gern-20251231
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
xANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the Fiscal Year Ended December 31, 2025
or
oTRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from ______ to ______.
Commission File Number: 000-20859
GERON CORPORATION
(Exact name of registrant as specified in its charter)
Registrant’s telephone number, including area code: (650) 473-7700
Securities registered pursuant to Section 12(b) of the Act:
Common Stock, $0.001 par value GERN The Nasdaq Stock Market LLC
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well‐known seasoned issuer, as defined in Rule 405 of the Securities Act. Yesx No o
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes oNo
x
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities
Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)
has been subject to such filing requirements for the past 90 days. Yesx No o
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted
pursuant to Rule 405 of Regulation S‐T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant
was required to submit such files). Yesx No o
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non‐accelerated filer, a smaller
reporting company, or emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting
company,” and “emerging growth company” in Rule 12b‐2 of the Exchange Act.
Large accelerated filer x Accelerated filer o
Non-accelerated filer o Smaller reporting company o
Emerging growth company o
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for
complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the
effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the
registered public accounting firm that prepared or issued its audit report. x
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the
registrant included in the filing reflect the correction of an error to previously issued financial statements. o
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based
compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). o
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b‐2 of the Act). Yes o No x
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The aggregate market value of voting and non‐voting common equity held by non‐affiliates of the registrant was approximately
$860,500,000 based upon the closing price of the registrant’s common stock on June 30, 2025 on the Nasdaq Global Select Market. The
calculation of the aggregate market value of voting and non‐voting common equity held by non‐affiliates of the registrant excludes shares of
common stock held by each officer, director and stockholder that the registrant concluded were affiliates on that date. This determination of
affiliate status is not necessarily a conclusive determination for other purposes.
As of February 20, 2026, there were640,544,661 shares of common stock outstanding.
DOCUMENTS INCORPORATED BY REFERENCE:
Document Form 10‐KParts
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TABLE OF CONTENTS
Page
PART I
Item 1. Business 5
Item 1A. Risk Factors 26
Item 1B. Unresolved Staff Comments 77
Item 1C. Cybersecurity 77
Item 2. Properties 78
Item 3. Legal Proceedings 79
Item 4. Mine Safety Disclosures 79
PART II
Item 6. [Reserved] 80
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 96
Item 8. Financial Statements and Supplementary Data 97
Item 9A. Controls and Procedures 139
Item 9B. Other Information 140
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 140
PART III
Item 10. Directors, Executive Officers and Corporate Governance 141
Item 11. Executive Compensation 141
Item 14. Principal Accountant Fees and Services 142
PART IV
Item 15. Exhibits and Financial Statement Schedules 143
RYTELO® and other trademarks or service marks of Geron Corporation appearing in this Annual Report on Form 10-K
(this "Report") are the property of Geron Corporation. This Report contains additional trade names, trademarks and service
marks of others, which are the property of their respective owners. We do not intend our use or display of other companies’
trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, these other
companies.
In this Report, unless otherwise indicated or the context otherwise requires, “Geron,” “the registrant,” “we,” “us,” and
“our” refer to Geron Corporation, a Delaware corporation, and its wholly owned subsidiaries, Geron UK Limited, a United
Kingdom company, and Geron Netherlands, B.V., a Dutch company.
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Forward‐Looking Statements
This Report, including “Business” in Part I, Item 1 of this Report and “Management’s Discussion and
Analysis of Financial Condition and Results of Operations” in Part II, Item 7 of this Report, contains forward‐looking
statements that involve risks and uncertainties, as well as assumptions that, if they never materialize or prove incorrect,
could cause the results of Geron Corporation, or Geron or the Company, to differ materially from those expressed or
implied by such forward‐looking statements. All statements other than statements of historical fact are statements that
could be deemed forward‐looking statements. In some cases, forward‐looking statements can be identified by the use of
terminology such as “may,” “expects,” “plans,” “intends,” “will,” “should,” “could,” “projects,” “believes,” “predicts,”
“anticipates,” “estimates,” “potential,” “seek,” or “continue” or the negative thereof or other comparable terminology. The
risks and uncertainties referred to above include, without limitation, risks and uncertainties related to: (a) whether we are
successful in commercializing RYTELO (imetelstat) for the treatment of certain patients with lower-risk myelodysplastic
syndromes, or lower-risk MDS, with transfusion dependent anemia; (b) whether the U.S. Food and Drug Administration, or
FDA, or European Commission, or EC, will approve RYTELO for other indications on the timelines that may be expected,
or at all; (c) our pursuit of paths to make RYTELO available to eligible patients with lower-risk MDS outside of the U.S.,
including in the European Union, or EU; (d) whether we overcome potential delays and other adverse impacts caused by
enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in
order to have the financial resources for and meet expected timelines and planned milestones; (e) whether regulatory
authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (f) whether
RYTELO may cause, or have attributed to it, adverse events that could delay or prevent the commencement and/or
completion of clinical trials, impact its regulatory approval, or limit its commercial potential; (g) whether the IMpactMF
Phase 3 trial for relapsed/refractory myelofibrosis, or R/R MF, has a positive outcome and demonstrates safety and
effectiveness to the satisfaction of the FDA and international regulatory authorities, and whether our projected rates for
death events differ from actual rates, which may cause the planned interim and final analyses to occur later than
anticipated; (h) whether any future safety or efficacy results of RYTELO treatment cause its benefit-risk profile to become
unacceptable; (i) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the
malignant stem and progenitor cells of the underlying disease; (j) whether we meet our post-marketing requirements and
commitments for RYTELO; (k) whether there are failures or delays in manufacturing or supplying sufficient quantities of
RYTELO or other clinical trial materials that impact commercialization of RYTELO or the continuation of the IMpactMF
trial and other clinical trials; (l) whether we are able to establish and maintain effective sales, marketing and distribution
capabilities, obtain adequate coverage and third-party payor reimbursement, and achieve adequate acceptance in the
marketplace; (m) whether we are able to obtain and maintain the exclusivity terms and scopes provided by patent and
patent term extensions, regulatory exclusivity, and have freedom to operate; (n) that we may be unable to successfully
commercialize RYTELO due to competitive products, or otherwise; (o) that we may not be able to establish partnerships to
commercialize RYTELO in the international markets where RYTELO may be approved for marketing; (p) whether we
stay in compliance with and satisfy our obligations under our debt and synthetic royalty agreements; and (q) the impact of
general economic, industry or political climate in the U.S. or internationally and the effects of macroeconomic conditions
on our business and business prospects, financial condition and results of operations; as well as other risks that are
described herein and that are otherwise described from time to time in our Securities and Exchange Commission reports
including, but not limited to, the factors described in “Risk Factors,” in Part I, Item 1A of this Report. Geron assumes no
obligation for and except as required by law, disclaims any obligation to update these forward‐looking statements to reflect
future information, events or circumstances.
Risk Factor Summary
Below is a summary of material factors that make an investment in our common stock speculative or risky.
Importantly, this summary does not address all of the risks and uncertainties that we face. You should understand that it is
not possible to predict or identify all such factors. Consequently, you should not consider this summary to be a complete
discussion of all potential risks or uncertainties that may substantially impact our business. Additional discussion of the
risks and uncertainties summarized in this risk factor summary, as well as other risks and uncertainties that we face, can be
found under “Risk Factors” in Part I, Item 1A of this Report. The summary below is qualified in its entirety by that more
complete discussion of such risks and uncertainties. Moreover, we operate in a competitive and rapidly changing
environment. New factors emerge from time to time and it is not possible to predict the impact of all of these factors on our
business, financial condition or results of operations. You should consider carefully the risks and uncertainties described
under “Risk Factors” in Part I, Item 1A of this Report as part of your evaluation of an investment in our common stock.
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Risks Related to the Commercialization of RYTELO® (Imetelstat)
•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.
•Although we have established commercial operations and sales, marketing and distribution
infrastructure for RYTELO, we have limited experience in sustaining and scaling these
operations and our commercialization efforts may be unsuccessful or less successful than
anticipated.
•If we are unable to continue to execute on our sales, marketing and distribution plans to
commercialize RYTELO, we may be unable to generate meaningful product revenue.
•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.
•We will be subject to pricing and reimbursement regulations in the European Union, or EU,
which may materially affect our ability to commercialize and receive reimbursement
coverage for RYTELO in the EU.
Risks Related to Regulatory Approval of RYTELO
•We may be unable to maintain regulatory approvals for RYTELO in the U.S. and the EU
for lower-risk MDS, which would severely and adversely affect our business and business
prospects, and might cause us to cease operations.
•Our regulatory 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.
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.
Risks Related to the Further Development of Imetelstat
•We cannot be certain that we will be able to continue to develop imetelstat or advance it in
clinical trials, or that we will be able to receive regulatory approval for imetelstat in any
other indications in the U.S., the EU or any other region, on a timely basis or at all.
•RYTELO may cause, or have attributed to it, undesirable or unintended side effects or other
adverse events that could halt or limit its further commercialization, delay or prevent its
regulatory approval in any other jurisdiction or indication, or cause us to delay or terminate
our clinical trials.
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•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.
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.
Risks Related to Our Operating Results, Financial Position and Need for Additional Capital
•We have a history of net losses and may not achieve consistent future profitability for some
time, if ever.
•Our failure to obtain additional capital, if and when needed, would force us to further delay,
reduce or eliminate the further development of RYTELO, or to halt the commercialization
of RYTELO, any of which would severely and adversely affect our financial results,
business and business prospects, and might cause us to cease operations.
Risks Related to 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.
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.
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.
•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, are costly to defend, 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.
Calculation of Aggregate Market Value of Non‐Affiliate Shares
For purposes of calculating the aggregate market value of shares of our common stock held by
non‐affiliates as set forth on the cover page of this Report, we have assumed that all outstanding shares are held by
non‐affiliates, except for shares held directly or indirectly by each of our executive officers and directors. In the case of 5%
or greater stockholders, we have not deemed any such stockholders to be affiliates given the lack of facts and
circumstances that would indicate that any such stockholders exercise, or have the ability to exercise, any control over
Geron. These assumptions should not be deemed to constitute an admission that all executive officers and directors are, in
fact, affiliates of Geron, or that there are no other persons who may be deemed to be affiliates of Geron. Further
information concerning shareholdings of our executive officers, directors and principal stockholders is incorporated by
reference in Part III, Item 12 of this Report.
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PART I
ITEM 1.BUSINESS
Company Overview
We are a commercial-stage biopharmaceutical company aiming to change lives by changing the course of
blood cancer. Our first-in-class telomerase inhibitor, RYTELO® (imetelstat), harnesses Nobel Prize winning science in a
treatment that scientific evidence suggests reduces proliferation of malignant cells, allowing production of new healthy
cells, which we believe drives differentiated clinical benefits, potentially altering the underlying course and modifying the
disease of these hematologic malignancies.
We commercially launched RYTELO in the U.S. in June 2024 following its approval by the U.S. Food and
Drug Administration, or FDA, on June 6, 2024 for the treatment of adult patients with low- to intermediate-1 risk
myelodysplastic syndromes, or lower-risk MDS, with transfusion-dependent, or TD, anemia requiring four or more red
blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-
stimulating agents, or ESAs. Lower-risk MDS is a progressive blood cancer with high unmet need, where many patients
with anemia become dependent on red blood cell transfusions, which can be associated with clinical consequences and
decreased quality of life. We believe that the results of our Phase 3 clinical trial, IMerge, in LR-MDS, favorable FDA label
and National Comprehensive Cancer Network, or NCCN®, Clinical Practice Guidelines in Oncology, or NCCN
Guidelines®, position RYTELO as a potential treatment that can compete for significant market segments in lower-risk
MDS, including second-line ESA ineligible patients regardless of prior treatment or RS status and first-line ESA ineligible
patients.
In March 2025, we received European Commission (EC) approval of RYTELO for the treatment of adults
with TD anemia due to lower-risk MDS without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had
an unsatisfactory response to or are ineligible for ESAs. RYTELO is the first and only telomerase inhibitor approved by the
EC, and the marketing authorization applies to all 27 European Union member states, and Iceland, Norway and
Liechtenstein. We are pursuing paths to make RYTELO available to eligible LR-MDS patients outside of the U.S.,
including in the EU. To enable paid access to patients outside the United States through approved Named Patient Programs
(NPPs), we have partnered with Tanner Pharma, a distributor with broad global reach to support patient access. To date,
our revenues pursuant to NPPs have been minimal.
In addition to lower-risk MDS, we are developing imetelstat for the treatment of other myeloid hematologic
malignancies. Our Phase 3 IMpactMF clinical trial is evaluating imetelstat in patients with intermediate-2 or high-risk
myelofibrosis, or MF, who have relapsed after or are refractory to treatment with a janus associate kinase inhibitor, or JAK
inhibitor, or relapsed/refractory MF, or R/R MF, with overall survival, or OS, as the primary endpoint. As of September
2025, the trial completed enrollment. Based on our current assumptions for event (death) rates in the trial, we expect the
interim analysis for OS in IMpactMF may occur in the second half of 2026 and the final analysis may occur in the second
half of 2028.
We believe that telomerase inhibition with imetelstat represents a novel mechanism of action with unique
benefits in hematologic malignancies and potentially in other tumor types.
Our Strategy
Our strategy is to maximize the value of our first-in-class telomerase inhibitor, RYTELO (imetelstat). This
includes maximizing the commercial opportunity for RYTELO in lower-risk MDS by investing in and executing on our
U.S. commercial efforts. We expect to deliver steady growth by executing across several key imperatives, including driving
new patient starts across all eligible lower-risk MDS population segments, particularly in second-line lower-risk MDS;
reinforcing with health care providers, or HCPs, the value of duration of treatment we have observed with RYTELO;
educating HCPs on appropriate management of patient safety with RYTELO; and leveraging strong payor access for
RYTELO. We are also pursing paths to bring RYTELO to eligible LR-MDS patients outside the United States including
the EU.
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We also plan to progress our development programs that could help identify potential additional indications
for imetelstat. This includes the Phase 3 IMpactMF trial, which, if positive and approved in label expansion, could
significantly increase the RYTELO commercial opportunity. Additionally, we plan to execute on our pipeline programs
and assess the data to understand the potential to develop imetelstat in additional hematologic malignancies and as a
potential combination therapy.
U.S. Commercialization of RYTELO
RYTELO is the first and only FDA approved telomerase inhibitor. The FDA label indicates that RYTELO
is approved for certain ESA ineligible or ESA relapsed/refractory lower-risk MDS patients, regardless of RS status. The
MDS NCCN Guidelines® include imetelstat as a Category 1 preferred option treatment in second-line RS+/RS- ESA-
eligible patients regardless of prior treatment options and as a Category 2A treatment for first-line ESA-ineligible RS+/RS-
patients. In October 2025, the MDS NCCN Guidelines® were updated to change from azacitadine to imetelstat as the
preferred option in first-line RS- ESA-ineligible patients.
Our commercial strategy is designed to ensure that RYTELO reaches eligible patients when they are most
likely to benefit.
Our commercial execution is focused on three core initiatives.
•First, targeted engagement with high-volume accounts that treat earlier-line patients.
•Second, we are investing in what we believe to be the most effective marketing channels.
This includes a strong emphasis on digital, non-personal promotion, and third-party
educational platforms designed to ensure consistent, high-quality messaging across multiple
touchpoints.
•Third, we are executing cross-functionally through effective account management
initiatives.
Our cross-functional customer-facing teams include over 60 key account managers, regional business
directors, regional marketers, regional access directors , and regional medical scientific directors. We offer a wide range of
resources to support access and affordability for eligible RYTELO patients, including our REACH4RYTELO® patient
support program, which provides a range of resources which are designed to support access and affordability to eligible
patients prescribed RYTELO.
Commercialization Plans for RYTELO Outside of the U.S.
In March 2025, we received European Commission approval, of RYTELO for the treatment of adults with
TD anemia due to lower-risk MDS. We are pursuing paths to make RYTELO available to eligible LR-MDS patients
outside of the U.S., including in the EU. We are preparing for the planned commercialization of RYTELO in select EU
markets in 2026. 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.To enable paid access to patients outside the United States through approved
Named Patient Programs (NPPs), we partnered with Tanner Pharma, a distributor with broad global reach to support
patient access. To date, revenues pursuant to NPPs have been minimal.
Background of Telomerase Inhibition in Hematologic Malignancies and Imetelstat Development
In the human body, normal growth and maintenance of tissues occurs by cell division. However, most cells
are only able to divide a limited number of times, and this number of divisions is regulated by telomere length. Telomeres
are repetitions of a deoxyribonucleic acid, or DNA, sequence located at the ends of chromosomes. They act as protective
caps to maintain stability and integrity of the chromosomes, which contain the cell’s genetic material. Normally, every time
a cell divides, the telomeres shorten. Eventually, they shrink to a critically short length, and as a result, the cell either dies
by apoptosis or stops dividing and senesces.
Telomerase is a naturally occurring enzyme that maintains telomeres and prevents them from shortening
during cell division, such as stem cells that must remain immortalized to support normal health. Telomerase consists of at
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least two essential components: a ribonucleic acid, or RNA, template, which binds to the telomere, and a catalytic subunit
with reverse transcriptase activity, which adds a specific DNA sequence to the chromosome ends. The 2009 Nobel Prize
for Physiology or Medicine was awarded to Drs. Elizabeth H. Blackburn, Carol W. Greider and Jack Szostak, former
Geron collaborators, for the discovery of how chromosomes are protected by both telomeres and telomerase.
Telomerase is upregulated in many tumor cells and malignant stem and progenitor cells, enabling the
continued and uncontrolled proliferation of the malignant cells that drive tumor growth and progression. We believe that
inhibiting telomerase may be an attractive approach to treating cancer because it may limit the proliferative capacity of
malignant stem and progenitor cells, which are believed to be important drivers of tumor growth and progression. We and
others have observed in various in vitro, ex vivo and rodent tumor models that inhibiting telomerase: (a) results in telomere
shortening and (b) arrests uncontrolled malignant cell proliferation and tumor growth.
Many myeloid hematologic malignancies, such as essential thrombocythemia, or ET, MF and MDS, have
been shown to arise from malignant stem and progenitor cells that express higher telomerase activity and have shorter
telomeres when compared to normal healthy cells. In vitro studies have suggested that tumor cells with short telomeres
may be especially sensitive to the anti‐proliferative effects of inhibiting telomerase.
Imetelstat, our proprietary telomerase inhibitor which was discovered and developed at Geron, was
designed to inhibit telomerase in malignant cells with continuously upregulated telomerase.
Imetelstat is a lipid conjugated 13‐mer oligonucleotide that we designed to be complementary to and bind
with high affinity to the RNA template of telomerase, thereby directly inhibiting telomerase activity. Imetelstat does not act
as an antisense inhibitor of protein translation. The compound has a proprietary thio‐phosphoramidate backbone, which is
designed to provide resistance to the effect of cellular nucleases, thus conferring improved stability in plasma and tissues,
as well as improved binding affinity to its target. To improve the ability of imetelstat to penetrate cellular membranes, we
conjugated the oligonucleotide to a lipid group. Imetelstat’s IC50, or half maximal inhibitory concentration, is 3 – 9 nM in
cell free assays.
We believe that imetelstat may have the potential to suppress the proliferation of malignant stem and
progenitor cells while transiently affecting normal cells. Early clinical data from a Phase 2 trial of imetelstat in patients
with ET, or the ET Trial, and a pilot study of imetelstat in patients with MF conducted at Mayo Clinic, or the Pilot Study,
suggested that imetelstat inhibits the progenitor cells of the malignant clones believed to be responsible for the underlying
diseases in a relatively select manner, indicating potential disease-modifying activity. These data were published in two
separate articles in a September 2015 issue of The New England Journal of Medicine. In the Phase 2 IMbark study, an
association of survival improvement and reduction in variant allele frequency, or VAF, was observed for high-risk
imetelstat-treated MF patients, results which were published in Journal of Clinical Oncology in 2021. Additionally, in the
Phase 2/3 IMerge study, SF3B1 VAF reduction was associated with longest transfusion independence, or TI, and with 8-
week, 24-week and 1-year TI duration in imetelstat-treated lower-risk MDS patients. These results were published in The
Lancet and at the European Hematology Association, or EHA, annual meeting in 2023.
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Pipeline Chart
Lower-Risk Myelodysplastic Syndromes (MDS)
MDS is a group of blood disorders in which the proliferation of malignant progenitor cells produces
multiple malignant cell clones in the bone marrow resulting in disordered and ineffective production of the myeloid
lineage, which includes red blood cells, white blood cells and platelets. In MDS, bone marrow and peripheral blood cells
may have abnormal, or dysplastic, cell morphology. MDS is frequently characterized clinically by severe anemia, or low
red blood cell counts, and low hemoglobin. In addition, other peripheral cytopenias, or low numbers of white blood cells
and platelets, may cause life‐threatening infections and bleeding. Transformation to acute myeloid leukemia, or AML, is
reported to occur in up to 30% of MDS cases and results in poorer overall survival.
MDS is the most common of the myeloid malignancies. There are approximately 64,000 people in the U.S.
living with the disease and approximately 21,000 reported new cases of MDS in the U.S. every year, according to
Clarivate/DRG MDS Syndicated Report 2025. MDS is primarily a disease of the elderly, with median age at diagnosis
around 70 years. The majority of patients, approximately 70%, fall into what are considered to be the lower-risk groups at
diagnosis, according to the International Prognostic Scoring System, or IPSS, which assigns relative risk of progression to
AML and overall survival by taking into account the presence of a number of disease factors, such as cytopenias and
cytogenetics.
Chronic anemia is the predominant clinical problem in patients who have lower-risk MDS. The current
standard of care for the treatment of lower-risk MDS is the use of ESAs as supportive care, and more recently luspatercept
to improve upon disease-associated chronic anemia. The majority of patients who no longer respond to ESAs or other
available drug therapies become dependent on red blood cell transfusions due to low hemoglobin. Serial red blood cell
transfusions can lead to elevated levels of iron in the blood and other tissues, which the body has no normal way to
eliminate. Iron overload is a potentially dangerous condition. Published studies in patients with MDS have shown that iron
overload resulting from regular red blood cell transfusions is associated with a poorer overall survival and a higher risk of
developing AML.
Phase 3 IMerge Trial in Lower-Risk MDS
Our regulatory approval in the U.S. for certain patients with lower-risk MDS and our EMA submission are
each based on positive data from the IMerge Phase 3 clinical trial. The trial met its primary endpoint of ≥ 8-week red blood
cell transfusion independence rate and a key secondary endpoint of ≥ 24-week red blood cell transfusion independence rate,
demonstrating highly statistically significant (i.e., p<0.001 for both) and clinically meaningful benefits with imetelstat
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treatment versus placebo. Furthermore, statistically significant and clinically meaningful efficacy results were observed in
the trial across key MDS patient subtypes, including patients who were ringed sideroblast positive, or RS positive, and
ringed sideroblast negative, or RS negative; patients with high (4-6 RBC units/8 weeks) and very high baseline transfusion
burden (>6 RBC units/8 weeks); and patients classified as Low or Intermediate-1 risk according to the IPSS. The most
common Grade 3/4 adverse reactions were neutropenia (72%) and thrombocytopenia (65%), which lasted a median
duration of less than two weeks, and in more than 80% of patients were resolved to Grade <2 in under four weeks.
Myelofibrosis (MF)
MF, a type of myeloproliferative neoplasm, is a chronic blood cancer in which abnormal or malignant
precursor cells in the bone marrow proliferate rapidly, causing scar tissue, or fibrosis, to form. As a result, normal blood
production in the bone marrow is impaired and may shift to other organs, such as the spleen and liver, which can cause
them to enlarge substantially. People with MF may have abnormally low or high numbers of circulating RBCs, white blood
cells or platelets, and abnormally high numbers of immature cells in the blood or bone marrow. MF patients can also suffer
from debilitating constitutional symptoms, such as drenching night sweats, fatigue, severe itching, or pruritus, abdominal
pain, fever and bone pain.
Approximately 70% of MF patients are classified as having Intermediate‐2 or High-risk disease, as defined
by the Dynamic International Prognostic Scoring System Plus described in a 2011 Journal of Clinical Oncology article.
Drug therapies currently approved by the FDA and other regulatory authorities for treating these MF patients include JAK
inhibitors, ruxolitinib, fedratinib and momelotinib, as well as pacritinib, a kinase inhibitor. Currently, no drug therapy is
approved for those patients who fail or no longer respond to JAK inhibitor treatment. A variety of best available therapies
are used in absence of an approved treatment for this patient population, and median survival is limited, representing a
significant unmet medical need.
Ongoing Phase 3 IMpactMF Trial in Relapsed/Refractory MF
Trial Design
IMpactMF, our Phase 3 clinical trial in relapsed/refractory MF, is an open label, 2:1 randomized, controlled
clinical trial designed to evaluate imetelstat (9.4 mg/kg administered by intravenous infusion over two hours every three
weeks) in approximately 320 patients. Patients relapsed after or refractory to a JAK inhibitor are defined as having an
inadequate spleen response or symptom response after treatment with a JAK inhibitor for at least six months, including an
optimal dose of a JAK inhibitor for at least two months. The best available therapy, or BAT, control arm of IMpactMF
excludes the use of JAK inhibitors. With respect to the trial design for IMpactMF, the FDA urged us to consider adding a
third dosing arm to assess a lower dose and/or a more frequent dosing schedule that might improve the planned 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, which evaluated a low and high doses, 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. We believe
existing data also suggest that lowering the dose would not result in a clinically meaningful reduction in toxicity. For these
reasons, we therefore determined not to add a third dosing arm to the trial design, and the FDA did not object to our
proposed imetelstat 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, 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.
The primary efficacy endpoint for IMpactMF is OS. Key secondary endpoints include symptom response;
spleen response; progression free survival; complete remission, partial remission or clinical improvement, as defined by the
International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria; duration of response;
safety; pharmacokinetics; and patient reported outcomes. There are IMpactMF sites across North America, South America,
Europe, Australia and Asia.
Current Status of IMpactMF
IMpactMF opened for patient screening and enrollment in December 2020. In September 2025, the trial
completed enrollment. Based on our current assumptions for event (death) rates in the trial, we expect the interim analysis
for OS in IMpactMF may occur in the second half of 2026 and the final analysis may occur in the second half of 2028.
Because these analyses are event-driven and it is uncertain whether actual rates for events will reflect current planning
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assumptions, the results may be available at different times than currently expected. At the interim analysis, if the pre-
specified statistical OS criterion is met, then we expect such data may potentially support the registration of imetelstat in
relapsed/refractory MF. Subject to protocol-specified stopping rules for futility, if the pre-specified OS criterion is not met
at the interim analysis, the trial will continue to the final analysis.
The timing and achievement of either or both of the planned analyses depend on numerous factors,
including blinded death rates, which have in the past been, and may continue to be, lower than our projections. In addition,
our ability to conduct and complete IMpactMF depends on whether we can obtain and maintain the relevant clearances
from regulatory authorities and other institutions to continue to conduct and complete the trial.
Improvement in Overall Survival and Potential Disease-Modifying Activity Observed in IMbark Phase 2
The IMbark Phase 2 clinical trial was designed to evaluate two dosing regimens of imetelstat (either 4.7
mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in patients with relapsed/refractory MF.
We previously reported efficacy and safety results from the IMbark Phase 2 clinical trial, including median
OS of 28.1 months for patients on the high dose arm of the study, which is almost twice the reported median OS of 14–16
months in medical literature. To evaluate this potential benefit, we conducted a post-hoc analysis of OS for patients treated
with imetelstat 9.4 mg/kg in IMbark compared to OS calculated from real world data, or RWD, collected at the Moffitt
Cancer Center for patients who had discontinued treatment with ruxolitinib, a JAK inhibitor, and who were subsequently
treated with BAT. To make a comparison between the IMbark data and RWD, a cohort from the real-world dataset was
identified that closely matched the IMbark patients, using guidelines for inclusion and exclusion criteria as defined in the
IMbark clinical protocol, such as platelet count and spleen size. Calculations from two propensity score analysis
approaches resulted in a median OS of 30.7 months for the imetelstat-treated patients from IMbark, which is more than
double the median OS of 12.0 months using RWD for patients treated with BAT. These analyses also showed a 65% – 67%
lower risk of death for the imetelstat-treated patients vs. BAT-treated patients. We believe these analyses suggest
potentially longer OS for imetelstat-treated relapsed/refractory MF patients in IMbark, compared to BAT in closely-
matched patients from RWD. However, 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. For these and other reasons, such comparative analyses and any
conclusions from such analyses should be considered carefully and with caution, and should not be relied upon as
demonstrative or otherwise predictive or indicative of any current or potential future clinical trial results of imetelstat in
relapsed/refractory MF, including IMpactMF.
In IMbark, patients also experienced other positive clinical outcomes, including symptom improvement,
spleen reduction and bone marrow fibrosis improvement. In June 2020, we reported correlation analyses from IMbark that
showed a trend of longer OS in patients who achieved symptom response, spleen volume reductions and improved bone
marrow fibrosis, in a dose-dependent manner. Furthermore, the reductions in the variant allele frequency of key driver
mutations in MF and the improvement in bone marrow fibrosis observed in IMbark have also been correlated to the
improvement in OS. We believe the improvement in bone marrow fibrosis, potential survival benefit, molecular data and
correlations from IMbark provide strong evidence of the potential for disease modification with imetelstat, which we
believe would differentiate imetelstat from currently approved treatments for MF, if approved.
The safety results observed in IMbark were consistent with prior clinical trials of imetelstat in hematologic
malignancies, and no new safety signals were identified. In the 9.4 mg/kg arm, reversible and manageable Grade 3/4
thrombocytopenia and neutropenia were reported in 24/59 patients (41%) and 19/59 patients (32%), respectively, without
significant clinical consequences. 1/59 patients (2%) had Grade 3 febrile neutropenia. 3/59 patients (5%) had Grade 3/4
bleeding. 6/59 patients (10%) had Grade 3/4 infections. Furthermore, more than 70% of the observed Grade 3/4 cytopenias
resolved to Grade 2 or lower by laboratory assessment within four weeks.
FDA Fast Track Designation
Fast Track designation provides opportunities for frequent interactions with FDA review staff, as well as
eligibility for priority review, if relevant criteria are met, and rolling review. Fast Track designation is intended to facilitate
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and expedite development and review of an NDA to address unmet medical needs in the treatment of serious or life-
threatening conditions. However, Fast Track designation does not accelerate conduct of clinical trials or mean that the
regulatory requirements are less stringent, nor does it ensure that imetelstat will receive marketing approval or that
approval will be granted within any particular timeframe. In addition, the FDA may withdraw Fast Track designation if it
believes that the designation is no longer supported by data emerging from the imetelstat clinical development program.
In October 2017, the FDA granted Fast Track designation to imetelstat for the treatment of adult patients
with TD anemia due to lower-risk MDS who do not have a non-del 5q abnormality and who are refractory or resistant to
treatment with an ESA (i.e., the treatment population in IMerge Phase 3).
In September 2019, the FDA granted Fast Track designation to imetelstat for the treatment of adult patients
with Intermediate-2 or High-Risk MF whose disease has relapsed after or is refractory to JAK inhibitor treatment (i.e., the
treatment population in IMpactMF).
Potential Additional Indications
IMproveMF: Phase 1 Combination Clinical Trial in Frontline Myelofibrosis (Frontline MF)
We are also evaluating imetelstat as a combination therapy in the Phase 1 IMproveMF clinical trial as a
first-line treatment for patients with Intermediate-1, Intermediate-2 or High-Risk myelofibrosis. Based on the dose
escalation findings in Part 1 of the study, presented at the American Society of Hematology, or ASH, annual meeting in
December 2024, imetelstat 9.4 mg/kg dosed every four weeks with ruxolitinib was the selected dose for the dose expansion
Part 2 of the study, which is currently enrolling patients.
IMpress: Investigator-Led Phase 2 Clinical Trial in Higher Risk Myelodysplastic Syndromes (Higher Risk MDS) and
Acute Myeloid Leukemia (AML)
Imetelstat is also being studied in an investigator-led IMpress Phase 2 clinical trial in Intermediate-2 or
High-Risk myelodysplastic syndromes, or higher-risk MDS, and acute myeloid leukemia, or AML, patients that are
relapsed or refractory to hypomethylating agent, or HMA, treatment. Based on observations from an interim analysis from
the first cohort, presented at ASH in December 2024, the protocol was amended to a more frequent dosing schedule for a
second cohort of patients being enrolled and treated with this modified schedule as of August 2024. These data were
presented at ASH in December 2025.
IMAGINE: Investigator-Led Phase 1/2 Clinical Trial in Relapsed/RefractoryAML
We are enrolling a Phase 1/2 investigator-led study, called IMAGINE, in relapsed/refractory AML, using a
combination approach of imetelstat and azacitidine with or without venetoclax.
Research Programs
Next Generation Telomerase Inhibitor Discovery
We have initiated a discovery program to identify lead compounds as a potential next generation oral
telomerase inhibitor. If the leads we have identified are optimized, we may conduct preclinical experiments that may serve
as a basis for potential future clinical testing. Discovery research is an uncertain and unpredictable process. As such, the
timing and nature of any results from this discovery effort are difficult to forecast. If we optimize lead compounds from
this discovery program, we expect to provide an update on our efforts at that time.
Preclinical Lymphoid Hematologic Malignancies
Academic research data suggests that certain lymphoid hematologic malignancies have higher telomerase
activity and shorter telomeres when compared to normal healthy cells. Based on this scientific hypothesis, we conducted a
preclinical research project with MD Anderson Cancer Center to determine the potential application of imetelstat in
lymphoid hematologic malignancies. The project was completed, and preliminary results of the research project were
published in Blood in November 2022. Exploring the utility of imetelstat in lymphoid hematologic malignancies remains
an area of interest for us.
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Intellectual Property and Regulatory Exclusivity
Intellectual property, including patent protection, is very important to our business. We file patent
applications in the U.S. and other jurisdictions, and we also rely on trade secret protection and contractual arrangements to
protect aspects of our business. An enforceable patent with appropriate claim coverage can provide an advantage over
competitors who may seek to employ similar approaches to develop therapeutics, and so the future commercial success of
RYTELO (imetelstat), and therefore our future success, will be in part dependent on our intellectual property strategy.
Our intellectual property strategy includes the early development of a technology, such as imetelstat,
followed by rounds of increasingly focused innovation around a product opportunity, including identification and definition
of a specific product candidate and uses thereof, manufacturing processes, product formulation and methods of treatment
and administration. The result of this process is that products in development are often protected by several families of
patent filings that are filed at different times during the development process and cover different aspects of the product.
Consequently, earlier filed, broad technology patents will usually expire ahead of patents covering later developments, such
as product formulations and methods of treatment and administration, so that patent expirations on a product may span
several years. Patent coverage may also vary from country to country based on the scope of available patent protection.
There are also opportunities to obtain an extension of patent coverage for a product in certain jurisdictions, which adds
further complexity to the determination of patent life.
From time to time, we may endeavor to monitor worldwide patent filings by third parties that are relevant
to our business. Based on this monitoring, we may determine that an action is appropriate to protect our business interests.
Such actions may include negotiating patent licenses where appropriate, filing oppositions against a patent, filing a request
for post grant review against a patent or filing a request for the declaration of an interference with a patent application or
issued patent.
The information provided in this section should be reviewed in the context of the section entitled “Risks
Related to Protecting Our Intellectual Property” described in “Risk Factors” in Part I, Item 1A of this Report.
RYTELO (imetelstat)
Summary
RYTELO was developed internally by us, and we hold global commercial rights to it. We own issued
patents related to RYTELO in the U.S., Europe and other jurisdictions. Although composition of matter patents generally
provide the most comprehensive coverage of a therapeutic product such as RYTELO, subsequent patent filings directed to
other aspects of RYTELO may also provide additional patent coverage with later expiration dates. In addition, it may be
possible to obtain patent term extensions of some patents in some jurisdictions for claims covering RYTELO or relating to
RYTELO, such as methods of treatment with RYTELO, which could further extend the patent term.
We have issued patents in the U.S., Europe and other jurisdictions that provide patent coverage into 2033
(not including any patent term extension) pertaining to the treatment of MDS and MF with RYTELO.
In the U.S., our method of treatment patent rights for MDS and MF expire in March 2033 (not including
any patent term extension). We also hold an issued patent in the U.S. covering the composition of matter of RYTELO
(imetelstat) that that was set to expire in December 2025 according to its original patent term, including patent term
adjustment for delays at the USPTO. Now that we have received approval for RYTELO in the U.S., we have applied for
patent term extensions under the provisions of the Drug Price Competition and Patent Term Restoration Act of 1984 (as
amended), or the Hatch-Waxman Act, which, if granted, could extend the patent term of either our method of treatment
patent for MDS and MF or our composition of matter patent by up to five years (but not beyond 14 years from the date of
approval). Our composition of matter patent was granted interim patent term extension under the Hatch-Waxman Act,
which extends its expiration date to December 2026, while a decision is being rendered on the patient term extension
application.
In Europe and other countries, our patent rights for use in MDS and MF expire in November 2033 (not
including any patent term extension). Our composition of matter patent coverage expired in September 2024. We plan to
seek patent term extension under a Supplementary Protection Certificate, or SPC, as permitted under European Council, or
EC, Regulation No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary
protection certificate of medicinal products (the Medicinal SPC Regulation), of one of our use patents, such as our patent
for use in MDS, in the European Economic Area, or the EEA, which could extend the patent term by up to five years.
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