business prospects, and might cause us to cease operations.

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Of the large number of drugs in development, only a small percentage complete the development and regulatory approval process and are successfully commercialized.

In addition, the lengthy review process and the unpredictability of future or ongoing clinical trials may result in a delay in obtaining, or our failure to obtain, regulatory approval for RYTELO in lower-risk MDS in any jurisdiction other than the U.S., and for relapsed/refractory MF or for any other indications, which could significantly harm our business and business prospects, and might cause us to cease operations.

and the EU, or our inability to obtain regulatory approval for RYTELO for relapsed/refractory MF or for any other indications, which could significantly harm our business and business prospects, and might cause us to cease operations.

Securing marketing approval requires the submission of extensive non-clinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish to the satisfaction of such regulatory authorities the product candidate’s safety and efficacy, as well as information about the product manufacturing process and any inspections of manufacturing facilities conducted by regulatory authorities through the filing of an NDA in the U.S.

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Although RYTELO is approved in the U.S.

in lower-risk MDS and the EMA has validated our MAA for RYTELO for lower-risk MDS, there can be no assurance that we will receive regulatory approval from the European Commission for the commercialization of RYTELO for lower-risk MDS in the EU in a timely manner, or at all.

Further, because non-clinical and clinical data are often susceptible to varying interpretations and analyses, the EMA may disagree with our interpretation of the data and may require additional clinical testing and/or further analyses from completed clinical or non-clinical trials before we can obtain regulatory approval and begin commercialization of RYTELO for lower-risk MDS in the EU, if at all, any of which could result in increased costs to us, or could delay or limit our ability to generate revenue from sales in the EU and adversely affect our commercial prospects.

Even though we reported positive top-line results from IMerge Phase 3 in January 2023 and received regulatory approval from the FDA in June 2024 to commercialize RYTELO in lower-risk MDS, the top-line results from IMerge Phase 3 are not necessarily predictive of RYTELO’s activity in other indications and for other pivotal trials that may be needed to support any application to the FDA or similar international regulatory authorities for such other indications, such as from IMpactMF.

Any of these events may result in a failure to further develop, obtain regulatory approval for or commercialize RYTELO in any indication other than lower-risk MDS in the U.S., which could severely and adversely affect our business and business prospects.

In addition, with respect to the trial design for IMpactMF, the FDA urged us to consider adding a third dosing arm to the trial to assess a lower dose and/or a more frequent dosing schedule that might improve the trial’s chance of success by identifying a less toxic regimen and/or more effective spleen response, one of the trial’s secondary endpoints.

Based on data from IMbark, we believe that testing a lower dose regimen would likely result in a lower median OS, which is the trial’s primary endpoint, in the imetelstat treatment arm.

Existing data also suggest that lowering the dose would not result in a clinically meaningful reduction in toxicity, and for these reasons we determined not to add a third dosing arm to the trial design and the FDA did not object to our proposed imetelstat sodium dose and schedule of 9.4 mg/kg every three weeks.

Our belief may ultimately be incorrect.

Therefore, our failure to add a third dosing arm could result in a failure to maintain regulatory clearance from the FDA and similar international regulatory authorities for relapsed/refractory MF, could result in the trial’s failure, or could otherwise delay, limit or prevent marketing approval of imetelstat for relapsed/refractory MF by the FDA or similar international regulatory authorities.

Regulatory authorities have substantial discretion in the approval process and can delay, limit or deny approval of RYTELO in other indications or outside of the U.S.

for any indication, or require us to conduct additional non-clinical or clinical testing or abandon a program for many reasons, including:

• disagreement with the design or implementation of our clinical trials, including our statistical analysis of trial results;

• failure to demonstrate that RYTELO’s efficacy results provide sufficient evidence of overall clinical benefit;

• unfavorable benefit-to-risk assessment, in the case of marginal efficacy and/or clinically relevant safety concerns, for any proposed indication;

• serious and unexpected drug-related side effects experienced by participants in our clinical trials or by individuals using RYTELO or drugs similar to RYTELO;

• disagreement with our interpretation of data from non-clinical studies or clinical trials;

• rejection by the FDA of foreign data included in any future supplemental NDA, or sNDA, submissions for any future indications and the non-applicability of this data to the U.S.

population and U.S.

medical practice;

• identification of critical issues as a result of a pre-approval health authority inspection that could negatively impact the integrity of data in the MAA and any future sNDA and lead to a rejection by the FDA, EMA, or similar international regulatory authorities;

• a determination by the EMA, or similar international regulatory authorities that regulatory approval for RYTELO should be narrowed or made more restrictive than our current approval in the U.S.

for lower-risk MDS, or any future indication for which approval is sought, if any;

• failure to satisfy the requirement to develop a risk management plan for the EU, including any post-marketing studies, as a potential condition to approval in the EU for lower-risk MDS;

• disagreement regarding the formulation, labeling and/or the specifications for RYTELO in the EU;

• the failure of the quality or stability of RYTELO to meet acceptable regulatory standards;

• the EMA or the competent authorities of the individual EU Member States or similar international regulatory authorities may lack resources or be delayed in conducting pre-approval inspections due to lack of resources or other reasons;

• we or any third-party service providers may be unable to demonstrate compliance with GMP, GCP, or other applicable regulatory and other requirements to the satisfaction of the FDA, the EMA, the competent authorities of the individual EU Member States or similar international regulatory authorities;

• changes in regulatory policies or approval processes, or potential reduction of unmet medical need with the entry of competitive therapies to the market, could render our clinical efficacy or safety data insufficient for approval.

Furthermore, in recent years, there has been increased public and political scrutiny on the FDA and similar international regulatory authorities with respect to the approval process for new drugs, and as a result regulatory authorities may apply more stringent regulatory standards, especially regarding drug safety, when reviewing regulatory submissions.

Any marketing approval that we may receive for RYTELO in the EU for lower-risk MDS, or in any other country for any other indication, may also be limited or subject to restrictions or post-approval commitments that increase our costs or render RYTELO not commercially viable, which would harm our business and business prospects.

and the EU in lower-risk MDS, there can be no assurance that we will receive regulatory approval for the commercialization of RYTELO for lower-risk MDS in any other jurisdiction or for any new indications.

Any marketing approval that we may receive for RYTELO in any other jurisdiction or for any other indication may also be limited or subject to restrictions or post-approval commitments that increase our costs or render RYTELO not commercially viable, which would harm our business and business prospects.

Regulatory authorities may also not approve the labeling claims that are necessary or desirable for the successful commercialization of a drug, such as RYTELO.

For example, although we received regulatory approval from the FDA in June 2024 to commercialize RYTELO in lower-risk MDS, any future regulatory clearances that we might obtain for RYTELO may be limited to fewer or narrower indications than we might request, or may be granted subject to the performance of post-marketing studies, which may impose further requirements or restrictions on the distribution or use of RYTELO, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria, and requiring treated patients to enroll in a registry.

For example, although we received regulatory approval from the FDA in June 2024, and from the EC in March 2025, to commercialize RYTELO in lower-risk MDS, any future regulatory clearances that we might obtain for RYTELO may be limited to fewer or narrower indications than we might request, or may be granted subject to the performance of post-marketing studies, which may impose further requirements or restrictions on the distribution or use of RYTELO, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria, and requiring treated patients to enroll in a registry.

These limitations and restrictions may limit the size of the market for RYTELO and affect reimbursement by third-party payors.

Future regulatory clearances, if any, may be limited to a smaller patient population, or may require a different drug formulation or a different manufacturing process, than we might in the future decide to seek.

Any delay in obtaining or failure to obtain required approvals of RYTELO in any other jurisdictions or for any other indications, or limitations on any regulatory approval that we might receive in the future, if any, could reduce the potential commercial use of RYTELO, and potential market demand for RYTELO and therefore result in decreased revenue for us from any commercialization of RYTELO in any other jurisdictions or for any other indications, any of which could severely and adversely affect our financial results and ability to raise additional capital, the price of our common stock, our business and business prospects, and might cause us to cease operations.

If we obtain regulatory approval to commercialize RYTELO in the EU for lower-risk MDS or any other indication, we may experience additional risks related to marketing outside of the U.S.

Any delay in obtaining or failure to obtain required approvals of RYTELO in any other jurisdictions or for any other indications, or limitations on any regulatory approval that we might receive in the future, if any, could reduce the potential commercial use of RYTELO, and potential market demand for RYTELO and therefore result in decreased revenue for us from any commercialization of RYTELO in any other jurisdictions or for any other indications, any of which could severely and adversely affect our financial results and ability to raise additional capital, if needed, the price of our common stock, our business and business prospects, and might cause us to cease operations.

The commercialization efforts we plan to undertake for RYTELO in the EU for lower-risk MDS may cause us to experience additional risks related to operating outside of the U.S.

that could materially adversely affect our business.

We are seeking regulatory approval to market RYTELO in the EU, and may be subject to additional risks, including, if regulatory approval is obtained from the European Commission, risks related to operating outside of the U.S., such as:

• European Commission and other foreign regulatory approvals, if any, may take longer and be more costly to obtain than approvals in the U.S., due to differing regulatory requirements in foreign countries;

• EMA and other regulatory authorities outside of the U.S.

may disagree with the design, implementation or results of our clinical trials or our interpretation of data from nonclinical studies or clinical trials;

• approval policies or regulations in the EU or of regulatory authorities outside of the U.S.

may significantly change in a manner rendering our clinical data insufficient for potential approval;

We have employees located outside of the U.S., conduct clinical trials outside of the U.S., and are preparing to commercialize RYTELO in select EU markets beginning in 2026, which may subject us to additional risks, including risks related to operating outside of the U.S., such as:

• we may experience unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements;

• risks of potential noncompliance with legal requirements applicable to privacy, data protection, information security and other matters;

• risks of potential noncompliance by us or by any third parties we engage with legal requirements applicable to privacy, data protection, information security and other matters;

• risks of potential noncompliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

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• business interruptions resulting from geopolitical actions, including war and terrorism.

For example, the current administration in the U.S.

has called for substantial changes to foreign trade policy and has recently proposed and imposed significant increases in tariffs on international trade and the renegotiation of international trade agreements.

We cannot predict what effects these and potential additional tariffs or renegotiation of existing international trade agreements will have on our business, including in the context of escalating global trade and political tensions.

However, such tariffs and other trade restrictions could increase our cost of doing business, reduce our gross margins or otherwise negatively impact our financial results.

See the risk factor entitled, “ Global trade issues and changes in and uncertainties with respect to trade policies and export regulations, including import and export license requirements, trade sanctions, tariffs and international trade disputes, could increase our costs and negatively impact net revenues from sales of RYTELO .”

These and other risks associated with international operations may materially adversely affect our ability to attain or maintain profitable operations.

Uncertainty in the regulatory framework and future legislation could lead to disruption in the execution of international multi-center clinical trials, the monitoring of adverse events through pharmacovigilance programs, the evaluation of the benefit-risk profiles of new medicinal products, and determination of marketing authorization across different jurisdictions.

Changes to existing regulations may add considerably to the time from clinical development to marketing authorization and commercialization of products in the EU and increase our costs.

Changes to existing regulations may add considerably to the time from clinical development to marketing authorization and commercialization of products in foreign jurisdictions and increase our costs.

We cannot predict the impact of such changes and future regulation on our business or the results of our operations.

Global trade issues and changes in and uncertainties with respect to trade policies and export regulations, including import and export license requirements, trade sanctions, tariffs and international trade disputes, could increase our costs and negatively impact net revenues from sales of RYTELO.

There is inherent risk, based on the complex relationships among the U.S.

and the countries in which we now conduct or may in the future conduct our business, that political, diplomatic, and national security factors can lead to

global trade restrictions and changes in trade policies and export regulations that may adversely affect our business and operations.

Compliance with applicable regulatory requirements regarding the export of products may create delays in the introduction of RYTELO in international markets, including in the EU, or, in some cases, prevent the export of RYTELO to some countries altogether.

Furthermore, U.S.

export control laws and economic sanctions prohibit the provision of certain products and services to countries, governments and persons targeted by U.S.

and other countries have imposed and may continue to impose new trade restrictions and export regulations, have levied tariffs and taxes on certain goods, and could continue to significantly increase tariffs on a broad array of goods, including pharmaceutical and biological products.

In April 2025, the U.S.

government imposed a 10% baseline global tariff, while suspending the imposition of higher “reciprocal” tariffs on numerous other territories until July 2025.

government has also specifically stated that the pharmaceutical industry will be subject to industry-specific tariffs and has initiated a related investigation into the national security effects of imported pharmaceuticals and their ingredients.

As such, we currently expect that the current pharmaceutical exemption will be short-lived and that such industry-specific pharmaceutical tariffs will ultimately be imposed by the U.S.

Although a significant portion of our supply chain for imetelstat is currently based in the U.S., the active pharmaceutical ingredient, or API, for imetelstat is manufactured in South Korea and our 47mg vial of RYTELO drug product is currently manufactured in Italy.

In addition, in the future we may choose to utilize other contract manufacturers for different presentations of imetelstat and source materials for our supply chain from other international jurisdictions.

Accordingly, such global or industry-specific tariffs, or the renegotiation of current international trade agreements, or other trade restrictions could result in additional costs on our business, including generally increasing our manufacturing costs, and may decrease our gross margins and increase our supply chain complexity.

Moreover, other governments have imposed and may continue to impose retaliatory tariffs, trade restrictions or trade barriers impacting RYTELO, which could impose additional costs and complexity on our business, including with respect to our planned commercialization of RYTELO in select EU markets in 2026 or restrict our ability to sell RYTELO in the EU or in other international markets where we may obtain approval of RYTELO .

Further, the continued threats of new or increased tariffs, sanctions, trade restrictions and trade barriers as well as ongoing changes in U.S.

and foreign government trade policies, including potential modifications to existing international trade agreements, have had and may continue to have a generally disruptive impact on the global economy and, therefore, could negatively impact revenues from sales of RYTELO.

Given the volatility and uncertainty regarding the scope and duration of such tariffs and other aspects of U.S.

and foreign government trade policies, the ultimate impact on our operations and financial results is uncertain and could be significant in the future.

Although orphan drug designation has been granted to RYTELO for the treatment of MDS and MF in the U.S.

and in the EU, these designations may not be maintained, which would eliminate the benefits associated with orphan drug designation, including market exclusivity, which could limit the period of exclusivity we are able to maintain for the commercialization of RYTELO, and would likely harm our business and business prospects.

The FDA granted orphan drug designation to RYTELO in June 2015 for the treatment of MF and for the treatment of MDS in December 2015, and the European Commission granted orphan drug designation in December 2015 to RYTELO for the treatment of MF and in July 2020 for the treatment of MDS.

The FDA granted orphan drug designation to RYTELO in June 2015 for the treatment of MF and for the treatment of MDS in December 2015, and the EC granted orphan drug designation in December 2015 to RYTELO for the treatment of MF and in July 2020 for the treatment of MDS.

Orphan drug exclusivity confers seven and 10 years of exclusivity in the U.S.

and E.U., respectively, following approval, subject to satisfying regulatory requirements.

The FDA has confirmed seven years of orphan drug exclusivity for RYTELO following its approval on June 6, 2024 for its approved indication in lower-risk MDS.

Designation as an orphan drug does not guarantee that any regulatory authority will accelerate regulatory review of, or ultimately approve, RYTELO for any indication, or at all, in the U.S., EU or any other country, nor does it limit the ability of any regulatory authority to grant orphan drug designation to product candidates of other companies that treat the same indications as RYTELO prior to RYTELO receiving any exclusive marketing approval.

We may lose orphan drug exclusivity for certain reasons, including if the FDA or the European Commission determines that the request for orphan drug designation was materially defective or if we cannot ensure sufficient quantities of RYTELO to meet the needs of patients with lower-risk MDS or MF.

and EU, respectively, following approval, subject to satisfying regulatory requirements.

The FD A has confirmed seven years of orphan drug exclusivity for RYTELO following its approval on June 6, 2024 for its approved indication in lower-risk MDS.

In connection with the EC's approval of RYTELO in the EU, the EMA's Committee of Orphan Medicinal Products reviewed and issued a positive opinion to maintain RYTELO's orphan drug designation in the EU for the treatment of certain patients with MDS.

Designation as an orphan drug does n ot guarantee that any regulatory authority will accelerate regulatory review of, or ultimately approve, RYTELO for any indication, or at all, in the U.S., EU or any other country, nor does it limit the ability of any regulatory authority to grant orphan drug designation to product candidates of other companies that treat the same indications as RYTELO prior to RYTELO receiving any exclusive marketing approval.

We may lose orphan drug exclusivity for certain reasons, including if the FDA or the EMA determines that the request for orphan drug designation was materially defective or if we cannot ensure sufficient quantities of RYTELO to meet the needs of patients with lower-risk MDS or MF.

Failure to maintain orphan designation status, or failure to agree to and complete any agreed upon pediatric plan, would lead to the inability to obtain or the loss of such regulatory exclusivity.

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Even after an orphan drug product is approved, such as the approval of RYTELO in the U.S.

for lower-risk MDS in June 2024, the FDA or the European Commission can subsequently approve a different drug with the same active moiety for the same condition, if the FDA or the European Commission concludes that the later drug is safer, more effective, or makes a major contribution to patient care.

in June 2024 and by the EC in March 2025 for certain patients with lower-risk MDS, the FDA or the EC can subsequently approve a

different drug with the same active moiety for the same condition, if the FDA or the EC concludes that the later drug is safer, more effective, or makes a major contribution to patient care.

The occurrence of any of these events could limit the period of exclusivity we are able to maintain for RYTELO, and may harm our business and business prospects.

In addition, for any other indication that we are currently or may in the future seek to develop or obtain regulatory approval for RYTELO, such as our pending MAA for RYTELO in lower-risk MDS in the EU, orphan drug designation will neither shorten the development time nor regulatory review time for RYTELO, and it does not give RYTELO any advantage in the regulatory review or approval process.

In addition, for any other indication that we are currently or may in the future seek to develop or obtain regulatory approval for RYTELO, orphan drug designation will neither shorten the development time nor regulatory review time for RYTELO, and it does not give RYTELO any advantage in the regulatory review or approval process.

Even though we reported positive top-line results from IMerge Phase 3 in January 2023 and received regulatory approval from the FDA in June 2024 to commercialize RYTELO in the U.S.

for lower-risk MDS, the top-line results from IMerge Phase 3 are not necessarily predictive of RYTELO’s activity in other indications, such as from IMpactMF.

Even though we reported positive top-line results from IMerge Phase 3 in January 2023 and received regulatory approval from the FDA in June 2024 and the EC in March 2025 to commercialize RYTELO in lower-risk MDS, the top-line results from IMerge Phase 3 are not necessarily predictive of RYTELO’s activity in other indications and for other pivotal trials that may be needed to support any application to the FDA or similar international regulatory authorities for such other indications, such as from IMpactMF.

Based on data from IMbark, our Phase 2 clinical trial that evaluated two doses of imetelstat in relapsed/refractory MF and the results of which our IMpactMF trial is based, we believe that testing a lower dose regimen would likely result in a lower median OS, which is the trial’s primary endpoint, in the imetelstat treatment arm.

Our belief may ultimately be incorrect.

Regulatory authorities have substantial discretion in the approval process and can delay, limit or deny approval of RYTELO in other jurisdictions or indications, or require us to conduct additional non-clinical or clinical testing or abandon a program for many reasons, including:

• disagreement with the design or implementation of our clinical trials, including our statistical analysis of trial results;

• failure to demonstrate that RYTELO’s efficacy results provide sufficient evidence of overall clinical benefit;

• unfavorable benefit-to-risk assessment, in the case of marginal efficacy and/or clinically relevant safety concerns, for any proposed indication;

• serious and unexpected drug-related side effects experienced by participants in our clinical trials or by individuals using RYTELO or drugs similar to RYTELO;

• disagreement with our interpretation of data from non-clinical studies or clinical trials;

• rejection by the FDA of foreign data included in any future supplemental NDA, or sNDA, submissions for any future indications and the non-applicability of this data to the U.S.

population and U.S.

medical practice;

• a determination by international regulatory authorities that regulatory approval for RYTELO should be narrowed or made more restrictive than our current approvals in the U.S.

and the EU for lower-risk MDS or any future indication for which approval is sought, if any;

• disagreement regarding the formulation, labeling and/or the specifications for RYTELO;

• the failure of the quality or stability of RYTELO to meet acceptable regulatory standards;

Any of these events may result in a failure to further develop, obtain regulatory approval for or commercialize RYTELO in any jurisdiction or in any indication other than lower-risk MDS in the U.S.

and the EU, which could severely and adversely affect our business and business prospects.

RISKS RELATED TO COMPLIANCE WITH HEALTHCARE LAWS

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Similar requirements and related consequences apply outside the U.S.

Enhanced governmental and private scrutiny over, or investigations or litigation involving, pharmaceutical manufacturer donations to patient assistance programs offered by charitable foundations may require us to modify our programs and could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.

To help patients afford our products, we have a patient assistance program and also occasionally make donations to independent charitable foundations that help financially needy patients.

These types of programs designed to assist patients in affording pharmaceuticals have become the subject of scrutiny.

In recent years, some pharmaceutical manufacturers were named in class action lawsuits challenging the legality of their patient assistance programs and support of independent charitable patient support foundations under a variety of federal and state laws.

At least one insurer also has directed its network pharmacies to no longer accept manufacturer co-payment coupons for certain specialty drugs the insurer identified.

Our patient assistance program and support of independent charitable foundations could become the target of similar litigation.

In addition, there has been regulatory review and enhanced government scrutiny of donations by pharmaceutical companies to patient assistance programs operated by charitable foundations.

For example, the Office of Inspector General of the U.S.

Department of Health & Human Services, or OIG, has established specific guidelines permitting pharmaceutical manufacturers to make donations to charitable organizations who provide co-pay assistance to Medicare patients, provided that such organizations are bona fide charities, are entirely independent of and not controlled by the manufacturer, provide aid to applicants on a first-come basis according to consistent financial criteria, and do not link aid to use of a donor’s product.

If we or our vendors or donation recipients are deemed to fail to comply with laws or regulations in the operation of these programs, we could be subject to damages, fines, penalties or other criminal, civil or administrative sanctions or enforcement actions.

We cannot ensure that our compliance controls, policies and procedures will be sufficient to protect against acts of our employees, business partners or vendors that may violate the laws or regulations of the jurisdictions in which we operate.

A government investigation could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.

If our business activities become subject to challenge under supranational, national, federal, state or international healthcare laws, including fraud and abuse, transparency, and health information privacy and security laws, we could face substantial penalties and our business, results of operations, financial condition and prospects could be adversely affected.

Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors and customers, may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations, including federal and state fraud and abuse laws, including anti-kickback and false claims laws;

data privacy and security laws, including the

Health Insurance Portability and Accountability Act, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH;

data privacy and security laws, including the Health Insurance Portability and Accountability Act, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH;

and transparency laws related to payments and/or other transfers of value made to physicians, other healthcare professionals and teaching hospitals.

These laws may constrain the business or financial arrangements and relationships through which we conduct our operations, including how we market, sell and distribute RYTELO.

For details regarding the restrictions under applicable federal and state healthcare laws and regulations that may affect our ability to operate, see Item 1 “Business-Government Regulation- Fraud and Abuse, and Transparency Laws and Regulations” in our 2023 Form 10-K.

Federal and state enforcement bodies have increased their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry.

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Congressional inquiries and federal and state legislative activity designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the price of drugs under Medicare, and reform government program reimbursement methodologies for drugs and biologics.

For details regarding these legislative and regulatory changes and proposed changes regarding the healthcare system that may affect our ability to operate, see Item 1 “Business - Healthcare Reform” in our 2023 Form 10-K.

If future legislation were to impose direct governmental price controls and access restrictions, it could have a significant adverse impact on our business and financial results.

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Such policy actions could have a material adverse impact on future sales of RYTELO in the U.S.

and outside the U.S.

RISKS RELATED TO THE FURTHER DEVELOPMENT OF RYTELO (IMETELSTAT)

We cannot be certain that we will be able to continue to develop RYTELO (imetelstat) or advance it in clinical trials, or that we will be able to receive regulatory approval for RYTELO in any other indications in the U.S., the EU or any other region, on a timely basis or at all.

We are wholly dependent on the success of RYTELO (imetelstat), which is our only product approved for marketing by the FDA and our ability to generate revenue from product sales and achieve profitability is wholly dependent on our ability to successfully commercialize RYTELO for lower-risk MDS or to expand its indications of use.

In this regard, in addition to lower-risk MDS, which is the only indication for which RYTELO has received marketing approval in the U.S., we are developing imetelstat for the treatment

of several myeloid hematologic malignancies.

the EU, and in any other jurisdictions where we may seek approval in the future.

RISKS RELATED TO THE FURTHER DEVELOPMENT OF IMETELSTAT

We cannot be certain that we will be able to continue to develop imetelstat or advance it in clinical trials, or that we will be able to receive regulatory approval for imetelstat in any other indications in the U.S., the EU or any other region, on a timely basis or at all.

We are wholly dependent on the success of RYTELO (imetelstat), which is our only approved product, and our ability to generate revenue from product sales and achieve profitability is wholly dependent on our ability to successfully commercialize RYTELO for lower-risk MDS or to expand its indications of use.

In this regard, in addition to lower-risk MDS, which is the only indication for which RYTELO has received marketing approval in the U.S.

and the EU, we are developing imetelstat for the treatment of several myeloid hematologic malignancies.

Our ability to further develop imetelstat and to expand its indications of use to other myeloid hematologic malignancies is subject to significant risks and uncertainties, including, among other things, our ability to:

• receive regulatory approval to commercialize RYTELO in lower-risk MDS from the European Commission without the requirement for the conduct and completion of additional pre-approval clinical trials or further analyses, testing or development commitments, if at all, any of which could result in increased costs to us, and delay, limit or preclude our ability to generate revenue in the EU;

• generate sufficient safety and efficacy data from the IMpactMF clinical trial to support any application for regulatory approval in relapsed/refractory MF, without clinically meaningful safety issues, side effects or dose-limiting toxicities related to imetelstat that may negatively impact its benefit-risk profile;

• ascertain that the use of imetelstat does not result in significant systemic or organ toxicities, including hepatotoxicity, or other safety issues resulting in an unacceptable benefit-risk profile;

• obtain additional capital when needed in order to enable us to further advance imetelstat clinical trials in other myeloid hematologic malignancies;

• obtain additional capital if and when needed in order to enable us to further advance imetelstat clinical trials in other myeloid hematologic malignancies;

• obtain and maintain required regulatory clearances and approvals to enable continued clinical development of imetelstat;

• enter into and maintain commercially reasonable arrangements with third parties to provide services needed to further research, develop and commercialize RYTELO, including maintaining the agreements with our contract research organizations, or CROs, and third-party manufacturers;

• recruit and retain sufficient qualified and experienced personnel to support the development and commercialization of RYTELO in potential other approved indications and outside the U.S.

• recruit and retain sufficient qualified and experienced personnel to support the development and commercialization of RYTELO in potential other approved indications and other jurisdictions outside of the U.S.

• enter into and maintain arrangements with third parties to provide services needed to support the commercialization of RYTELO for territories outside of the U.S.

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• obtain appropriate coverage and reimbursement levels for the cost of RYTELO from governmental authorities, private health insurers and other third-party payors;

• obtain, maintain and enforce adequate intellectual property and regulatory exclusivity for RYTELO both in the U.S.

and globally.

If we are not able to successfully achieve these goals and overcome other challenges that we may encounter in the research, development, manufacturing and commercialization of RYTELO in indications other than lower-risk MDS, we may be forced to abandon our development and/or commercialization of RYTELO in indications other than lower-risk MDS, which could severely harm our business, prospects and our ability to raise additional capital.

• obtain, maintain and enforce adequate intellectual property and regulatory exclusivity for RYTELO in the U.S., EU and globally.

Our clinical trials of imetelstat could be interrupted, delayed, terminated or abandoned for a variety of reasons which could severely and adversely affect our financial results, business and business prospects.

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• obtaining and/or maintaining regulatory clearances in the U.S.

or other countries to commence, conduct or modify current or potential future clinical trials of imetelstat, in a timely manner, or at all;

or other jurisdictions to commence, conduct or modify current or potential future clinical trials of imetelstat, in a timely manner, or at all;

• investigational new drug applications, or INDs, and equivalent submissions in other countries for imetelstat being placed on full or partial clinical hold, suspended or subject to other requirements by the FDA or other similar international regulatory authorities;

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• manufacturing sufficient quantities that meet our specifications, cost and quality requirements, and timelines for imetelstat, or for other clinical trial materials, in a manner that meets the quality standards of the FDA and other similar international regulatory authorities, and responding to any disruptions to drug supply, clinical trial materials or quality issues that may arise;

• the effects of macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues;

• the effects of macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, changes in tariffs or other trade restrictions, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues;

• complying with current and future regulatory requirements, policies or guidelines, including domestic and international laws and regulations pertaining to fraud and abuse, transparency, and the privacy and security of health information;

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• third-party clinical contractors, including investigators or our CROs not performing our clinical trials according to our anticipated schedule or consistent with the clinical trial protocol, good clinical practices, or GCP, or other regulatory requirements, or not performing data collection or analyses in a timely or accurate manner.

Failures or delays with respect to any of these events could adversely affect our ability to conduct or complete the clinical trials being conducted by us or our investigators, or to commence, conduct and complete potential future clinical trials of imetelstat, which could increase development costs, or interrupt, further delay or halt our development, of imetelstat, any of which could severely and adversely affect our financial results, business and business prospects.

RYTELO (imetelstat) may cause, or have attributed to it, undesirable or unintended side effects or other adverse events that could halt or limit its commercialization, delay or prevent its regulatory approval in any other jurisdiction or indication, or cause us to delay or terminate our clinical trials.

In addition, recent actions by the current administration in the U.S.

to limit federal agency budgets and personnel have resulted in reductions in the FDA's budget and employees, which may lead to slower response times, longer review periods, delayed inspections or other disruptions that we cannot currently predict.

Failures or delays with respect to any of the foregoing events and such disruptions in the timely review and processing of our regulatory submissions and inspections could adversely affect our ability to conduct or complete the clinical trials being conducted by us or our investigators, or to commence, conduct and complete potential future clinical trials of imetelstat, which could increase development costs, or interrupt, further delay or halt our development, of imetelstat, any of which could severely and adversely affect our financial results, business and business prospects.

RYTELO may cause, or have attributed to it, undesirable or unintended side effects or other adverse events that could halt or limit its further commercialization, delay or prevent its regulatory approval in any other jurisdiction or indication, or cause us to delay or terminate our clinical trials.

RYTELO (imetelstat) has been administered only to a limited number of patients in clinical trials.

While the FDA granted approval of RYTELO based on the data included in our NDA, including data from the Phase 3 IMerge trial, we do not know whether the results when a larger number of patients receive RYTELO from commercial use, including results related to safety, will be consistent with the results from earlier clinical trials that served as the basis for its approval.

While the FDA and the EC granted approval of RYTELO based on the data included in our NDA and MAA, respectively, including data from the Phase 3 IMerge trial, we do not know whether the results when a larger number of patients receive RYTELO from commercial use, including results related to safety, will be consistent with the results from earlier clinical trials that served as the basis for its approval.

In addition, because remaining patients in ongoing clinical trials continue to receive imetelstat, additional or more severe toxicities or safety issues may be observed, and the benefit-risk profile of imetelstat will continue to be assessed, including the risk of hepatotoxicity, severe cytopenias, fatal bleeding with or without any associated thrombocytopenia, patient injury or death.

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If any of these actions were to occur, it could result in significant expense and delay or limit our ability to generate sales revenues.

Further, as a result of commercialization of RYTELO (imetelstat), or in current or potential future clinical trials, RYTELO may cause, or have attributed to it, undesirable or unintended side effects or other adverse events affecting its safety or efficacy that could interrupt, further delay or halt its commercialization or current or potential future clinical trials.

Further, as a result of commercialization of RYTELO, or in current or potential future clinical trials, RYTELO may cause, or have attributed to it, undesirable or unintended side effects or other adverse events affecting its safety or efficacy that could interrupt, further delay or halt its commercialization or current or potential future clinical trials.

In this regard, adverse events and dose-limiting toxicities observed in previous and ongoing clinical trials include:

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If such toxicities or other safety issues identified as a result of our commercialization of RYTELO or in any clinical trial are determined by us, the FDA or similar international regulatory authorities to result in an unacceptable benefit-risk profile, then:

• the FDA could withdraw or restrict regulatory approval for RYTELO in the U.S.

for lower-risk MDS;

• additional information supporting the benefit-risk profile of RTYELO may be requested by the FDA or similar international regulatory authorities and if any such information is not available or, if available, not deemed acceptable, regulatory approval could be withdrawn by the FDA in the U.S., and/or current clinical trials could be suspended, terminated, or placed on clinical hold by the FDA or similar international regulatory authorities;

• the FDA and EC could withdraw or restrict regulatory approval for RYTELO in the U.S.

and EU, respectively, for lower-risk MDS;

• additional information supporting the benefit-risk profile of RYTELO may be requested by the FDA or similar international regulatory authorities and if any such information is not available or, if available, not deemed acceptable, regulatory approval could be withdrawn by the FDA in the U.S.

and the EC in the EU, and/or current clinical trials could be suspended, terminated, or placed on clinical hold by the FDA or similar international regulatory authorities;

• the ability to retain enrolled patients in our current clinical trials may be negatively affected, resulting in incomplete data sets and the inability to adequately assess the benefit-risk profile of RYTELO in a specific patient population;

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• RYTELO may not receive or maintain regulatory clearances and approvals required to enable its continued development.

The occurrence of any of these events could interrupt, further delay, or halt, our commercialization or RYTELO or its further development, and as a result, could preclude the commercialization of RYTELO in any additional indications, as well as increase costs for continued development in additional indications, which would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, business and business prospects, any of which might cause us to cease operations.

adverse effect on our results of operations, financial condition and ability to raise additional capital, business and business prospects, any of which might cause us to cease operations.

Results and data we disclosed from prior non-clinical studies and clinical trials may not predict success in later clinical trials, and we cannot assure you that any ongoing or future clinical trials of imetelstat, including IMpactMF, will lead to similar results and data that could potentially enable us to obtain any further regulatory approvals.

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Many companies in the biopharmaceutical industry have frequently suffered significant setbacks in later clinical trials, even after achieving promising results in earlier non-clinical studies or clinical trials.

In general, Phase 3 clinical trials with larger numbers of patients or longer durations of therapy may fail to replicate efficacy and safety results observed in earlier clinical trials, such as IMbark, and if this were to occur with IMpactMF, this would adversely affect future development prospects of imetelstat, and as a result, impact the potential commercialization of imetelstat in relapsed/refractory MF, which would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, business and business prospects, any of which might cause us to cease operations.

In general, Phase 3 clinical trials with larger numbers of patients or longer durations of therapy may fail to replicate efficacy and safety results observed in earlier clinical trials, such as the results observed in IMbark, and if this were to occur with IMpactMF, this would adversely affect future development prospects of imetelstat, and as a result, impact the potential commercialization of imetelstat in relapsed/refractory MF, which would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, if needed, business and business prospects, any of which might cause us to cease operations.

Furthermore, non-clinical and clinical data are often susceptible to varying interpretations and analyses.

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Potential biases are introduced by factors which include, for example, the selection of the patients included in the analyses, misclassification in the matching process, the small sample size, and estimates that may not represent the outcomes for the true treated patient population.

Failure to achieve results supporting a positive benefit-risk profile in current or potential future imetelstat clinical trials would interrupt, further delay, or halt, any development of imetelstat, which would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, business and business prospects.

Further, preliminary data are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial.

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Thus, reported data should be considered carefully and with caution, and not relied upon as indicative of future clinical results.

Such additional data could result in a lower benefit-risk profile than initially expected, which could halt the commercialization of RYTELO, hinder the potential success of IMpactMF, IMproveMF or IMpress, or cause us to abandon further development of imetelstat entirely.

Such additional data could result in a lower benefit-risk profile than initially

expected, which could halt the commercialization of RYTELO, hinder the potential success of IMpactMF, IMproveMF or IMpress, or cause us to abandon further development of imetelstat entirely.

Top-line results and data may differ from future results of the same study, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.

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If we or any of our CROs fail to comply with applicable GCP requirements, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, or similar international regulatory authorities, may require us to perform additional clinical trials.

We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our

clinical trials comply with GCP or other applicable regulations.

We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials comply with GCP or other applicable regulations.

In addition, our clinical trials must be conducted with imetelstat produced under applicable GMP regulations.

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Our ability to comply with these regulations and standards may be contingent upon activities conducted by third parties, and if they fail to perform in accordance with contractual obligations and legal requirements, our development of imetelstat may be interrupted, further delayed or halted.

Any failures by us or third parties noted above would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, business and business prospects, including the commercialization of RYTELO, any of which might cause us to cease operations.

Any failures by us or third parties noted above would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, if needed, business and business prospects, including the commercialization of RYTELO, any of which might cause us to cease operations.

Furthermore, the execution of clinical trials and the subsequent compilation and analysis of the data produced, including the interim and final analyses for IMpactMF, requires coordination among various parties.

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If the quality or accuracy of the clinical data obtained, compiled or analyzed by third parties is compromised due to their failure to adhere to our clinical trial protocols, GCP or GMP requirements, or for any other reason, we may need to enter into new arrangements with alternative third parties, which would cause delay, and could be difficult, costly or impossible.

Switching or adding CROs, investigators, vendors and other third parties involves additional costs and delays because of the time it takes to finalize a contract with a new CRO and for their commencement of work.

Switching or adding clinical research organizations, or CROs, investigators, vendors and other third parties involves additional costs and delays because of the time it takes to finalize a contract with a new CRO and for their commencement of work.

Although we carefully manage our relationships with our CROs, investigators, vendors and other third parties, we and any of these third parties may nonetheless encounter challenges or delays in the future, which could have a material and adverse impact on our business and business prospects.

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This could result in a delay in approval, or rejection, of any future applications for regulatory approval of imetelstat, including in any additional indications by the FDA.

We do not control the conduct of current or any potential future investigator-led clinical trials, and data from such trials could show marginal efficacy and/or clinically relevant safety concerns related to imetelstat resulting in an unfavorable benefit-risk assessment that could materially and adversely impact our ongoing clinical trials, or our imetelstat development program as a whole.

We do not control the design or administration of investigator-led clinical trials, nor the submission, approval or maintenance of any IND or international equivalent filings required to conduct these clinical trials.

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Accordingly, regulatory authorities may closely scrutinize the data collected from these investigator-led clinical trials.

In addition, any investigator-led clinical trials could show marginal efficacy and/or clinically relevant safety concerns that could delay, limit or preclude the further clinical development or marketing approval of RYTELO in any indication, including lower-risk MDS in the EU.

To the extent that the results of any investigator-led clinical trials raise safety or other concerns, regulatory authorities may withdraw or restrict approval for RYTELO, question the results of such investigator-led clinical trials, or question the results of any of our clinical trials.

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Any of the foregoing would delay or preclude any future marketing approvals for RYTELO and could cause us to discontinue our development of it, which would severely harm our business and prospects and could potentially cause us to cease operations.

Risks Related to Manufacturing RYTELO (IMETELSTAT)

RISKS RELATED TO MANUFACTURING RYTELO

Failure by us to maintain a manufacturing supply chain to appropriately and adequately supply RYTELO for commercial and future clinical uses would adversely affect our ability to commercialize RYTELO and result in a further delay in or cessation of clinical trials, and our business and business prospects could be severely harmed, and we could cease operations.

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• reliance on third-party manufacturers and suppliers, whose efforts we do not control;

• supply chain issues, including the timely availability of product and management of shelf-life, including raw materials, drug substance, and drug product and other supplies, any of which may be impacted by a number of factors, including the effects of macroeconomic or other global conditions;

• supply chain issues, including the timely availability of product and management of shelf-life, including raw materials, API, and drug product and other supplies, and the cost of procuring the foregoing, any of which may be impacted by a number of factors, including the effects of macroeconomic or other global conditions, such as

increased tariffs, renegotiation of existing international trade agreements, escalating trade tensions and other trade restrictions;

• shortage of qualified personnel at any of our third party suppliers;

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and could cause financial and reputational harm.

If third parties that manufacture RYTELO fail to perform as needed, the commercial and clinical supply of RYTLEO will be limited, and we may be unable to successfully commercialize RYTELO or conduct or complete current or potential future clinical trials.

Our RYTELO manufacturing supply chain relies, and will continue to rely, solely upon third-party manufacturers to perform certain manufacturing, quality control, and other technical and scientific work with respect to RYTELO, as well as to supply starting materials and manufacture drug substance and drug product for our commercialization of RYTELO, as well as current and potential future clinical trials.

While we have established arrangements with third parties for the manufacture of RYTELO, our manufacturing supply chain is highly specialized, and as such we are reliant upon a small group of third-party manufacturers to supply starting materials, drug substance and drug product.

Failure by such third-party manufacturers to perform in a timely manner and in compliance with all regulatory requirements, or at all, could further delay, perhaps substantially, or preclude our ability to commercialize RYTELO and/or pursue further development of RYTELO on our own, increase our costs, result in lost sales, and otherwise negatively affect our financial results, business and business prospects.

In this regard, recent FDA inspections of one of our third-party drug product manufacturers identified certain deficiencies in the manufacturer’s processes and facilities which, while not directly related to the FDA approval or ongoing production of RYTELO, could impact the manufacturer’s ability to produce and deliver products, including RYTELO, if not remediated by the manufacturer, and could lead to delays or shortages in drug supply, or the inability to manufacture or ship drug supply necessary for non-clinical and clinical activities and commercialization.

We expect to rely on third-party manufacturers to produce and deliver sufficient quantities of RYTELO and other materials to support commercialization and clinical trials on a timely basis and to comply with applicable regulatory requirements.

If third parties that manufacture RYTELO fail to perform as needed, the commercial and clinical supply of RYTELO could be interrupted or limited, and we may be unable to successfully commercialize RYTELO or conduct or complete current or potential future clinical trials.

Our RYTELO manufacturing supply chain relies, and will continue to rely, solely upon third-party manufacturers to perform certain manufacturing, quality control, and other technical and scientific work with respect to RYTELO, as well as to supply starting materials and manufacture the API and drug product for our commercialization of RYTELO, as well as current and potential future clinical trials.

Failure by such third-party manufacturers to perform in a timely manner and in compliance with all regulatory requirements, or at all, or the termination of one of our supply agreements before we have retained and established an acceptable alternative supplier, could lead to delays or shortages in drug supply , perhaps substantially, that are necessary for our clinical activities and commercialization of RYTELO.

In addition, we plan to retain additional third-party manufacturers to provide redundancy in our supply chain;

however, we may be unable to do so on a timely basis on terms that are acceptable to us, or at all.

Any of the foregoing could increase our costs, result in lost sales and delays in our clinical trials, and otherwise have a material adverse effect on our financial results, business and business prospects.

We expect to rely on third-party manufacturers to produce and deliver sufficient quantities of RYTELO and other materials to support our commercialization of RYTELO and clinical trials on a timely basis and to comply with applicable regulatory requirements.

We do not have direct control over these third-party personnel or operations.

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• delays and disruptions experienced by third-party manufacturers that adversely impact the ability of such parties to fulfill their contractual obligations to us, including to provide the quantities of RYTELO required to meet commercial and clinical needs;

• capacity limitations and scheduling constraints experienced by third-party manufacturers due to scheduling and other commitments, and queued manufacturing activities in contracted facilities;

• capacity limitations and scheduling constraints experienced by third-party manufacturers due to scheduling, maintenance and other commitments, and queued manufacturing activities in contracted facilities;

• requirements by regulatory authorities to validate and qualify significant activities for any current or additional manufacturer, which could involve technology transfer, new testing, compliance inspections, and would likely require FDA or comparable foreign regulatory authority approval;

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• the possible mislabeling by third-party manufacturers of finished drug product for both commercial and clinical use, potentially resulting in product recall and harm to our business;

• decisions by third-party manufacturers to exit the contract manufacturing business during the time required to supply clinical trials or to successfully produce, store and distribute RYTELO to meet commercial needs;

• compliance by third-party manufacturers with GMP standards mandated by the FDA and state agencies and other government regulations, including foreign governing regulations, corresponding to similar international regulatory authorities, including any deficiencies identified during regulatory inspections, such as those identified in a recent FDA inspection of one of our third-party manufacturers;

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• inadequate storage or maintenance at contracted facilities resulting in theft or spoilage;

• natural disasters that affect contracted facilities.

• natural disasters that affect contracted facilities, including manufacturing, warehousing, and distribution facilities.

Each of these risks could lead to delays or shortages in drug supply, or the inability to manufacture or ship drug supply necessary for commercialization, and non-clinical and clinical activities, which could severely and adversely affect our financial results, business and business prospects.

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These third-party manufacturers may not be willing or able to achieve such capacity increases, cost reductions, or regulatory and compliance standards, and even if they do, such achievements may not be at commercially reasonable costs.

Changing manufacturers may be prolonged and difficult due to inherent technical complexities, regulatory risks, and because the number of potential manufacturers for oligonucleotide products is limited.

It may be difficult or impossible for us to find a replacement manufacturer on acceptable terms, or at all.

Risks Related to Our OPERATING RESULTS, Financial Position and Need For Additional CAPITAL

We have a history of net losses.

We expect to continue to incur net losses for the foreseeable future and may not achieve consistent future profitability for some time, if ever.

Changing or adding alternative manufacturers may be prolonged, difficult and expensive, due to inherent technical complexities, regulatory risks, and because the number of potential manufacturers for oligonucleotide products is limited.

It may be difficult or impossible for us to find a replacement or alternative manufacturer on acceptable terms, or at all.

RISKS RELATED TO OUR OPERATING RESULTS AND FINANCIAL POSITION

We have a history of net losses and may not achieve consistent future profitability for some time, if ever.

We are incurring and have incurred net losses every year since our operations began in 1990, except for one.

As of September 30 2024, our accumulated deficit was approximately $1.7 billion.

As of March 31, 2025, our accumulated deficit was approximately $1.8 billion.

Losses have resulted principally from costs incurred in connection with our research and development activities and from general and administrative costs associated with our operations.

In addition, we expect to experience increased negative cash flow for the foreseeable future as we fund our operations and imetelstat clinical development activities and research programs continue, and we continue with the commercialization of RYTELO, including as a result of our obligation to pay Royalty Pharma revenue interest payments under the Royalty Pharma Agreement.

Although we have recently begun to commercialize RYTELO, our revenue and profit potential is unproven and our very limited operating history as a commercial company makes our future operating results difficult to predict.

We will need to generate significant revenues to achieve consistent future profitability.

We may never achieve consistent future profitability.

Although we have recently begun to commercialize RYTELO, our revenue and profit potential is unproven and our limited operating history as a commercial company makes our future operating results difficult to predict.

If we do not generate sufficient revenue from commercial sales of RYTELO, or if we experience unforeseen events or choose to make other investments in our business, we may continue to experience negative cash flow as we fund our operations and imetelstat clinical development activities and research programs, and continue with the commercialization of RYTELO, including as a result of our obligation to pay royalty payments under the Royalty Pharma Agreement and service our debt obligations.

We will need to generate significant revenues to achieve consistent future profitability, and we may never achieve consistent future profitability.

Even if we do become profitable in the future, we may not be able to sustain or increase profitability on a quarterly or annual basis.

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Our operating results are difficult to predict and will likely fluctuate from quarter to quarter and year to year.

Due to the approval by the FDA in June 2024 of RYTELO for lower-risk MDS and the limited historical sales data, RYTELO sales will be difficult to predict from period to period and as a result, you should not rely on RYTELO sales results in any period as being indicative of future performance.

Sales of RYTELO may be below our own guidance or the expectations of securities analysts or investors in the future.

To the extent that we do not meet our guidance or the expectations of analysts or investors, our stock price may be adversely impacted, perhaps significantly.

Due to the limited historical sales data of RYTELO in lower-risk MDS since its approval by the FDA in June 2024, RYTELO sales will be difficult to predict from period to period and as a result, you should not rely on RYTELO sales results in any period as being indicative of future performance.

Sales of RYTELO have in the past been below the expectations of securities analysts and investors, and sales of RYTELO have been and may in the future be below prior sequential or prior period sales, our own guidance and/or the expectations of securities analysts and investors.

To the extent that we do not meet our guidance, our financial projections or estimates, or the expectations of analysts or investors, our stock price may be adversely impacted, perhaps significantly.

For example, following our release of earnings for the

quarter and year ended December 31, 2024, our stock price declined significantly.

We believe that our quarterly and annual results of operations may be affected by a variety of factors, including:

• the level of demand for RYTELO;

• the overall level of demand for RYTELO in its approved indication, including across the breadth of the eligible patient segments;

• the extent to which coverage and reimbursement for RYTELO is available from government and health administration authorities, private health insurers, managed care programs and other third-party payors;

discount percentage resulting from price increases we may take in the future, or due to different levels of utilization by entities entitled to government rebates and discounts and changes in patient demographics;

• changes in the amount of deductions from gross sales, including government-mandated rebates, chargebacks and discounts that can vary because of changes to the government discount percentage, including increases in the government discount percentage resulting from price increases we may take in the future, or due to different levels of utilization by entities entitled to government rebates and discounts and changes in patient demographics;

• increases in the scope of eligibility for customers to purchase RYTELO at the discounted government price or to obtain government-mandated rebates on purchases of RYTELO;

• changes in our cost of sales;

• the timing and level of revenue interest payments under the Royalty Pharma Agreement;

• the timing and level of royalty payments under the Royalty Pharma Agreement;

• the timing, cost and level of investment in our sales and marketing efforts to support RYTELO sales;

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• expenditures we may incur to develop and/or commercialize any additional products, product candidates, or technologies that we may develop, in-license, or acquire.

Further, changes in our operations, such as increased development, manufacturing and clinical trial expenses in connection with RYTELO, or our undertaking of additional programs, business activities, or entry into strategic transactions, including potential future acquisitions of products, technologies or businesses may also cause significant fluctuations in our expenses.

Further, changes in our operations, such as increased development, manufacturing and clinical trial expenses, or our undertaking of additional programs, business activities, or entry into strategic transactions, including potential future acquisitions of products, technologies or businesses may also cause significant fluctuations in our expenses.

In addition, we measure compensation cost for stock-based awards made to employees at the grant date of the award, based on the fair value of the award, and recognize the cost as an expense over the employee’s requisite service period.

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As a result, our operating results in future periods could be below our guidance or the expectations of securities analysts or investors, which could cause the trading price of our common stock to decline, perhaps significantly.

Our failure to obtain additional capital when needed would force us to further delay, reduce or eliminate the further development of RYTELO, or to halt the commercialization of RYTELO, any of which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

Our financial projections and estimates are subject to significant risks, assumptions, and uncertainties, and our actual results may differ materially.

These projections and estimates include estimates of the total addressable market for RYTELO, assumptions regarding patient market share and duration of therapy for patients receiving RYTELO, as well as assumptions regarding our ability to meet demand and assumptions regarding our future costs of goods.

These projections and estimates are subject to various factors beyond our control, including, for example, the level of demand for RYTELO, the extent to which coverage and reimbursement for RYTELO is available from government and health administration authorities, private health insurers, managed care programs and other third-party payors, increased costs in the supply chain, including as a result of increased tariffs, renegotiation of existing international trade agreements, escalating trade tensions and other trade restrictions, increased labor costs, changes in the regulatory environment, the impact of global health crises or macroeconomic or other global conditions, and changes in our senior management team.

Our financial projections and estimates constitute forward-looking statements, are for illustrative purposes only and should not be relied upon as necessarily being indicative of future results.

The assumptions and estimates underlying such financial projections and estimates are inherently uncertain and are subject to a wide variety of significant business,

economic, competitive and other risks and uncertainties.

Actual results may differ materially from the results contemplated by the financial projections.

Our independent auditors have not studied, reviewed, compiled or performed any procedures with respect to the projections, and accordingly, they did not express an opinion or provide any other form of assurance with respect thereto.

While all financial projections, estimates and targets are necessarily speculative, we believe that the preparation of financial projections involves increasingly higher levels of uncertainty the further out the projection, estimate or target extends from the date of preparation.

Accordingly, there can be no assurance that the prospective results are indicative of our future performance or that actual results will not differ materially from those presented in the financial projections or estimates.

Our failure to obtain additional capital, if and when needed, would force us to further delay, reduce or eliminate the further development of RYTELO, or to halt the commercialization of RYTELO, any of which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

Successful drug development and commercialization requires significant amounts of capital.

As of September 30, 2024, we had approximately $378.9 million in cash, cash equivalents, restricted cash and marketable securities.

On a pro forma basis, including gross proceeds from the upfront payment under the Royalty Pharma Agreement and the Tranche A Loan, and after repayment of our existing debt under the Hercules Loan Agreement, we had approximately $542.4 million in cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2024.

Based on our current operating plans and assumptions, we believe that our existing cash, cash equivalents, and marketable securities (including the $250 million received under the Pharmakon Loan Agreement and the Royalty Pharma Agreement), together with anticipated revenues from U.S.

sales of RYTELO, will be sufficient to fund our projected operating requirements for at least the next 12 months from the date of this filing.

We believe that our projected financial resources will be sufficient to (i) support commercial launch of RYTELO in the U.S.

and potential launch in the EU, (ii) complete the Phase 3 IMpactMF trial in relapsed/refractory MF, (iii) invest in supply chain redundancy for RYTELO, and (iv) fund our general working capital requirements.

If we do not generate sufficient funds from commercial sales of RYTELO, or if we experience regulatory delays or other unforeseen events or choose to make other investments in our business, we may require additional funding, which could include a combination of public or private equity offerings, debt financings (including additional tranches under the Pharmakon Loan Agreement, if available), collaborations, strategic alliances, licensing arrangements or marketing and distribution arrangements, which may not be possible.

If adequate funds are not available on a timely basis, if at all, our RYTELO commercialization efforts may be adversely affected and we may be unable to pursue further development of imetelstat, which would severely harm our business and we might cease operations.

Despite FDA approval of RYTELO in June 2024, the outcome of any clinical activities and/or regulatory approval process is highly uncertain, and we cannot reasonably estimate whether our future development activities may succeed;

whether we will obtain regulatory approval for RYTELO in the EU in lower-risk MDS, or in any other jurisdictions or indications we are pursuing or may in the future pursue, or whether we will be able to effectively commercialize RYTELO in the U.S.

for lower-risk MDS or other potential indications, if at all.

As of March 31, 2025, we had approximately $457.5 million in cash, cash equivalents, restricted cash and marketable securities.

While we believe that, based on our current operating plans and assumptions, our existing cash, cash equivalents, and marketable securities, together with anticipated net revenues from sales of RYTELO, will be sufficient to fund our projected operating requirements for the foreseeable future, if we do not generate net revenues from commercial sales of RYTELO at the levels we anticipate, if we experience unforeseen events or choose to make other investments in our business, or our assumptions regarding our projected operating expenses are otherwise incorrect, we may require additional funding, which could include a combination of public or private equity offerings, debt financings (including additional tranches under the Pharmakon Loan Agreement, if available), collaborations, strategic alliances, licensing arrangements or marketing and distribution arrangements, which may not be possible.

For example, changes in our operations, such as increased development, manufacturing and clinical trial expenses, or our undertaking of additional programs, business activities, or entry into strategic transactions, including potential future acquisitions of products, technologies or businesses, may cause our operating expenses to increase, perhaps significantly, which could require us to raise additional funding.

If adequate funds are not available to us when we need them, our RYTELO commercialization efforts may be adversely affected and we may be unable to pursue further development of imetelstat, which would severely harm our business and we might cease operations.

Despite approval of RYTELO in the U.S.

in June 2024 and in the EU in March 2025, the outcome of any clinical activities and/or regulatory approval process is highly uncertain, and we cannot reasonably estimate whether our future development activities may succeed, whether we will obtain regulatory approval for RYTELO in any other jurisdictions or indications we are pursuing or may in the future pursue, or whether we will be able to effectively commercialize RYTELO for lower-risk MDS in the U.S., the EU or other potential jurisdictions or indications, if at all.

We may never recoup our investment in any RYTELO development, which would adversely affect our financial condition and our business and business prospects, and might cause us to cease operations.

In addition, our plans and timing expectations could be further delayed or interrupted by the effects of macroeconomic or other global conditions, including those resulting from inflation, rising interest rates, prospects of a recession, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues.

In addition, our plans and timing expectations could be further delayed or interrupted by the effects of macroeconomic or other global conditions, including those resulting from further changes in tariffs and other trade restrictions, renegotiation of existing international trade agreements or further escalation of trade tensions, inflation, rising interest rates, prospects of a recession, government shutdowns, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues.

Further, our future capital requirements are difficult to forecast and will depend on many factors, including:

• the accuracy of the assumptions underlying our estimates for our capital needs;

• the level of sales and market acceptance of RYTELO;

• the scope, progress, timing, magnitude and costs of non-clinical and clinical development, manufacturing and commercialization of imetelstat, including potential commercialization in the EU for lower-risk MDS, or in any other jurisdictions or other indication we may pursue, subject to clearances and approvals by the FDA and similar international regulatory authorities;

• the overall level of sales and market acceptance of RYTELO;

• the scope, progress, timing, magnitude and costs of non-clinical and clinical development, manufacturing and commercialization of RYTELO, including commercialization in the U.S.

and any commercialization in the EU for lower-risk MDS, or in any other jurisdictions or other indication we may pursue, subject to clearances and approvals by the FDA and similar international regulatory authorities;

• delays or disruptions in opening sites, screening and enrolling patients or treating and following patients, in our current or any potential future clinical trials of RYTELO;

• the costs, timing and outcomes of regulatory reviews or other regulatory actions related to RYTELO, including with respect to our MAA submission for RYTELO in the EU for lower-risk MDS;

• the costs, timing and outcomes of regulatory reviews or other regulatory actions related to RYTELO;

• the costs of preparing, filing and prosecuting patent applications and maintaining, enforcing and defending intellectual property-related claims;

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• the extent to which we acquire or in-license other drugs and technologies, or invest in businesses, products or technologies, although we currently have no commitments or agreements relating to any of these types of transactions, or to which we out-license RYTELO;

• the extent to which we are able to enter into and conduct successful arrangements with third parties, including for the commercialization and marketing of RYTELO in certain regions outside of the U.S., if approved for commercialization;

• the extent and scope of our selling, general and administrative expenses, including expenses associated with potential future litigation;

• the extent to which we are able to enter into and conduct successful commercialization arrangements with third parties, including for the commercialization and marketing of RYTELO in the EU and in any other regions outside of the U.S., if approved for commercialization in such other regions;

• expenses associated with the pending putative securities class action and shareholder derivative lawsuits and potential additional related lawsuits, as well as any other litigation;

• the extent and scope of our selling, general and administrative expenses, including expenses associated with pending and potential future litigation;

• our level of indebtedness and associated debt service obligations;

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• the costs of enabling our personnel to work remotely, including providing supplies, equipment and technology necessary for them to perform their responsibilities.

Until we can generate a sufficient amount of revenue from sales of RYTELO to finance our cash requirements, which we may never achieve, we expect to finance future cash needs through a combination of public or private equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements and other marketing and distribution arrangements, which may not be possible.

Availability of such financing sources may be negatively impacted by any further delays in our clinical trials, regulatory developments, or the other risks described in this section.

Additional financing through public or private debt or equity financings, including pursuant to the 2023 Sales Agreement with B.

In the event we need to raise additional capital to fund our business, including pursuant to the 2023 Sales Agreement with B.

Riley Securities, Inc., the Tranche B Loan and the Tranche C Loan under the Pharmakon Loan Agreement, which are subject to certain funding conditions;

capital lease transactions or other financing sources, may not be available on acceptable terms, or at all.

capital lease transactions or other financing sources, such additional capital may not be available on acceptable terms, or at all.

We may be unable to raise equity capital, or may be forced to do so at a stock price or on other terms that could result in substantial dilution of ownership for our stockholders.

The receptivity of the public and private debt and equity markets to proposed financings has been substantially affected by uncertainty in the general economic, market and political climate due to the effects of macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues, and may in the future be affected by other factors which are unpredictable and over which we have no control.

The receptivity of the public and private debt and equity markets to proposed financings has been substantially affected by uncertainty in the general economic, market and political climate due to the effects of macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, further changes in tariffs and other trade restrictions, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues, and may in the future be affected by other factors which are unpredictable and over which we have no control.

These effects have increased market volatility and could result in a significant long-term disruption of global financial markets, which could reduce or eliminate our ability to raise additional funds through financings, and could negatively impact the terms upon which we may raise those funds.

Similarly, these macroeconomic conditions have created extreme volatility and disruption in the capital markets and is expected to have further global economic consequences.

If the equity and credit markets deteriorate, including as a result of macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive.

If we are unable to effectively commercialize RYTELO, or raise additional capital or establish alternative collaborative arrangements with third-party collaborative partners for

RYTELO when needed, the development and commercialization of RYTELO may be further delayed, altered or abandoned, which might cause us to cease operations.

If the equity and credit markets deteriorate, including as a result of macroeconomic or other global conditions, such as further changes in tariffs and other trade restrictions and uncertainty around further escalation of trade tensions and renegotiation of existing international trade agreements, inflation, rising interest rates, prospects of a recession, government shutdowns, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive.

If we are unable to effectively commercialize RYTELO, or raise additional capital, if needed, or establish alternative collaborative arrangements with third-party collaborative partners for RYTELO when needed, the development

and commercialization of RYTELO may be further delayed, altered or abandoned, which might cause us to cease operations.

In addition, we may seek additional capital due to market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.

Due to uncertainty in the general economic, market and political climate, we may determine that it is necessary or appropriate to raise additional funds proactively to meet longer-term anticipated operating plans.

To the extent that we raise additional capital through the sale of equity or convertible debt securities, including pursuant to the 2023 Sales Agreement, your ownership interest as a stockholder may be diluted, and the terms may include liquidation or other preferences that materially and adversely affect your rights as a stockholder.

In addition, we have borrowed, and in the future may borrow, additional capital from institutional and commercial banking sources to fund imetelstat development and our future growth, including pursuant to our Pharmakon Loan Agreement or potentially pursuant to new arrangements with different lenders.

We may borrow funds on terms under agreements, such as the Pharmakon Loan Agreement, that include restrictive covenants, including covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

To the extent that we raise additional capital through the sale of equity or convertible debt securities, including pursuant to the 2023 Sales Agreement, our stockholders may be diluted, and the terms may include liquidation or other preferences that could materially and adversely affect the rights of our existing stockholders.

In addition, we have borrowed, and in the future may borrow, additional capital from institutional and commercial banking sources to fund development and our future growth, including pursuant to our Pharmakon Loan Agreement or potentially pursuant to new arrangements with different lenders.

We may borrow funds on terms under agreements, such as our Pharmakon Loan Agreement, that include restrictive covenants, including covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

Moreover, if we raise additional funds through alliance, collaborative or licensing arrangements with third parties, we may have to relinquish valuable rights to RYTELO or our technologies or grant licenses on terms that are not favorable to us.

Risks Related to our Indebtedness and liabilities

RISKS RELATED TO OUR INDEBTEDNESS AND ROYALTY PAYMENT OBLIGATIONS

Our level of indebtedness and debt service obligations could adversely affect our financial condition and may make it more difficult for us to fund our operations.

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(a) a Tranche B Loan of $75.0 million, which is available until December 31, 2025 and is available at our option, subject to certain customary and limited conditions;

and (b) the Tranche C Loan of $50.0 million, which is available through December 31, 2025, subject to certain conditions including achieving a certain revenue milestone on or prior to November 30, 2025.

If we do not achieve such revenue milestone within the required timeline, we will not be eligible to draw funds under the Tranche C Loan under the Pharmakon Loan Agreement.

and (b) a Tranche C Loan of $50.0 million, which is available until December 31, 2025, subject to certain conditions including achieving a certain revenue milestone on or prior to November 30, 2025.

If we do not achieve such revenue milestone within the required timeline, we will not be eligible to draw down the Tranche C Loan.

In addition, before we would consider drawing down any of the remaining tranches under the Pharmakon Loan Agreement, if available, we must first satisfy ourselves that we will have access to future alternate sources of capital, such as from commercial revenues or the equity capital markets or debt capital markets, in order to repay any additional principal borrowed, which we may be unable to do, in which case, our liquidity and ability to fund our operations may be substantially impaired.

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This indebtedness may create additional financing risk for us, particularly if our business or prevailing financial market conditions are not conducive to paying off or refinancing the outstanding debt obligations at maturity.

If we are able to draw down any of the remaining tranches under the Pharmakon Loan Agreement, our indebtedness will increase, which would further increase our risk of being unable to pay off or refinance our outstanding debt obligations at maturity.

If we draw down any of the remaining tranches under the Pharmakon Loan Agreement, our indebtedness will increase, which would further increase our risk of being unable to pay off or refinance our outstanding debt obligations at maturity.

Our indebtedness could also have important negative consequences, including:

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• our failure to comply with the obligations of our affirmative and restrictive covenants in the Pharmakon Loan Agreement could result in an event of default that, if not cured or waived, would permit the Lenders to accelerate our obligation to repay this indebtedness, and the Lenders could seek to enforce their security interest in the assets securing such indebtedness.

In addition, we may borrow additional capital in the future to fund imetelstat development and our future growth, including pursuant to the Pharmakon Loan Agreement or potentially pursuant to new arrangements with different lenders.

In addition, we may borrow additional capital in the future to fund clinical development and our future growth, including pursuant to the Pharmakon Loan Agreement or potentially pursuant to new arrangements with different lenders.

To the extent additional debt is added to our current debt levels, the risks described above could increase.

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The Pharmakon Loan Agreement imposes operating and other restrictions on us.

Such restrictions will affect, and in many respects limit or prohibit, our ability and the ability of any future subsidiaries to, among other things:

Such restrictions will affect, and in many respects limit or prohibit, our ability and the ability of our subsidiaries to, among other things:

• dispose of certain assets;

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We may not be able to engage in any of these activities or engage in these activities on desirable terms, which could result in a default on our debt obligations.

Failure to satisfy our current and future debt obligations under the Pharmakon Loan Agreement or to comply with certain covenants in the Pharmakon Loan Agreement could result in an event of default, the occurrence and continuance of which provide the Lenders with the right to demand immediate repayment of all outstanding obligations under the Pharmakon Loan Agreement (and in the case of certain insolvency, liquidation, bankruptcy or similar events, automatically requires immediate repayment of all outstanding obligations under the Pharmakon Loan Agreement), and to exercise remedies against us and the collateral securing the Pharmakon Loan Agreement.

Failure to satisfy our current and future debt obligations under the Pharmakon Loan Agreement or to comply with certain covenants in the Pharmakon Loan Agreement could result in an event of default, the occurrence and continuance of which provides the lenders with the right to demand immediate repayment of all outstanding obligations under the Pharmakon Loan Agreement (and in the case of certain insolvency, liquidation, bankruptcy or similar events, automatically requires immediate repayment of all outstanding obligations under the Pharmakon Loan Agreement), and to exercise remedies against us and the collateral securing the Pharmakon Loan Agreement.

These events of default include, among other things:

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• failure to observe covenants under the Pharmakon Loan Agreement and ancillary collateral documents, which failure, in certain limited cases, is not cured within 10 or 20 days;

• the occurrence of a material adverse change or a withdrawal event in respect to RYTELO;

• the occurrence of a withdrawal event in respect to RYTELO;

• the occurrence of a material adverse change;

• material misrepresentations;

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Our business, financial condition and results of operations could be materially adversely affected as a result of any of these events.

The Royalty Pharma Agreement places restrictions on our operational flexibility.

The Royalty Pharma Agreement contains covenants that impose on us certain obligations with respect to revenue payments, diligence, reporting, indemnification and includes restriction on intellectual property transfers and out-licenses, and certain other actions.

The Royalty Pharma Agreement places certain restrictions on our operational flexibility.

The Royalty Pharma Agreement contains covenants that impose on us certain obligations with respect to royalty payments, diligence, reporting, indemnification and includes restriction on intellectual property transfers and out-licenses, and certain other actions.

The Royalty Pharma Agreement also limits our ability to create or incur liens or dispose of certain assets related to imetelstat.

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RISKS RELATED TO PROTECTING OUR INTELLECTUAL PROPERTY

If we are unable to obtain and maintain sufficient intellectual property protection for RYTELO, both in the U.S.

If we are unable to obtain and maintain sufficient intellectual property protection and relevant regulatory exclusivities for RYTELO, both in the U.S.

and in other countries, our competitors could develop and commercialize products similar or identical to RYTELO, and our ability to successfully commercialize RYTELO may be adversely affected.

Protection of our proprietary technology is critically important to our business.

Our success and the success of our commercialization and planned future development of RYTELO will depend on our ability to protect our technologies and RYTELO through patents and other intellectual property rights.

Our success and the success of our commercialization and planned future development of RYTELO will depend on our ability to protect our technologies and RYTELO through patents, regulatory exclusivity, and other intellectual property rights.

Our success will depend in part on our ability to obtain, maintain, enforce, and extend our patents and maintain trade secrets, both in the U.S.

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In addition to our patents covering RYTELO, we also expect to rely on regulatory exclusivity, including orphan drug exclusivity of up to 7 years in the U.S.

and 10 years in the E.U.

following approval, to protect our rights to commercialize RYTELO for its approved uses, but such regulatory exclusivity may be limited or withdrawn.

and 10 years in the EU following approval, to protect our rights to commercialize RYTELO for its approved uses, but such regulatory exclusivity may be limited or withdrawn.

See “ Risks Related to Regulatory Approval of RYTELO -- Although orphan drug designation has been granted to RYTELO for the treatment of MDS and MF in the U.S.

In addition to orphan drug exclusivity, we expect to rely on other forms of regulatory exclusivity to protect our ability to commercialize RYTELO.

In the U.S., New Chemical Entity, or NCE, exclusivity would entitle us to four

years of data exclusivity and one year of market exclusivity, for a total of five years of NCE exclusivity from the date of approval of the first-approved indication.

Our request for NCE exclusivity is still pending with FDA, and might not be awarded or could be awarded and then later withdrawn.

In Europe, New Active Substance, or NAS, exclusivity is expected to entitle us to eight years of data exclusivity and two years of market exclusivity, for a total of ten years of NAS exclusivity for the first-approved indication, but as with other forms of regulatory exclusivity, NAS exclusivity could be limited or withdrawn.

Loss or impairment of our intellectual property rights related to RYTELO might further delay or halt ongoing or potential future clinical trials of RYTELO and any applications for regulatory approval, and might further delay or preclude any future development or commercialization of RYTELO by us.

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Obtaining and maintaining our patent rights depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for noncompliance with these requirements.

Patent and Trademark Office, or the Patent Office, and various governmental patent agencies in other countries require compliance with a number of procedural, documentary, fee payment, periodic maintenance fees, renewal fees, annuity fees and various other government fees on patents and/or patent applications.

The USPTO and various governmental patent agencies in other countries require compliance with a number of procedural, documentary, fee payment, periodic maintenance fees, renewal fees, annuity fees and various other government fees on patents and/or patent applications.

Failure to respond to official actions within prescribed time limits, and nonpayment of fees, for example, maintenance fees, renewal fees, and annuity fees could result in abandonment or lapse of a patent or patent application, resulting in partial or complete loss of patent rights in the jurisdiction.

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In the U.S., the Hatch-Waxman Act permits one patent per approved product to receive a patent term extension of up to five years beyond its normal expiration.

The length of the patent term extension is typically calculated as one half of the clinical trial

period plus the entire period of time during the review of the NDA by the FDA, minus any time of delay by us during these periods.

The length of the patent term extension is typically calculated as one half of the clinical trial period plus the entire period of time during the review of the NDA by the FDA, minus any time of delay by us during these periods.

There is also a limit on the patent term extension to a term that is no greater than fourteen years from drug approval.

Only one U.S.

patent may be eligible for patent term extension under the Hatch-Waxman Act.

We have applied to the Patent Office for patent term extension of some of our patents.

Once the Patent Office and the FDA determine the extension period for each proposed eligible patent, we will select the one patent to be extended.

patent may receive patent term extension under the Hatch-Waxman Act.

We have applied to the USPTO for patent term extension of some of our patents.

Once the USPTO and the FDA determine the extension period for each proposed eligible patent, we will select the one patent to be extended.

We expect to apply any patent term extension that is granted in the U.S.

to our method of treatment patent for MDS and MF that expires on March 15, 2033.

If such patent term extension is granted, we expect the term of the patent to extend through August 2037, although such timing is subject to approval by the Patent Office as part of its review of our application for patent term extension and could differ from our calculation.

Currently, communication of patent term extension approval and the length of the granted extension period by the Patent Office may occur up to four years from filing of an application for patent term extension.

Accordingly, we will decide on the specific patent to be extended only after such communication from the Patent Office.

If such patent term extension is granted, we expect the term of the patent to extend through August 2037, although such timing is subject to approval by the USPTO as part of its review of our application for patent term extension and could differ from our calculation.

Currently, communication of patent term extension approval and the length of the granted extension period by the USPTO may occur up to several years from filing of an application for patent term extension.

Accordingly, we will decide on the specific patent to be extended only after such communication from the USPTO.

Similar extensions are also available in certain countries and territories outside the U.S., such as in Japan, and in Europe as Supplementary Protection Certificates, or SPCs.

However, we might not be granted a patent term extension at all because of failure to satisfy any of the numerous applicable requirements.

Moreover, the applicable authorities, including the FDA and the Patent Office in the U.S., and any equivalent regulatory authorities and patent offices in other countries, may not agree with our assessment of whether such extensions are available, may refuse to grant extensions to our patents, or may grant more limited extensions than we request and could be less than five years.

Moreover, the applicable authorities, including the FDA and the USPTO in the U.S., and any equivalent regulatory authorities and patent offices in other countries, may not agree with our assessment of whether such extensions are available, may refuse to grant extensions to our patents, or may grant more limited extensions than we request and could be less than five years.

If we select and are granted a patent term extension on a recently filed and issued patent, we may not receive the full benefit of a possible patent term extension, if at all.

Moreover, in some countries, including the U.S., the scope of protection for claims under such patent term extensions, if any, does not extend to the full scope of the claims but is limited to the product composition as approved and, for a method of treatment patent, is limited to the approved indications.

Moreover, in some countries, the scope of protection for claims under patent term extension, if any, is limited to the product composition as approved and, for a method of treatment patent, to the approved

If we do not have sufficient patent life and regulatory exclusivity to protect RYTELO, our financial results, business and business prospects would be materially and adversely affected, which might cause us to cease operations.

In Europe and other countries, our composition of matter patent coverage expired in September 2024, and our method of treatment patent rights for MDS and MF expire in November 2033.

Our method of treatment patents may be eligible for patent term extension of up to five years under a Supplementary Protection Certificate, or SPC, permitted under European Council (EC) Regulation No.

469/2009, or the European SPC Regulation, upon receipt of drug product approval, such as, for example, our method of treatment patent for MDS.

Our method of treatment patents may be eligible for patent term extension of up to five years under an SPC, permitted under European Council (EC) Regulation No.

469/2009, or the European SPC Regulation, upon receipt of marketing authorization, such as, for example, our method of treatment patent for MDS.

In Europe, we have separate method of treatment patents covering MDS and MF, and a SPC may only be applied to one patent.

Accordingly, in countries of the European Economic Area, or EEA, we must rely on regulatory exclusivity and our method of treatment patents.

Accordingly, in countries of the EEA, we must rely on regulatory exclusivity and our method of treatment patents.

If regulatory approval of RYTELO occurs after a patent has expired in a country that does not allow interim patent term extensions, as is the case in many countries and territories including Europe, we will be unable to obtain any patent term extension of that expired patent, and the duration of our patent rights may be limited.

Accordingly, in Europe and such other similar countries and territories, we will not be able to seek patent term extension of our composition of matter patent, as it expired in September 2024.

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The validity, scope and enforceability of any patents listed in the Orange Book that cover RYTELO or its methods of use can be challenged by third parties and may not protect us from generic or innovator competition.

If a third party files an application under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act or an abbreviated new drug application, or ANDA, under Section 505(j) to obtain permission to sell a generic version of RYTELO, and relies in whole or in part on studies conducted by or for us, the third-party will be required to certify to the FDA that either:

If a third party files an application under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act or an abbreviated new drug application, or ANDA, under Section 505(j) to obtain permission to sell a generic or follow-on version of RYTELO, and relies in whole or in part on studies conducted by or for us, the third-party will be required to certify to the FDA that either:

(1) there is no patent information listed in the Orange Book with respect to our NDA for RYTELO;

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A certification that the new product will not infringe the Orange Book-listed patents for RYTELO, or that such patents are invalid, is called a paragraph IV certification.

If the third-party submits a paragraph IV certification to the FDA, a notice of the paragraph IV certification must also be sent to us once the third-party’s ANDA is accepted for filing by the FDA.

If the third-party submits a paragraph IV certification to the FDA, a notice of the paragraph IV certification must also be sent to us within 20 days after the third-party’s ANDA is accepted for filing by the FDA.

We may then initiate a lawsuit to defend the patents identified in the notice.

The filing of a patent infringement lawsuit within 45 days of receipt of the notice automatically prevents the FDA from approving the third-party’s ANDA until the earliest of 30 months or the date on which the patent expires, the lawsuit is settled, or the court reaches a decision in the infringement lawsuit in favor of the third-party.

If the product has NCE exclusivity and the notice is given and the suit filed in the fifth year of exclusivity, the regulatory stay extends until 7.5 years after approval of the reference product.

If we do not file a patent infringement lawsuit within the required 45-day period, the third-party’s ANDA will not be subject to the 30-month stay of FDA approval.

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Furthermore, if we are engaged in intellectual property litigation, there would be public announcements of filings, briefings, hearings, motions or other interim proceedings or developments.

If securities analysts or investors perceive these events to be negative, it could have an adverse effect on the price of our common shares.

If securities analysts or investors perceive these events to be negative, it could have an adverse effect on the price of our common stock.

Many companies have encountered significant problems in protecting and defending intellectual property rights in jurisdictions outside the U.S.

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Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations.

Depending on actions by Congress, the federal courts, and the Patent Office, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents or patents that we might obtain in the future.

Depending on actions by Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents or patents that we might obtain in the future.

Similarly, changes in patent law and regulations in other countries or jurisdictions or changes in the governmental bodies that enforce them or changes in how the relevant governmental authority enforces patent laws or regulations may weaken our ability to obtain new patents or to enforce our existing patents or patents that we may obtain in the future.

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For example, where more than one party seeks U.S.

patent protection for the same technology in patent applications that are subject to the law before the implementation of the AIA, the Patent Office may declare an interference proceeding in order to ascertain the party to which the patent should be issued.

patent protection for the same technology in patent applications that are subject to the law before the implementation of the AIA, the USPTO may declare an interference proceeding in order to ascertain the party to which the patent should be issued.

Patent interferences are typically complex, highly contested legal proceedings, subject to appeal.

They are usually expensive and prolonged and can cause significant delay in the issuance of patents.

Our pending patent applications or our issued patents, or those we have licensed and may license from others, may be drawn into interference proceedings or be challenged through post-grant review procedures or litigation, any of which could delay or prevent the issuance of patents, or result in the loss of issued patent rights.

or result in the loss of issued patent rights.

We may not be able to obtain from our past or future collaborators the information needed to support our patent rights which could result in the loss of important patent rights.

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patents and those we have licensed and may license from others, even those issued before March 16, 2013.

A third party could attempt to use the Patent Office procedures to invalidate patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.

A third party could attempt to use the USPTO procedures to invalidate patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action.

patents owned or licensed by us may therefore be subject to post-grant review procedures, as well as other forms of review and re-examination.

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Occurrence of any of these events could materially and adversely affect our business and might cause us to cease operations.

We have a global trademark, RYTELO, for our product and failure to maintain such trademark could adversely affect our business.

We have a global trademark, RYTELO, which is the commercial trade name for imetelstat.

During trademark registration proceedings, we may receive rejections or fail to maintain such registrations.

Although we are given an opportunity to respond to those rejections, we may be unable to overcome such rejections.

In addition, opposition or cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings.

If our United States trademark application which forms the basis for our international registration, or IR, for our commercial trade name is refused, withdrawn, or abandoned within the first 5 years of our IR, we will lose our IR registrations which could adversely affect our business.

We may be unable to maintain or enforce our current and future trademarks or trademark applications, and if we fail to satisfy the applicable regulatory requirements, we may not have enforceable trademark rights or registrations in such jurisdictions.

We have a registered trademark, RYTELO, for our product and failure to maintain such trademark could adversely affect our business.

We have a registered trademark, RYTELO, which is the commercial trade name for imetelstat, in a number of countries and regions, including in the U.S.

Opposition or cancellation proceedings, however, may be filed against our trademarks, and our trademarks may not survive such proceedings.

If our United States trademark application which forms the basis for our international registration, or IR, for our commercial trade name is withdrawn or abandoned within the first 5 years of our IR, we will lose our IR registrations which could adversely affect our business.

We may be unable to maintain or enforce our current and future trademarks, and if we fail to satisfy the applicable regulatory requirements, we may not have enforceable trademark rights or registrations in such jurisdictions.

Our product trademark, RYTELO, is approved by the FDA and the EMA.

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Our ability to successfully commercialize RYTELO in the U.S.

for lower-risk MDS, and to continue to develop RYTELO in other myeloid hematologic malignancies depends to a significant extent on the skills, experience and efforts of our executive officers and key members of our staff.

and in the EU for lower-risk MDS, and to continue to develop RYTELO in other myeloid hematologic malignancies depends to a significant extent on the skills, experience and efforts of our executive officers and key members of our staff.

In addition, we need to recruit, maintain, motivate and integrate additional personnel with expertise and experience in sales, marketing, market access, commercial operations, pricing, clinical science, biostatistics, clinical operations, pharmacovigilance, quality, manufacturing, regulatory affairs, medical affairs, legal affairs, and compliance to enable us to further commercialize and further develop RYTELO.

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If we do not effectively manage the expansion of our operations, we could experience weaknesses in our infrastructure and ability to comply with applicable legal and regulatory requirements and regulations, operational mistakes or shortcomings, loss of business opportunities, loss of employees and reduced productivity among remaining employees.

If we seek to establish potential future collaborative arrangements for RYTELO, we may be unable to establish such collaborative arrangements on acceptable terms, or at all, and may have to delay, alter or abandon commercialization or further development of RYTELO.

Management transition creates uncertainties and could harm our business.

Over the past few years, we have experienced significant changes in executive leadership, and more could occur.

For example, effective March 10, 2025, we appointed Dawn C.

Bir, a current member of our board of directors, as our Interim President and Chief Executive Officer to serve in such capacity while we conduct a search for a permanent Chief Executive Officer.

In addition, in November 2024, we appointed a new EVP of Research and Development, and, in September 2024, we appointed a new EVP, Chief Commercial Officer.

Changes to company strategy, which can often

times occur with the appointment of new executives, can create uncertainty, may negatively impact our ability to execute quickly and effectively, and may ultimately be unsuccessful.

In addition, executive leadership transition periods are often difficult as the new executives gain detailed knowledge of our operations, and friction can result from changes in strategy and management style.

Management transition inherently causes some loss of institutional knowledge, which can negatively affect strategy and execution.

Until we integrate new personnel, and unless they are able to succeed in their positions, we may be unable to successfully manage and grow our business, and our results of operations and financial condition could suffer as a result.

In any event, changes in our organization as a result of executive management transition may have a disruptive impact on our ability to implement our strategy and could have a material adverse effect on our financial condition and our business and business prospects.

We may be unable to establish potential future collaborative arrangements for RYTELO on acceptable terms, or at all, and as a result, may have to delay, alter or abandon commercialization or further development of RYTELO.

We intend to develop RYTELO broadly for hematologic malignancies, and to commercialize, market and sell RYTELO in the U.S.

for lower-risk MDS and potentially in the EU for the same indication.

We may seek to self-commercialize or seek a collaborative partner or partners, at an appropriate time, to assist us in the potential development and commercialization of RYTELO outside the U.S., and to provide funding for such activities.

and in the EU for certain patients with lower-risk MDS.

At this time, we do not plan to commercialize R YTELO independently in the EU or in any other regions outside the U.S.

where RYTELO may be approved for marketing in the future.

Accordingly, we currently intend to seek contractual arrangements, strategic partnerships, collaborations, alliances or licensing arrangements with a third-party partner or partners to assist us in the commercialization of RYTELO in the EU and in any other regions outside the U.S.

where RYTELO may be approved for marketing in the future.

We face significant competition in seeking appropriate collaborative partners, and these potential collaborative arrangements are complex and time consuming to negotiate, document and implement.

Our ability to seek and establish potential collaborative arrangements may be impacted by delays in marketing approvals of RYTELO in lower-risk MDS in the EU and in reporting results from IMpactMF, as well as the period of the patent term for our intellectual property portfolio and market exclusivity for RYTELO.

In addition, the terms of our Pharmakon Loan Agreement may limit our ability to enter into certain collaborative arrangements and any future debt agreements may continue or further limit our ability to enter into such agreements.

We may not be able to establish collaborative arrangements on acceptable terms, or at all.

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If we are unable to negotiate collaborative arrangements, we may have to:

• delay or curtail the additional development of RYTELO;

• delay or abandon the commercialization of RYTELO outside of the U.S.;

• delay, curtail or abandon the additional development of RYTELO;

• delay, curtail or abandon the commercialization of RYTELO in jurisdictions where it is approved;

• reduce the scope of potential future sales or marketing activities;

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• potentially adverse tax consequences, including changes in applicable tax laws and regulations;

• potentially costly trade laws, tariffs, export quotas, custom duties or other trade restrictions, and any changes to them;

• potentially costly trade laws, further increases to tariffs, renegotiation of existing international trade agreements, and changes to export quotas, custom duties or other trade restrictions, including as a result of recent changes implemented by the current administration in the U.S.;

• compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

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• workforce uncertainty in countries where labor unrest is more common than in the U.S.

In addition, our international operations in the U.K.

and the Netherlands expose us to fluctuations in currency exchange rates between the British pound, the Euro and the U.S.

Given the volatility of currency exchange rates, there is no assurance that we will be able to effectively manage currency transaction and/or conversion risks.

To date, we have not entered into derivative instruments to offset the impact of foreign exchange fluctuations, which fluctuations could have an adverse effect on our financial condition and results of operations.

We may not be able to obtain or maintain sufficient insurance on commercially reasonable terms or with adequate coverage against potential liabilities in order to protect ourselves against claims such as product liability or personal injury claims arising from our commercialization of RYTELO, claims related to clinical trial conduct, or claims related to data protection.

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Being unable to obtain or maintain product liability, clinical trial liability, cybersecurity or other insurance for our business activities in the future on acceptable terms or with adequate coverage against potential liabilities would have a material adverse effect on our business, and could cause us to limit or cease our commercialization and further development of RYTELO.

In the past, we and certain of our officers have been named as defendants in securities class action lawsuits and shareholder derivative lawsuits.

Potential similar or related lawsuits that may be filed in the future, could result in substantial damages, divert management’s time and attention from our business, and have a material adverse effect on our results of operations.

Any such lawsuits, or other lawsuits to which we are subject, will be costly to defend or pursue and are uncertain in their outcome.

We are not currently a party to any material pending legal proceedings.

However, securities class action lawsuits and/or derivative lawsuits have often been brought against companies, including biotechnology and biopharmaceutical companies, that experience volatility in the market price of their securities.

We and certain of our current and former officers and directors have been named as defendants in securities class action lawsuits and derivative lawsuits.

These lawsuits, and any other lawsuits to which we are subject, will be costly to defend or pursue and are uncertain in their outcome.

Securities class action lawsuits and/or derivative lawsuits have often been brought against companies, including biotechnology and biopharmaceutical companies, that experience volatility in the market price of their securities.

This risk is especially relevant for us because we often experience significant stock price volatility in connection with our activities.

On March 13 and March 14, 2025, we and certain of our current and former officers were named as defendants in two putative securities class action lawsuits filed in the United States District Court for the Northern District of California captioned Debestani v.

Geron Corporation, et al.

3:25-cv-02507-CRB and Potvin v.

Geron Corporation, et al.

3:25-cv-02563-CRB, respectively.

Both lawsuits allege violation of Sections 10(b) and 20(a) of the Securities Exchange Act of 1934, as amended, and Rule 10b-5 promulgated thereunder in connection with allegedly false and misleading statements concerning the commercial potential of RYTELO.

The plaintiffs allege, among other things, that we overstated RYTELO's commercial potential by making materially false and misleading statements and/or concealing material adverse facts concerning RYTELO's commercial potential, including the lack of awareness among healthcare providers for RYTELO, the burden of monitoring requirements in administering the drug, and the impacts of seasonality and existing competition on RYTELO's sales, and that our stock price dropped when we disclosed in our earnings call on February 26, 2025 that we had observed flat revenue trends over the prior few months.

The plaintiffs seek damages and interest, and an award of reasonable costs, including attorneys' and experts' fees.

In addition, on April 15, 2025 and April 16, 2025, three purported stockholders filed derivative complaints, each filed in the United States District Court for the Northern District of California, captioned Bishop v.

Scarlett, et al., No.

3:25-cv-03356, Lerner v.

Scarlett, et al.

3:25-cv-03401, and Willis v.

Scarlett, et al., No:

3:25-cv-03396, respectively.

The three lawsuits name certain of our current and former directors and officers and allege that they breached their fiduciary duties and violated federal securities laws by issuing allegedly false and misleading statements concerning the commercial potential of RYTELO.

The allegations in each of the three derivative complaints are substantially similar to the

two aforementioned securities class action lawsuits, which these lawsuits are premised on.

The plaintiff seeks damages and interest, and an award of reasonable costs, including attorneys' and experts' fees.

The plaintiffs in Bishop v.

Scarlett, et al.

and Willis v.

Scarlett, et al .

also seek punitive damages.

We have also been subject to securities class action lawsuits in the past.

In 2020, three securities class action lawsuits were filed against us and certain of our officers.

One of the lawsuits was voluntarily dismissed, and final judgment with respect to the other two lawsuits was entered in October 2023.

One of the lawsuits was voluntarily dismissed, and we settled the other two lawsuits and a final judgment was entered in October 2023.

In 2020 and 2021, seven shareholder derivative actions were filed in a number of courts, naming as defendants certain of our then current officers and certain of our then current and former members of our board.

All seven of the shareholder derivative actions have been dismissed with prejudice.

While we have settled these lawsuits, it is possible that additional lawsuits might be filed, or allegations might be received from stockholders, with respect to these same or other matters and also naming us and/or our officers and directors as defendants.

All seven of the shareholder derivative actions were dismissed with prejudice.

It is possible that additional lawsuits might be filed, or allegations might be received from stockholders, with respect to these same matters as alleged in the pending lawsuits or other matters and also naming us and/or our officers and directors as defendants.

Such lawsuits and any other related lawsuits are subject to inherent uncertainties, and the actual defense and disposition costs will depend upon many unknown factors.

We could be forced to expend significant resources in the defense of any additional lawsuits, and we may not prevail.

Monitoring, initiating and defending against legal actions is time-consuming for our management, is likely to be expensive and may detract from our ability to fully focus our internal resources on our business activities.

We could be forced to expend significant resources in any potential future lawsuits, and we may not prevail in such lawsuits.

Additionally, we may not be successful in having any such lawsuits dismissed or settled within the limits of our insurance coverage.

A decision adverse to our interests in any legal proceedings, could result in the payment of substantial damages, or possibly fines, and could have a material adverse effect on our business, our stock price, cash flow, results of operations and financial condition.

The outcome of the pending lawsuits and any other related lawsuits is necessarily uncertain.

We could be forced to expend significant resources and may incur substantial legal fees and costs in the defense of the pending lawsuits and any related or additional lawsuits, and we may not prevail.

Monitoring, initiating and defending against legal actions is also time-consuming for our management, is likely to be expensive and may detract from our ability to fully focus our internal resources on our business activities.

Given the early stage of these lawsuits and the inherent uncertainly of litigation, we cannot predict how long it may take to resolve the pending lawsuits or the amount of costs we may incur, or the potential outcome or the possible amount of any damages we may be required to pay.

A decision adverse to our interests in the pending lawsuits or in similar or related litigation, could result in the payment of substantial damages or settlements, or possibly fines, and, although we maintain liability insurance, we may not be successful in having any such lawsuits dismissed or settled within the limits of our insurance coverage.

If any judgement or settlement against us and costs or expenses associated with the pending litigation exceed our insurance coverage or insurance coverage is denied, we may be forced to bear some or all of these costs and expenses directly, which could be substantial and could have a material adverse effect on our business, our stock price, cash flow, results of operations and financial condition.

We may be subject to third-party litigation, and such litigation would be costly to defend or pursue and uncertain in its outcome.

Our business may bring us into conflict with our licensees, licensors, or others with whom we have contractual or other business relationships, or with our competitors or others whose interests differ from ours.

Our commercial launch of RYTELO may result in product or personal injury disputes, or other disputes with health care providers, patients or other third parties as a result of our commercialization efforts.

Our commercialization of RYTELO may result in product or personal injury disputes, or other disputes with health care providers, patients or other third parties as a result of our commercialization efforts.

We may experience employment-related disputes.

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RISKS RELATED TO INFORMATION TECHNOLOGY SYSTEMS, DATA SECURITY AND DATA PRIVACY

If our information technology systems or data, or those of third parties upon which we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including regulatory investigations or actions;

If our information technology systems or data, or those of third parties with whom we work, are or were compromised, we could experience adverse consequences resulting from such compromise, including regulatory investigations or actions;

fines and penalties;

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and other adverse consequences.

In the ordinary course of our business, we (and third parties upon which we rely) collect, receive, store, use, transfer, make accessible, protect, secure, dispose of, transmit, disclose, or otherwise process (commonly known as processing) proprietary, confidential, and sensitive data, including personal data (such as health-related data and participant study related data), intellectual property, and trade secrets (collectively, sensitive information).

In addition, we rely on third-party service providers to establish and maintain appropriate information technology and data security protections over the information technology systems they provide us to operate our critical business systems, including cloud-based infrastructure and systems, employee email, and data storage and management systems.

In the ordinary course of our business, we (and third parties with whom we work) collect, receive, store, use, transfer, make accessible, protect, secure, dispose of, transmit, disclose, or otherwise process (commonly known as processing) proprietary, confidential, and sensitive data, including personal data (such as health-related data and participant study related data), intellectual property, and trade secrets (collectively, sensitive information).

In addition, we rely on third-party service providers to establish and maintain appropriate information technology and data security protections, including disaster recovery and business continuity procedures, over the information technology systems they provide us to operate our critical business systems, including cloud-based infrastructure and systems, employee email, and data storage and management systems.

However, except for contractual duties and obligations, we have limited ability to control or monitor third parties’ safeguards and actions related to such matters, and these third parties may not have adequate information security measures in place.

Furthermore, while we may be entitled to damages if our third-party service providers fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.

Most of our employees work remotely, resulting in increased risks to our information technology systems and data, as employees utilize network connections, computers, and devices outside our premises and networks, including working at home and while in transit and in public locations.

Most of our employees work remotely, resulting in increased risks of loss or theft of company devices as well as increased risks to our information technology systems and data, as employees utilize network connections, computers, and devices outside our premises and networks, including working at home and while in transit and in public locations.

Additionally, the prevalent use of mobile devices that access our sensitive information increases the risk of security incidents.

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Furthermore, we may discover security issues that were not found during due diligence of such acquired or integrated entities, and it may be difficult to integrate companies into our information technology environment and security program.

Our information technology systems, including in our remote work environment, and those of the third parties upon which we rely, have been in the past and may continue to be vulnerable to evolving threats.

Our information technology systems, including in our remote work environment, and those of the third parties with whom we work, have been in the past and may continue to be vulnerable to evolving threats.

These threats are prevalent, continue to increase, and come from a variety of sources such as traditional “hackers,” threat actors, “hacktivist,” organized criminal threats actors, or internal bad actors, personnel (such as through theft, error or misuse), sophisticated nation states and nation-state-supported actors.

These threats include, but are not limited to, social-engineering attacks, targeted phishing campaigns, malicious code or malware, unauthorized intrusions, denial-of-service attacks, personnel misconduct or errors, ransomware attacks, supply-chain attacks, software bugs, computer viruses, server malfunctions, software, hardware or data center failures, loss of data or other information technology assets, natural disasters, terrorism, war, telecommunication and electrical failures and attacks enhanced or facilitated by artificial intelligence, or AI, and other similar threats.

In particular, ransomware attacks are becoming increasingly prevalent and severe and can lead to significant interruptions in operations, loss of data and income, reputational harm, and diversion of funds.

In particular, ransomware attacks are becoming increasingly prevalent and severe and can lead to significant interruptions in operations, loss of sensitive data and income, reputational harm, and diversion of funds.

If we were to experience such an attack, extortion payments might alleviate the negative impact of a ransomware attack, but we might be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.

Similarly, supply-chain attacks and attacks on clinical trial sites as well as regulatory and health authorities have increased in frequency and severity, and we cannot guarantee that third parties and infrastructure in our supply chain or our third-party partners’ supply chains, or of clinical trial sites and regulatory and health authorities, have not been compromised or that they do not contain exploitable defects or bugs that could result in a breach of or disruption to our information technology systems or the third-party information technology systems that support us and the services provided to us.

For example, in February 2024, a service provider that processes clinical trial data experienced a security incident that resulted in certain of the service provider’s information systems being unavailable for a limited period of time.

For example, in February 2024, one of our service providers that processes clinical trial data experienced a security incident that resulted in certain of the service provider’s information systems being unavailable for a limited period of t ime.

Based on the service provider’s forensic investigation findings that were shared with us, we believe that this incident did not have a material impact on us, our clinical trials or clinical trial participants.

As another example, in March 2024, we learned about another security incident, involving another service provider, that processes personnel data for our limited number of UK personnel and directors of Geron UK Ltd.

As another example, in March 2024, we learned about another security incident, involving another service provider, that processes personnel dat a for our limited number of UK personnel and directors of Geron UK Ltd.

Following the service provider’s forensic investigation, the service provider informed us that it did not determine the specific data involved or the incident’s impact.

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Any of these or similar incidents or threats may result in unauthorized, unlawful or accidental loss, corruption, access, modification, destruction, alteration, acquisition or disclosure of sensitive information, such as clinical trial data or information, intellectual property, proprietary business data and personal data.

The costs to us to attempt to protect against such security incidents could be significant, including potentially requiring us to modify our business, and while we have implemented security measures, policies and procedures designed to protect our information technology systems and to identify and remediate vulnerabilities, such measures may not be fully implemented, complied with or successful in protecting our systems and information.

The costs to us to attempt to protect against such security incidents could be significant, including potentially requiring us to modify our business, and while we have implemented security measures, policies and procedures designed to protect our information technology systems from cybersecurity threats and to identify and remediate vulnerabilities, such measures may not be fully implemented, complied with or successful in protecting our systems and information.

We may expend significant resources or modify our business activities (including our clinical trial activities) to try to protect against security incidents.

We may be unable in the future to detect vulnerabilities in our information technology systems because such threats and techniques change frequently, are sophisticated in nature, and may not be detected until after a security incident has occurred.

We may be unable in the future to detect cybersecurity threats or vulnerabilities in our information technology systems because such threats and techniques change frequently, are sophisticated in nature, and may not be detected until after a security incident has occurred.

We may also experience security breaches that may remain undetected for an extended period.

Even if identified, we may be unable to adequately investigate or remediate incidents or breaches due to attackers increasingly using

tools and techniques that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence.

Even if identified, we may be unable to adequately investigate or remediate incidents or breaches due to attackers increasingly using tools and techniques that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence.

Unremediated high risk or critical vulnerabilities pose material risks to our business, particularly due to the reliance on software vendors to adequately patch and implement fixes to address critical or high-risk vulnerabilities in a timely manner.

Further, we may be materially impacted by software updates applied by our software vendors if such updates cause significant downtime to our systems.

If we or third parties upon which we rely experience or are perceived to have experienced a breach, we may experience adverse consequences.

If we or third parties with whom we work experience or are perceived to have experienced a breach, we may experience material adverse consequences.

These consequences may include:

government enforcement actions (for example, investigations, fines, penalties, audits, and inspections), interruptions in our operations, including disruption of our commercialization and development efforts, interruptions or restrictions on processing sensitive data (which could result in delays in obtaining, or our inability to obtain, regulatory approvals and significantly increase our costs to recover or reproduce the data), reputational harm, litigation (including class action claims), indemnification obligations, negative publicity, financial loss, and other harms.

In addition, such a breach may require public notification of the breach.

In addition, such a breach may require public notification of the breach, or we may choose to voluntarily notify relevant stakeholders, or take other actions, such as providing credit monitoring and identity theft protection services, and we have done so in the past.

Such disclosures are costly, and the disclosure or the failure to comply with such requirements could lead to adverse consequences.

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There can be no assurance that the limitations of liability in our contracts would be enforceable or adequate or would otherwise protect us from liabilities, damages, or claims relating to our data privacy and security obligations.

In addition, failure to maintain effective internal accounting controls related to data security breaches and cybersecurity in general could impact our ability to produce timely and accurate financial statements and could subject us to regulatory scrutiny.

If we fail to successfully implement or upgrade our enterprise resource planning and other information systems, our business and results of operation could be adversely impacted.

We periodically implement or upgrade new or enhanced enterprise resource planning, or ERP, and other business systems in order to better manage our business operations.

Implementation or upgrade of new business processes and information systems requires the commitment of significant personnel, training and financial resources, and entails risks to our business operations.

If we do not successfully implement ERP and other information systems improvements, or if there are delays or difficulties in implementing these systems, we may not realize anticipated productivity improvements or cost efficiencies, and we may experience operational difficulties and challenges in effectively managing our business, all of which could result in quality issues, reputational harm, lost market and revenue opportunities, and otherwise adversely affect our business, financial condition and results of operations.

For example, we are currently in the process of implementing new ERP and other information systems to help us manage our operations and financial reporting.

This project has required and may continue to require investment of capital and human resources, the re-engineering of processes of our business, and the attention of many employees who would otherwise be focused on other aspects of our business.

Costs and risks inherent in this transition may include disruptions to business continuity, administrative and technical problems, interruptions or delays in sales, expenditure overruns, delays in paying our suppliers and employees, and data migration issues.

If we do not properly address or mitigate these issues, this could result in increased costs and diversion of resources, negatively impacting our operating results and ability to effectively manage our business.

Additionally, if we do not effectively implement the ERP system as planned, or the ERP system does not operate as intended, the effectiveness of our internal control over financial reporting could be negatively affected.

We are subject to stringent and changing U.S.

In addition, failure to maintain effective internal

accounting controls related to data security breaches and cybersecurity in general could impact our ability to produce timely and accurate financial statements and could subject us to regulatory scrutiny.

We and third parties with whom we work are subject to stringent and changing U.S.

and foreign laws, regulations, rules, contractual obligations, industry standards, policies and other obligations related to data privacy and security.

Our actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions;

Our (or the third parties with whom we work) actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions;

fines and penalties;

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Outside the U.S., an increasing number of laws, regulations, and industry standards apply to data privacy and security.

For example, the EU’s General Data Protection Regulation (GDPR) (EU) 2016/679, or the EU GDPR, imposes strict requirements on the processing of personal data.

Under the EU GDPR, government regulators may impose temporary or definitive bans on data processing, as well as fines in the event of violations.

In addition, we may be unable to transfer personal data from the EEA and other jurisdictions to the U.S.

For example, the European Union’s General Data Protection Regulation, or the EU GDPR, and the United Kingdom’s GDPR, or the UK GDPR (collectively, the “GDPR”), impose strict requirements on the processing of personal data.

For example, under GDPR, government regulators may impose temporary or definitive bans on data processing, fines of up to 20 million Euros under the EU GDPR, 17.5 million pounds sterling under the UK GDPR or, in each case, 4% of annual global revenue, whichever is greater;

or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.

In addition, we may be unable to transfer personal data from the EEA, the UK and other jurisdictions to the U.S.

or other countries due to data localization requirements or limitations on cross-border data flows.

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If there is no lawful manner for us to transfer personal data from the EEA, the UK, or other jurisdictions to the U.S., or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.

Some EEA regulators have prevented companies from transferring personal data out of the EEA for allegedly violating the EU GDPR’s cross-border data transfer limitations.

Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators, individual litigants, and activist groups, and some EEA regulators have prevented companies from transferring personal data out of the EEA for allegedly violating the EU GDPR’s cross-border data transfer limitations.

Likewise, we expect that there will continue to be new proposed laws, regulations and industry standards relating to data privacy and security in the U.S.

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Additionally, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020, or CPRA, collectively CCPA, imposes obligations on businesses to which it applies.

These obligations include, but are not limited to, providing specific disclosures in privacy notices and affording California residents certain rights related to their personal data.

These obligations include, but are not limited to, providing

specific disclosures in privacy notices and affording California residents certain rights related to their personal data.

The CCPA allows for statutory fines for noncompliance.

While the CCPA contains limited exceptions for clinical trial data, the CCPA’s implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future.

In addition, the CPRA establishes a California Privacy Protection Agency to implement and enforce the CPRA, which could increase the risk of an enforcement action, and applies to personal information of business representatives and employees.

Other states have also enacted data privacy and security laws.

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If we are unable to use generative AI, it could make our business less efficient and result in competitive disadvantages.

In addition to data privacy and security laws, we may be contractually subject to industry standards adopted by industry groups and may become subject to such obligations in the future.

We may also be bound by other contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful.

We may publish privacy policies, marketing materials, and other statements, such as compliance with certain certifications or self-regulatory principles, regarding data privacy and security.

If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.

In addition to data privacy and security laws, we are contractually subject to industry standards adopted by industry groups and we are, and may become in the future, subject to such obligations.

We are also be bound by other contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful.

We may publish privacy policies, marketing materials, white papers, and other statements, such as statements relating to compliance with certain certifications or self-regulatory principles concerning data privacy and security.

Regulators in the United States are increasingly scrutinizing these statements, and if these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.

It is possible that, in the future, we may fail or be perceived to have failed to comply with applicable data privacy and security obligations.

Moreover, despite our best compliance efforts, we may not be successful in achieving compliance if our personnel or third parties whom we rely on fail to comply with such obligations, which could negatively impact our business operations and compliance posture.

If we or the third parties on which we rely fail, or are perceived to have failed, to address or comply with data privacy and security obligations, we could face significant consequences.

Moreover, despite our best compliance efforts, we may not be successful in achieving compliance if our personnel or third parties with whom we work fail to comply with such obligations, which could negatively impact our business operations and compliance posture.

If we or the third parties with whom we work fail, or are perceived to have failed, to address or comply with data privacy and security obligations, we could face significant consequences.

These consequences may include, but are not limited to, government enforcement actions;

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or revision or restructuring of our operations.

Moreover, clinical trial participants or research subjects about whom we or our vendors obtain

information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information.

Moreover, clinical trial participants or research subjects about whom we or our vendors obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information.

RISKS RELATED TO OUR COMMON STOCK AND FINANCIAL REPORTING

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Historically, our stock price has been extremely volatile.

Between October 1, 2014 and September 30, 2024, our stock has traded as high as $6.38 per share and as low as $0.89 per share.

Between October 1, 2023 and September 30, 2024, the price has ranged between a high of $5.34 per share and a low of $1.64 per share.

Between January 1, 2015 and March 31, 2025, our stock has traded as high as $6.38 per share and as low as $0.89 per share.

Between April 1, 2024 and March 31, 2025, the price has ranged between a high of $5.34 per share and a low of $1.46 per share.

The significant market price fluctuations of our common stock have been due to and may in the future be influenced by a variety of factors, including:

• the level of RYTELO sales in the U.S.;

• the level of RYTELO sales;

• announcements regarding regulatory approval or non-approval of RYTELO in any other jurisdictions or indications, or specific label indications for RYTELO;

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• announcements regarding the further research and development of RYTELO, or adverse efficacy or safety results of, further delays in the commencement, enrollment or conduct of, discontinuation of, or further modifications or refinements to any current or potential future clinical trials, for any reason, or our inability, for any reason, to successfully continue the development of RYTELO;

• our ability to obtain additional capital when needed to further advance our development program;

• changes in laws or regulations applicable to RYTELO, including laws or regulations concerning the commercialization of RTYELO or clinical trial requirements for approval or other regulatory developments related to RYTELO;

• our ability to obtain additional capital if and when needed to further advance our development program;

• changes in laws or regulations applicable to RYTELO, including laws or regulations concerning the commercialization of RYTELO or clinical trial requirements for approval or other regulatory developments related to RYTELO;

• announcements of technological innovations, new commercial products, or clinical progress or lack thereof by us, potential future collaborative partners or our competitors;

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• the size and growth of the market opportunity for RYTELO in its currently approved and any potential future approved indications;

• disputes or other developments relating to RYTELO proprietary rights, including patents, litigation matters and our ability to obtain, enforce and defend patent protection for our technologies;

• disputes or other developments relating to RYTELO proprietary rights, including patents, litigation matters and our ability to obtain, enforce and defend patent protection and maintain regulatory exclusivity for RYTELO and our technologies;

• the terms and timing of any future collaboration agreements for the further development and commercialization of RYTELO that we may establish;

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• increased or continuing operating losses;

• general domestic and international market conditions or market conditions relating to the biopharmaceutical and pharmaceutical industries, especially given the volatility caused by macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues;

• general domestic and international market conditions or market conditions relating to the biopharmaceutical and pharmaceutical industries, especially given the volatility caused by macroeconomic or other global conditions, such as inflation, rising interest rates, prospects of a recession, government shutdowns, further changes in tariffs and other trade restrictions, bank failures and other disruptions to financial systems, civil or political unrest, military conflicts, pandemics or other health crises and supply chain and resource issues;

• perceptions of the biotechnology and pharmaceutical industry by the public, legislature, regulators and the investment community;

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• sales of stock by our officers and directors;

• announcements of or developments concerning any litigation;

• announcements of or developments concerning pending and potential future litigation;

• actions instituted by activist shareholders or others;

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• the occurrence of any other risks and uncertainties discussed under the heading “Risk Factors.”

In addition, as further discussed in the Risk Factor above entitled “ We and certain of our current and former officers and directors have been named as defendants in securities class action lawsuits and derivative lawsuits.

These lawsuits, and any other lawsuits to which we are subject, will be costly to defend or pursue and are uncertain in their outcome ,” we and certain of our current and former officers and directors have been named as defendants in securities class action and derivative lawsuits.

Such lawsuits have often been instituted against companies, including us, whose securities have experienced periods of volatility in market price.

The pending lawsuits and any lawsuits brought against us in the future could result in substantial costs and divert our management’s attention and resources, which could have a material adverse effect on our financial condition and business operations and lead to increased volatility in our stock price and a decrease in the value of our stockholders’ investment in our securities.

Our failure to maintain compliance with the continued listing requirements of the Nasdaq Global Select Market may result in our common stock being delisted from the Nasdaq Global Select Market, which could negatively impact the price of our common stock, liquidity, our ability to access the capital markets and our stockholders’ ability to sell their shares.

Our common stock is currently listed on the Nasdaq Global Select Market, or Nasdaq, under the symbol “GERN.” The listing standards of Nasdaq provide that a company, in order to qualify for continued listing, must maintain a minimum stock price of $1.00 and satisfy standards relative to minimum stockholders’ equity, minimum market value of publicly held shares and various additional requirements.

Historically, our stock price has been extremely volatile and recently, our stock has traded as low as $1.17 per share.

While our common stock is currently listed on Nasdaq, we can give no assurance that we will be able to maintain compliance with the continued listing requirements for Nasdaq.

If we fail to maintain compliance with any such continued listing requirement, there can also be no assurance that we will be able to regain compliance with any such continued listing requirement in the future or that our common stock will not be delisted in the future.

If Nasdaq delists our securities from trading on its exchange for failure to meet the listing standards, we and our stockholders could face significant negative consequences including:

• limited availability of market quotations for our securities;

• a determination that the common stock is a “penny stock” which would require brokers trading in the common stock to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for shares of common stock;

• a limited amount of analyst coverage, if any;

• a decreased ability to issue additional securities or obtain additional financing in the future.

Delisting from Nasdaq could also result in other negative consequences, including the potential loss of confidence by suppliers, customers and employees, the loss of institutional investor interest and fewer business development opportunities.

Provisions in our charter, bylaws and Delaware law may inhibit potential acquisition bids for us, which may adversely affect the market price of our common stock and/or prevent holders of our common stock from benefiting from what they believe may be the positive aspects of acquisitions and takeovers.

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The application of the Federal Forum Provision means that suits brought by our stockholders to enforce any duty or liability created by the Securities Act must be brought in federal court and cannot be brought in state court, and our stockholders cannot waive compliance with the federal securities laws and the rules and regulations thereunder.

While the Delaware courts have determined that such choice of forum provisions are facially valid and several state trial courts have enforced such provisions and required that suits asserting Securities Act claims be filed in federal court, there is no guarantee that courts of appeal will affirm the enforceability of such provisions, and a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions.

federal court, there is no guarantee that courts of appeal will affirm the enforceability of such provisions, and a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions.

In such an instance, we would expect to vigorously assert the validity and enforceability of the exclusive forum provisions of our amended and restated bylaws.

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Any payment of cash dividends will depend upon our financial condition, results of operations, capital requirements and other factors, and will be at the discretion of our board of directors.

In addition, the terms of our Pharmakon Loan Agreement prevent us from paying dividends and any future debt agreements may continue to preclude us from paying dividends.

In addition, the terms of our Pharmakon Loan Agreement restrict our ability to pay dividends and any future debt agreements may continue to or further restrict our ability to pay dividends.

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.

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• curtailment of our operations.

Failure to achieve and maintain effective internal controls in accordance with Section 404 of the Sarbanes-Oxley Act of 2002 could have a material adverse effect on our business and stock price.

Our business could be negatively impacted by environmental, social and corporate governance, or ESG, matters or our reporting of such matters.

There is an increasing focus from certain investors, employees, partners, and other stakeholders concerning ESG matters.

We may be, or be perceived to be, not acting responsibly in connection with these matters, which could negatively impact us.

For example, we currently do not report our environmental emissions and absent a legal requirement to do so we currently do not plan to report our environmental emissions, and lack of reporting could result in certain investors declining to invest in our common stock.

Furthermore, the criteria by which our ESG practices, including our initiatives and public goals, are assessed may change due to the evolution of the sustainability landscape, which could result in greater expectations of us and may cause us to undertake costly initiatives to satisfy new criteria.

If we are unable to respond effectively to these changes to the sustainability landscape, governments, customers, and investors may conclude that our policies and/or actions with respect to ESG matters are inadequate.

If we fail or are perceived to have failed to achieve previously announced public goals or to accurately disclose our progress on such goals or initiatives, our reputation, business, financial condition and results of operations could be adversely impacted.

Failure to maintain effective internal controls in accordance with Section 404 of the Sarbanes-Oxley Act of 2002 could have a material adverse effect on our business and stock price.

Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, requires that we establish and maintain an adequate internal control structure and procedures for financial reporting.

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Although we are committed to continue to improve our internal control processes and we will continue to diligently and vigorously review our internal control over financial reporting in order to ensure compliance with Section 404 requirements, any control system, regardless of how well designed, operated and evaluated, can provide only reasonable, not absolute, assurance that its objectives will be met.

Moreover, we are currently in the process of implementing new ERP and other information systems to help us manage our operations and financial reporting.

However, there is an increased risk that changing controls may be ineffective during the implementation and this ERP system may place additional burdens on employees to learn and adapt our processes to effectively operate under the ERP system.

If the ERP system does not operate as intended, the effectiveness of our internal control over financial reporting could be negatively impacted.

Moreover, in 2024 we implemented a new ERP and other information systems to help us manage our operations and financial reporting.

However, any failure of the ERP system that we implemented in 2024 to operate as intended could negatively impact the effectiveness of our internal control over financial reporting.

Therefore, we cannot assure you that material weaknesses or significant deficiencies will not exist or otherwise be discovered in the future, particularly in light of our increased reliance on personnel working remotely.

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In addition, under current U.S.

federal income tax law, federal net operating losses incurred in taxable years beginning after December 31, 2017, can be carried forward indefinitely, but the deductibility of such federal net operating losses is limited to 80% of taxable income.

Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point cumulative change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes (such as research and development tax credits) to

offset its post-change taxable income or taxes may be limited.

Changes in our stock ownership, some of which are outside of our control, may have resulted in, or other future changes could result in, an ownership change.

Changes in our stock ownership have occurred in the past, and future ownership changes, some of which may be outside our control, could occur in the future, as a result of shifts in our stock ownership.

If a limitation were to apply, utilization of a portion of our domestic net operating loss and tax credit carryforwards could be limited in future periods, and a portion of the carryforwards may expire before being available to reduce future income tax liabilities, which could adversely impact our financial position.

At the state level, there may be periods during which the use of net operating loss carryforwards is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.

For example, in June 2024, California enacted legislation that, with certain exceptions, suspends the use of California net operating losses to offset California income and limits the use of California business tax credits to offset California taxes, for taxable years beginning after 2023 and before 2027.

It is also uncertain if and to what extent various states will conform to current U.S.

5 unchanged sentences

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What changed 10-Q

Item 1A. Risk Factors