GERON CORP (GERN) Risk Factors

ITEM 1A. RISK FACTORS

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. 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

Our near-term prospects are wholly dependent on RYTELO. We have limited experience with the commercialization of

RYTELO, and if we are unable to successfully commercialize RYTELO in the U.S. for lower-risk MDS, or to expand its

indication of use, our ability to generate meaningful revenue or achieve profitability will be materially and adversely

affected.

In June 2024, we received FDA approval to commercialize RYTELO in the U.S. for certain patients with

lower-risk MDS, and we initiated a commercial launch of RYTELO in the U.S. in that indication. While we have generated

revenue from U.S. sales of RYTELO since mid-2024, the commercialization of RYTELO marks our first effort to

commercially launch a product candidate, and our ability to grow revenue on a sustained basis has not yet been proven.

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

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U.S. for lower-risk MDS or to expand its indications of use. We may not be able to successfully commercialize RYTELO

for a number of reasons, including:

•we may not be able to establish or demonstrate in the medical community the safety and

efficacy of RYTELO and its potential advantages over, and side effects compared to,

existing treatments;

•physicians may be reluctant to prescribe RYTELO until longer-term efficacy and safety

data exists;

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

•we may not be able to increase physician adoption of RYTELO through our

commercialization strategy and plans, including any potential amendments or adjustments

to those plans;

•our inability to achieve and maintain revenue growth in the near future under our current

commercialization strategy and plans or any potential further amendments or adjustments

thereto;

•potential future changes in the reimbursement and coverage policies of government and

private payors such as Medicare, Medicaid, insurance companies, health maintenance

organizations and other plan administrators;

•the relative position of RYTELO as compared to alternative treatment options in healthcare

guidelines and recommendations, such as those developed the National Comprehensive

Cancer Network, or NCCN, and similar guidelines and recommendations outside the U.S.;

•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;

•our projections regarding the market opportunities for RYTELO may not be accurate, and

the actual market for RYTELO may be smaller than we estimate;

•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 for lower-risk MDS or for any other indications, including relapsed/refractory

MF;

•changed or increased regulatory restrictions;

•changes to the label for RYTELO that further restrict how we market and sell RYTELO,

including adverse events observed in ongoing and future studies of imetelstat, such as our

Phase 3 IMpactMF clinical trial;

•the capabilities of third party manufacturers may adversely affect the success of our

commercialization of RYTELO;

•we may need additional financial or other resources that might not be available to us to

successfully commercialize RYTELO; and

•we may not be able to maintain adequate commercial supplies of RYTELO to meet demand

or at an acceptable cost or at all.

Moreover, commercialization of RYTELO may not generate sufficient revenue from product sales, and we

may not become profitable in the near term, or at all. In any event, if we are unable to successfully commercialize

RYTELO in the U.S. for lower-risk MDS, or to expand its indications of use, our ability to generate meaningful revenue

from product sales and achieve profitability will be materially and adversely affected, which in turn would severely and

adversely affect our financial results, business and business prospects, and might cause us to cease operations.

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Although we have established commercial operations and sales, marketing and distribution infrastructure for RYTELO

in the U.S., our commercialization strategy may ultimately 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 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. Our initial commercialization efforts in the U.S. have not to date achieved meaningful

sales growth.  Our RYTELO sales trends and resulting revenue have been and may continue to be variable. Net product

revenue was approximately $48.0 million in the fourth quarter of 2025, $47.2 million in the third quarter of 2025, and

$49.0 million in the second quarter of 2025.  In an effort to better execute on our plans to commercialize RYTELO and

generate more meaningful product revenue, we decided to focus our  commercial execution on targeted engagement with

high-volume accounts that treat earlier-line patients, and invest in non-personal promotion and third-party education to

reach the full breath of the eligible patient population, while cross-functionally collaborating for effective account

management. However, our revised strategy to drive RYTELO commercial growth may still 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 meet or grow projected RYTELO net

product revenue in future periods. In particular, our strategy may not drive new patient starts in lower-risk MDS U.S.

patients, particularly in second-line lower-risk MDS, 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. If we are unsuccessful in accomplishing our

objectives from our commercialization efforts and strategy, we may not be able to generate meaningful revenue from the

commercialization of RYTELO in lower-risk MDS, or may require significant additional capital and financial resources to

do make further investment in our commercial operations. Any of these outcomes would severely and adversely affect our

financial results, business and business prospects, and might cause us to cease operations.

In December 2025, we announced a strategic restructuring plan designed to position us for long-term value

creation and improve our financial discipline. However, there can be no assurance that our recent restructuring will result in

long-term value creation or that our commercialization strategy will result in meaningful improvement in our sales

performance. Additionally, we may determine that we need further changes in the future that require additional hiring or

other organizational changes to adequately support our strategy, which could further increase our costs. As such, we

continue to 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, retain

and effectively train marketing, sales and medical personnel as needed and equip them with compliant and effective

materials, our efforts to successfully commercialize RYTELO could be adversely affected.

Further, 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. where we might seek marketing

authorization in the future, we will need to develop these capabilities, which we plan to do at this time by working with

experienced third-party contractors or commercialization partners. Doing so will require additional investment of capital

and time. 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. 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.

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. 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

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

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

In the U.S. 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. with respect to drug pricing, including specialty drug pricing

practices, in light of the rising cost of prescription drugs and biologics. Specifically, there have been U.S. 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.

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

developing increasingly sophisticated methods of controlling healthcare costs, such as by limiting coverage and the amount

of reimbursement for particular medications. 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 includes several provisions to lower prescription drug costs for people with

Medicare and reduce drug spending by the federal government, including the Medicare Drug Price Negotiation Program,

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. Further, the final CY 2026 Medicare Physician Fee

Schedule rule, issued by the Centers for Medicare & Medicaid Services, among other things, increases bona fide service

fee documentation requirements, defines “bundled arrangement,” to require “unbundling” of both contingent and non-

contingent discounts and includes sales of Part B units at the Maximum Fair Price in average sales price calculations. These

changes could lower reimbursement for Medicare Part B utilization and require manufacturers to comply with new,

uncertain or complex reporting obligations and drug pricing documentation practices.

Further, no uniform policy requirement for coverage and reimbursement for drug products exists among

third-party payors in the U.S. As a result, the coverage determination process is often time-consuming and costly, and it

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.

Although we have received a permanent and product-specific J-Code (J0870) for RYTELO which became

effective on January 1, 2025, coverage may significantly change or may be more limited than the indications 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 the reimbursement amount is inadequate, we may not be able to successfully commercialize RYTELO, which

would negatively impact our business and business prospects.

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. Managed care organizations, as well as Medicaid and

other government authorities, continue to seek price discounts. At the state level, legislatures have increasingly passed

legislation and implemented regulations designed to control pharmaceutical and biologic product pricing, including price or

patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and

transparency measures, and, in some cases, to encourage importation from other countries and bulk purchasing. Due to the

volatility in the current economic and market dynamics, we are unable to predict the impact of any unforeseen or unknown

legislative, regulatory, payor or policy actions, which may include cost containment and healthcare reform measures. Such

policy actions could have a material adverse impact on future sales of RYTELO in the U.S., the EU, and in any other

jurisdictions where we may seek approval in the future.

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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.

Our strategy to drive sales growth and our ongoing commercialization efforts has not to date achieved and

may not in the future achieve the rate of market acceptance by the healthcare community or breadth of eligible patient

segments that we expect, which may require us to, among others, 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

revenue in future periods. While our current priority is to drive new patient starts across appropriate second-line patients 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:

•the clinical indications for which RYTELO is or may in the future be approved;

•the establishment and demonstration to the medical community of the clinical efficacy and

safety of RYTELO;

•the ability to demonstrate that RYTELO is superior to alternatives on the market at the time,

including with respect to efficacy, safety, cost or route of administration;

•the willingness of medical professionals to prescribe, and patients to use, RYTELO, or to

continue to use RYTELO;

•the publication of favorable safety or efficacy data concerning RYTELO by third parties or

us;

•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, 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 for new indications;

•the effectiveness of sales, marketing and distribution infrastructure for RYTELO;

•the ability of the third-party distributors and specialty pharmacies we contract with to

process prescriptions and dispense RYTELO and the processes required to place orders

with such distributors and specialty pharmacies;

•the extent to which RYTELO is approved for inclusion on formularies in hospitals and

managed care organizations;

•the pricing of RYTELO, both in absolute terms and relative to alternative treatments;

•the availability of coverage and adequate reimbursement by government and third-party

payors; and

•the willingness of patients to pay out-of-pocket in the absence of coverage by third-party

payors, including governmental authorities.

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. 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.

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

business may suffer.

We are commercializing RYTELO in lower-risk MDS, and the addressable patient population in lower-risk

MDS is based on our estimates. These estimates, which have been derived from a variety of sources, including scientific

literature, surveys of clinics, patient foundations and market research, may prove to be incorrect. Further, new information

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

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 impact on sales of RYTELO in the future and may limit its growth

potential. Our commercialization of RYTELO in the U.S. 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 approved by the FDA and similar international regulatory authorities, which would

preclude us from marketing 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.

Our market opportunity may also be limited by the pricing, reimbursement and access we are able to

achieve for RYTELO, the quality and expiration of our intellectual property rights and regulatory exclusivity, duration of

RYTELO treatment in lower-risk MDS and future competitor treatments that enter the market. 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.

We face competition from existing products, product candidates and technologies, and competitors may develop new

products and technologies. If these products, product candidates or technologies are deemed by the healthcare

community to be 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 may provide us with certain

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 titled “Competition” in Part I, Item 1, titled “Business” in this

Report.

Many of our competitors, either alone or with their strategic partners, 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. 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. 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

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that are safer, more effective, more convenient to administer to patients, or less costly than RYTELO, 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 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. While we have entered into agreements with each of these parties, they

may not perform as agreed, our strategic priorities may change or they may terminate their agreements with us. Further, an

inability by our distributors or specialty pharmacies to meet our patients’ needs may lead to reputational harm or patient

loss. 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 will be subject to pricing 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 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. 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.

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

example, within the EU member states may restrict the range of medicinal products for which their national health

insurance systems provide reimbursement and may control the prices of medicinal products for human use. Reference

pricing used by various EU Member States and parallel distribution, or arbitrage between low-priced and high-priced EU

Member States, can further reduce prices. 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. 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. and generally prices tend to be significantly lower.

Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement

levels within the country of publication and other countries. If pricing is set at unsatisfactory levels or if reimbursement of

RYTELO is unavailable or limited in scope or amount, our revenues from sales and the potential profitability of RYTELO

in those countries would be negatively affected.

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RISKS RELATED TO REGULATORY APPROVAL OF RYTELO

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

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.

The regulatory frameworks and practices of the FDA, EMA/EC and comparable authorities in other

countries may change over time, and we cannot predict the nature, timing, or impact of any such developments. We cannot

project with certainty if or when we might submit or gain regulatory approval for RYTELO for other indications or in other

jurisdictions. The FDA, EMA/EC and other regulatory authorities exercise broad discretion throughout the product review

and approval process, including in determining the specific conditions for submission, including the requirement for a pre-

approval inspection of RYTELO’s listed manufacturing facility. As a result, the FDA, EMA/EC and other authorities may

delay or extend application review, may decline to accept an application for substantive review, or may conclude, after

review, that the information provided is inadequate to obtain or maintain approval of RYTELO. Any such decision could

materially and adversely affect the timing of potential approval and our business prospects. If the FDA, for instance,

determines that an NDA is not sufficiently complete for filing or issues a complete response letter, or CRL, requiring

additional data or clarification, we may be required to resubmit the application and any such resubmission or CRL‑driven

delays could significantly postpone review and potential approval RYTELO for other indications. Even if we resubmit an

NDA, it remains uncertain whether the FDA will ultimately accept the completed application or additional data, and any

such outcome could delay or prevent approval of RYTELO for other indications.

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

for lower-risk MDS, or delays in obtaining, failing 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;

•impede, halt or increase the costs of our activities and plans for clinical development;

•diminish any competitive advantages that may have been available to us; or

•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, 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, including if regulatory inspectors identify regulatory noncompliance by third-party manufacturers

requiring remediation, may result in restrictions on the product or manufacturer, including import restrictions, seizure, and

withdrawal of the product from the market, or may otherwise cause manufacturing delays and supply disruptions.

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. 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;

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•we may be required to recall RYTELO, seek to change the way it is administered, conduct

additional costly, time-consuming and burdensome clinical trials or change the labeling of

the product;

•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;

•RYTELO may be rendered less competitive and sales, if any, may decrease;

•our reputation may suffer generally among clinicians and patients;

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

resolving claims;

•regulatory authorities may refuse to approve supplements to approved applications filed by

us, or may suspend or revoke license approvals; or

•we may be required to change or stop ongoing clinical trials of RYTELO, which would

negatively impact the development of RYTELO 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. and EU, we will be subject to similar requirements, considerations and risks in other regions.

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.

Our regulatory approval for RYTELO in lower-risk MDS in the U.S. and EU are subject to non-clinical,

clinical and manufacturing post-marketing requirements and/or commitments, including the requirement to assess the long-

term safety of RYTELO (imetelstat) in the Phase 3 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 extension to the Phase 3 IMerge trial. 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, 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 on the timeline required or at

all, or any other regulatory requirements, including the FDA’s regulation of promotional claims, or later discovery of

previously unknown problems with RYTELO, or our manufacturers, or manufacturing processes for RYTELO, may result

in actions such as:

•adverse regulatory inspection findings;

•restrictions on RYTELO manufacturing, distribution or use;

•restrictions on, or prohibitions against, marketing, importing or exporting RYTELO;

•additional post-marketing requirements or commitments;

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•fines, untitled letters, warning letters or the withdrawal of RYTELO from the market;

•voluntary or mandatory product recalls or public notification or medical product safety

alerts to healthcare professionals;

•suspension or termination of ongoing clinical trials of imetelstat in other indications;

•suspension of review or refusal to approve pending applications or supplements to approved

applications;

•exclusion from participation in government-funded healthcare programs and/or eligibility

for the award of government contracts for RYTELO; suspension or withdrawal of

regulatory approval for RYTELO;

•significant civil, criminal and administrative penalties, including fines, restitutions or

disgorgement of profits or revenues;

•product seizure or detentions;

•injunctions or the imposition of civil or criminal penalties; and

•adverse publicity.

The imposition of any of these penalties or other commercial limitations, including equivalent penalties or

commercial limitations imposed by foreign regulatory authorities, could severely and adversely affect our financial results,

business and business prospects, including the commercialization of RYTELO, and might cause us to cease operations.

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

Any government investigation of alleged violations of law could require us to spend significant time and

resources in response and could generate negative publicity. 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 U.S. or abroad.

If we are unable to fulfill the post-marketing requirements and commitments established by the FDA, or

that may be or are 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.

Furthermore, in connection with our marketing authorization for RYTELO in the EU for certain patients

with TD anemia due to lower-risk MDS, 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, 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.

Failure to comply with EU and EU Member State laws that apply to the conduct of clinical trials,

manufacturing approval, marketing authorization of medicinal products and marketing of such products, both before and

after grant of the marketing authorization, or with other applicable regulatory requirements, or failure to complete post-

marketing requirements on the timeline required, may result in administrative, civil or criminal penalties. This could also

result in delays or refusal to authorize the conduct of clinical trials, or to grant marketing authorization, product

withdrawals and recalls, product seizures, suspension, withdrawal or variation of the marketing authorization, total or

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partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions,

suspension of licenses, fines and criminal penalties, among others. 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.

We may never receive regulatory approval for RYTELO in any other jurisdictions or for any new

indications. It can take many years to obtain approval, if approval is obtained at all. 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 ongoing or future clinical trials may

result in a delay in obtaining, or our failure to obtain, regulatory approval for RYTELO in lower-risk MDS in any

jurisdictions other than the U.S. and the EU, or for other indications, such as relapsed/refractory MF, in any jurisdictions.

Failure to obtain approval could significantly harm our business and business prospects, render our significant clinical

development expenditures unrecoverable, 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 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. 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,

including relapsed/refractory MF or any other 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 and requirements 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, 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, if needed, the price of

our common stock, 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.

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 ten years of

exclusivity in the U.S. and EU, respectively, following approval, subject to satisfying regulatory requirements. The FDA

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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. On March 7, 2025, the EC granted marketing authorization for RYTELO as an orphan

medicinal product indicated for the treatment of adult patients with TD anemia due to very low, low or intermediate risk

MDS without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or

are ineligible for erythropoietin-based therapy.

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 if such products are able to demonstrate superiority to RYTELO.

We may lose orphan drug exclusivity in the U.S. for certain reasons, including if the FDA 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. In the EU, orphan designation may be lost before marketing authorization if it is established that

the criteria for orphan designation are no longer met. Failure to maintain orphan designation status would lead to the

inability to obtain or the loss of associated regulatory exclusivity.

Even if we maintain orphan drug exclusivity for RYTELO in the U.S., the exclusivity may not effectively

protect RYTELO from all competition because different drugs with different active moieties can be approved for the same

condition or a drug containing the same active moiety or principal molecular structure can be approved for a different

indication. Even after an orphan drug product is approved, such as the approval of RYTELO in the U.S. in June 2024 for

certain patients with lower-risk MDS, the FDA can subsequently grant orphan designation to a different drug with the same

active moiety for the same condition, if the FDA 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, allow competitive products to enter the market, and 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, orphan drug designation will neither shorten the development time nor regulatory review time for RYTELO

in the US and other comparable jurisdictions, and it does not give RYTELO advantages in the regulatory review or

approval process. Notably, there have been legal challenges to aspects of FDA’s regulations and policies concerning the

exclusivity provisions of the Orphan Drug Act, including whether two drugs are the same drug product. Future challenges

could lead to changes that affect the protections potentially afforded to our products in ways that are difficult to predict.

Similarly, in the EU, orphan market exclusivity may not effectively protect RYTELO from all competition.

Following the authorization of RYTELO as an orphan medicinal product by the EC in March 2025 for certain patients with

lower-risk MDS, the EC can subsequently approve similar orphan medicinal products for the same therapeutic indication or

if we are unable to supply RYTELO in sufficient quantities or if a similar medicinal product with the same orphan

indication is shown to be safer, more effective or otherwise clinically superior to the original orphan medicinal product. If

it is established that the criteria for orphan designation are no longer met inter alia where it is shown that the product is

sufficiently profitable, EU orphan market exclusivity may be reduced to six instead of 10 years, allowing similar medicinal

products for the same therapeutic indication to the market sooner. In the EU, orphan drug designation for any additional

indication we may pursue for RYTELO does confer certain regulatory advantages—such as protocol assistance—but it

does not shorten development timelines or accelerate the EMA’s overall review process.

In April 2023, the EC published a proposal to reform the current pharmaceutical framework, including

revision of orphan market exclusivity. The new legislation, if adopted, is expected to start to apply from mid-2028. The

proposal to reform the current pharmaceutical framework intends to revise the orphan drug designation and exclusivity

regime. In the latest version of the proposal, orphan market exclusivity will be reduced from the current 10 years to 9 years.

Extension by another two years will be possible for so-called “breakthrough orphan medicinal products”. Previous drafts

also included the concept of “global orphan marketing authorization”, which would no longer grant additional separate

orphan market exclusivity for second or further orphan therapeutic indications. Although the final text has not yet been

published and RYTELO for the treatment of MDS is and remains regulated under the current regulatory framework,

authorization of future indications may be affected by the new legislation.

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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 in relapsed/

refractory MF.

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 in relapsed/refractory MF.

In addition, with respect to the trial design for IMpactMF, our Phase 3 trial in relapsed/refractory MF, 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 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. 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 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;

•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 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;

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•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;

•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, 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; or

•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.

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.

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.

RISKS RELATED TO COMPLIANCE WITH HEALTHCARE LAWS

Our relationships with healthcare providers, including physicians and third-party payors, the methods by which we

promote RYTELO, and the content of our promotional materials and programs, are subject to applicable promotional,

anti-kickback, fraud and abuse, and other healthcare laws and regulations, and our failure to comply with these laws

could expose us to criminal sanctions, civil penalties, exclusion from federal health care programs, contractual

damages, reputational harm and may adversely affect our business and financial results.

The FDA strictly regulates the promotional claims that may be made about drug products. In particular,

FDA asserts that a product may not be promoted for uses that are not approved by the FDA as reflected in the product’s

approved labeling. The FDA, DOJ and other agencies actively enforce regulations related to the promotion and

advertisement of pharmaceutical products. If our promotional materials or methods were found to have violated the Food,

Drug, and Cosmetic Act, or False Claims Act, we could be subject to Warning or Untitled Letters, or to significant civil,

criminal, or administrative penalties, which could inhibit our ability to commercialize RYTELO and generate revenue,

require us to expend significant time and resources in response, and generate negative publicity.

Healthcare professionals, including but not limited to physicians, nurses, medical directors, hospitals,

pharmacies, pharmacy benefit managers, group purchasing organizations, wholesalers, insurers, and all individuals

employed by such entities (collectively, HCPs), and patients, caregivers, patient advocacy organizations, or medical

societies, may influence the recommendation and prescription of RYTELO. There is ongoing government focus on the

relationships between the pharmaceutical industry and HCPs or others who can influence the prescription or

recommendation of products, and common industry activities that we may engage in such as speaker programs, advisory

boards, consulting agreements with HCPs, relationships with charitable foundations providing copayment assistance, and

relationships with patient organizations and patients continue to receive increased governmental attention.

Our arrangements with HCPs and others who have the ability to influence the recommendation and

prescription of RYTELO may expose us to broadly applicable federal and state fraud and abuse and other healthcare laws

and regulations, 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; 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

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affect our ability to operate, see Item 1 “Business-Government Regulation- Fraud and Abuse, and Transparency Laws and

Regulations” of this Report.

Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors

available, it is possible that some of our business activities could be subject to challenge under one or more of such laws.

For example, 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 under the AKS and other federal and state

laws in recent years.  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.

While we maintain a comprehensive compliance program designed with the goal of ensuring that our

practices and the activities of our third party contractors and employees fall within the scope of available statutory

exceptions and regulatory safe harbors whenever possible, and otherwise comply with applicable laws, it is possible that

government authorities may disagree with our assessment, find fault with the conduct of our employees or contractors or

conclude that our business practices do not comply with current or future statutes, regulations or case law involving

applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of

these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and

administrative penalties, damages, fines, exclusion from government funded healthcare programs, such as Medicare and

Medicaid, and the curtailment or restructuring of our operations. Even if we are not determined to have violated these laws,

government investigations into these issues typically require the expenditure of significant resources and generate negative

publicity, or could result in related shareholder lawsuits, any of which would adversely affect our business, financial

condition, results of operations and prospects.

Foreign, 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. If our operations are found to be in violation of any of these or any other healthcare

and privacy-related regulatory laws that may apply to us, our ability to operate our business and our results of operations

could be adversely affected by:

•the imposition of significant civil, criminal and administrative penalties, damages, monetary

fines, disgorgement and imprisonment;

•possible exclusion from participation in Medicare, Medicaid and other federal healthcare

programs or comparable foreign programs;

•reputational harm;

•diminished profits and future earnings;

•additional reporting requirements and oversight if we become subject to a corporate

integrity agreement or similar agreement to resolve allegations of non-compliance with

these laws; and

•curtailment of our operations.

Defending against any such actions can be costly, time-consuming and may require significant financial

and personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought

against us, our business may be impaired.

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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:

•generate sufficient safety and efficacy data from the IMpactMF, IMproveMF, IMpress and

IMAGINE clinical trials, as well as our studies in frontline MF and acute myeloid leukemia

or high-risk MDS, to support any application for regulatory approval, 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, 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 and for territories outside of the U.S. in compliance with applicable

laws;

•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. and the EU;

•achieve acceptance of RYTELO treatment by patients and the relevant medical

communities;

•compete effectively with other approved treatments in lower-risk MDS, and relapsed/

refractory MF, if imetelstat is approved in relapsed/refractory MF, and potentially other

myeloid hematologic malignancies;

•obtain appropriate coverage and reimbursement levels for the cost of RYTELO from

governmental authorities, private health insurers and other third-party payors; and

•obtain, maintain and enforce adequate intellectual property and regulatory exclusivity for

RYTELO in the U.S., EU 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 and business prospects.

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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.

The conduct and completion of our clinical trials could be interrupted, delayed or abandoned for a variety

of reasons, including as a result of clinical trial failures, suspensions, terminations or delays related to:

•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 OS as a trial endpoint, which inherently requires prolonged periods of clinical

observation and follow-up, 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;

•use of trial endpoints, including patient-reported outcomes, that necessitate a

comprehensive analysis of the resulting data to determine trial outcomes;

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

•contracting with a sufficient number of clinical trial sites to conduct current and potential

future clinical trials, and ensuring that such contracts contain all necessary terms and

conditions required by applicable laws, including providing for valid mechanisms to engage

in cross-border data transfers, as well as identifying, recruiting and training suitable clinical

investigators;

•obtaining or accessing necessary clinical data in accordance with appropriate clinical or

quality practices and regulatory requirements, in a timely and accurate manner to ensure

complete data sets;

•responding to safety findings, recommendations or conclusions by the data safety review

committees, independent data monitoring committees and/or expert committees of current

and potential future clinical trials of imetelstat based on emerging data occurring during

such clinical trials;

•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, 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;

•reaching agreement on acceptable terms and on a timely basis, if at all, with collaborators,

physician investigators, vendors and other third parties located in the U.S. or other

countries, including our CROs, laboratory service providers and clinical trial sites, on all

aspects of clinical development and collaborating with them successfully; and

•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

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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. 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.

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 cannot be certain whether the results as 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. New data relating to imetelstat, including from adverse event reports and our

post-marketing requirements in the U.S., and from ongoing clinical trials of imetelstat, may result in changes to the product

label and may adversely affect sales, or result in withdrawal of imetelstat from the market. The FDA and regulatory

authorities in other jurisdictions may also consider the new data in reviewing our marketing applications for additional

indications and/or in other jurisdictions, or impose post-approval requirements. 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, 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:

•hematologic toxicities, such as profound and/or prolonged thrombocytopenia or

neutropenia;

•bleeding events, with or without thrombocytopenia, including Grade 3/4 bleeding events;

•febrile neutropenia;

•hepatotoxicity and liver function test abnormalities, as well as hepatic failure;

•gastrointestinal events;

•infection events, with or without neutropenia, including Grade 3/4 infection events;

•muscular and joint pain;

•fatigue;

•headache; and

•infusion-related reactions.

If patients experience similar or more severe adverse events, or new or unusual adverse events, or if the

FDA or other similar international regulatory authorities determine that efficacy and safety data from our

commercialization efforts or in clinical trials do not support an adequate benefit-risk profile to justify continued treatment

of patients, then the FDA or other similar international regulatory authorities may halt or restrict the commercialization of

RYTELO or place one or more of our INDs on clinical hold, as occurred in March 2014. If this were to occur, there could

be a significant delay in, or possible termination of, one or more of our clinical trials, and our commercialization efforts

could be halted, which might cause us to cease operations. If such toxicities or other safety issues identified as a result of

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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 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;

•additional, unexpected clinical trials or non-clinical studies may be required to be

conducted; or

•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 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, as well as any data disclosed as a result

of an interim analysis, may not predict success in later clinical trials or the final analysis, 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.

The design of a clinical trial can determine whether its results will support regulatory approval of a product,

and flaws in the trial design may not become apparent until the clinical trial is well advanced or during the approval

process after the trial is completed. A clinical trial design that is considered appropriate for regulatory approval includes a

sufficiently large sample size with appropriate statistical power, as well as proper control of bias, to allow a meaningful

interpretation of the results. The preliminary results of imetelstat clinical trials with smaller sample sizes can be

disproportionately influenced by the impact the treatment had on a few individuals, which limits the ability to generalize

the results across a broader community, making the trial results of clinical trials with smaller sample sizes less reliable than

trials with a larger number of patients. As a result, there may be less certainty that imetelstat will achieve a statistically

significant effect in any future clinical trials.

Further, success in non-clinical testing and early clinical trials, including Phase 2 clinical trials, such as

IMbark, does not ensure that later clinical trials will be successful, nor does it predict final clinical trial results. In addition,

even though we reported positive top-line results from IMerge Phase 3 in January 2023, this does not ensure that any other

clinical trials of imetelstat will be successful. Later stage clinical trials of imetelstat may fail to show an acceptable benefit-

risk profile despite having progressed through non-clinical studies and initial clinical trials. 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 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.

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

some instances, there can be significant variability between different clinical trials of imetelstat due to numerous factors,

including changes in trial procedures set forth in trial protocols, differences in the size and type of patient populations, and

changes in and adherence to the dosing regimens. For example, although the statistical analyses comparing IMbark data to

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closely matched real world data, or RWD, published in the September 2021 issue of the Annals of Hematology, suggest

potentially favorable OS in relapsed/refractory MF patients treated with imetelstat, compared to bipolar androgen therapy

using closely matched patients’ RWD, such comparative analyses between RWD and our clinical trial data have several

limitations. For instance, the analyses create a balance between treatment groups with respect to commonly available

covariates, but do not take into account the unmeasured and unknown covariates that may affect the outcomes of the

analyses. 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, if needed, 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. We also make assumptions, estimations, calculations and conclusions as part of our analyses of

data, and we may not have received or had the opportunity to fully and carefully evaluate all data. Additional or updated

safety and efficacy data from current or potential future clinical trials of imetelstat may result in a benefit-risk profile that

does not justify the continued development and/or potential regulatory approval of imetelstat in a particular patient

population, or at all. Any data reported from IMpactMF may materially differ from and be less positive than data

previously reported from IMbark. 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,

IMpress or IMAGINE, or cause us to abandon further development of imetelstat entirely.

Top-line or interim 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.

Moreover, as remaining patients in IMerge Phase 3 continue to be treated and followed under the extension phase of the

trial and longer-term outcomes are assessed, these additional and more mature data may alter the benefit-risk profile of

imetelstat in an adverse manner, including with respect to OS. Material adverse differences in future results, compared to

preliminary, interim or top-line data, could severely and adversely affect our financial results, business and business

prospects, including the commercialization of RYTELO, and might cause us to cease operations.

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 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. 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. However, these third parties are not our employees, and except for

contractual duties and obligations, we have limited ability to control their performance, or the amount or timing of

resources that they devote to imetelstat. For example, we have retained CROs to support our clinical development

activities, and any failure by our CROs to perform their contractual obligations, or disputes with our CROs about the

quality of their performance or other matters, could further delay or halt our clinical development activities. These third

parties may also have relationships with other commercial entities, some of which may compete with us. Under certain

circumstances, these third parties may terminate their agreements with us without cause and upon immediate written notice.

Although we rely on third parties to conduct our clinical trials, we remain responsible for ensuring that each

clinical trial is conducted in accordance with its investigational plan and protocol, and applicable laws. Moreover, the FDA

and similar international regulatory authorities require us to comply with GCP regulations and standards for conducting,

monitoring, recording and reporting the results of clinical trials to ensure that the data and results are scientifically credible

and accurate, and that the rights, integrity and confidentiality of patients participating in clinical trials are protected,

including being adequately informed of the potential risks. Regulatory authorities enforce these GCP requirements through

periodic inspections of trial sponsors, principal investigators and trial sites. 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

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upon inspection by a given regulatory authority, such regulatory authority will determine whether 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. Our failure to comply with these regulations may require us to repeat clinical

trials. 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, 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. In order for

these functions to be carried out effectively and efficiently, it is imperative that these parties communicate and coordinate

with one another. 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. 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.

In addition, certain principal investigators for our clinical trials serve as scientific advisors or consultants to

us from time to time and receive compensation in connection with such services. Under certain circumstances, we may be

required to report some of these relationships to the FDA or comparable foreign regulatory authorities. The FDA or

comparable foreign regulatory authorities may conclude that a financial relationship between us and a principal investigator

has created a conflict of interest or otherwise affected conduct of the trial. The FDA or comparable foreign regulatory

authorities may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the

clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of 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.

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. In addition,

we do not have control over the timing and reporting of the data from any such investigator-led clinical trials. A delay in

the timely completion of or reporting of data from any current or potential future investigator-led clinical trial could have a

material adverse effect on our ability to maintain regulatory approval for RYTELO in lower-risk MDS, or to further

develop or advance it in clinical trials, as such delays may impede our ability to generate necessary supplemental clinical

evidence, fulfill post-marketing commitments or requirements, or provide regulatory authorities with timely safety and

efficacy data needed to support ongoing approval or future development.

Investigator-led clinical trials may be conducted under less rigorous clinical standards than those used in

company-sponsored clinical trials. 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. 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. Safety concerns arising from future investigator-led

clinical trials could result in withdrawal of approval of RYTELO, partial or full clinical holds being placed on our INDs by

the FDA or other similar international regulatory authorities, as occurred in March 2014, which would further delay or

prevent us from commercializing RYTELO or advancing it into further clinical development. Any of the foregoing would

delay or preclude any future marketing approvals for RYTELO and could cause us to discontinue our development, which

would severely harm our business and prospects and could potentially cause us to cease operations.

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RISKS RELATED TO MANUFACTURING RYTELO (IMETELSTAT)

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.

The manufacture of RYTELO (imetelstat) must comply with applicable regulatory standards for

commercial uses and current and potential future clinical trials. The process of manufacturing RYTELO is complex and

subject to several risks, including:

•the ability to consistently manufacture and attain sufficient production yields with

acceptable quality control and quality assurance to meet market demand for our

commercialization of RYTELO, as well as the needs for continuing clinical trials;

•our ability to maintain existing commercial supply agreements and to establish additional or

alternative supply agreements if necessary, including our ability to successfully transfer

manufacturing technology and attain regulatory approval at any such additional or

alternative suppliers;

•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, 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; and

•regulatory acceptance and compliance with regulatory requirements, which are less well-

defined for oligonucleotide products than for small molecule drugs and vary in each

country.

As a result of these and other risks, we may be unable to maintain a manufacturing infrastructure and

supply chain capable of providing RYTELO for clinical and commercial use, which would delay or adversely affect our

RYTELO commercialization efforts; result in lost sales; 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; and

could cause financial and reputational harm.

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. 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 and drug product, and we rely on a single source to

supply the API for RYTELO. 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. For example, one of our third-party

manufacturers received a warning letter from the FDA due to certain deficiencies in the manufacturer’s process and

facilities that were not in compliance with FDA requirements and regulations governing the manufacturing, processing,

packing and holding of drug product. While not related to the production of RYTELO, if the warning letter is not timely

remediated by the manufacturer, it 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.

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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. 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. Reliance on these third-party manufacturers is

subject to numerous risks, including:

•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 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;

•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;

•the inability of third-party manufacturers to timely formulate and manufacture RYTELO or

to produce or ship RYTELO in the quantities or of the quality required to meet commercial

and clinical needs;

•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 our commercial needs or before we establish an acceptable alternative

supplier;

•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 the warning letter issued

to one of our third-party manufacturers;

•breach or termination of manufacturing or supply contracts;

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

•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.

In addition, third-party manufacturers and/or any other manufacturers may need to make substantial

investments to enable sufficient capacity increases and cost reductions, and to implement those regulatory and compliance

standards necessary for successful commercialization of RYTELO. 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 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.

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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 December 31, 2025, our accumulated deficit was approximately $1.9 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. Although we began commercializing RYTELO in June 2024, the commercial potential of

and our ability to successfully commercialize RYTELO remains unproven, and our limited operating history as a

commercial company makes our future operating results difficult to predict. We expect that our sales revenue may continue

to vary from period to period as a result of the evolving effects of our commercialization strategy and as our

commercialization efforts otherwise progress. 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. Our failure to achieve

consistent future profitability could negatively impact the market price of our common stock and our ability to sustain

operations.

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

year. 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 releases of earnings for both of the

quarters and years ended December 31, 2025 and 2024, our stock price declined significantly both times. As a result of this

volatility, our stockholders may not be able to sell their common stock at or above the price they paid for their common

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

•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;

•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 royalty payments under the Royalty Pharma Agreement;

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

•the timing, cost and level of investment in our research and development activities involving imetelstat and

potential future product candidates; and

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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, 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. As the

variables that we use as a basis for valuing these awards change over time, including our underlying stock price, the

magnitude of the expense that we must recognize may vary significantly.

For these and other reasons, it is difficult for us to accurately forecast future sales of RYTELO, operating

expenses or future profits or losses. 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 further decline,

perhaps significantly.

Our financial projections and estimates are subject to significant risks, assumptions, and uncertainties, and our actual

results may differ materially.

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

December 31, 2025, we had approximately $401.1 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, if available, under the Pharmakon Loan Agreement (as defined below), 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

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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 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:

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

•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;

•the costs of preparing, filing and prosecuting patent applications and maintaining, enforcing

and defending intellectual property-related claims;

•the costs of manufacturing, developing, commercializing and marketing RYTELO,

including with respect to third-party vendors and service providers and our ability to

achieve any meaningful reduction in manufacturing costs;

•the sales price for RYTELO, including the availability of coverage and adequate third-party

reimbursement for RYTELO;

•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 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;

•the costs of maintaining and operating facilities in California and New Jersey, as well as

higher expenses for travel;

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•macroeconomic or other global conditions that may reduce our ability to access equity or

debt capital or other financing on preferable terms, which may adversely affect future

capital requirements and forecasts; and

•the costs of enabling our personnel to work remotely, including providing supplies,

equipment and technology necessary for them to perform their responsibilities.

In the event we need to raise additional capital to fund our business, including pursuant to the 2026 Sales

Agreement with TD Cowen (as defined below), 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, 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, 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

are expected to have further global economic consequences. If the equity and credit markets deteriorate, 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 2026 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 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, including by limiting our operating and financial flexibility.

On November 1, 2024, we entered into the Pharmakon Loan Agreement, which we amended on January 5,

2026. We drew the Tranche A Loan of $125.0 million on November 1, 2024 and as of November 1, 2024, the total

outstanding principal amount under the Pharmakon Loan Agreement was $125.0 million. The tranches for the remaining

$125.0 million available to us under the Pharmakon Loan Agreement are as follows: (a) a Tranche B Loan of $75.0

million, which is available for us to request at our option until July 30, 2026, subject to certain customary and limited

conditions; and (b) a Tranche C Loan of $50.0 million, which is available for us to request until July 30, 2026, subject to

certain conditions, including us reaching a specified trailing twelve-month RYTELO revenue milestone on or prior to June

30, 2026. 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

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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.

All obligations under the Pharmakon Loan Agreement are secured by substantially all of our assets,

including our intellectual property. Further, the terms of the Pharmakon Loan Agreement place restrictions on our

operating and financial flexibility, and limit or prohibit our ability to dispose of certain assets, change our line of business,

and engage in other significant transactions. 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;

•change our line of business;

•engage in mergers, acquisitions or consolidations;

•incur additional indebtedness;

•create liens on assets;

•pay dividends and make contributions or repurchase our capital stock; and

•engage in certain transactions with affiliates.

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 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:

•we will need to repay the indebtedness by making payments of interest and principal, which

will reduce the amount of cash available to finance our operations, our research and

development efforts and other general corporate activities; and

•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 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.

We may not have cash available in an amount sufficient to enable us to make interest or principal payments on our

indebtedness when due.

Our ability to make scheduled interest payments on or to refinance our indebtedness depends on our future

performance and ability to raise additional sources of cash, which is subject to economic, financial, competitive and other

factors beyond our control. If we are unable to generate sufficient cash to service our debt, we may be required to adopt one

or more alternatives, such as selling assets, restructuring our debt or obtaining additional equity capital on terms that may

be onerous or highly dilutive. If we desire to refinance our indebtedness, our ability to do so will depend on the state of the

capital and lending markets and our financial condition at such time. 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 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

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exercise remedies against us and the collateral securing the Pharmakon Loan Agreement. These events of default include,

among other things:

•insolvency, liquidation, bankruptcy or similar events;

•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 withdrawal event in respect to RYTELO;

•the occurrence of a material adverse change;

•material misrepresentations;

•certain cross-default of third-party indebtedness or certain default or termination events of

hedging assessments;

•certain money judgments being entered against us which are not timely paid, discharged or

stayed; and

•our assets are attached or seized.

In the event of default, the lenders could accelerate all of the amounts due under the Pharmakon Loan

Agreement. Under such circumstances, we may not have enough available cash or be able to raise additional funds through

equity or debt financings to repay such indebtedness at the time of such acceleration. We may be required to delay, limit,

reduce or terminate our RYTELO development or commercialization efforts or grant to others rights to develop and market

RYTELO. The lenders could also exercise their rights to take possession and dispose of the collateral securing the

Pharmakon Loan Agreement, which collateral includes substantially all of our property including, without limitation, our

intellectual property, subject to certain exceptions. 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 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 restrictions on intellectual property transfers and out-

licenses, and certain other actions. For example, we are obligated to make royalty payments each quarter based on U.S. net

sales of RYTELO at the royalty rates set forth in the Royalty Pharma Agreement, until the date when the aggregate Royalty

Payments equal or exceed 1.65 times the Purchase Price, if this occurs by June 30, 2031. However, in the event we are

unable to repay our obligation to Royalty Pharma before June 30, 2031, we will be required to make royalty payments

equal to or exceeding 2.0 times the Purchase Price thereafter, which may negatively impact our business, financial

condition and results of operations. The Royalty Pharma Agreement also limits our ability to create or incur liens or

dispose of certain assets related to imetelstat. We have no rights to repurchase the revenue interests in RYTELO sold to

Royalty Pharma (other than in connection with a change of control event), thereby limiting our ability to eliminate future

applicability of the covenants contained in the Royalty Pharma Agreement. Compliance with these covenants may limit our

flexibility in operating our business and our ability to take actions that might otherwise be advantageous to us and our

stockholders.

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, 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, 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. and in other countries.

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As a result of the Leahy-Smith America Invents Act, or the AIA, in March 2013, the U.S. transitioned to a

first-inventor-to-file system under which, assuming the other requirements for patentability are met, the first inventor to file

a patent application is entitled to the patent. However, since the publication of discoveries in scientific or patent literature

tends to lag behind actual discoveries by at least several months and sometimes several years, we are not able to be certain

upon filing a patent application that the persons or entities that we name as inventors or applicants in our patent

applications were the first to invent the inventions disclosed therein, or the first to file patent applications for these

inventions. Thus, our ability to protect our patentable intellectual property depends, in part, on our ability to be the first to

file patent applications with respect to our inventions, or inventions that were developed by our former collaboration

partner and assigned to us, for the future development, commercialization and manufacture of RYTELO. As a result, if we

are not the first inventor-to-file, we may not be able to obtain patents for discoveries that we otherwise would consider

patentable and that we consider to be significant to the future success of RYTELO. Delay in the filing of a patent

application for any purpose, including further development or refinement of an invention, may result in the risk of loss of

patent rights.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our

patents may be challenged in the courts or patent offices in the U.S. and in other countries. Such challenges may result in

loss of exclusivity or in patent claims being narrowed, invalidated, or held unenforceable, which could limit our ability to

stop others from using or commercializing RYTELO or our technology and/or limit the duration of the patent protection

for RYTELO and our technology.

While we have method-of-use patents that protect the use of RYTELO for the treatment of certain diseases,

this type of patent does not prevent a generic competitor from making and marketing a product that is identical to RYTELO

for an indication that is outside the scope of our approved use after our composition-of-matter patents or their patent term

extensions, and any regulatory exclusivities have expired. 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 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. 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.”

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 the EU, imetelstat is designated as a New Active Substance, or

NAS. For this NAS, regulatory data protection entitles us to eight years of data exclusivity and two years of market

exclusivity, for a total of ten years in parallel to orphan market exclusivity.

In the event that we are unsuccessful in obtaining, maintaining, enforcing and extending our patents and

other intellectual property rights or having our licensors maintain the intellectual property rights we have licensed, the

value of RYTELO and/or our technologies will be adversely affected, and we may not be able to further develop or

commercialize RYTELO. 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. Occurrence

of any of these events would materially and adversely affect our financial results, business and business prospects, and

might cause us to cease operations.

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 U.S. 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

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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. In such an event, potential competitors might be able to enter the market with the same or similar

products to RYTELO, and this circumstance could harm our financial condition, business and business prospects. In

addition, if we are responsible for patent prosecution and maintenance of patent rights in-licensed to us or jointly owned

with us, any of the foregoing could expose us to liability to the applicable patent owner or patent co-owner.

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

Patents have a limited lifespan. In the U.S., the natural expiration of a patent is generally 20 years after its

first effective nonprovisional filing date. As a result, our intellectual property may not provide us with sufficient patent

rights to exclude others from commercializing products similar or identical to RYTELO.

In the U.S., the Hatch-Waxman Act permits one patent per approved product to receive one patent term

extension of up to five years beyond its normal expiration. The USPTO, in consultation with the FDA, reviews and

approves the application for any patent term extension or restoration. The length of the patent term extension is typically

calculated as one half of period between the effective date of an IND and the submission date of an NDA less any time the

sponsor did not act with due diligence during the period, plus the time between the submission date of an NDA and the

approval of that application less any time the sponsor did not act with due diligence during the period. There is also a limit

on the patent term extension to a term that is no greater than fourteen years from drug approval. We have applied to the

USPTO for patent term extension of some of our patents. 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. If 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 USPTO and could

differ from our calculation.

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, including:

•failure to adhere to the required filing deadlines;

•submission of a patent term extension application after the underlying patents have expired;

•failure to exercise due diligence during clinical development or regulatory review; or

•failure to otherwise meet the applicable criteria.

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. 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 jurisdictions, 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 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 an SPC may only be applied for once with respect to a product. Accordingly, in countries of the European Economic

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

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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 jurisdictions and territories including in 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 jurisdictions and territories, we will not be able to seek patent term extension of our

composition of matter patent, as it expired in September 2024.  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.

Additionally, there are regulations for the listing of patents in the Approved Drug Products with

Therapeutic Equivalence Evaluations, or the Orange Book. Some of our patents have been listed in the Orange Book.

Manufacturers of generic drugs may challenge the listing. If an appropriate patent covering RYTELO is not listed in the

Orange Book or is subsequently removed from the Orange Book, a manufacturer of generic drugs would not be required to

provide advance notice to us of any abbreviated NDA filed with the FDA to obtain permission to sell a generic version of

RYTELO. Any of the foregoing could harm our competitive position, business, financial condition, results of operations

and prospects.

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 FDCA 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; (2) the patents listed in

the Orange Book have expired; (3) the listed patents have not expired, but will expire on a particular date and approval is

sought after patent expiration; or (4) the listed patents are invalid or will not be infringed by the manufacture, use or sale of

the third-party’s generic product. 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 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 after the NDA holder’s receipt of the notice of

Paragraph IV Certification, the expiration of the patent, certain settlements of the lawsuit, 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.  However, if an appropriate patent covering RYTELO is not listed in the Orange

Book or is subsequently removed from the Orange Book, a manufacturer of generic drugs would not be required to provide

advance notice to us of any abbreviated NDA filed with the FDA to obtain permission to sell a generic version of

RYTELO. Any of the foregoing could harm our competitive position, business, financial condition, results of operations

and prospects.

Our issued U.S. patents covering RYTELO or its methods of use may not provide adequate protection from

competitive products if competitors receive approval of an ANDA application or are able to design around the patents. One

or more competitors may circumvent these patents by filing a marketing application with the FDA for a competitive

product containing the active moiety in RYTELO and successfully challenging the validity of the patents or successfully

designing around the patents. Any successful challenge and/or designing around one or more of the patents could result in a

generic version of RYTELO being commercialized before the expiration of the patents.

If the patents covering RYTELO or its methods of use are successfully challenged or designed around, or if

we are unsuccessful in enforcing our patents against generics, we could face competition prior to the expiration of these

patents, which could have a material adverse effect on our business, financial condition, results of operations and prospects.

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Changes in U.S. or international patent law or interpretations of such patent laws could diminish the value of our

patents in general, thereby impairing our ability to protect our technologies and RYTELO.

The patent positions of pharmaceutical and biopharmaceutical companies, including ours, are highly

uncertain and involve complex legal and technical questions. In particular, legal principles for biotechnology and

pharmaceutical patents in the U.S. and in other countries are evolving, and the extent to which we will be able to obtain

patent coverage to protect our technologies and RYTELO, or enforce or defend issued patents, is uncertain.

For instance, the U.S. has enacted and implemented wide-ranging patent reform legislation, including AIA,

signed into law on September 16, 2011. The U.S. 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 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, regulations in other

jurisdictions or 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. Occurrence of these events and/or 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.

In 2012, the European Patent Package, or EU Patent Package, was approved and included regulations with

the goal of providing for the possibility of a single Unitary Patent covering the Contracting Member States, and a new

Unified Patent Court, or UPC, for litigation of Unitary Patents and as well as European patents not opted out from the UPC

system. The EU Patent Package entered into force fully in June 2023 and currently covers 18 EU Member States. As of

June 1, 2023, all European patents, including those issued prior to June 1, 2023 in principle fall under the jurisdiction of the

UPC and allow for the possibility of obtaining injunctions for the UPC Member States and are at risk of central revocation

at the UPC in participating UPC Member States. Under the EU Patent Package, patent holders are permitted to “opt out”

their European patents (but not their Unitary Patents) from the UPC on a patent-by-patent basis during an initial seven year

transitional period after June 1, 2023. Owners of European patent applications who receive notice of grant after the EU

Patent Package came into effect could, for the UPC Member States, either obtain a Unitary Patent or validate the European

patent nationally and optionally file an opt-out demand. The EU Patent Package may increase the uncertainties and costs

surrounding the enforcement or defense of our issued European patents and pending applications. The full impact on future

European patent filing strategy and the enforcement or defense of our issued European patents in European jurisdictions

and/or the UPC is not fully known.

Filing, prosecuting, maintaining, defending and enforcing patents for RYTELO and our technologies in all

countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries

outside the U.S. are less extensive than those in the U.S. The requirements for patentability may differ in certain countries,

particularly in developing countries; thus, even in countries where we do pursue patent protection, there can be no

assurance that any patents will be issued with claims that cover RYTELO and our technologies.

We may be involved in lawsuits to protect or enforce our patents or other intellectual property rights, which could be

expensive, time consuming and unsuccessful, and which could result in the invalidity or unenforceability of our patents

covering RYTELO or its methods of use.

Competitors may infringe, misappropriate or otherwise violate our patents or other intellectual property

rights. To counter infringement or unauthorized use, we may be required to file and prosecute legal claims against one or

more third parties, which can be expensive and time-consuming, even if ultimately successful.

The initiation of a claim against a third party by us may also cause the third party to bring counter claims

against us, such as claims asserting that our patents are invalid or unenforceable. Grounds for a validity challenge could be

an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, non-enablement or

lack of written description or non-statutory subject matter. 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

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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. The standards that courts use to interpret patents are not always applied predictably or uniformly

and can change, particularly as new technologies develop. As a result, we cannot predict with certainty how much

protection, if any, will be given to our patents if we attempt to enforce them and they are challenged in court and if any

such lawsuits will ultimately be resolved successfully. Further, even if we prevail, the infringer may file an appeal and the

court judgment may be overturned and/or that an adverse decision may be issued by an appeals court relating to the validity

or enforceability of our patents. An adverse result in any litigation or defense proceedings could put one or more of our

patents at risk of being invalidated or interpreted narrowly in a manner insufficient to achieve our business objectives. Even

if we establish infringement, we may not seek, or the court may decide not to grant, an injunction against further infringing

activity and instead award only monetary damages, which may or may not be an adequate remedy.

If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least

part, and perhaps all, of any future patent protection for RYTELO, which could have a material adverse effect on our

business, financial condition, results of operations and prospects. Additionally, any adverse outcome could allow third

parties to commercialize RYTELO and compete directly with us, without payment to us.

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 stock.

Many companies have encountered significant problems in protecting and defending intellectual property

rights in jurisdictions outside the U.S. The legal systems of certain countries, particularly certain developing countries, do

not favor the enforcement of patents, trade secrets and other intellectual property protection, particularly those relating to

biotechnology and pharmaceutical products, which could make it difficult for us to stop the infringement of our patents or

marketing of competing products in violation of our proprietary rights generally. For example, many countries outside the

U.S. have compulsory licensing laws under which a patent owner must grant licenses to third parties. Proceedings to

enforce our patent rights in jurisdictions outside the U.S. could result in substantial costs and divert our efforts and

attention from other aspects of our business, and could put our patents at risk of being invalidated or interpreted narrowly.

We may not be able to protect our intellectual property rights in the U.S or worldwide and challenges to our owned or

licensed patent rights would result in costly and time-consuming legal proceedings that could prevent or limit

development or commercialization of RYTELO.

Our patents or those patent rights we have licensed, including patent rights that we may seek with respect to

inventions made by past or future collaborators, may be challenged through administrative or judicial proceedings, which

could result in the loss of important patent rights. 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 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 delays 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.

Under the AIA, interference proceedings between patent applications filed on or after March 16, 2013, have

been replaced with other types of proceedings, including derivation proceedings. The AIA also includes post-grant review

procedures subjecting U.S. 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. 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

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. U.S. 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

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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.

Certain jurisdictions, such as Europe, China, Japan, New Zealand and Australia, permit third parties to file

third party observations, oppositions or invalidation trials against granted patents and/or patent applications. Because we

seek to enable potential global commercialization of RYTELO, securing both proprietary protection and freedom to operate

outside of the U.S. is important to our business.

Third party proceedings such as oppositions and invalidation trials require significant time and costs, and if

we are unsuccessful or are unable to commit these types of resources to protect our RYTELO patent rights, we could lose

our patent rights and we could be prevented or limited in the development and commercialization of RYTELO.

As more groups become engaged in scientific research and product development in the areas of telomerase

biology and hematologic malignancies, the risk of our patents, or patents that we have in-licensed, being challenged

through patent interferences, derivation proceedings, IPRs, post-grant proceedings, oppositions, invalidation trials, re-

examinations, litigation or other means will likely increase. Challenges to our patents through these procedures would be

extremely expensive and time-consuming, even if the outcome was favorable to us. An adverse outcome in a patent dispute

could severely harm our ability to further develop or commercialize RYTELO, or could otherwise have a material adverse

effect on our business, and might cause us to cease operations, by:

•causing us to lose patent rights in the relevant jurisdiction(s);

•subjecting us to litigation, or other types of proceedings aimed at preventing us from

commercializing RYTELO in the relevant jurisdiction(s);

•requiring us to obtain licenses to certain patents and patent applications;

•forcing us to cease using the disputed technology; or

•requiring us to develop or obtain alternative technologies.

We may be subject to infringement claims that are costly to defend, and such claims may limit our ability to use disputed

technologies and prevent us from pursuing research, development, manufacturing or commercialization of RYTELO.

The commercial success of RYTELO will depend upon our ability to research, develop, manufacture,

market and sell RYTELO without infringing or otherwise violating the intellectual property and other proprietary rights of

third parties. There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries, and

many pharmaceutical companies, including potential competitors, have substantial patent portfolios. Since we cannot be

aware of all intellectual property rights potentially relating to RYTELO and its uses, we do not know with certainty that

RYTELO, or the commercialization thereof, does not and will not infringe or otherwise violate any third party’s

intellectual property. For example, we are aware that certain third parties have or may be prosecuting patents and patent

estates that may relate to RYTELO, and while these patents have expired, or we believe that a reasonable court should find

they are invalid and/or would not be infringed by the manufacture, use or sale of RYTELO, it is possible that the owner(s)

of these patents will assert claims against us in the future.

In the event our technologies infringe the rights of others or require the use of discoveries and technologies

controlled by third parties, we may be prevented from pursuing research, development, manufacturing or

commercialization of RYTELO, or may be required to obtain unblocking licenses from such third parties, develop

alternative non-infringing technologies, which we may not be able to do at an acceptable cost or on acceptable terms, or at

all, or cease the commercialization and continued development of RYTELO. If we are unable to resolve an infringement

claim successfully, we could be subject to an injunction that would prevent us from commercializing RYTELO and could

also require us to pay substantial damages.

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. Our success therefore depends significantly on our ability to

operate without infringing patents and the proprietary rights of others.

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We may become aware of discoveries and technologies controlled by third parties that are advantageous or

necessary to further develop or manufacture RYTELO. Under such circumstances, we may initiate negotiations for licenses

to other technologies as the need or opportunity arises. We may not be able to obtain a license to a technology required to

pursue the research, development, manufacturing or commercialization of RYTELO on commercially favorable terms, or

at all, or such licenses may be terminated on certain grounds, including as a result of our failure to comply with any

material obligations under such licenses. If we do not obtain a necessary license or if such a license is terminated, we may

need to redesign such technologies or obtain rights to alternative technologies, which may not be possible, and even if

possible, could cause further delays in the development efforts for RYTELO and could increase the development and/or

production costs of RYTELO. In cases where we are unable to license necessary technologies, we could be subject to

litigation and prevented from pursuing research, development, manufacturing or commercialization of RYTELO, which

would materially and adversely impact our business. Failure by us to obtain rights to alternative technologies or a license to

any technology that may be required to pursue research, development, manufacturing or commercialization of RYTELO

would further delay current and potential future clinical trials of RYTELO and any applications for regulatory approval,

impair our ability to sell RYTELO, and therefore result in decreased sales of RYTELO for us. Occurrence of any of these

events could materially and adversely affect our business and might cause us to cease operations.

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. and Europe. Our product trademark, RYTELO, is approved for use as name

of the imetelstat medicinal product by the FDA and the EC. Opposition or cancellation proceedings, however, may be filed

against our trademarks, and our trademarks may not survive such proceedings. If our U.S. 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.

We may become involved in disputes with past or future collaborator(s) over intellectual property inventorship,

ownership or use, and publications by us, or by investigators, scientific consultants, research collaborators or others.

Such disputes could impair our ability to obtain patent protection or protect our proprietary information, which, in

either case, could have a significant impact on our business.

Inventions discovered under research, material transfer or other collaboration agreements may become

jointly owned by us and the other party to such agreements in some cases and may be the exclusive property of either party

in other cases. Under some circumstances, it may be difficult to determine who invents and owns a particular invention, or

whether it is jointly owned, and disputes can arise regarding inventorship, ownership and use of those inventions. These

disputes could be costly and time-consuming, and an unfavorable outcome could have a significant adverse effect on our

business if we are not able to protect or license rights to these inventions. In addition, clinical trial investigators, scientific

consultants and research collaborators generally have contractual rights to publish data and other proprietary information,

subject to review by the trial sponsor. Publications by us, or by investigators, scientific consultants, previous employees,

research collaborators or others, either with permission or in contravention of the terms of their agreements with us or with

our past or future collaborators, may impair our ability to obtain patent protection or protect proprietary information, which

could have a material adverse effect on our business and might cause us to cease operations.

Much of the information and know-how that is critical to our business is not patentable, and we may not be able to

prevent others from obtaining this information and establishing competitive enterprises.

In addition to patent and trademark protection, we rely on trade secrets to protect our proprietary

technology, especially in circumstances in which we believe patent protection is not appropriate or available. We attempt to

protect our proprietary technology in part by entering into confidentiality agreements with our employees, consultants,

collaborators and contractors. However, certain consultants and third parties with whom we have business relationships,

and to whom in some cases we have disclosed trade secrets and other proprietary knowledge, may also provide services to

other parties in the medical device/pharmaceutical industry, including companies, universities and research organizations

that are developing competing products. In addition, some of our former employees who were exposed to certain of our

trade secrets and other proprietary knowledge in the course of their employment may seek employment with, and become

employed by, our competitors. We cannot provide assurance that these agreements will not be breached, that we would

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have adequate remedies for any breach, or that our trade secrets will not otherwise become known or be independently

discovered by competitors, any of which would harm our business significantly.

Trade secret protection does not prevent independent discovery of the technology or proprietary

information or use of the same. Competitors may independently duplicate or exceed our technology in whole or in part. If

any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right

to prevent them, or those to whom they communicate it, from using that technology or information to compete with us in

countries where we do not have patent protection.

RISKS RELATED TO MANAGING OUR GROWTH AND OTHER BUSINESS OPERATIONS

Our strategic restructuring plan and the associated workforce reduction implemented in December 2025 may not result

in anticipated savings and long-term value creation, could result in total costs and operating expenses that are greater

than expected and could disrupt our business.

In connection with our strategic restructuring plan announced in December 2025, we implemented a

workforce reduction, representing approximately one-third of our workforce prior to the reduction in headcount. We may

not realize, in full or in part, the anticipated benefits on our 2026 operating expenses from our restructuring efforts due to

unforeseen difficulties, delays or unexpected costs. We incurred approximately $17.0 million in restructuring and

restructuring-related charges for the year ended December 31, 2025, primarily consisting of one-time employee severance

payments, healthcare and related benefits, and other employee-related costs, and we estimate the workforce reduction will

be substantially completed in the first quarter of 2026. If we are unable to realize the expected operational efficiencies and

cost savings from the restructuring, our operating results and financial condition could be adversely affected. We also

cannot guarantee that we will not have to undertake additional workforce reductions or restructuring activities in the future.

Furthermore, our workforce reduction may be disruptive to our operations, or could yield unanticipated consequences, such

as attrition beyond planned staff reductions, or disruptions in our day-to-day operations. Our workforce reductions could

also harm our ability to attract and retain qualified management, scientific, clinical, and manufacturing personnel who are

critical to our business. Any failure to attract or retain qualified personnel could prevent us from successfully developing

and commercializing our product candidates in the future, if approved.

We may be unable to successfully retain or recruit key personnel to support the commercialization and further

development of RYTELO or to otherwise successfully manage our growth.

Our ability to successfully commercialize RYTELO in the U.S. 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.

We face intense competition for qualified individuals from numerous pharmaceutical, biopharmaceutical

and biotechnology companies, as well as academic and other research institutions, and competition in our geographic

regions is particularly intense. The substantial risks and uncertainties related to our commercialization and further

development of RYTELO, and the risks and uncertainties regarding our future business viability could have an adverse

impact on our ability to retain and recruit qualified personnel. We may also face higher than expected personnel costs in

order to attract new personnel due to shortages in qualified applicants, or to maintain our current management and

personnel due to the increased number of opportunities in the biotechnology sector. If we are unable to successfully retain,

motivate and incentivize our existing personnel, or to attract, assimilate and retain other highly qualified personnel in the

future on acceptable terms, our ability to commercialize and further develop RYTELO will be impaired, and our business

and the price of our common stock would be adversely impacted.

In addition, our personnel are currently performing their duties in multiple jurisdictions, and if we are

unable or fail to comply with employment, tax, benefits and other laws in such jurisdictions, we may face penalties, fines or

litigation.

Our future financial performance and our ability to develop, manufacture and commercialize RYTELO

depends, in part, on our ability to effectively manage any future growth. Our management may have to divert financial and

other resources, as well as devote a substantial amount of time, to managing growth activities, such as enhancing

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operational, financial and management processes and systems. 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.

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, 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 October 2025, we

appointed a new EVP, Chief Commercial Officer and in November 2024, we appointed a new EVP of Research and

Development. Additionally, in connection with our strategic restructuring plan announced in December 2025, we

implemented a workforce reduction, representing approximately one-third of our workforce prior to the reduction in

headcount.  Changes to company strategy, which can often times occur with the appointment of new executives and

departure of prior 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 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 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.

Although we intend  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.

We intend to develop RYTELO broadly for hematologic malignancies, and to continue to commercialize,

market and sell RYTELO in the U.S. for certain patients with lower-risk MDS ourselves. At this time, we do not plan to

commercialize RYTELO independently in the EU (or in any other regions outside of the U.S. where RYTELO may be

approved for marketing in the future). Accordingly, we plan to work with experienced third parties for the

commercialization and marketing of RYTELO in the EU, including on critical path activities for the planned launch of

RYTELO in the EU, such as reimbursement, Health Technology Assessment, or HTA, submissions, market access and

distribution, and we may otherwise seek collaborative 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. We face

significant competition in seeking appropriate collaborative partners, and these potential collaborative arrangements are

complex and time consuming to negotiate, document and implement. 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. In this regard, collaborative arrangements with third parties may require us to

relinquish material rights, including revenue from commercialization, or assume material ongoing development obligations

that we would have to fund or otherwise support.

If we are unable to negotiate collaborative arrangements, we may have to:

•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; or

•increase our expenditures and undertake development or commercialization activities at our

own expense, which will require additional capital than our current resources.

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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:

•the increased complexity and costs inherent in managing international operations in

geographically disparate locations;

•challenges and costs of complying with diverse regulatory, financial and legal requirements,

which are subject to change at any time;

•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, including in connection with new Trump administration changes;

•compliance with tax, employment, immigration and labor laws for employees living or

traveling abroad;

•challenges inherent in efficiently managing employees in diverse geographies, including the

need to adapt systems, policies, benefits and compliance programs to differing labor and

other regulations;

•natural disasters, political and economic instability, including terrorism and civil and

political unrest, outbreak of health epidemics, and the resulting global economic and social

impacts; and

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

We may experience additional risks related to operating outside of the U.S. that could materially adversely affect our

business.

We have employees located outside of the U.S., conduct clinical trials outside of the U.S., and are pursuing

paths to make  RYTELO available to LR-MDS patients outside of the U.S., including in the EU, 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 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;

•increased taxes outside of the U.S., including withholding and payroll taxes;

•significant foreign currency fluctuations, which could result in increased operating expenses

and reduced revenue, and other obligations incident to doing business in another country;

•difficulties staffing and managing operations outside of the U.S.;

•complexities associated with managing multiple payor reimbursement regimes and

government payors in foreign countries;

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

•potential liability under the Foreign Corrupt Practices Act of 1977 or comparable

regulations outside of the U.S.; and

•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 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

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trade agreements, scope and nature of tariffs in the future, including as a result of litigation or or other challenges, 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 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.”

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 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. These and other

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

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. sanctions. The 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. Notwithstanding the U.S. Supreme Court’s recent decision invalidating tariffs

imposed under the International Emergency Economic Powers Act, the magnitude and impact of tariffs are uncertain and

are subject to a variety of factors, including the effective date and duration of additional tariffs, changes in the amount,

scope and nature of tariffs in the future, including as a result of litigation or other challenges, any retaliatory tariffs that

other countries may impose in response to tariffs levied by the United States and any mitigating actions that may become

available.

The ongoing trade tensions between the U.S. and other jurisdictions have resulted in multiple rounds of

tariffs and potential tariffs affecting pharmaceuticals and pharmaceutical ingredients, including finished drug products,

manufacturing equipment, and related supplies. In April 2025, the U.S. government imposed a 10% baseline global tariff

and in August 2025, the U.S. imposed higher “reciprocal” tariffs on numerous other territories, including EU Member

States and South Korea. While the U.S. Supreme Court recently issued a ruling invalidating tariffs imposed by the Trump

administration under the International Emergency Economic Powers Act, other tariffs imposed by the U.S. government

remain in place, including the 10% global tariff imposed by the Trump administration under Section 122 of the Trade Act

of 1974 following the U.S. Supreme Court decision. Moreover, the Bureau of Industry and Security, U.S. Department of

Commerce, has initiated an investigation to determine whether pharmaceutical ingredients, including finished drug product,

manufactured outside the U.S. pose a national security risk and should be subject to additional tariffs.  Unlike consumer

goods, pharmaceuticals face unique regulatory constraints that make rapid supply chain adjustments particularly difficult

and costly. 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.

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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 significant 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.

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.

Our business exposes us to potential product liability and other risks that are inherent in the testing,

manufacturing and marketing of human therapeutic products. We may become subject to product liability or personal

injury claims related to the commercialization of RYTELO, or claims related to clinical trial conduct, including if the use

of RYTELO is alleged to have injured patients, such as injuries alleged to arise from any hepatotoxicity or hemorrhagic

event associated with the use of RYTELO. We currently have product liability and clinical trial liability insurance that we

believe is adequate, but we may experience losses in excess of our coverage or that are not covered by our insurance, and

we may not be able to maintain this type of insurance for the commercialization of RYTELO, or any of our current or

potential future clinical trials of RYTELO. In addition, this type of insurance may become too expensive for us to afford

because of the highly risky and uncertain nature of commercialization of RYTELO, clinical trials generally and the high

cost of insurance for our business activities. We may be unable to obtain or maintain clinical trial insurance in all of the

jurisdictions where we conduct current or potential future clinical trials. In addition, business liability, product liability and

cybersecurity insurance are becoming increasingly expensive, particularly for biotechnology and pharmaceutical

companies, and the pool of insurers offering insurance coverage to biotechnology and pharmaceutical companies generally

is becoming smaller, making it more difficult to obtain insurance for our business activities at a reasonable price, or at all.

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.

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. 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 Dabestani v. Geron Corporation, et al., No. 3:25-cv-02507 and Potvin v. Geron Corporation, et al.,

No. 3:25-cv-02563, 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. 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 August 8, 2025, lead plaintiffs filed a consolidated

amended complaint. On October 7, 2025, we filed our motion to dismiss the consolidated amended complaint.  A hearing

on the motion to dismiss is scheduled for March 19, 2026.

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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., No. 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. 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.

On August 29, 2025, a purported stockholder made a demand on our board of directors to commence a civil

action against certain of our current and former directors for breaching their fiduciary duties and violating the securities

laws by issuing allegedly false and misleading statements concerning the commercial potential of RYTELO.  On

September 19, 2025, the board of directors responded that it would defer a final decision on the demand given the other

pending derivative lawsuits and the Securities Class Action.  On October 7, 2025, the purported stockholder filed a suit in

the United States District Court for the Northern District of California, captioned Jae Hyung v. Bir, et al., No. 3:25-

cv-08575.  The derivative lawsuit names certain of our current and former directors and officers. The allegations in the

derivative lawsuit are substantially similar to the Securities Class Action and the aforementioned derivative lawsuits.  The

plaintiffs seek damages and an award of reasonable costs, including attorneys’ and experts’ fees. On January 23 and

February 19, 2026, respectively, two additional purported stockholders each made a similar demand on our board of

directors.

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 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 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. 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 judgment 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

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. We may become involved in performance or other disputes with the CROs we have retained to support

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our clinical development activities, or with other third parties such as service providers, vendors, manufacturers, suppliers

or consultants. If we are unable to resolve those conflicts on terms that are satisfactory to all parties, we may become

involved in litigation brought by or against us.

Lawsuits are subject to inherent uncertainties, and defense and disposition costs depend upon many

unknown factors. Despite the availability of insurance, we may incur substantial legal fees and costs in connection with

litigation. Lawsuits could result in judgments against us that require us to pay damages, enjoin us from certain activities, or

otherwise negatively affect our legal or contractual rights, which could have a significant adverse effect on our business. In

addition, the inherent uncertainty of such litigation could lead to increased volatility in our stock price and a decrease in the

value of our stockholders’ investment in our securities.

We are subject to U.S. and certain foreign export and import controls, sanctions, embargoes, anti-corruption laws, and

anti-money laundering laws and regulations. Compliance with these legal standards could impair our ability to compete

in domestic and international markets. We can face criminal liability and other serious consequences for violations,

which can harm our business.

We are subject to export control and import laws and regulations, and other state and national anti-bribery

and anti-money laundering laws in the countries in which we conduct activities. Anti-corruption laws are interpreted

broadly and prohibit companies and their employees, agents, contractors, and other collaborators from authorizing,

promising, offering, or providing, directly or indirectly, improper payments or anything else of value to recipients in the

public or private sector. We may engage third parties to sell our products outside the U.S., to conduct clinical trials, and/or

to obtain necessary permits, licenses, patent registrations, and other regulatory approvals. We have direct or indirect

interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other

organizations. We can be held liable for the corrupt or other illegal activities of our employees, agents, contractors, and

other collaborators, even if we do not explicitly authorize or have actual knowledge of such activities. Any violations of the

laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss

of export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and

other consequences.

RISKS RELATED TO INFORMATION TECHNOLOGY SYSTEMS, DATA SECURITY AND DATA PRIVACY

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; litigation; fines and penalties; a disruption of our business operations, including our clinical trials;

reputational harm; loss of revenue and profits; and other adverse consequences.

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 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 the initial cyber security assessments that we conduct for critical service providers and contractual duties and

obligations, we have limited ability to control or monitor third parties’ safeguards and actions related to such matters.

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 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.

Future or past business transactions, such as acquisitions or integrations, could expose us to additional

cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or

integrated entities’ systems and technologies. 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.

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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,

“hacktivists,” organized criminal threats actors, or internal bad actors, personnel, 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 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, or remediate and recover compromised systems in a timely manner.

Such incidents or threats may result in unauthorized, unlawful or accidental loss, corruption, access,

modification, destruction, alteration, acquisition or disclosure of sensitive 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 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. 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 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, 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.

In addition to experiencing a security incident, third parties may gather, collect, or infer sensitive

information about us from public sources, data brokers, or other means that reveals competitively sensitive details about

our organization and could be used to undermine our competitive advantage or market position. Additionally, sensitive

information of the Company could be leaked, disclosed, or revealed as a result of or in connection with our employees’,

personnel’s, or vendors’ use of generative AI technologies.

Many of our contracts with relevant stakeholders include obligations relating to the safeguard of sensitive

information, and a breach could lead to claims against us by such stakeholders. 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,

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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. While we do maintain cyber liability

insurance, our insurance coverages may not be sufficient in type or amount to cover us against any such losses, claims, or

liabilities related to security breaches, cyber-attacks, cyber intrusion, or other related breaches or disruptions.

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 (or the third parties with whom we work) actual or perceived failure to comply with such obligations could lead to

regulatory investigations or actions; litigation; fines and penalties; disruptions of our business operations; reputational

harm; loss of revenue and profits; and other adverse business impacts.

In the ordinary course of business, we process personal data and other sensitive data, including proprietary

and confidential business data, trade secrets, intellectual property, clinical trial participant data, and other sensitive third-

party data. 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 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. This evolution may create uncertainty in our business; affect us or our collaborators’, service providers’ and

contractors’ ability to operate in certain jurisdictions or to collect, store, transfer, use and share personal data; necessitate

the acceptance of more onerous obligations in our contracts; result in liability; or impose additional costs on us. These

obligations may necessitate changes to our information technologies, systems, and practices and to those of any third

parties that process personal data on our behalf. In addition, these obligations may require us to change our business model.

Outside the U.S., an increasing number of laws, regulations, and industry standards apply to data privacy

and security. 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. The EEA and other

jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries. In

particular, the EEA and the UK have significantly restricted the transfer of personal data to the U.S. and other countries

whose privacy laws it believes are inadequate. Other jurisdictions may adopt similarly stringent interpretations of their data

localization and cross-border data transfer laws. Although there are currently various mechanisms that may be used to

transfer personal data from the EEA and UK to the U.S. in compliance with law, such as the EEA and UK’s standard

contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S. Data Privacy

Framework and the UK extension thereto, these mechanisms are subject to legal challenges, and there is no assurance that

we can satisfy or rely on these measures to lawfully transfer personal data to the U.S. 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. Additionally, companies that transfer personal

data out of the EEA and UK to other jurisdictions, particularly to the U.S., 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. For example, HIPAA, as amended by HITECH, imposes specific

requirements relating to the privacy, security, and transmission of individually identifiable health data. 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

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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 data of business representatives and employees. Other

states have also enacted data privacy and security laws. For example, Virginia passed the Consumer Data Protection Act,

and Colorado passed the Colorado Privacy Act, both of which differ from the CPRA and became effective in 2023. If we

become subject to new data privacy and security laws, at the state level or otherwise, the risk of enforcement action against

us could increase because we may become subject to additional obligations, and the number of individuals or entities that

can initiate actions against us may increase.

In Europe, the Network and Information Security Directive (“NIS2”) regulates resilience and incident

response capabilities of entities operating in a number of sectors, including the health sector. Non-compliance with NIS2

may lead up to administrative fines of a maximum of 10 million Euros or up to 2% of the total worldwide revenue of the

preceding fiscal year.

Our employees and personnel use generative AI technologies to perform their work, and the disclosure and

use of personal data in generative AI technologies is subject to various privacy laws and other privacy obligations.

Governments have passed and are likely to pass additional laws regulating generative AI. Our use of this technology could

result in additional compliance costs, regulatory investigations and actions, and lawsuits. 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 are contractually subject to industry standards adopted by

industry groups and we are, and may become in the future, subject to such obligations. 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. 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. Regulators in the

U.S. 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 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; litigation;

additional reporting requirements and/or oversight; bans on processing personal data; orders to destroy or not use personal

data; and imprisonment of company officials. Any of these events could have a material adverse effect on our reputation,

business, or financial condition, including: interruptions or stoppages in our business operations including, as relevant,

clinical trials; inability to process personal data or to operate in certain jurisdictions; limited ability to continue to develop

or commercialize RYTELO; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or

revision or restructuring of our operations.

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.

Historically, our stock price has been extremely volatile. Between January 1, 2015 and December 31, 2025,

our stock has traded as high as $6.38 per share and as low as $0.89 per share. Between January 1, 2025 and December 31,

2025, the price has ranged between a high of $3.60 per share and a low of $1.07 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 and market opportunity for future sales of RYTELO;

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•announcements regarding regulatory approval or non-approval of RYTELO in any other

jurisdictions or indications, or specific label indications for RYTELO, or restrictions,

warnings or limitations in its use;

•announcements regarding the research and development of imetelstat, 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, or our inability to successfully continue the development of imetelstat;

•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;

•adverse developments concerning our manufacturers, including our inability to obtain

adequate product supply for RYTELO or inability to do so at acceptable prices;

•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 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;

•announcements of significant acquisitions, strategic partnerships, collaborations, joint

ventures or capital commitments by us or our competitors;

•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,

•perceptions of the biotechnology and pharmaceutical industry by the public, legislature,

regulators and the investment community;

•our failure to meet the estimates and projections of the investment community or general

public;

•publication of commentary, articles or research reports about us or our industry, or positive

or negative recommendations or withdrawal of research coverage by securities analysts,

bloggers, news media or other third parties;

•actual or expected sales of common stock by stockholders;

•announcements of or developments concerning pending and potential future litigation;

•actions instituted by activist shareholders or others;

•other events or factors that are beyond our control; and

•the occurrence of any other risks and uncertainties discussed under the heading “Risk

Factors.”

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. 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, may 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

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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 $0.89 per share through February 20, 2026. 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; and

• 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.

Provisions of our charter documents and bylaws may make it substantially more difficult for a third party to

acquire control of us and may prevent changes in our management, including provisions that prevent stockholders from

taking actions by written consent, divide the board of directors into separate classes with terms of office that are structured

to prevent all of the directors from being elected in any one year and set forth procedures for nominating directors and

submitting proposals for consideration at stockholders’ meetings.

In addition, our certificate of incorporation provides our board of directors with the authority to issue up to

3,000,000 shares of undesignated preferred stock and to determine or alter the rights, preferences, privileges and

restrictions granted to or imported upon these shares without further vote or action by our stockholders. The issuance of

shares of preferred stock may delay or prevent a change in control transaction without further action by our stockholders.

As a result, the market price of our common stock may be adversely affected.

If in the future, we issue preferred stock that has preference over our common stock with respect to the

payment of dividends or upon our liquidation, dissolution or winding up, or if we issue preferred stock with voting rights

that dilute the voting power of our common stock, the rights of holders of our common stock or the market price of our

common stock could be adversely affected.

Provisions of Delaware law may also inhibit potential acquisition bids for us or prevent us from engaging

in business combinations. In addition, we have individual severance agreements with our executive officers and a

company-wide severance plan, either of which could require a potential acquirer to pay a higher price. Either collectively

or individually, these provisions may prevent holders of our common stock from benefiting from what they may believe are

the positive aspects of acquisitions and takeovers, including the potential realization of a higher rate of return on their

investment from these types of transactions.

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The exclusive forum provisions in our amended and restated bylaws could limit our stockholders’ ability to obtain a

favorable judicial forum for disputes with us or any of our directors, officers, or employees, or the underwriters of any

offering giving rise to such claim, which may discourage lawsuits with respect to such claims.

Our amended and restated bylaws provide that, unless we consent to the selection of an alternative forum,

the Court of Chancery of the State of Delaware (or, if and only if the Court of Chancery of the State of Delaware lacks

subject matter jurisdiction, any state court located within the State of Delaware or, if and only if all such state courts lack

subject matter jurisdiction, the federal district court for the District of Delaware) will be the sole and exclusive forum for:

•any derivative claim or cause of action or proceeding brought on our behalf;

•any claim or cause of action for breach of a fiduciary duty owed by any of our current or

former directors, officers or other employees, or our stockholders, to us or to our

stockholders;

•any claim or cause of action against us or any of our current or former directors, officers or

other employees, or our stockholders, arising pursuant to any provision of the General

Corporation Law of the State of Delaware, our certificate of incorporation, or our bylaws;

•any claim or cause of action seeking to interpret, apply, enforce or determine the validity of

our certificate of incorporation or bylaws;

•any claim or cause of action as to which the General Corporation Law of the State of

Delaware confers jurisdiction on the Court of Chancery of the State of Delaware; or

•any claim or cause of action against us or any of our current or former directors, officers or

other employees, or our stockholders, governed by the internal affairs doctrine or otherwise

related to our internal affairs.

In addition, Section 22 of the Securities Act creates concurrent jurisdiction for federal and state courts over

all claims brought to enforce any duty or liability created by the Securities Act of 1933, as amended, or the Securities Act,

or the rules and regulations thereunder. Our amended and restated bylaws provide that the federal district courts of the

United States of America will, to the fullest extent permitted by law, be the exclusive forum for resolving any complaint

asserting a cause of action arising under the Securities Act, or the Federal Forum Provision, including for all causes of

action asserted against any defendant named in such complaint. For the avoidance of doubt, this provision is intended to

benefit and may be enforced by us, our officers and directors, the underwriters to any offering giving rise to such

complaint, and any other professional entity whose profession gives authority to a statement made by that person or entity

and who has prepared or certified any part of the documents underlying the offering. 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. 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. This may require significant additional costs associated with resolving such action in other

jurisdictions, which costs could be borne by stockholders, and there can be no assurance that the provisions will be

enforced by a court in those other jurisdictions.

Any person or entity purchasing or otherwise acquiring or holding any interest in any of our securities shall

be deemed to have notice of and consented to the exclusive forum provisions in our amended and restated bylaws,

including the Federal Forum Provision. These provisions could limit a stockholder’s ability to bring a claim in a judicial

forum that it finds favorable for disputes with us or any of our directors, officers, or other employees, or our stockholders

or the underwriters of any offering giving rise to such claims, which may discourage lawsuits with respect to such claims.

Furthermore, if a court were to find the exclusive forum provisions contained in our bylaws to be inapplicable or

unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions,

which could have a material and adverse impact on our business and our financial condition.

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We do not intend to pay cash dividends on our common stock in the foreseeable future.

We do not anticipate paying cash dividends on our common stock in the foreseeable future. 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 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.

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. Misconduct by these parties

could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violate the

FDA’s or similar international regulatory authorities’ regulations, including those laws requiring the reporting of true,

complete and accurate information; manufacturing standards; healthcare fraud and abuse laws and regulations; or laws that

require the true, complete and accurate reporting of financial information or data. Specifically, sales, marketing and

business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud,

kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of

pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business

arrangements.

Activities subject to these laws also involve the improper use or misrepresentation of information obtained

in the course of clinical trials or creating fraudulent data in our non-clinical studies or clinical trials, which could result in

regulatory sanctions and serious harm to our reputation. It is not always possible to identify and deter misconduct by our

employees and third parties, and the precautions we take to detect and prevent this activity may not be effective in

controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or

lawsuits stemming from a failure to be in compliance with such laws or regulations. Additionally, we are subject to the risk

that a person could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against

us, and we are not successful in defending ourselves or asserting our rights, those actions could adversely affect our

business, financial condition, results of operations or prospects through:

•the imposition of civil, criminal and administrative penalties, damages and monetary fines;

•possible exclusion from participation in Medicare, Medicaid and other federal healthcare

programs;

•contractual damages;

•reputational harm;

•diminished potential profits and future earnings; and

•curtailment of our operations.

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. Our Annual Reports on Form 10-K must contain

an annual assessment by management of the effectiveness of our internal control over financial reporting and must include

disclosure of any material weaknesses in internal control over financial reporting that we have identified. In addition, our

independent registered public accounting firm must provide an opinion annually on the effectiveness of our internal control

over financial reporting. As described further below, we identified a material weakness in our internal control over

financial reporting that existed as of September 30, 2025, which we remediated as of December 31, 2025. However, in the

future, any testing by us conducted in connection with Section 404, or any testing by our independent registered public

accounting firm, may reveal additional deficiencies in our internal control over financial reporting that are deemed to be

material weaknesses or that may require prospective or retroactive changes to our financial statements or identify other

areas for further attention or improvement.

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The requirements of Section 404 are ongoing and also apply to future years. We expect that our internal

control over financial reporting will continue to evolve as our business develops, including in connection with our

commercialization of RYTELO. Although we are committed to continue to improve our internal control processes and we

will continue to review our internal control over financial reporting, any control system, regardless of how well designed,

operated and evaluated, can provide only reasonable, not absolute, assurance that its objectives will be met. .

Therefore, we cannot assure you that additional 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.

If material weaknesses or other significant deficiencies continue to occur, such weaknesses or deficiencies could result in

misstatements of our results of operations, restatements of our financial statements, a decline in our stock price, or other

material adverse effects on our business, reputation, results of operations, financial condition or liquidity.

We have previously identified a material weakness in our internal control over financial reporting and may identify

additional material weaknesses in the future or otherwise fail to maintain an effective system of internal controls, which

may result in material misstatements of our consolidated financial statements or cause us to fail to meet our periodic

reporting obligations.

A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial

reporting, such that there is a reasonable possibility that a material misstatement of a company’s annual or interim financial

statements will not be prevented or detected on a timely basis. We previously identified a material weakness in internal

control related to the design and operation of certain Information Technology General Controls, or ITGCs, related to user

access and program change management for our Enterprise Resource Planning and payment processing systems.

Consequently, IT application controls and IT dependent manual business process controls that rely upon information from

these systems, were also deemed ineffective. Although the material weakness identified did not result in any material

misstatements in our consolidated financial statements for the periods presented in this Report and there were otherwise no

changes to our previously issued financial statements, our management concluded that these control deficiencies existed as

of September 30, 2025 and constitute a material weakness. Accordingly, our internal control over financial reporting and

our disclosure controls and procedures were not effective as of September 30, 2025. While we subsequently remediated

this material weakness as of December 31, 2025, we cannot assure you that there will not be material weaknesses or

significant deficiencies in our internal control over financial reporting in the future. Our failure to implement and maintain

effective internal control over financial reporting could result in errors in our consolidated financial statements that could

result in a restatement of our previously issued financial statements and could cause us to fail to meet our periodic reporting

obligations, any of which could diminish investor confidence in us and cause a decline in the price of our common stock

Changes in tax laws or regulations that are applied adversely to us or our customers may have a material adverse effect

on our business, cash flow, financial condition or results of operations.

New income, sales, use, excise or other tax laws, statutes, rules, regulations or ordinances could be enacted

at any time, which could affect the tax treatment of our domestic and foreign sales and earnings. Any new taxes could

adversely affect our domestic and international business operations and our business and financial condition. Further,

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

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 tax reform legislation

could have a material impact on the value of our deferred tax assets, could result in significant one-time charges, and could

increase our future United States tax expense.

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, federal net operating losses incurred in

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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. 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.