Company Overview
| Company Name |
STEMLINE THERAPEUTICS INC |
| Company Address |
750 LEXINGTON AVENUE
NEW YORK, NY 10022 |
| Company Phone |
212-831-1111 |
| Company Website |
www.stemline.com |
| CEO |
Ivan Bergstein |
| Employees (as of 11/30/2012) |
8 |
| State of Inc |
DE |
| Fiscal Year End |
12/31 |
| Status |
Priced (1/29/2013) |
| Proposed Symbol |
STML |
| Exchange |
Nasdaq SmallCap Market |
| Share Price |
$10.00 |
| Shares Offered |
3,317,644 |
| Offer Amount |
$33,176,440.00 |
| Total Expenses |
$2,700,000.00 |
| Shares Over Alloted |
0 |
| Shareholder Shares Offered |
-- |
| Shares Outstanding |
6,960,914 |
| Lockup Period (days) |
180 |
| Lockup Expiration |
7/29/2013 |
| Quiet Period Expiration |
3/11/2013 |
| CIK |
0001264587 |
We estimate that the net proceeds from our issuance and sale of 3,317,644 shares
of our common stock in this offering will be approximately $27.8 million, based
on the initial public offering price of $10.00 per share, and after deducting
underwriting discounts and commissions and offering expenses payable by us. If
the representative of the underwriters exercises its over-allotment option in
full, we estimate that the net proceeds from this offering will be approximately
$32.4 million, based on the initial public offering price of $10.00 per share,
and after deducting underwriting discounts and commissions and offering expenses
payable by us.
We intend to use the net proceeds from this offering for clinical development of
SL-401 and SL-701 and other general corporate purposes:
º SL-401. We plan to complete a pivotal Phase 2b single-arm trial of
SL-401 in patients with BPDCN. We plan to use approximately
$1.5 million to complete the BPDCN trial. We also plan to advance
SL-401 into a registration-directed randomized Phase 2b clinical trial
to treat adult AML patients as a third-line treatment. We plan to use
approximately $7 million to initiate and advance the AML trial to an
interim analysis at 60 and 90 patients.
º SL-701. We plan to advance SL-701 into a Phase 2b clinical trial to
treat pediatric patients with malignant glioma. We also plan to
initiate a Phase 2b clinical trial of SL-701 in adult second-line GBM.
We plan to use approximately $1 million, together with funding we are
seeking to obtain from the National Cancer Institute, or NCI, for the
pediatric trial, to complete these trials.
º The remaining proceeds will be used for general corporate purposes.
This expected use of the net proceeds from this offering represents our
intentions based upon our current plans and business conditions. The amounts and
timing of our actual expenditures may vary significantly depending on numerous
factors, including the progress of our development efforts, the status of and
results from clinical trials, as well as any collaborations that we may enter
into with third parties for our product candidates, and any unforeseen cash
needs. As a result, our management will retain broad discretion over the
allocation of the net proceeds from this offering.
The net proceeds from this offering and our existing financial resources will
not be sufficient to enable us to complete our planned registration-directed
randomized Phase 2b clinical trial of SL-401 in third-line AML in its entirety,
unless the trial is stopped early at an interim analysis at 90 or fewer
patients. We expect to need to raise additional capital in order to complete
this clinical trial, but the timing and extent of the additional capital needed
to do so will depend on the interim analysis timing and results. We believe that
our existing cash, cash equivalents and marketable securities, together with the
net proceeds from this offering, will be sufficient to fund our operations and
our capital expenditures for at least the next 12 months.
Pending our use of the net proceeds from this offering, we intend to invest the
net proceeds in a variety of capital preservation investments, including
short-term, investment grade, interest bearing instruments and U.S. government
securities.
The biotechnology and pharmaceutical industries are characterized by rapidly
advancing technologies, intense competition and a strong emphasis on proprietary
products. While we believe that our scientific knowledge, technology, and
development experience provide us with competitive advantages, we face potential
competition from many different sources, including major pharmaceutical,
specialty pharmaceutical and biotechnology companies, academic institutions and
governmental agencies and public and private research institutions. Any product
candidates that we successfully develop and commercialize will compete with
existing therapies and new therapies that may become available in the future.
There are several biopharmaceutical companies whose primary focus appears to be
developing therapies against CSCs, including Boston Biomedical, Inc., Eclipse
Therapeutics, Inc., OncoMed Pharmaceuticals, Inc. and Verastem, Inc. There are
also several biopharmaceutical companies that do not appear to be primarily
focused on CSCs, but may be developing at least one CSC-directed compound. These
companies include Astellas Pharma US, Inc., Boehringer Ingelheim GmbH, Dainippon
Sumitomo Pharma Co. Ltd., Geron Corp., GlaxoSmithKline plc, ImmunoCellular
Therapeutics, Ltd, Macrogenics Inc., Micromet, Inc. (an Amgen, Inc. Company),
Pfizer Inc., Roche Holding AG, Sanofi U.S. LLC, and others.
Many of our competitors may have significantly greater financial resources and
expertise in research and development, manufacturing, preclinical testing,
conducting clinical trials, obtaining regulatory approvals and marketing
approved products than we do. Mergers and acquisitions in the pharmaceutical,
biotechnology and diagnostic industries may result in even more resources being
concentrated among a smaller number of our competitors. These competitors also
compete with us in recruiting and retaining qualified scientific and management
personnel and establishing clinical trial sites and patient registration for
clinical trials, as well as in acquiring technologies complementary to, or
necessary for, our programs. Small or early stage companies may also prove to be
significant competitors, particularly through collaborative arrangements with
large and established companies.
The key competitive factors affecting the success of all of our product
candidates, if approved, are likely to be their efficacy, safety, convenience,
price, the level of generic competition and the availability of reimbursement
from government and other third-party payors.
Our commercial opportunity could be reduced or eliminated if our competitors
develop and commercialize products that are safer, more effective, have fewer or
less severe side effects, are more convenient or are less expensive than any
products that we may develop. Our competitors also may obtain FDA or other
regulatory approval for their products more rapidly than we may obtain approval
for ours, which could result in our competitors establishing a strong market
position before we are able to enter the market. In addition, our ability to
compete may be affected in many cases by insurers or other third-party payors
seeking to encourage the use of generic products. If our therapeutic product
candidates are approved, we expect that they will be priced at a significant
premium over any competitive generic products.
The most common methods of treating patients with cancer are surgery, radiation
and drug therapy, including chemotherapy, hormone therapy and targeted drug
therapy. These therapies are numerous and varied in their design, therapeutic
application and mechanism of action. As a result, they may provide significant
competition for any of our product candidates for which we obtain market
approval. In addition to currently marketed oncology therapies, there are also a
number of products in late stage clinical development to treat cancer. These
products in development may provide efficacy, safety, convenience and other
benefits that are not provided by currently marketed therapies. As a result,
they may provide significant competition for any of our product candidates for
which we obtain market approval.
Competition for SL-401
There are a limited number of drugs approved for the treatment of adult AML, and
these include the traditional chemotherapies cytarabine, daunorubicin, and other
anthracyclines which have been marketed for many years and are both currently
available in generic formulations. There are a number of companies working to
develop new treatments for AML, including Cyclacel Pharmaceuticals, Inc.,
Sunesis Pharmaceuticals Inc., Genzyme Corporation (now a Sanofi company), Clavis
Pharma ASA, Ambit Biosciences Corporation, Celgene Corporation, Eisai Co. Ltd.
and Celator Pharmaceuticals, Inc., among others.
Unlike many of these drug candidates, SL-401 has been developed to target both
tumor bulk and CSCs and, to date, has been shown to spare the bone marrow of
toxicity. While SL-401 is currently being developed as a single agent, its
favorable safety profile suggests the potential to safely combine it with other
agents.
Competition for SL-701
There are a limited number of drugs used for the treatment of brain cancer,
including Temodar® (Merck & Co., Inc.), nitrosureas including Gliadel® (Eisai
Co., Inc.), and Avastin® (Roche Holding AG). There are a number of
companies working to develop brain cancer therapeutics with programs in clinical
testing including Roche Holding AG, Novartis AG, Merck & Co., Inc., Celldex
Therapeutics, Inc., ImmunoCellular Therapeutics, Ltd. and others.
Unlike many of these drug candidates, SL-701 has been developed to target both
tumor bulk and CSCs. While SL-701 is currently being developed as a single
agent, its favorable safety profile suggests the potential to safely combine it
with other agents.
Company Description
We are a clinical-stage biopharmaceutical company focused on discovering,
acquiring, developing and commercializing proprietary therapeutics that target
both cancer stem cells, or CSCs, and tumor bulk. We believe that we are
developing the most clinically advanced pipeline of anti-CSC therapeutics
and
that we hold a broad portfolio of CSC-focused intellectual property,
establishing us as a leader in the CSC field. Among the therapeutic candidates
in our portfolio, we are currently developing two clinical-stage product
candidates, SL-401 and SL-701, for which we hold global marketing rights. The
lead indications for SL-401, a biologic targeted therapy (a therapy designed to
preferentially target cancer cells), are blastic plasmacytoid dendritic cell
neoplasm, or BPDCN, a rare hematologic cancer, and acute myeloid leukemia, or
AML. The lead indications for SL-701, a therapeutic cancer vaccine comprised of
synthetic peptides that correspond to specific targets, called epitopes, on CSCs
and tumor bulk of brain cancer, are pediatric and adult brain cancer. In
completed Phase 1/2 clinical trials, both SL-401 and SL-701 have demonstrated
single agent activity (activity as a stand-alone therapy), including instances
of durable complete responses, or CRs, which is the disappearance of all signs
of cancer in response to treatment. In addition, SL-401 and SL-701 have
demonstrated a longer overall survival, or OS, in patients compared with that
achieved in the past with traditional therapies. We plan to complete a pivotal
Phase 2b single-arm trial of SL-401 in patients with relapsed or refractory
BPDCN, with overall response rate as the primary endpoint. We also plan to
advance SL-401 into a registration-directed randomized Phase 2b clinical trial
to treat adult relapsed or refractory AML patients who failed two previous
treatments (i.e., third-line AML) with CR rate and OS as co-primary endpoints. A
registration-directed trial is one designed to meet FDA expectations necessary
for marketing approval. We plan to advance SL-701 into a Phase 2b clinical trial
to treat pediatric patients with malignant glioma. In addition, we plan to
advance SL-701 into a Phase 2b clinical trial in adult patients with
glioblastoma, or GBM, who failed one previous treatment (i.e., second-line GBM).
We have a proprietary discovery platform, StemScreen R, for the discovery of
novel CSC-targeted compounds, from which we have discovered or validated several
of our clinical and preclinical product candidates and which we believe may be
instrumental in the discovery of additional new therapies targeting a wide range
of cancer types.
The field of CSCs is a new area of cancer biology with the potential to
fundamentally alter the approach to oncology drug development. CSCs have been
identified in virtually all major tumor types, including leukemia and cancers of
the brain, breast, colon, prostate and pancreas. CSCs are the highly malignant
"seeds" of a tumor that self-renew and generate more mature cells that comprise
the bulk of the tumor, or "the tumor bulk." As such, we believe that CSCs are
responsible for tumor initiation, propagation, and metastasis. Many of the
characteristics of CSCs, such as their slow growth, presence of multi-drug
resistance proteins, anti-cell death mechanisms, and increased activity of
cellular mechanisms that repair damaged DNA, may enable CSCs to resist
therapeutic agents traditionally used to treat cancer. Further, while standard
therapies may initially shrink tumors by targeting the tumor bulk, which
excludes CSCs, we believe there is a large body of evidence indicating that
treatment failure, tumor relapse and poor survival are largely the result of the
failure of conventional cancer treatments to eradicate CSCs. Accordingly, we
believe that targeting CSCs, in addition to the tumor bulk, may represent a
major advance in the fight against cancer.
Since our inception in 2003, we have leveraged our knowledge of CSCs to
anticipate and establish a leadership position in this new field of oncology.
During this time, we have developed or strategically in-licensed key
intellectual property, built and validated a drug discovery platform and
developed clinically active drug candidates. We believe that our early and
comprehensive effort to develop a new generation of oncology therapeutics that
target CSCs as well as the tumor bulk provides us with a significant competitive
advantage.
Our most advanced product candidates are SL-401 and SL-701.
º SL-401 is a clinically active biologic targeted therapy directed to
the interleukin-3 receptor, or IL-3R. IL-3R is overexpressed (present
at higher levels, as compared with normal tissues) on both the CSCs
and tumor bulk of multiple hematologic cancers, including AML. In
contrast, IL-3R is not expressed on normal bone marrow stem cells that
form the components of blood. SL-401 demonstrated single agent
anti-tumor activity in a completed Phase 1/2 clinical trial of 80
patients with advanced hematologic cancers, including 59 patients with
relapsed or refractory AML and three patients with BPDCN. With only a
single cycle of treatment, SL-401 induced either a reduction in
leukemia blasts (i.e., tumor bulk) or disease stabilization in 46%
(27/59) of relapsed or refractory AML patients. This included two
durable CRs, and seven partial responses, or PRs. Two additional CRs
occurred after a single cycle of SL-401 in heavily pre-treated
patients with BPDCN, a rare and aggressive hematologic malignancy that
highly overexpresses IL-3R. Notably, a single cycle of SL-401 improved
the median OS of the 35 most heavily pretreated AML patients who had
failed at least two previous therapies (i.e., third-line or greater)
by more than two-fold compared with historical data. Moreover, a
single cycle of SL-401 administered at therapeutically relevant doses
(i.e., the maximum tolerated dose, or MTD, or one or two dose levels
below the MTD) improved the median OS by more than three-fold compared
with the historical median OS. In future trials, we intend to
administer multiple cycles of SL-401, which we believe may further
increase its efficacy with respect to both clinical response and
survival. Importantly, SL-401 was not toxic to the bone marrow, which
was predicted based on the absence of IL-3R on normal bone marrow stem
cells, and is a key differentiating feature relative to many other
hematologic cancer therapies. The lack of overlapping toxicities
between SL-401 and traditional therapeutics indicates that SL-401 may
be combined with standard therapeutic regimens used in early stages of
AML. The Phase 1/2 clinical trial has been completed for relapsed or
refractory AML patients. A Phase 2 trial of SL-401 is currently open
for other hematologic malignancies, including high risk
myelodysplastic syndrome, or MDS, and chronic myeloid leukemia, or
CML. The IND for SL-401 was filed on September 15, 2003 by its
sponsor, Dr. Arthur E. Frankel of the Scott and White Cancer Research
Institute. Dr. Frankel currently holds the IND.
We plan to complete a pivotal Phase 2b single-arm trial of SL-401 in
patients with relapsed or refractory BPDCN, with overall response rate as
the primary endpoint. We also plan to advance SL-401 into a
registration-directed randomized Phase 2b clinical trial to treat adult AML
patients as a third-line multiple cycle treatment with CR rate and OS as
co-primary endpoints. In addition, we plan to evaluate SL-401 as
consolidation and/or maintenance therapy in patients with AML who are in CR
following chemotherapy but have a high risk of disease recurrence, as well
as in first- and/or second-line AML in combination with chemotherapy, and
potentially in certain lymphoid and plasma cell cancers.
In February 2011, SL-401 received Orphan Drug designation from the FDA for
the treatment of AML. We plan to seek Orphan Drug designation from the FDA
for SL-401 in the treatment of BPDCN. We hold an exclusive worldwide
license with respect to SL-401.
º SL-701 is a clinically active therapeutic cancer vaccine comprised of
synthetic peptides that correspond to epitopes on CSCs and tumor bulk
of brain cancer. In two completed Phase 1/2 clinical trials, SL-701
demonstrated single agent anti-tumor activity in pediatric patients
with malignant glioma, including newly diagnosed brainstem glioma, or
BSG, and other high-grade gliomas, or HGGs, as well as low-grade
gliomas, or LGGs, and in adult patients with refractory or recurrent
GBM, and other HGGs. SL-701 induced tumor shrinkage or disease
stabilization in 86% (19/22) of patients in the pediatric study, and
59% (13/22) of patients in the adult study. This includes two CRs and
six PRs. The OS of adult patients with recurrent or refractory GBM and
other HGGs who were treated with SL-701 was increased compared with
historical results for similar patients treated with a wide range of
therapies. The INDs for SL-701 were filed by their sponsor,
Dr. Hideho Okada of the University of Pittsburgh School of Medicine,
on April 21, 2005 and December 28, 2007. Dr. Okada currently holds the
INDs.
We plan to advance SL-701 into a Phase 2b clinical trial for the treatment
of pediatric patients with malignant glioma. We also plan to initiate a
Phase 2b clinical trial in adult second-line GBM. There are also clinical
trials currently open for adult patients with LGG.
We hold an exclusive worldwide license with respect to SL-701.
We have developed a proprietary discovery platform, StemScreen R, for the
identification of novel CSC-targeted compounds. StemScreen R contrasts with
traditional drug discovery methods that have been designed to identify compounds
that target tumor bulk, not CSCs. StemScreen R includes an assay that utilizes
live cells to track CSCs in their natural state during high throughput
screening, which is a method that permits the rapid testing of many compounds on
a small scale for enhanced efficiency. We believe this approach represents a
major technological advance because not only is it CSC-focused and high
throughput, but it also does not require artificial manipulation to create
CSC-like cells as other systems do. We have utilized StemScreen R to discover a
number of our product candidates. We believe that this platform may be
instrumental in the discovery of new compounds targeting a wide range of cancer
types.
Our intellectual property portfolio includes 13 issued patents and more than 30
pending patent applications in the United States and abroad. This portfolio
includes owned and exclusively in-licensed intellectual property that we believe
is early and broad with respect to the use of CSC-directed therapeutics and
diagnostics (including companion diagnostics), as well as drug discovery.
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We were incorporated under the laws of the State of Delaware in August 2003.
Our principal executive offices are located at 750 Lexington Avenue, Sixth
Floor, New York, New York 10022 and our telephone number is (646) 502-2310.
Our website address is www.stemline.com.