What changed in this filing

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Item 1. Legal Proceedings

2022-08-11 compared with 2022-05-09 · 168 added, 154 removed, 1196 unchanged (21% of the section changed)

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Risks Related to COVID-19

The COVID-19 pandemic has affected and continues to affect our ability to conduct clinical trial activities, causing delays in our current Phase 3 clinical trials, IMerge Phase 3 and IMpactMF, and may delay IMproveMF, our planned Phase 1 combination clinical trial in frontline Intermediate-2 or High-risk myelofibrosis, or frontline MF, and our planned investigator-led clinical trials in acute myeloid leukemia, or AML, and Intermediate-2 or High-risk myelodysplastic syndromes, or higher risk MDS.

The COVID-19 pandemic has affected and continues to affect our ability to conduct clinical trial activities, causing delays in our current Phase 3 clinical trials, IMerge Phase 3 and IMpactMF, and may delay IMproveMF, our Phase 1 combination clinical trial in frontline Intermediate-2 or High-risk myelofibrosis, or frontline MF, and our planned investigator-led clinical trials in acute myeloid leukemia, or AML, and Intermediate-2 or High-risk myelodysplastic syndromes, or higher risk MDS.

Additionally, the COVID-19 pandemic may delay and disrupt regulatory activities and our manufacturing and supply chain and have other adverse effects on our business and operations.

Risks Related to Our Financial Position and Indebtedness and Need For Additional Financing

AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF.

We will require substantial additional funding to further advance the imetelstat program, including through the completion of IMpactMF, IMproveMF and the planned investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF.

If we are unable to raise this capital when needed, we would be forced to delay, reduce or eliminate our research and development activities and other operations or commercialization efforts which would have a material adverse effect on our business that might cause us to cease operations.

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achieve adequate efficacy in IMerge Phase 3 to obtain regulatory approval, (i) in light of our decision to shorten the follow-up period after the last patient has been enrolled from 15 months to 12 months to enable an earlier clinical cut-off date for the primary analysis, which may result in the exclusion of clinical responses that could occur after the earlier clinical cut-off date for the primary analysis, (ii) inability to conduct the primary analysis for IMerge Phase 3, including due to further difficulties in retaining patients in the treatment or follow-up phases of the trial or (iii) for any other reasons;

obtain substantial additional capital in order to enable us to conduct our operations and further advance the imetelstat program, including through the completion of IMpactMF and the planned exploratory studies in new indications, including IMproveMF and investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF;

obtain substantial additional capital in order to enable us to conduct our operations and further advance the imetelstat program, including through the completion of IMpactMF, IMproveMF and the planned investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF;

develop clinical plans for, and successfully commence, conduct and complete potential future clinical trials of imetelstat, such as IMproveMF, and one or more investigator-led clinical trials that we plan to support in AML and higher risk MDS;

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recruit and retain sufficient qualified and experienced personnel to support the development and potential commercialization of imetelstat, including to conduct and complete IMerge Phase 3 and IMpactMF, and potential future clinical trials of imetelstat.

If we are not able to successfully achieve the above-stated goals and overcome other challenges that we may encounter in the research, development, manufacturing and potential commercialization of imetelstat, we may be forced to abandon our development of imetelstat, which would severely harm our business and prospects, and might cause us to cease operations.

IMerge Phase 3 and IMpactMF, and potential future clinical trials of imetelstat, could be interrupted, delayed, terminated or abandoned for a variety of reasons, including due to the COVID-19 pandemic, civil unrest or military conflicts around the world, including the current military conflict between Ukraine and Russia, which could severely and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

Currently, the active clinical trials of imetelstat are IMerge Phase 2, IMerge Phase 3 and IMpactMF.

Potential future clinical trials of imetelstat include IMproveMF, the exploratory Phase 1 trial of imetelstat in frontline MF that we plan to conduct, and one or more potential investigator-led clinical trials in AML and higher risk MDS that we plan to support.

If we are not able to successfully achieve the above-stated goals and overcome other challenges that we may encounter in the research, development, manufacturing and potential commercialization of imetelstat, we may be forced to abandon our development of imetelstat, which would severely harm our business, prospects and our ability to raise additional capital, and might cause us to cease operations.

Our current and potential future clinical trials of imetelstat, could be interrupted, delayed, terminated or abandoned for a variety of reasons, including due to the COVID-19 pandemic, civil unrest or military conflicts around the world, including the current military conflict between Ukraine and Russia, which could severely and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.*

Currently, the active clinical trials of imetelstat are IMerge Phase 2, IMerge Phase 3, IMpactMF, and IMproveMF, which was opened for enrollment in May 2022.

Potential future clinical trials of imetelstat include one or more potential investigator-led clinical trials in AML and higher risk MDS that we plan to support.

The fluidity and dynamic nature of the COVID-19 pandemic precludes any firm estimates as to the ultimate effect COVID-19 will have on our current and potential future clinical trials, our operations and our business, all of which depend on the continued worldwide progress toward managing this health crisis.

Although vaccine distribution, including booster shots, is progressing in many countries, the emergence of COVID-19 variants and subvariants, and the resurgence of COVID-19 cases in certain regions of the world causes further uncertainty and unpredictability on clinical trial activities, including clinical site initiations, patient screening and enrollment, as well as constraints on available sites and site personnel.

Although vaccine distribution, including booster shots, is being conducted in many countries, the emergence of COVID-19 variants and subvariants, and the resurgence of COVID-19 cases in many parts of the world causes further uncertainty and unpredictability on clinical trial activities, including clinical site initiations, patient screening and enrollment, as well as constraints on available sites and site personnel.

Even though we have completed patient enrollment in IMerge Phase 3, the pace of enrollment was slower than planned due to the COVID-19 pandemic.

Site personnel resources for IMpactMF remain constrained in the countries where we plan to conduct the trial, due to the negative impact of COVID-19 and number of competing trials in MF and other oncology indications.

Site personnel resources for IMpactMF remain constrained in the countries where we plan to conduct the trial, due to the negative impact of COVID-19, as well as a number of competing trials in MF and other oncology indications.

Under current planning assumptions for IMpactMF, we expect that the interim analysis may occur in 2024 and the final analysis in 2025.

However, because the analyses for IMpactMF are event-driven, the results may be available at different times than currently expected.

In addition, the conduct and completion of IMerge Phase 3 and IMpactMF, and commencement and conduct of any potential future clinical trials of imetelstat, including IMproveMF, and the investigator-led clinical trials in AML and higher risk MDS that we plan to support, could be interrupted, delayed or abandoned for a variety of reasons, including as a result of failures or delays related to:

In addition, the conduct and completion of IMerge Phase 3, IMpactMF, and IMproveMF, and commencement and conduct of any potential future clinical trials of imetelstat, including the investigator-led clinical trials in AML and higher risk MDS that we plan to support, could be interrupted, delayed or abandoned for a variety of reasons, including as a result of the COVID-19 pandemic, the conflict between Ukraine and Russia or failures or delays related to:

successfully retaining patients in, and conducting and completing, IMerge Phase 3, including completing the primary analysis for IMerge Phase 3;

overcoming enrollment and operational challenges related to opening new clinical sites and conducting and completing IMpactMF due to the effects of the COVID-19 pandemic, while also competing with clinical trials for other investigational drugs in the same patient population;

patient recruitment, enrollment, or retention, clinical site initiation, or retention problems associated with civil unrest or military conflicts around the world, including specifically the current military conflict between Ukraine and Russia, which could affect clinical sites participating in IMerge Phase 3 and IMpactMF, or other sites if the conflict spreads or has effects on countries outside of Ukraine and Russia;

patient recruitment and enrollment in IMproveMF, the Phase 1 clinical trial of imetelstat in combination with ruxolitinib in frontline MF, which was opened for enrollment in May 2022;

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

or other countries to conduct clinical trials, such as obtaining or maintaining regulatory clearances to commence, conduct or modify current or potential future clinical trials of imetelstat, in a timely manner, or at all, which could, for example, prevent us from, or result in substantial delays in, conducting or completing IMerge Phase 3 and IMpactMF, or commencing potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS;

or other countries to conduct clinical trials, such as obtaining or maintaining regulatory clearances to commence, conduct or modify current or potential future clinical trials of imetelstat, in a timely manner, or at all, which could, for example, prevent us from, or result in substantial delays in, conducting or completing IMerge Phase 3, IMpactMF and IMproveMF, or commencing potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS;

maintaining the INDs and equivalent submissions in other countries for imetelstat without such INDs and/or equivalent submissions in other countries being placed on full or partial clinical hold, suspended or subject to other requirements by the FDA or other regulatory authorities;

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use of trial endpoints that inherently require prolonged periods of clinical observation or analysis of the resulting data to determine trial outcomes;

manufacturing sufficient quantities of imetelstat, or other clinical trial materials, in a manner that meets the quality standards of the FDA and other regulatory authorities, and responding to any disruptions to drug supply, clinical trial materials or quality issues that may arise, including as a result of limitations in available manufacturing capacity due to obligations to manufacture and distribute vaccines to address the COVID-19 pandemic;

temporary or permanent shut down of contract manufacturing facilities due to violations of good manufacturing practices, or GMP, regulations or other

applicable requirements;

infections or cross-contaminations of product candidates in the manufacturing process;

or capacity limitations;

manufacturing sufficient quantities of imetelstat, or other clinical trial materials, in a manner that meets the quality standards of the FDA and other regulatory authorities, and responding to any disruptions to drug supply, clinical trial materials or quality issues that may arise, including as a result of a) limitations in available manufacturing capacity due to obligations to manufacture and distribute vaccines to address the COVID-19 pandemic;

b) temporary or permanent shut down of contract manufacturing facilities due to violations of good manufacturing practices, or GMP, regulations or other applicable requirements;

c) infections or cross-contaminations of product candidates in the manufacturing process;

d) or capacity limitations;

ensuring the ability to manufacture and supply imetelstat at acceptable costs for potential future clinical trials of imetelstat and potential commercial uses;

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third-party contractors becoming debarred, disqualified or suspended or otherwise penalized by the FDA or other similar international regulatory authorities for violations of applicable regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or all of the data produced by such contractors in support of any applications for regulatory approval;

obtaining timely review and clearances by regulatory authorities for any clinical protocol amendments, modifications to our manufacturing process which may be sought for current and potential future clinical trials of imetelstat, including responding to questions or comments from these authorities in a timely and adequate manner, which could, for example, prevent us from conducting or completing IMerge Phase 3 and IMpactMF, or commencing potential future clinical trials of imetelstat;

obtaining institutional review board or ethics committee approvals for clinical trial protocols or protocol amendments, including any future refinements to the trial design we may seek for IMerge Phase 3 and IMpactMF, or as a result of changes in regulatory requirements and policies, which could, for example, prevent us from conducting or completing IMerge Phase 3 or IMpactMF, and commencing potential future clinical trials of imetelstat.

prevent us from conducting or completing IMerge Phase 3, IMpactMF or IMproveMF, or commencing potential future clinical trials of imetelstat;

obtaining institutional review board or ethics committee approvals for clinical trial protocols or protocol amendments, including any future refinements to the trial design we may seek for IMerge Phase 3, IMpactMF or IMproveMF, or as a result of changes in regulatory requirements and policies, which could, for example, prevent us from conducting or completing IMerge Phase 3, IMpactMF or IMproveMF, and commencing potential future clinical trials of imetelstat.

We could also encounter delays if a clinical trial is suspended or terminated.

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changes in governmental regulations or administrative actions.

Failures or delays with respect to any of the aforementioned events could adversely affect our ability to conduct or complete IMerge Phase 3 and IMpactMF, or to commence, conduct and complete potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, which could increase development costs, or interrupt, further delay or halt our development or potential commercialization of imetelstat, any of which could severely and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

Failures or delays with respect to any of the aforementioned events could adversely affect our ability to conduct or complete IMerge Phase 3, IMpactMF and IMproveMF, or to commence, conduct and complete potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, which could increase development costs, or interrupt, further delay or halt our development or potential commercialization of imetelstat, any of which could severely and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

Further difficulties retaining patients in IMerge Phase 3 and enrolling or retaining patients in IMpactMF, whether as a result of the effects of the COVID-19 pandemic, the military conflict between Ukraine and Russia or for any other reasons, could further delay or otherwise adversely affect our clinical development and commercialization activities, which would cause our business and business prospects to be severely harmed, and we might cease operations.*

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Further challenges in retaining patients in IMerge Phase 3 and screening, enrolling and retaining patients in IMpactMF, whether as a result of the effects of the COVID-19 pandemic, geopolitical events, or for any other reasons, may further delay our conduct of such trials, or cause them to be discontinued.

For example, we have clinical trial sites in Ukraine and Russia, and nearby European countries, and if political or civil conditions require it, our clinical trial sites may need to delay or suspend clinical trial activities.

In addition, enrollment and retention of patients in IMerge Phase 3 or IMpactMF could be disrupted by geopolitical events, including civil or political unrest (such as the current military conflict between Ukraine and Russia).

For example, we have clinical trial sites in Ukraine and Russia, and nearby European countries, and have experienced, and may continue to experience, delays and suspensions in clinical trial activities at clinical sites in Ukraine and Russia due to the current political and civil unrest conditions, including delays in clinical site initiations, patient screening and enrollment, as well as constraints on available sites and site personnel.

If we experience further difficulties in retaining patients in the treatment or follow-up phase of IMerge Phase 2 and IMerge Phase 3, whether as a result of the effects of the COVID-19 pandemic, geopolitical events, or for any other reasons, our ability to continue to assess longer-term durability of RBC-TI responses would be adversely affected.

The retention of patients in IMerge Phase 3 and the enrollment and retention of patients in IMpactMF, depend on many factors, such as:

The retention of patients in IMerge Phase 3 and the enrollment and retention of patients in IMpactMF and IMproveMF, depend on many factors, such as:

our ability to identify and screen patients who meet the patient eligibility criteria specified in the protocol;

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the risk that patients enrolled in any imetelstat clinical trial will drop out of the trial before completion due to lack of efficacy, adverse side effects, investigator decision, progressive disease, COVID-19 or COVID-19-related or geopolitical event-related site activities and restrictions, alternate treatments being approved for the indication, or personal issues.

In addition, IMpactMF has competed and will continue to compete with, and potential future clinical trials of imetelstat such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS will compete with, other clinical trials for product candidates that are in the same therapeutic areas with imetelstat, and such trials may also be conducted at the same clinical sites.

In addition, IMpactMF has competed and will continue to compete with, and earlier stage clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, will compete with, other clinical trials for product candidates that are in the same therapeutic areas with imetelstat, and such trials may also be conducted at the same clinical sites.

This competition is reducing the number of clinical sites and hospital staff available to participate in IMpactMF, as well as the number and type of patients available to enroll or remain in current and potential future imetelstat clinical trials.

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infusion-related reactions.

If patients in any clinical trials of imetelstat, including IMerge Phase 3, IMpactMF or any potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, experience similar or more severe adverse events, or new or unusual adverse events, or if the FDA or other regulatory authorities determine that efficacy and safety data in current or potential future clinical trials of imetelstat do not support an adequate benefit-risk profile to justify continued treatment of patients, then the FDA or other regulatory authorities may again place one or more of the INDs for imetelstat on clinical hold, as occurred in March 2014.

If patients in any clinical trials of imetelstat, including IMerge Phase 3, IMpactMF, IMproveMF or any potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, experience similar or more severe adverse events, or new or unusual adverse events, or if the FDA or other regulatory authorities determine that efficacy and safety data in current or potential future clinical trials of imetelstat do not support an adequate benefit-risk profile to justify continued treatment of patients, then the FDA or other regulatory authorities may again place one or more of the INDs for imetelstat on clinical hold, as occurred in March 2014.

If this were to occur, there would be a significant delay in, or possible termination of, such clinical trial or all the imetelstat clinical trials, which might cause us to cease operations.

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In addition, because additional data are being generated from these trials, 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, and any other severe adverse effects that may be associated with life-threatening clinical outcomes.

The occurrence of any of the aforementioned events could interrupt, further delay, or halt, any development and potential commercialization of imetelstat by us, as well as increase costs to develop imetelstat, which would have a severe adverse effect on our results of operations, financial condition, business prospects and the future of imetelstat, any of which might cause us to cease operations.

The occurrence of any of the aforementioned events could interrupt, further delay, or halt, any development and potential commercialization of imetelstat by us, as well as increase costs to develop imetelstat, which would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, business prospects and the future of imetelstat, any of which might cause us to cease operations.

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.

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For example, we shortened the follow-up period after the last patient has been enrolled from 15 months to 12 months to enable an earlier clinical cut-off date for the primary analysis in IMerge Phase 3.

Although we expect the data from the primary analysis as of the earlier clinical cut-off date to be sufficiently mature to assess the safety and efficacy of imetelstat, including durability of transfusion independence, our decision to shorten the follow-up period after the last patient has been enrolled may result in clinical

responses that could occur after the 12-month clinical cut-off date being excluded from the primary analysis.

The exclusion of this data from the primary analysis could reduce the overall top-line efficacy results, including durability of transfusion independence, which could result in the trial’s failure, or could limit or prevent marketing approval of imetelstat in lower risk MDS by the FDA or regulatory authorities in other countries.

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Patients in both the initial and expansion cohorts were naïve to both HMA and lenalidomide and were non-del(5q).

We believe the observed difference in eight-week RBC-TI rate between the 13-patient initial cohort and the 25-patient expansion cohort may be attributable to factors such as the maturity of the data at the time of the data snapshot, since the median follow-up time of the expansion cohort at the time of the data snapshot was less than half the length of time the 13-patient initial cohort had been followed when their data were first reported, or the higher overall baseline transfusion burden of the expansion cohort.

We believe the observed difference in eight-week RBC-TI rate between the 13-patient initial cohort and the 25-patient expansion

cohort may be attributable to factors such as the maturity of the data at the time of the data snapshot, since the median follow-up time of the expansion cohort at the time of the data snapshot was less than half the length of time the 13-patient initial cohort had been followed when their data were first reported, or the higher overall baseline transfusion burden of the expansion cohort.

Although the latest reported eight-week RBC-TI rate of 42% in June 2020 is higher than that reported in the data snapshot from the second quarter of 2018, we cannot assure you that the eight-week RBC-TI rate of patients enrolled in IMerge Phase 3 will be comparable to what has been reported in the 13-patient initial cohort, the 25-patient expansion cohort, or the combined cohorts in IMerge Phase 2.

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 IMerge Phase 2 and IMbark, and if this were to occur with IMerge Phase 3 or IMpactMF, this would adversely affect future development prospects of imetelstat and may cause us to cease operations.

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

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In addition, the potential improvement in survival observed in the 9.4 mg/kg dosing arm in IMbark will need to be further assessed in IMpactMF, and similar results, including potential improvement in survival, if any, with respect to any patient population or patient population subgroup, may not be observed in IMpactMF.

Likewise, although the statistical analyses comparing IMbark data to closely matched real world data, or RWD, reported at the EHA Annual Congress meeting in June 2019 suggest favorable OS for imetelstat-treated patients with Intermediate-2 or High-risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor, or relapsed/refractory MF, compared to BAT using closely matched patients’

Likewise, although the statistical analyses comparing IMbark data to closely matched real world data, or RWD, published in the September 2021 issue of the Annals of Hematology suggest favorable OS for imetelstat-treated patients with Intermediate-2 or High-risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor, or relapsed/refractory MF, compared to BAT using closely matched patients’

RWD, such comparative analyses between RWD and our clinical trial data have several limitations.

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

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.

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 and potential commercialization of imetelstat by us, which would have a severe adverse effect on our results of operations, financial condition, business prospects and the future of imetelstat, any of which might cause us to cease operations.

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.

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 and potential commercialization of imetelstat by us, which would have a severe adverse effect on our results of operations, financial condition and ability to raise additional capital, business prospects and the future of imetelstat, any of which might cause us to cease operations.

Interim, “snapshot,”

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in September 2018, our former collaboration partner’s decision to terminate its imetelstat collaboration agreement with us.

Further delay, suspension or abandonment of our development of imetelstat in myeloid hematologic malignancies, including to conduct and complete IMerge Phase 3 and IMpactMF, and to plan for, commence, conduct and complete potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, could have a material adverse effect on the future of imetelstat and our business prospects, and we might cease operations.

Further delay, suspension or abandonment of our development of imetelstat in myeloid hematologic malignancies, including to conduct and complete IMerge Phase 3, IMpactMF, IMproveMF, and to plan for, commence, conduct and complete potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, could have a material adverse effect on the future of imetelstat and our business prospects, and we might cease operations.

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

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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 imetelstat clinical trials, including IMerge Phase 3 and IMpactMF, we remain responsible for ensuring that each clinical trial is conducted in accordance with its investigational plan and protocol, and applicable laws.

Although we rely on third parties to conduct our imetelstat clinical trials, including IMerge Phase 3, IMpactMF and IMproveMF, 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 regulatory authorities in other countries 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.

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

In addition, our clinical trials must be conducted with imetelstat produced under applicable current good manufacturing practices, or cGMP, 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, which would further delay the process for any regulatory approval.

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, business prospects and the future of imetelstat, any of which might cause us to cease operations.

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

We also are required to register imetelstat clinical trials that we sponsor and post the results of certain completed clinical trials on certain government-sponsored databases, such as ClinicalTrials.gov, within certain timeframes.

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A delay in the timely completion of or reporting of data from any potential future investigator-led clinical trial could have a material adverse effect on our ability to further develop imetelstat or to advance imetelstat to subsequent clinical trials.

Investigator-led clinical trials are often conducted under less rigorous clinical standards than those used in company-sponsored clinical trials.

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 potential future investigator-led clinical trials could show marginal efficacy and/or clinically relevant safety concerns that could delay the further clinical development or marketing approval of imetelstat for any indication.

To the extent that the results of any potential future investigator-led clinical trials raise safety or other concerns regarding imetelstat, regulatory authorities may question the results of such investigator-led trials, or question the results of our current Phase 3 clinical trials, IMerge Phase 3 and IMpactMF, and planned Phase 1 clinical trial, IMproveMF.

Safety concerns arising from any potential future investigator-led clinical trials could result in partial or full clinical holds being placed on the imetelstat INDs by the FDA or other regulatory authorities, as occurred in March 2014, which would further delay or prevent us from advancing imetelstat into further clinical development and cause us to discontinue our development of imetelstat, which would severely harm our business and prospects, and could potentially cause us to cease operations.

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further delay or preclude any revenue we may receive from the future commercialization of imetelstat, if any.

Before we can seek to obtain regulatory approval for the commercial sale of imetelstat, we need to demonstrate that imetelstat is safe and effective in IMerge Phase 3, IMpact MF or potential additional clinical trials of imetelstat.

Before we can seek to obtain regulatory approval for the commercial sale of imetelstat, we need to demonstrate that imetelstat is safe and effective in IMerge Phase 3, IMpactMF or potential additional clinical trials of imetelstat.

We will need to complete significant additional research, manufacturing activities and clinical testing as well as other assessments before we can submit any application to the FDA or similar regulatory authorities in other countries for regulatory approval of imetelstat, including confirming compliance with EMA and FDA regulatory commitments.

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The exclusion of this data from the primary analysis could reduce the overall top-line efficacy results, including durability of transfusion independence,

which could result in the trial’s failure, or could otherwise delay, limit or prevent marketing approval of imetelstat in lower risk MDS by the FDA or regulatory authorities in other countries.

The exclusion of this data from the primary analysis could reduce the overall top-line efficacy results, including durability of transfusion independence, which could result in the trial’s failure, or could otherwise delay, limit or prevent marketing approval of imetelstat in lower risk MDS by the FDA or regulatory authorities in other countries.

If imetelstat cannot be successfully developed in our current Phase 3 clinical trials, IMerge or IMpactMF, our business and business prospects would be severely and adversely affected, and we might cease operations.

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

For example, future regulatory clearances, if any, that we might obtain for imetelstat

may be limited to fewer or narrower indications than we might request, or may be granted subject to the performance of post-marketing studies.

For example, future regulatory clearances, if any, that we might obtain for imetelstat may be limited to fewer or narrower indications than we might request, or may be granted subject to the performance of post-marketing studies.

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.

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Failure to achieve continued compliance with government regulations could delay or halt potential commercialization of imetelstat.

Approved products and their manufacturers are subject to continual review, and discovery of previously unknown problems with a product or its manufacturer may result in restrictions on the product or manufacturer, including import restrictions, seizure and

withdrawal of the product from the market.

If approved for commercial sale, future sales of imetelstat will be subject to government regulation related to numerous matters, including the processes of:

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Failure by us to establish and/or maintain a manufacturing supply chain to appropriately and adequately supply imetelstat for future clinical and commercial uses would result in a further delay in or cessation of clinical trials and a further delay in our ability to obtain regulatory approvals of imetelstat, and our business and business prospects could be severely harmed, and we could cease operations.

Imetelstat must meet applicable regulatory standards for current and potential future clinical trials and potential commercial uses.

Imetelstat manufacturing must comply with applicable regulatory standards for current and potential future clinical trials and potential commercial uses.

The process of manufacturing imetelstat is complex and remains subject to several risks, including:

the ability to scale-up and attain sufficient production yields with appropriate quality control and quality assurance, and to establish commercial supply agreements;

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

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

supply chain issues, including the timely availability and shelf life requirements of raw materials and other supplies, any of which may be impacted by a number of factors, including the effects of the COVID-19 pandemic;

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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 where imetelstat might be sold or used.

As a result of these and other risks, we may be unable to establish and/or maintain a manufacturing supply chain capable of providing imetelstat for IMerge Phase 3, IMpactMF, and/or potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, and potential future commercial uses, which would delay or result in a cessation of IMerge Phase 3, IMpactMF, or potential future clinical trials of imetelstat.

As a result of these and other risks, we may be unable to establish and/or maintain a manufacturing supply chain capable of providing imetelstat for IMerge Phase 3, IMpactMF and IMproveMF, and/or potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, and potential future commercial uses, which would delay or result in a cessation of IMerge Phase 3, IMpactMF, IMproveMF or potential future clinical trials of imetelstat.

Occurrence of any such events would further delay or preclude any applications for regulatory approval and therefore further delay or preclude our ability to earn revenue from the commercialization, if any, of imetelstat, which would severely and adversely affect our financial results, business and business prospects, and might cause us to cease operations.

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Failure by such third-party manufacturers to perform in a timely manner, or at all, could further delay, perhaps substantially, or preclude our ability to pursue imetelstat development on our own, increase our costs and otherwise negatively affect our financial results, business and business prospects.

We may not be able to

obtain imetelstat from third-party manufacturers on acceptable terms, or at all.

We may not be able to obtain imetelstat from third-party manufacturers on acceptable terms, or at all.

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

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for example, we have experienced manufacturing schedule delays at one of our contract manufacturers due to government mandated manufacturing for high priority COVID-19 vaccines in connection with Operation Warp Speed, and we anticipate that other delays, or potential shortages of consumable manufacturing supplies, may continue throughout 2022;

requirements by regulatory authorities to validate and qualify significant activities for any replacement manufacturer, which could involve new testing and compliance inspections;

the inability to execute timely contracts with additional third-party manufacturers and suppliers on acceptable terms, or at all;

requirements by regulatory authorities to validate and qualify significant activities for any current or replacement manufacturer, which could involve new testing and compliance inspections;

the inability to execute timely contracts with third-party manufacturers and suppliers on acceptable terms, or at all;

the inability of third-party manufacturers to timely formulate and manufacture imetelstat or to produce or ship imetelstat in the quantities or of the quality required to meet clinical and commercial needs, whether due to the effects of the COVID-19 pandemic or any other reasons;

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 imetelstat to meet commercial needs;

compliance by third-party manufacturers with cGMP standards mandated by the FDA and state agencies and other government regulations corresponding to similar regulatory authorities in other countries;

compliance by third-party manufacturers with GMP standards mandated by the FDA and state agencies and other government regulations corresponding to similar regulatory authorities in other countries;

breach or termination of manufacturing or supply contracts;

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Each of these risks 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.

For example, manufacturing delays could adversely impact the conduct or completion of imetelstat clinical trials, such as IMerge Phase 3, IMpactMF or commencement of potential future clinical trials, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, or preclude or delay potential future commercial sales, which could severely and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

For example, manufacturing delays could adversely impact the conduct or completion of imetelstat clinical trials, such as IMerge Phase 3, IMpactMF and IMproveMF or commencement of potential future clinical trials, such as the planned investigator-led clinical trials in AML and higher risk MDS, or preclude or delay potential future commercial sales, which could severely and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

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 Phase 3 clinical trials and commercial production of imetelstat.

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We may not be able to enter into suitable commercial supply agreements, or to achieve sufficient scale increases or cost reductions necessary for successful commercial production of imetelstat.

Failure to achieve necessary cost reductions could result in decreased sales, if any, for us, which would materially and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

Failure to achieve necessary cost reductions could result in decreased sales or reduced gross margins, if any, for us, which would materially and adversely affect our financial results, business and business prospects, and the future of imetelstat, and might cause us to cease operations.

RISKS RELATED TO COVID-19

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The ongoing COVID-19 pandemic and public health safety measures taken in response to COVID-19 have had a significant impact, both direct and indirect, on businesses, as significant reductions in business-related activities have occurred, clinical development and regulatory activities have been curtailed, delayed or suspended and supply chains have been disrupted.

We have allowed limited voluntary access to our offices in California and New Jersey to employees who have been vaccinated, but almost all of our employees continue to work remotely.

We have allowed voluntary access to our offices in California and New Jersey to employees who have been vaccinated.

While almost all of our employees continue to work remotely without any significant disruption to our business, the effects of our policies regarding remote working may negatively impact productivity, disrupt our business and continue to delay our imetelstat development program and clinical trial timelines, the magnitude of which will depend, in part, on the length and severity of the restrictions and other limitations on our ability to conduct our business in the ordinary course.

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Restrictions on travel, availability of site personnel, and diversion of hospital staff and resources to COVID-19 patients, have disrupted our clinical trial operations, as well as patient recruitment in many areas, resulting in a slowdown in patient enrollment and/or deviations from or disruptions in key clinical trial activities, such as opening, initiating and monitoring clinical trial sites.

Like many other biopharmaceutical companies, we have experienced and continue to experience delays in clinical site initiations and patient screening and enrollment in our clinical trials, IMerge Phase 3 and IMpactMF, due to the COVID-19 pandemic, which have impacted our trial operations.

Although vaccine distribution, including booster shots, is being conducted in many countries, the emergence of COVID-19 variants and subvariants, and the resurgence of COVID-19 cases in parts of the world causes further uncertainty and unpredictability on clinical trial activities, including clinical site initiations, patient screening and enrollment.

Like many other biopharmaceutical companies, we have experienced and continue to experience delays in clinical site initiations and patient screening and enrollment in our clinical trials, IMerge Phase 3, IMpactMF and IMproveMF, due to the COVID-19 pandemic, which have impacted our trial operations.

Even though we have completed patient enrollment in IMerge Phase 3, the pace of enrollment was slower than planned.

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Because these analyses are event-driven, the results may be available at different times than currently expected.

If the effects of the COVID-19 pandemic continue and persist for an extended period of time and/or become more severe, we could experience further disruptions to our clinical development timelines, continued delays in enrollment and clinical trial site initiation in IMpactMF and potential delays in IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, and other disruptions that could severely impact our business and the imetelstat development program, including those resulting from:

If the effects of the COVID-19 pandemic continue and/or become more severe, we could experience further disruptions to our clinical development timelines, including continued delays in enrollment and clinical trial site initiation in IMpactMF and potential delays in IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, and other disruptions that could severely impact our business and the imetelstat development program, including those resulting from:

new, continued or heightened difficulties in opening clinical trial sites for patient screening and enrollment and recruiting clinical site investigators and clinical site staff;

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substantial reduction of healthcare resources available for the conduct of clinical trials, including the temporary postponement of clinical trial activities at certain hospitals serving as our clinical trial sites and diversion of hospital staff away from the conduct of our clinical trials, such as those experienced by us to date;

interruption of, or delays in receiving, supplies of imetelstat from our CMOs due to among other things, staffing shortages, production slowdowns or stoppages, shipping delays, shortages in raw materials or laboratory supplies because of ongoing efforts to address the pandemic, limitations in available capacity at contract manufacturing vendors or drug distribution service providers due to obligations to manufacture and distribute vaccines to address the spread of COVID-19, disruptions in supply chain and production systems and import/export complications;

interruption of, or delays in receiving, supplies of imetelstat from our third-party manufacturers due to among other things, staffing shortages, production slowdowns or stoppages, shipping delays, shortages in raw materials or laboratory supplies because of ongoing efforts to address the pandemic, limitations in available capacity at contract manufacturing vendors or drug distribution service providers due to obligations to manufacture and distribute vaccines to address the spread of COVID-19, disruptions in supply chain and production systems and import/export complications;

interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial subject visits and study procedures (particularly any procedures that may be deemed non-essential), which may impact the integrity of subject data and clinical study endpoints;

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limitations on employee resources that would otherwise be focused on the conduct of our clinical trials, product development, manufacturing, and general company operations, including because of sickness of employees or their families, the desire of employees to avoid contact with large groups of people, an increased reliance on working from home, or mass transit disruptions.

These and other factors arising from the effects of the COVID-19 pandemic could further adversely impact our ability to conduct and complete IMerge Phase 3, and to enroll, conduct and complete IMpactMF and any potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, and could otherwise materially and adversely affect our business and business prospects, our financial condition and the future of imetelstat.

These and other factors arising from the effects of the COVID-19 pandemic could further adversely impact our ability to conduct and complete IMerge Phase 3, and to enroll, conduct and complete IMpactMF and IMproveMF and any potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, and could otherwise materially and adversely affect our business and business prospects, our financial condition and the future of imetelstat.

In addition, we rely on third-party CROs and other third parties to assist us with clinical trial activities.

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efforts and attention on the approval of other therapeutics or other activities related to COVID-19 could likewise impact the timeliness of regulatory authority responses and the processing of regulatory submissions for imetelstat.

In any event, if the effects of the COVID-19 pandemic continue and persist for an extended period of time and/or become more severe, we may experience significant disruptions to our clinical development timelines, which would materially and adversely affect our business and business prospects, our financial condition and the future of imetelstat.

In any event, if the effects of the COVID-19 pandemic become more severe, we may experience more significant disruptions to our clinical development timelines, which would materially and adversely affect our business and business prospects, our financial condition and the future of imetelstat.

While at this time we believe that we have sufficient drug supply for IMerge Phase 3 and IMpactMF, we could experience disruptions to our supply chain, as well as delays or limitations in our ability to obtain sufficient materials for the manufacture of imetelstat for our current and potential future clinical trials.

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For example, we have experienced manufacturing schedule delays at one of our contract manufacturers due to government mandated manufacturing of high priority COVID-19 vaccines in connection with Operation Warp Speed, and we anticipate other delays, or potential shortages of consumable manufacturing supplies, may continue throughout 2022.

The effects of the COVID-19 pandemic have increased market volatility and could result in a significant long-term disruption of global financial markets, reducing or eliminating our ability to raise additional capital.

We will require additional funding to further advance the imetelstat program, including through the completion of IMpactMF and the planned exploratory studies in new indications, including IMproveMF and investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF.

In addition, the global economic slowdown caused by the COVID-19 pandemic could materially and adversely affect our business and the value of our common stock.

The effects of the COVID-19 pandemic, as well as broader economic conditions, including inflation, rising interest rates and the prospects for recession, have increased market volatility and could result in a significant long-term disruption of global financial markets, reducing or eliminating our ability to raise additional capital.

In addition, the global economic slowdown caused by, among other things, the COVID-19 pandemic and the military conflict between Ukraine and Russia, as well as inflation, rising interest rates and the prospects for recession, could materially and adversely affect our business and the value of our common stock.

As a result of these factors, our ability to raise additional capital may be impaired which could negatively affect our liquidity, our business and business prospects and the future of imetelstat.

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Such developments include continued spread of COVID-19 variants and subvariants in the U.S.

and other countries and the potential emergence of other SARS-CoV-2 variants that may prove especially contagious or virulent, the ultimate duration and severity of the pandemic, travel restrictions, quarantines, social distancing, shipping delays and business closure requirements in the U.S.

and other countries and the potential emergence of new variants or additional sub-variants that may prove especially contagious or virulent, the ultimate duration and severity of the pandemic, travel restrictions, quarantines, social distancing, shipping delays and business closure requirements in the U.S.

and in other countries, and the effectiveness of vaccination programs and other actions taken globally to treat and manage this health crisis.

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Successful drug development and commercialization requires significant amounts of capital.

Under current planning assumptions, we believe our existing capital resources, including the net proceeds from the public offering completed in April 2022, and projected future proceeds of up to $124.3 million from the exercise of currently outstanding warrants will be sufficient to fund our projected level of operations, which includes preparatory activities for potential U.S.

commercial launch of imetelstat in lower risk MDS, until the end of 2023.

Absent these projected warrant proceeds, under current planning assumptions, we believe our existing capital resources, including the net proceeds from the public offering completed in April 2022, will be sufficient to fund our projected level of operations, which includes preparatory activities for potential U.S.

commercial launch of imetelstat in lower risk MDS, until the end of the second quarter of 2023.

Under current planning assumptions, we believe our existing capital resources, including the potential future proceeds of up to $124.3 million from the exercise of currently outstanding warrants and potential drawdowns of up to $50.0 million under the recently expanded Loan Agreement that are subject to our achievement of certain clinical and regulatory milestones and satisfaction of certain capitalization and other requirements, would be sufficient to fund our projected level of operations, which includes stage-gated activities for potential U.S.

commercial launch of imetelstat in lower risk MDS, until the middle of 2024.

Absent these potential warrant proceeds and availability of debt drawdowns under the Loan Agreement, under current planning assumptions, we believe our existing capital resources will be sufficient to fund our projected level of operations, which includes stage-gated activities for potential U.S.

commercial launch of imetelstat in lower risk MDS, until the end of the third quarter of 2023.

Importantly, our ability to raise additional capital to fund our operations after the end of the third quarter of 2023 will be substantially dependent on the top-line results from IMerge Phase 3.

If the top-line results from IMerge Phase 3 are negative, inconclusive or otherwise do not meet the expectations of investors, analysts and our lenders, our ability to raise additional capital to fund our operations after the end of the third quarter of 2023 will be substantially impaired, which might cause us to cease operations.

In any event, we will require substantial additional funding to further advance the imetelstat program, including through the completion of IMpactMF and IMproveMF and the planned investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF.

In addition, our ability to commercialize imetelstat in the U.S., if regulatory approval is granted, depends on us being able to establish sales and marketing capabilities.

Because the outcome of any clinical activities and/or regulatory approval process is highly uncertain, we cannot reasonably estimate whether any development activities we may undertake will succeed, and we may never recoup our investment in any imetelstat 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 will be further delayed or interrupted if COVID-19 or pandemic conditions continue unabated, or worsen, creating further limitations on our clinical trial activities, or could be disrupted by civil or political unrest (such as the current military conflict between Ukraine and Russia).

In addition, our plans and timing expectations will be further delayed or interrupted if COVID-19 or pandemic conditions worsen, creating further limitations on our clinical trial activities, or could be disrupted by civil or political unrest (such as the current military conflict between Ukraine and Russia).

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

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the scope, progress, timing, magnitude and costs of clinical development, manufacturing and potential commercialization of imetelstat, including the number of indications being pursued, subject to clearances and approvals by the FDA and similar regulatory authorities in other countries;

the scope, progress, duration, results and costs of current clinical trials, including IMerge Phase 3 and IMpactMF, and potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, as well as non-clinical studies and assessments of imetelstat;

delays or disruptions in opening sites, screening and enrolling patients or treating and following patients, in IMpactMF or any potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, whether as a result of the effects of the COVID-19 pandemic, the effects of the current military conflict between Ukraine and Russia or for any other reasons;

the scope, progress, duration, results and costs of current clinical trials, including IMerge Phase 3, IMpactMF and IMproveMF, and potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, as well as non-clinical studies and assessments of imetelstat;

delays or disruptions in opening sites, screening and enrolling patients or treating and following patients, in IMpactMF and IMproveMF or any potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, whether as a result of the effects of the COVID-19 pandemic, the effects of the current military conflict between Ukraine and Russia or for any other reasons;

the costs, timing and outcomes of regulatory reviews or other regulatory actions related to imetelstat, such as obtaining and maintaining regulatory clearances and approvals for IMerge Phase 3 and IMpactMF in the U.S.

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the costs of manufacturing imetelstat, including our ability to achieve any meaningful reduction in manufacturing costs;

the costs of multiple third-party vendors and service providers, including our CROs and CMOs, to pursue the development, manufacturing and potential commercialization of imetelstat;

the costs of multiple third-party vendors and service providers, including our CROs and third-party manufacturers, to pursue the development, manufacturing and potential commercialization of imetelstat;

our ability to establish, enforce and maintain collaborative or other strategic arrangements for research, development, clinical testing and manufacturing of imetelstat and potential future commercialization and marketing;

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the costs and timing necessary to build a sales force in the U.S.

to market and sell imetelstat, should it receive regulatory approval;

and potentially other countries to market and sell imetelstat, should it receive regulatory approval;

the sales price for imetelstat, if any;

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the costs of maintaining and operating facilities in California and New Jersey, telecommunications and administrative oversight, as well as higher expenses for travel;

broader economic conditions, including inflation, rising interest rates and the prospects for recession, that may reduce our ability to access debt capital or financing on preferable terms, which may adversely affect future capital requirements and forecasts;

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

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Additional financing through public or private debt or equity financings, including pursuant to the 2020 Sales Agreement with B.

Riley Securities, the remaining $25.0 million Tranche C drawdown under the Loan Agreement to the extent available, capital lease transactions or other financing sources may not be available on acceptable terms, or at all.

Riley Securities, the remaining tranches of up to $75.0 million available under the Loan Agreement, subject to the achievement of certain clinical and regulatory milestones and satisfaction of certain capitalization and other requirements, including approval by an investment committee comprised of Hercules and SVB, capital lease transactions or other financing sources 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 caused by the effects of the COVID-19 pandemic, and may in the future be affected by other factors which are unpredictable and over which we have no control.

The receptivity of the public and private debt and equity markets to proposed financings has been substantially affected by uncertainty in the general economic, market and political climate caused by the effects of the COVID-19 pandemic, the current military conflict between Ukraine and Russia and general economic conditions, and may in the future be affected by other factors which are unpredictable and over which we have no control.

In this regard, the effects of the COVID-19 pandemic 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.

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We cannot assure you that our existing capital resources, future interest income, and potential future sales of our common stock, including under the 2020 Sales Agreement with B.

Riley Securities or potential future drawdown, if available, of the remaining $25.0 million of Tranche C under our Loan Agreement, will be sufficient to fund our operating plans.

In this regard, under the Loan Agreement, our ability to draw down any funds under Tranche C is subject to certain conditions, including approval by an investment committee comprised of Hercules and SVB.

Without investment committee approval, we will not be eligible to draw down any funds under Tranche C of the Loan Agreement, and we will need to obtain additional or alternative financing to advance our development of imetelstat.

In any event, we will require additional funding to further advance the imetelstat program, including through the completion of IMpactMF and the planned exploratory studies in new indications, including IMproveMF and investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF, and our need for additional funds may arise sooner than planned.

If adequate funds are not available on a timely basis, if at all, we may be unable to pursue further development, including completing IMpactMF, or commencing, conducting or completing potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, or pursuing potential commercialization of imetelstat, which would severely harm our business and we might cease operations.

Riley Securities or potential future drawdowns, if available, of the remaining up to $75.0 million under the Loan Agreement, will be sufficient to fund our operating plans.

In this regard, under the Loan Agreement, our

ability to draw down any funds is subject to our achievement of certain clinical and regulatory milestones and satisfaction of certain capitalization requirements and other conditions, including approval by an investment committee comprised of Hercules and SVB.

Without such approval, we will not be eligible to draw down any funds under the final $25.0 million tranche of the Loan Agreement, and we will need to obtain additional or alternative financing to advance our development of imetelstat.

If adequate funds are not available on a timely basis, if at all, we may be unable to pursue further development, including completing IMpactMF and IMproveMF, or commencing, conducting or completing potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, or pursuing potential commercialization of imetelstat, which would severely harm our business and we might cease operations.

We currently have no source of product revenue and may never become profitable.

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In addition, we are incurring and have incurred operating losses every year since our operations began in 1990, except for one.

As of March 31, 2022, our accumulated deficit was approximately $1.3 billion.

As of June 30, 2022, our accumulated deficit was approximately $1.3 billion.

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

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Our license agreements related to our hTERT technology have expired or been terminated due to expiration of the underlying hTERT patents, and will not generate any significant revenues.

We have no ongoing collaborations related to imetelstat and have no current plans to enter into any corporate collaboration, partnership or license agreements that result in revenues.

We have no ongoing collaborations related to imetelstat and have no current plans to enter into any corporate collaboration, partnership or license agreements that result in revenues, although we may seek a collaborative partner or partners, at an appropriate time, to assist us in the potential development and commercialization of imetelstat, especially outside the U.S., and to provide funding for such activities.

We also expect to experience increased negative cash flow for the foreseeable future as we fund our operations and imetelstat clinical development activities advance and research programs continue.

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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.*

Under the Loan Agreement, drawdowns are available in three tranches, or Tranches A, B and C, subject to certain terms and conditions, including, with respect to Tranche C, approval by an investment committee comprised of Hercules and SVB.

Concurrently with the closing of the Loan Agreement, we borrowed $25.0 million of Tranche A.

In June 2021, we drew down the remaining $10.0 million available under Tranche A and in December 2021, we drew down $15.0 million available under Tranche B.

Without investment committee approval, we will not be eligible to draw funds under Tranche C of the Loan Agreement, and we will need to obtain additional or alternative financing to advance our development of imetelstat.

As of June 30, 2022, the total outstanding principal amount under the Loan Agreement is $50.0 million.

The tranches for the remaining $75.0 million available to us under the Loan Agreement are as follows:

a) the first remaining tranche of $20.0 million is available within 30 days of the achievement of certain clinical and financial milestones until September 15, 2023, subject to the achievement of such milestones;

b) the second remaining tranche of $10.0 million is available from January 1, 2023 until December 15, 2023, subject to the achievement of certain clinical and regulatory milestones, and satisfaction of certain other requirements;

c) the third remaining tranche of $20.0 million is available from September 15, 2023 until September 15, 2024, subject to the achievement of certain clinical and regulatory milestones, and satisfaction of certain capitalization requirements;

and d) the final remaining tranche of $25.0 million is available through December 31, 2024, subject to approval by an investment committee comprised of Hercules and SVB.

Without the achievement of the required clinical and regulatory milestones and satisfaction of certain capitalization and other requirements, we will not be eligible to draw funds under the first three remaining tranches.

If we do not receive investment committee approval, we will not be eligible to draw funds under the final remaining tranche under the Loan Agreement.

If we are not able to draw additional funds under the Loan Agreement, we will need to obtain additional or alternative financing to advance our development of imetelstat.

Such additional or alternative financing may not be available on attractive terms, if at all, and could be more costly for us to obtain.

In addition, before we would consider drawing down Tranche C of the Loan Agreement, if available, we must first satisfy ourselves that we will have access to future alternate sources of capital, such as from 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.

In addition, before we would consider drawing down any of the remaining tranches under the Loan Agreement, if available, we must first satisfy ourselves that we will have access to future alternate sources of capital, such as from 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.

As a result, our development of imetelstat and other research and development programs could be significantly delayed, which would materially adversely affect our business, business prospects, financial condition and operating results.

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

If we are able to draw down Tranche C, our indebtedness will increase, which would further increase our risk of being unable to pay off or refinance our outstanding debt obligations at maturity.

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

Our indebtedness could also have important negative consequences, including:

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engage in certain transactions with affiliates.

The Loan Agreement, as amended in August 2021, also contains financial covenants requiring us to maintain a cash balance in an amount greater than or equal to $30.0 million, commencing June 1, 2022, which balance minimum could be reduced to $20.0 million upon achievement of certain regulatory milestones.

Under the amended Loan Agreement, if we enter into certain licensing transactions, this cash covenant requirement would increase to $35.0 million.

The Loan Agreement, as recently amended in June 2022, also contains financial covenants.

Beginning June 1, 2022 and prior to receiving potential regulatory approval for imetelstat, if any, we are required to maintain a minimum cash balance in an amount equal to the greater of:

50% of the outstanding principal amount under the Loan Agreement or $30.0 million.

Under the Loan Agreement, if we enter into certain licensing transactions, this cash covenant requirement would increase to $35.0 million.

After the potential regulatory approval for imetelstat, if any, the minimum cash requirement may be satisfied through one of the following three options, as elected by us:

a) maintaining a cash balance in an amount not less than 40% of the outstanding principal amount under the Loan Agreement;

b) maintaining a cash balance in an amount not less than 25% of the outstanding principal amount under the Loan Agreement, if our market cap is or exceeds $750.0 million;

or c) maintaining six month net product revenues of at least 70% of net product revenues forecasted by us, should any potential regulatory approval for imetelstat be obtained.

The breach of any of these restrictive covenants or any other terms of the Loan Agreement would accelerate our obligation to repay our indebtedness under the Loan Agreement, which could have a material adverse effect on our business, business prospects and financial position.

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

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.

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 Loan Agreement could result in an event of default.

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We intend to develop imetelstat broadly for hematologic malignancies, and to potentially commercialize, market and sell imetelstat in the U.S.

We may seek another collaborative partner or partners, at an appropriate time, to assist us in the potential development and commercialization of imetelstat, especially outside the U.S., and to provide funding for such activities.

We may seek a collaborative partner or partners, at an appropriate time, to assist us in the potential development and commercialization of imetelstat, especially 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.

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Moreover, given the significant risks and uncertainties regarding the future imetelstat development program, potential collaborative partners may be reluctant to enter into new collaborative arrangements with us, or may only be willing to do so on terms that are not favorable to us.

As a result, we may not be successful in finding a new collaborative partner or partners on favorable terms, if at all.

As a result, we may not be successful in finding a collaborative partner or partners on favorable terms, if at all.

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

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

In order to advance the imetelstat program, including through completion of IMerge Phase 3 and IMpactMF, or to commence, conduct and complete potential future clinical trials of imetelstat, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, as well as undertaking potential commercialization activities for imetelstat in the U.S., we will need to

raise substantial additional capital.

In order to advance the imetelstat program, including through completion of IMerge Phase 3, IMpactMF and IMproveMF, or to commence, conduct and complete potential future clinical trials of imetelstat, such as the planned investigator-led clinical trials in AML and higher risk MDS, as well as undertaking potential commercialization activities for imetelstat in the U.S., we will need to raise substantial additional capital.

In addition, if we elect to increase our expenditures to fund imetelstat development or commercialization activities outside the U.S., we will be required to substantially increase our personnel resources and we will need to obtain substantial further capital, which may not be available to us on acceptable terms, or at all.

If we are unable to raise substantial additional capital, we will not be able to further advance the imetelstat program, including through the completion of IMpactMF and the planned exploratory studies in new indications, including IMproveMF and investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF to generate product revenues.

If we are unable to raise substantial additional capital, we will not be able to further advance the imetelstat program, including through the completion of IMpactMF, IMproveMF and the planned investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF to generate product revenues.

Establishing the infrastructure necessary to further develop, commercialize, market and sell imetelstat worldwide will require substantial resources and may divert the attention of our management and key personnel and negatively impact our imetelstat development or commercialization efforts in the U.S.

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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.

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 cease our development of imetelstat.

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motion for class certification.

Discovery has commenced and will be completed by August 2, 2022.

Trial is scheduled to begin on October 31, 2022.

Discovery has commenced and will be completed by October 14, 2022.

Trial is scheduled to begin on January 17, 2023.

Between April 23, 2020 and June 8, 2021, seven shareholder derivative actions were filed, naming as defendants certain of our current officers and certain current and former members of our board.

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On October 12, 2021, we filed our motion to dismiss the consolidated amended complaint.

The Court of Chancery of the State of Delaware heard oral argument on the motion on February 15, 2022, but has not yet issued an order deciding the motion;

The Court of Chancery of the State of Delaware heard oral argument on the motion on February 15, 2022, and, on June 22, 2022, issued an order staying its decision on our motion to dismiss until after the trial in the consolidated class action lawsuit described above;

The consolidated shareholder derivative actions filed in the U.S.

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Subsequent to the grant of class certification on April 2, 2022, in the consolidated class action lawsuit described above, on May 3, 2022, the Northern District entered an order providing plaintiffs until June 7, 2022, to file an amended complaint.

The parties will have fifteen calendar days from plaintiffs filing of an amended complaint, or until June 22, 2022, to submit a stipulation regarding further proceedings.

The Northern District has also scheduled an initial case management conference to occur on July 14, 2022;

On June 7, 2022, plaintiffs filed an amended shareholder derivative complaint.

On July 6, 2022, the Northern District entered an order staying the consolidated shareholder derivative actions filed in the Northern District until the earlier of either a public announcement of a settlement in the consolidated class action lawsuit described above or a final, non-appealable judgment in the consolidated class action lawsuit described above;

Our motion to dismiss the shareholder derivative action pursuant to the forum selection clause in our amended and restated bylaws was filed in the Superior Court of California for the County of San Mateo on August 5, 2021.

At the hearing on the motion to dismiss on November 2, 2021, the court granted our motion to dismiss and stayed the case until April 19, 2022.

At the case management conference on April 19, 2022, the court continued the stay until June 14, 2022, when the court will hold a further hearing to decide whether the case should be dismissed.

At the case management conference on April 19, 2022, the court continued the stay until June 14, 2022.

At the case management conference on June 14, 2022, the court continued the stay until December 13, 2022, when it will hold a further case management conference.

It is possible that additional lawsuits will be filed, or allegations received from stockholders, with respect to these same 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 such

lawsuits is necessarily uncertain.

The outcome of such lawsuits is necessarily uncertain.

We could be forced to expend significant resources in the defense of the pending lawsuits and any additional lawsuits, and we may not prevail.

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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 imetelstat or our technology and/or limit the duration of the patent protection for imetelstat and our technology.

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 imetelstat or our technology and/or limit the duration of the patent protection for imetelstat and our technology.

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 imetelstat and/or our technologies will be adversely affected, and we may not be able to further develop or potentially commercialize imetelstat.

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If we fail to apply for applicable patent term extensions or adjustments, we will have a more limited time during which we can enforce our granted patent rights.

Should we seek a patent term extension, we may not be granted any such patent term extension and/or the applicable time period of such patent term extension could be less than five years.

Should we seek a patent term extension, we may not be granted any such

patent term extension and/or the applicable time period of such patent term extension could be less than five years.

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

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It is possible that implementation of the EU Patent Package will occur in the fourth quarter of 2022 or the first half of 2023.

If the EU Patent Package is ratified and in effect, all European patents, including those issued prior to ratification, would by default automatically fall under the jurisdiction of the UPC and allow for the possibility of obtaining pan-European injunctions.

If the EU Patent Package is ratified and in effect, all European patents, including those issued prior to ratification, would by default

automatically fall under the jurisdiction of the UPC and allow for the possibility of obtaining pan-European injunctions.

Under the EU Patent Package as currently proposed, once the UPC is established, patent holders are permitted to “opt out”

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They are usually expensive and prolonged and can cause significant delay in the issuance of patents.

Our pending patent applications or our issued patents, or those we have licensed and may license from others, may be drawn into interference proceedings or be challenged through post-grant review procedures or litigation, any of which could delay

or prevent the issuance of patents, or result in the loss of issued patent rights.

We may not be able to obtain from our past or future collaborators the information needed to support our patent rights which could result in the loss of important patent rights.

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Proceedings to enforce our patent rights, even if obtained, in jurisdictions outside the U.S.

could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at

risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us.

could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us.

We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful.

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We may not be able to obtain a license to a technology required to pursue the research, development, manufacture or commercialization of imetelstat 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 imetelstat and could increase the development and/or production costs of imetelstat.

could increase the development and/or production costs of imetelstat.

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 imetelstat, which would materially and adversely impact our business.

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Both the FDA and the EMA typically conduct a review of proposed product names, including an evaluation of potential for confusion with other product names.

If the FDA or the EMA objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA and the EMA.

If the FDA or the EMA rejects all of our proposed proprietary product names, we may be required to expend additional time and resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA and the EMA.

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.

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

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

clinical data to date indicating potential

disease-modifying activity with imetelstat treatment;

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

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immunomodulators, such as Revlimid (lenalidomide) by Celgene Corporation, a Bristol-Myers Squibb Corporation, or Celgene;

hypomethylating agents, such as

Vidaza (azacitidine) by Celgene and manufacturers of generic azacitidine;

hypomethylating agents, such as Vidaza (azacitidine) by Celgene and manufacturers of generic azacitidine;

Dacogen (decitabine) by Otsuka America Pharmaceutical, Inc.

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Other therapies currently in Phase 3 development in lower risk MDS, some of which may obtain regulatory approval earlier than imetelstat include roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, by FibroGen, Inc;

Onureg (oral azacytidine) by Bristol-Myers Squibb Corporation, or BMS;

and Hengqu (hetrombopag), an oral nonpeptide thrombopoietin receptor agonist, by Jiangsu Hengrui Pharmaceutical.

In addition, there are multiple Phase 1 and Phase 2 clinical trials of other agents being developed for lower risk MDS, including but not limited to:

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a lower dose of ASTX727, an oral formulation of decitabine and cedazuridine, referred to as ASTX727 LD, by Astex;

ATX030, an oral formulation of azacitidine and cedazuridine, by Astex;

ASTX030, an oral formulation of azacitidine and cedazuridine, by Astex;

R289, an oral inhibitor of interleukin receptor-associated kinases 1 and 4, or IRAK1/4, by Rigel Pharmaceuticals, Inc.;

and a combination treatment regimen of luspatercept and lenalidomide by Bristol Myers Squibb Corporation.

a combination treatment regimen of luspatercept and lenalidomide by BMS;

and HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, by BMS.

If approved for commercial sale for the treatment of MF, imetelstat would compete against currently approved JAK inhibitors:

Jakafi (ruxolitinib) by Incyte Corporation and Inrebic (fedratinib) by Celgene, as well as a kinase inhibitor, Vonjo (pacritinib), by CTI Biopharma Corp., which was approved in February 2022 for the treatment of adults with intermediate or high-risk primary or secondary myelofibrosis with a platelet count below 50 ×

Jakafi (ruxolitinib) by Incyte Corporation, or Incyte, and Inrebic (fedratinib) by Celgene, as well as a kinase inhibitor, Vonjo (pacritinib), by CTI Biopharma Corp., which was approved in February 2022 for the treatment of adults with intermediate or high-risk primary or secondary myelofibrosis with a platelet count below 50 ×

Other treatment modalities for MF include hydroxyurea for the management of splenomegaly, leukocytosis, thrombocytosis and constitutional symptoms;

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navitoclax, a BCLXL, BCL-2 and BCLW inhibitor, by AbbVie, Inc.;

and parsaclisib, a PI3K delta inhibitor, by Incyte Corporation.

Other approaches for MF currently under investigation that could compete with imetelstat in the future include luspatercept, a TGF-beta inhibitor, by Acceleron (acquired by Merck in November 2021), in collaboration with Celgene;

and parsaclisib, a PI3K delta inhibitor, by Incyte.

Other approaches for MF currently under investigation that could compete with imetelstat in the future include luspatercept, in collaboration with Celgene;

PRM-151, an anti-fibrosis antibody, by Promedior, Inc.

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DISC-0974, a monoclonal antibody against hemojuvelin (HJV) by DISC Management Inc.;

and KER-050, an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-beta receptor in combination with ruxolitinib, by Keros Therapeutics.

KER-050 in combination with ruxolitinib, by Keros Therapeutics;

CK0804, an allogeneic T-regulatory cell agent, by Cellenkos, Inc.

in collaboration with Incyte;

and a mutated-CALR vaccine, a peptide-based vaccine, from the Icahn School of Medicine at Mount Sinai.

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

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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.

Assuming we obtain coverage for imetelstat by a

third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high.

Assuming we obtain coverage for imetelstat by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high.

If imetelstat is approved for commercial sale, patients are unlikely to use it unless coverage is provided, and reimbursement is adequate to cover all or a significant portion of its cost.

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and some jurisdictions in other countries are considering or have enacted legislative and regulatory proposals to contain healthcare costs, as well as to improve quality and expand access.

For example, in March 2010, the ACA was signed into law, which included a number of provisions of importance to the biopharmaceutical industry.

For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the ACA was signed into law, which included a number of provisions of importance to the biopharmaceutical industry.

There have been judicial and Congressional challenges to certain aspects of the ACA, and it is possible that the ACA will be subject to judicial or Congressional challenges in the future.

For example, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,”

In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,”

with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

We expect that other healthcare reform measures that may be adopted in the future may result in more rigorous coverage criteria and lower reimbursement, and additional downward pressure on the price that may be charged for imetelstat.

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

data privacy and security laws, including HIPAA, as amended by HITECH;

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

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

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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 preclinical studies or clinical trials, which could result in regulatory sanctions and serious harm to our reputation.

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.

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Historically, our stock price has been extremely volatile.

Between April 1, 2012 and March 31, 2022, our stock has traded as high as $7.79 per share and as low as $0.75 per share.

Between April 1, 2021 and March 31, 2022, the price has ranged between a high of $2.23 per share and a low of $0.99 per share.

Between July 1, 2012 and June 30, 2022, our stock has traded as high as $7.79 per share and as low as $0.75 per share.

Between July 1, 2021 and June 30, 2022, the price has ranged between a high of $1.74 per share and a low of $0.99 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:

announcements regarding the research and development of imetelstat, or results of, further delays in the commencement, enrollment or conduct of, discontinuation of, or further modifications or refinements to any clinical trials of imetelstat, including IMerge Phase 3 or IMpactMF, for any reason, or our inability, for any reason, to successfully continue the development of imetelstat;

obtaining substantial additional capital, on commercially reasonable terms, necessary to further advance the imetelstat program, including through the completion of IMpactMF and the planned exploratory studies in new indications, including IMproveMF and investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF;

obtaining substantial additional capital, on commercially reasonable terms, necessary to further advance the imetelstat program, including through the completion of IMpactMF and IMproveMF and the planned investigator-led trials in AML and higher risk MDS, as well as conducting the clinical, regulatory and potential commercialization activities necessary to potentially bring imetelstat to market in lower risk MDS and refractory MF;

preliminary, interim or final clinical trial data reported with respect to current or potential future clinical trials of imetelstat, and investor perceptions thereof;

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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, which would hurt our financial condition and results of operations and divert management’s attention and resources, which could result in delays of IMerge Phase 3 and IMpactMF and/or could preclude or delay potential future clinical trials, such as IMproveMF and planned investigator-led clinical trials in AML and higher risk MDS, or could preclude or delay commercialization efforts.

The pending lawsuits and any lawsuits brought against us in the future could result in substantial costs, which would hurt our financial condition and results of operations and divert management’s attention and resources, which could result in delays of IMerge Phase 3, and IMpactMF and IMproveMF and/or could preclude or delay potential future clinical trials, such as the planned investigator-led clinical trials in AML and higher risk MDS, or could preclude or delay commercialization efforts.

We may fail to continue to meet the listing standards of Nasdaq, and as a result our common stock may be delisted, which could have a material adverse effect on the liquidity of our common stock.

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The sale of a substantial number of shares may adversely affect the market price of our common stock.

As of March 31, 2022, we had 675,000,000 shares of common stock authorized for issuance and 323,736,875 shares of common stock outstanding.

Additionally, as of March 31, 2022, we had reserved 134,217,526 shares of our common stock for future issuance pursuant to our stock option and equity incentive plans and outstanding warrants.

Adding to these amounts, on April 1, 2022, we completed an underwritten public offering of 53,333,334 shares of our common stock and a pre-funded warrant to purchase 18,095,238 shares of our common stock, also known as the 2022 pre-funded warrant, together with accompanying warrants to purchase 35,714,286 shares of our common stock, also known as the 2022 stock purchase warrants.

As of June 30, 2022, we had 675,000,000 shares of common stock authorized for issuance and 377,664,759 shares of common stock outstanding.

Additionally, as of June 30, 2022, we had reserved 199,327,500 shares of our common stock for future issuance pursuant to our stock option and equity incentive plans and outstanding warrants.

Future sales of our common stock or the perception that such sales could occur, or the issuance of common stock to fund our operations and imetelstat development, including pursuant to the 2020 Sales Agreement with B.

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In addition, we rely on third party service providers to establish and maintain appropriate information technology and data security protections over the information technology systems they provide us to operate our critical business systems, including cloud-based infrastructure and systems, employee email, and data storage and management systems.

However, except for contractual duties and obligations, we have limited ability to control their

safeguards and actions related to such matters, and these third parties may not have adequate information security measures in place.

However, except for contractual duties and obligations, we have limited ability to control their safeguards and actions related to such matters, and these third parties may not have adequate information security measures in place.

We may share or receive sensitive information with or from third parties.

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In the ordinary course of business, we process personal data and other sensitive data, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials, and sensitive third-party data.

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

We are therefore subject to or affected by numerous data privacy and security obligations, such as various federal,

state, local and foreign laws, regulations, guidances, industry standards, external and internal privacy and security policies, contracts, and other obligations governing the processing of personal data by us and on our behalf.

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

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For example, the European Union’s General Data Protection Regulation (GDPR) (EU) 2016/679, or the EU GDPR, imposes strict requirements on the processing of personal data.

Under the EU GDPR, government regulators may impose temporary or definitive

bans on data processing, as well as fines of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater.

Under the EU GDPR, government regulators may impose temporary or definitive bans on data processing, as well as fines of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater.

Certain jurisdictions, including the EU and the UK, have enacted data localization laws and cross-border personal data transfer laws, which would make it more difficult to transfer information across jurisdictions (such as transferring or receiving personal data that originates in the EU or in other foreign jurisdictions).

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bans on processing personal data;

orders to destroy or not use personal data;

orders to destroy or not use personal

and imprisonment of company officials.

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Business disruptions could seriously harm our future revenue and financial condition and increase our costs and expenses.

unrest (such as the current military conflict between Ukraine and Russia), terrorism, insurrection or war, and other natural or man-made disasters or business interruptions.

Our operations, and those of our CROs, suppliers, and other contractors and consultants, could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, public health pandemics or epidemics (including, for example, the ongoing COVID-19 pandemic), geopolitical events, including civil or political unrest (such as the current military conflict between Ukraine and Russia), terrorism, insurrection or war, and other natural or man-made disasters or business interruptions.

Furthermore, other events, such as the armed conflict between Russia and Ukraine, could lead to sanctions, embargoes, supply shortages, regional instability, geopolitical shifts, cyberattacks, other retaliatory actions, and adverse effects on macroeconomic conditions, currency exchange rates, and financial markets, which could adversely impact our operations and financial results, as well as those of third parties with whom we conduct business.

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Therefore, we cannot assure you that material weaknesses or significant deficiencies will not exist or otherwise be discovered in the future, particularly in light of our increased reliance on personnel working remotely as a result of the COVID-19 pandemic.

If material weaknesses or other significant deficiencies 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.

If material weaknesses or other significant deficiencies 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.

UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS

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

What changed 10-Q

Item 1. Legal Proceedings