Full Press Release Details
Our business is subject to various
risks, including those described below. You should carefully consider these risk
factors, together with all of the other information included in our Annual Report on Form 10-K for the year ended December 31, 2011 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2012. Any of these
risks could materially adversely affect our business, operating results and
financial condition. We have marked with an asterisk (*) those risks described
below that reflect substantive changes from, or additions to, the risks
described under Part I, Item 1A, Risk Factors included in our Quarterly Report
on Form 10-Q for the quarter ended June 30, 2012.
RISKS RELATED TO OUR
Our business is at an early stage of
development, and we must overcome numerous risks and uncertainties to become
Our business is at an early stage of
development, and we do not yet have product candidates in late-stage clinical
trials or any products commercially available. Our ability to develop product
candidates to and through commercial launch is subject to our ability to, among
achieve success in our ongoing Phase 2 clinical trials and
potential future Phase 3 clinical trials;
collaborate successfully with clinical trial
sites, academic institutions, physician investigators, clinical research organizations and other third
manufacture product candidates at commercially
obtain required regulatory clearances and
maintain and enforce adequate intellectual
property protection for our product candidates; and
obtain financing on commercially reasonable terms
to fund our operations.
There are many reasons why we may
need to delay or abandon efforts to research, develop or obtain regulatory
approvals to market our product candidates, including as a result of a product
candidate failing at any stage of the development process for any or all of the
indications we are pursuing or if we otherwise determine for business or
financial reasons to delay or discontinue development of that product candidate
for any or all indications. For example, in September 2012 we announced that, as
a result of an unplanned interim efficacy analysis, we were discontinuing our
Phase 2 clinical trial of imetelstat in metastatic breast cancer, or MBC,
because median progression-free survival in the imetelstat arm was shorter than
in the comparator arm. We also announced in September 2012 that an unplanned
interim efficacy analysis of our Phase 2 clinical trial of imetelstat in
advanced non-small cell lung cancer, or NSCLC, suggested that the pre-specified
success criteria were unlikely to be met, and, as a consequence, it is doubtful
that we will advance imetelstat forward into Phase 3 clinical development for
NSCLC. If we observe similar or other negative results in our other ongoing Phase
2 clinical trials evaluating imetelstat in essential thrombocythemia and
multiple myeloma, we may be further delayed or prevented from advancing
imetelstat into Phase 3 clinical development or we may otherwise determine to
discontinue our development of imetelstat, which would severely harm our
business and our prospects.
Our current product candidates
require significant additional clinical testing prior to regulatory approval in
the United States and other countries, and we do not expect that any of our
current product candidates will be commercially available for a number of years,
if ever. It may also be difficult to assess the success or failure of any of our
clinical trials for many reasons, including but not limited to the subjectivity
and changing landscape that accompanies the benefit-to-risk assessment in any
given patient population, and because subpopulation data might not be available
at the time we report top-line data or other results. Our product candidates
also may prove to have undesirable and unintended side effects or other
characteristics adversely affecting their safety, efficacy or cost-effectiveness
that could prevent or limit their approval for marketing and successful
commercial use, or that could delay or prevent the commencement and/or
completion of clinical trials for our product candidates.
Our product candidates may not prove
to be more effective for treating disease than current therapies. Competitors or
other third parties may also have proprietary rights that prevent us from
developing and marketing our product candidates, or our competitors may sell
similar, superior or lower-cost products that make our product candidates
unsuitable for marketing. Our product candidates also may not be able to be
manufactured in commercial quantities at an acceptable cost. Any of the
foregoing factors could delay or prevent us from developing, commercializing and
marketing our product candidates, which would materially adversely affect our
Our research and development
programs are subject to numerous risks and uncertainties. *
The science and technology of
telomere biology and telomerase, as well as receptor-targeting peptides that
cross the blood-brain barrier (BBB), are relatively new. There is no precedent
for the successful commercialization of therapeutic product candidates based on
these technologies. In addition, we, our licensees, and our collaborators must
undertake significant research and development activities to develop product
candidates based on these technologies, which will require significant
additional funding and may take years to accomplish, if ever.
Because of the significant
scientific, regulatory and commercial milestones that must be reached for any of
our research and development programs to be successful, any program, or any
aspect of a program, may be delayed or abandoned, even after we have expended
significant resources on it. Our decision to discontinue our Phase 2 clinical
trial of imetelstat in MBC, despite the investment of significant resources on
that trial, is an example of this. Any further delay or abandonment of our
programs in telomerase technology or receptor-targeting peptide technology to
cross the BBB would have a material adverse effect on and may result in the failure of
In our Phase 1 clinical trials of
imetelstat, we observed dose-limiting toxicities, including thrombocytopenia
when the drug was used as a single agent, and neutropenia when the drug was used
in combination with paclitaxel, as well as a low incidence of severe infusion
reactions. We also did not observe single-agent efficacy with imetelstat in our
Phase 1 program. Further, the information we have related to the ability of
GRN1005 to penetrate brain tissue and its anti-tumor activity is preliminary and
based on Phase 1 clinical trials conducted by Angiochem. In the Phase 1 trials
of GRN1005, Grade 4 neutropenia was the primary dose-limiting toxicity observed.
In addition, in our Phase 2 clinical trial of GRN1005 in brain metastases
arising from breast cancer, we amended our trial protocol to reduce the starting
dosage from 650 mg/m2 to 550 mg/m2 as a result of premature withdrawals from the