What changed in this filing

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Item 1A. Risk Factors

2025-08-06 compared with 2025-05-07 · 121 added, 129 removed, 1234 unchanged (17% of the section changed)

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• 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 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.

• 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 will be subject to pricing, drug marketing, post-market 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

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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.

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

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.

• 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.

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.

Risks Related to the Further Development of Imetelstat

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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 could be interrupted or limited, and we may be unable to successfully commercialize RYTELO or conduct or complete current or potential future clinical trials.

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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

• 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.

• 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.

Risks Related to Protecting Our Intellectual Property

• 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.

• 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.

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.

• 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 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.

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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, 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.

For example, RYTELO sales trends have been and may continue to be variable.

Net product revenue was approximately $49.0 million in the second quarter of 2025, $39.4 million in the first quarter of 2025, and $47.5 million in the fourth quarter of 2024.

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.

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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.

In particular, our strategy may not 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 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.

Any of these outcomes 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.

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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.

Although we received marketing authorization for RYTELO in the EU for the treatment of certain adult patients with TD 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.

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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.

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.

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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 is critical to market acceptance of RYTELO.

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

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

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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.

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.

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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.

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.

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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.

A discussion of current and potential future competitors of RYTELO can be found in the sub‑section titled “Competition” in Part I, Item 1, titled “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.

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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.

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 patent protection or product commercialization earlier 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.

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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 March 2025, we received marketing authorization for RYTELO in the EU for the treatment of adult patients with 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.

If we, or a regulatory authority, discover 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.

Moreover, product labeling, advertising and promotion for RYTELO will be subject to regulatory requirements and continuing regulatory review.

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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 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.

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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• manufacturing;

• advertising and promoting;

• advertising and promotion;

• selling and marketing;

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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.

RYTELO is approved outside the U.S.

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

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• additional post-marketing requirements or commitments;

warning letters, withdrawal of RYTELO from the market;

• warning letters or the withdrawal of RYTELO from the market;

• product recalls;

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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.

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.

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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.

and an MAA in the EU.

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 the product candidate’s safety and efficacy to the satisfaction of such regulatory authorities, as well as information about the product manufacturing process and any inspections of manufacturing facilities conducted by regulatory authorities through the filing of a New Drug Application, or NDA, in the U.S.

and a Marketing Authorization Application, or MAA, in the EU.

Although RYTELO is approved in the U.S.

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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 .”

See the risk factor titled, “ 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.

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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.

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.

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

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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.

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 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.

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

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

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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.

We may lose orphan drug exclusivity for certain reasons, including if the FDA or the European Medicines Agency, or 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.

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.

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.

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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, 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.

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 on, 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.

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• 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;

• we or any third-party service providers may be unable to demonstrate compliance with GMP, good clinical practices, or 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.

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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.

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.

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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” of this Report.

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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and some jurisdictions outside the U.S., there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could impact our business.

Generally, there has been increasing legislative and enforcement interest in the U.S.

Generally, there has been

increasing legislative and enforcement interest in the U.S.

with respect to drug pricing, including specialty drug pricing practices, in light of the rising cost of prescription drugs and biologics.

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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 this Report.

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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• patient recruitment, enrollment and retention challenges and operational delays, including in connection with opening new clinical trial sites, while also competing with clinical trials for other investigational drugs in the same patient population;

• use of trial endpoints such as overall survival, that inherently require prolonged periods of clinical observation or analysis of the resulting data to determine trial outcomes, including the need for a certain number of events, or deaths, to occur in IMpactMF prior to the interim or final analysis in that trial of overall survival;

• use of trial endpoints such as OS, that inherently require prolonged periods of clinical observation or analysis of the resulting data to determine trial outcomes, including the need for a certain number of events, or deaths, to occur in IMpactMF prior to the interim or final analysis in that trial of OS;

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

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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, 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;

• the effects of macroeconomic or other global conditions, such as inflation, fluctuations in 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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or other countries, including our CROs, laboratory service providers and clinical trial sites, on all aspects of clinical development and collaborating with them successfully;

• 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.

• 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, GCP, or other regulatory requirements, or not performing data collection or analyses in a timely or accurate manner.

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

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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.

The occurrence of any of these events could interrupt, further delay, or halt our commercialization of 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.

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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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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We do not have the ability to independently conduct clinical trials.

Therefore, we rely on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, service providers, vendors, suppliers and consultants, to conduct clinical trials of imetelstat.

Therefore, we rely on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, service providers, vendors,

suppliers and consultants, to conduct clinical trials of imetelstat.

The third parties we contract with for execution of our current and potential future clinical or investigator-sponsored trials of imetelstat play a critical role in the conduct of these trials and the subsequent collection and analysis of data.

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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 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.

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.

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 development program as a whole.

unfavorable benefit-risk assessment that could materially and adversely impact our ongoing clinical trials, or our 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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• 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, 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;

• supply chain issues, including the timely availability of product and management of shelf-life, including raw materials, active pharmaceutical ingredient, or 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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result in lost sales;

delay or result in a cessation of our current or potential future clinical trials;

delay or result in a cessation of our current or potential future

clinical trials;

delay or preclude potential future regulatory approvals of RYTELO in other jurisdictions or indications;

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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 this regard, a recent FDA inspection of one of our third-party manufacturers identified certain deficiencies in the manufacturer’s processes and facilities which, while not related to the 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.

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

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• the inability to execute timely contracts or production orders with any additional third-party manufacturers and suppliers that we may identify on acceptable terms, or at all;

• 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;

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

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

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

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

As of June 30, 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.

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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.

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:

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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.

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.

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Successful drug development and commercialization requires significant amounts of capital.

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

As of June 30, 2025, we had approximately $432.6 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.

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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 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.

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, fluctuations in 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:

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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, 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.

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, fluctuations in 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 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.

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, fluctuations in 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.

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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.

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.

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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 contains covenants that impose on us certain obligations with respect to royalty payments, diligence, reporting, indemnification and includes restrictions 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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Moreover, even if competitors do not actively promote their product for our approved indications, physicians may prescribe or use these generic products “off-label,” which would result in decreased sales for us.

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

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

and ten 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.

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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.

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.

or preclude any future development or commercialization of RYTELO by us.

Furthermore, such loss of intellectual property rights could impair our ability to exclude others from commercializing products similar or identical to RYTELO and therefore result in decreased sales for 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.

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.

Patent and Trademark Office, or 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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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, 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.

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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 EEA, we must rely on regulatory exclusivity and our method of treatment patents.

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.

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.

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Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant material information from the USPTO, or made a materially misleading statement, during prosecution.

Third parties may also raise similar validity claims before the USPTO in post-grant proceedings such as ex parte reexaminations, IPR or post-grant review, or oppositions or similar proceedings outside the U.S., in parallel with litigation or even outside the context of litigation.

Third parties may also raise similar validity claims before the USPTO in post-grant proceedings such as ex parte reexaminations, inter partes review, or IPR, or post-grant review, or oppositions or similar proceedings outside the U.S., in parallel with litigation or even outside the context of litigation.

In an infringement proceeding, a court may decide that a patent of ours is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question.

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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.

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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The AIA also includes post-grant review procedures subjecting U.S.

patents to post-grant review procedures similar to European oppositions, such as inter partes review, or IPR, covered business method post-grant reviews and other post-grant reviews.

patents to post-grant review procedures similar to European oppositions, such as IPR, covered business method post-grant reviews and other post-grant reviews.

This applies to all our U.S.

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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.

In addition, the IPR process under the AIA permits any person, whether they are accused of infringing the patent at issue or not, such as entities associated with hedge funds, to challenge the validity of certain patents.

In addition, the IPR process under the AIA permits any person, whether they are accused of infringing the patent at issue or not, such as entities associated with hedge funds, to

challenge the validity of certain patents.

Significant impairment of our RYTELO patent rights could severely and adversely affect our financial results, business and business prospects, which might cause us to cease operations.

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In addition, while our past collaboration agreements have terminated, we are still subject to indemnification obligations to certain collaborators, including with respect to claims of third-party patent infringement.

In addition to infringement claims, in the future we may also be subject to other claims relating to intellectual property, such as claims that we have misappropriated the trade secrets of third parties.

In addition to infringement claims, in the future we may also be subject to other claims relating to intellectual property, such

as claims that we have misappropriated the trade secrets of third parties.

Our success therefore depends significantly on our ability to operate without infringing patents and the proprietary rights of others.

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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.

trademark application which forms the basis for our international registration, or IR, for our commercial trade name is withdrawn or abandoned within the first five 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.

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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.

For example, on August 6, 2025, we announced the appointment of Harout Semerjian as our President and Chief Executive Officer and a member of our board of directors, effective August 7, 2025.

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.

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.

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• increase our expenditures and undertake development or commercialization activities at our own expense, which will require additional capital than our current resources.

We have established subsidiaries in the United Kingdom and the Netherlands, which exposes us to additional costs and risks.

The wholly-owned subsidiaries we have established in the U.K.

and the Netherlands subject us to certain additional costs and risks associated with doing business outside the U.S., including:

We have established subsidiaries in the United Kingdom, or UK, and the Netherlands, which exposes us to additional costs and risks.

The wholly-owned subsidiaries we have established in the UK, and the Netherlands subject us to certain additional costs and risks associated with doing business outside the U.S., including:

• the increased complexity and costs inherent in managing international operations in geographically disparate locations;

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• workforce uncertainty in countries where labor unrest is more common than in the U.S.

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.

injury claims arising from our commercialization of RYTELO, claims related to clinical trial conduct, or claims related to data protection.

Our business exposes us to potential product liability and other risks that are inherent in the testing, manufacturing and marketing of human therapeutic products.

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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.

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The plaintiffs seek damages and interest, and an award of reasonable costs, including attorneys' and experts' fees.

On May 29, 2025, the Court consolidated the Dabestani and Potvin cases into one consolidated action captioned In re Geron Corporation Securities Litigation , or the Securities Class Action, and appointed lead plaintiffs and counsel for lead plaintiffs.

On June 10, 2025, the Court ordered plaintiffs to file a consolidated amended complaint by August 8, 2025.

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.

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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 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.

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also seek punitive damages.

On May 16, 2025, the Court consolidated the three derivative complaints into one consolidated action captioned In re Geron Corporation Derivative Litigation , or the Consolidated Derivative Action.

On June 17, 2025, the Court stayed the Consolidated Derivative Action pending a final ruling on the anticipated motion to dismiss in the Securities Class Action.

We have also been subject to securities class action lawsuits in the past.

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We are therefore subject to or affected by numerous data privacy and security obligations, such as federal, state, local and foreign laws, regulations, guidance, industry standards, external and internal privacy and security policies, contracts, and other obligations governing the processing of personal data.

These obligations may change, are subject to differing interpretations and may be inconsistent among jurisdictions or conflict.

These obligations may change, are subject to differing interpretations and may be inconsistent or conflict among jurisdictions.

The global data protection landscape is rapidly evolving, and implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future.

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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 are also 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.

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Historically, our stock price has been extremely volatile.

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.

Between July 1, 2015 and June 30, 2025, our stock has traded as high as $6.38 per share and as low as $0.89 per share.

Between July 1, 2024 and June 30, 2025, the price has ranged between a high of $5.06 per share and a low of $1.17 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:

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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, 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;

• 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, fluctuations in 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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• 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.

In addition, as further discussed in the Risk Factor above titled “ We and certain of our current and former officers and directors have been named as defendants in securities class action lawsuits and derivative lawsuits.

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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.

Historically, our stock price has been extremely volatile and recently, our stock has traded as low as 1.09 per share through August 1, 2025.

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.

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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.

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.

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.

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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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.

Our employees, independent contractors, principal investigators, clinical trial sites, contract research organizations, consultants or vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.

Our employees, independent contractors, principal investigators, clinical trial sites, CROs, consultants or vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.

We are exposed to the risk that our employees, independent contractors, principal investigators, clinical trial sites, CROs, consultants or vendors may engage in fraudulent or other illegal activity.

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Further, existing tax laws, statutes, rules, regulations or ordinances could be interpreted, changed, modified or applied adversely to us.

Future guidance from the U.S.

Internal Revenue Service and other tax authorities with respect to such legislation may adversely affect us, and certain aspects of such legislation could be repealed or modified in the future, which could have an adverse effect on us.

For example, the Inflation Reduction Act of 2022 included provisions that impacted the U.S.

federal income taxation of corporations, including imposing a minimum tax on the book income of certain large corporations and an excise tax on certain corporate stock repurchases that is imposed on the corporation repurchasing such stock.

.In addition, the U.S.

government recently enacted legislation commonly referred to as the One Big Beautiful Bill Act, that (along with other recent U.S.

federal tax reform) has resulted in significant changes to the taxation of business entities including, among

other changes, changes to the taxation of income derived from international operations, changes in the deduction and amortization of research and development expenditures, and limitations on the deductibility of business interest.

Future guidance from the Internal Revenue Service and other tax authorities with respect to any legislation may affect us, and certain aspects of such legislation could be repealed or modified or sunset in future years.

Changes in corporate tax rates, the realization of net deferred tax assets relating to our U.S.

operations, the taxation of earnings from other countries, and the deductibility of expenses or future tax reform legislation could have a material impact on the value of our deferred tax assets, could result in significant one-time charges in the current or future taxable years, and could increase our future U.S.

For example, under the Tax Cuts and Jobs Act of 2017, effective January 1, 2022, research and experimental expenses must be capitalized for tax purposes and amortized over five years for research activities conducted in the United States and over fifteen years for research activities conducted outside the United States, instead of being deducted in the year incurred.

Unless this provision is modified or repealed by Congress, or the U.S.

Department of the Treasury issues regulations narrowing its application, our future tax obligations could be increased, which could harm our operating results.

The impact of this provision will depend on multiple factors, including the amount of research and experimental expenses we incur, whether we achieve sufficient income to fully utilize such deductions and whether we conduct our research and experimental activities inside or outside the United States.

Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.

Our net operating loss carryforwards attributable to tax years beginning before January 1, 2018 could expire unused and be unavailable to offset future income tax liabilities.

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 in a taxable year is limited to 80% of taxable income in such year.

In addition, 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 in a taxable year is limited to 80% of taxable income in such year.

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.

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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.

federal income tax law.

UNREGISTERED SALES OF EQUITY SECURITIES, USE OF PROCEEDS, AND ISSUER PURCHASES OF EQUITY SECURITIES

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 1A. Risk Factors