CASI Pharmaceuticals, Inc (DE) - Annual Report: 2006 (Form 10-K)
FORM 10-K
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D. C., 20549
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15 (d) OF
THE SECURITIES EXCHANGE ACT OF 1934
THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2006
Commission file number 0-20713
ENTREMED, INC.
(Exact name of registrant as specified in its charter)
Delaware | 58-1959440 | |
(State of Incorporation) | (I.R.S. Employer Identification No.) | |
9640 Medical Center Drive, Rockville, MD | 20850 | |
(Address of principal executive offices) | (Zip Code) |
Registrants telephone number, including area code: (240) 864-2600
Securities registered pursuant to Section 12 (b) of the Act: None
Securities registered pursuant to Section 12(g) of the Act: Common Stock, Par Value $0.01 Per Share
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule
405 of the Securities Act. Yes o No þ
Indicate by check mark if the registrant is not required to file reports pursuant to Section
13 or 15 (d) of the Act. Yes o No þ
Indicate by check mark whether the registrant (1) has filed all reports required to be filed
by Section 13 or 15 (d) of the Securities Exchange Act of 1934 during the preceding 12 months (or
for such shorter period that the registrant was required to file such reports), and (2) has been
subject to such filing requirements for the past 90 days. Yes þ No o
Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation
S-K is not contained herein, and will not be contained, to the best of registrants knowledge, in
definitive proxy or information statements incorporated by reference in Part III of this form 10-K
or any amendment to this Form 10-K þ
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated
filer, or a non-accelerated filer. (See definition of accelerated filer and large accelerated
filer in Rule 12b-2 of the Exchange Act). (Check one):
Large accelerated filer o Accelerated filer þ Non-accelerated filer o
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the
Act). Yes o No þ
As of June 30, 2006, the aggregate market value of the shares of common stock held by
non-affiliates was approximately $108,679,233.
As of February 28, 2007, 84,890,998 shares of the Companys common stock were outstanding.
Documents Incorporated By Reference
Portions of the Registrants Proxy Statement for its 2007 Annual Meeting of Stockholders (the
Proxy Statement), to be filed with the Securities and Exchange Commission, are incorporated by
reference to Part III of this Form 10-K Report.
ENTREMED, INC.
FORM 10-K FISCAL YEAR ENDED DECEMBER 31, 2006
FORM 10-K FISCAL YEAR ENDED DECEMBER 31, 2006
Contents and Cross Reference Sheet
Form 10-K | Form 10-K | Form 10-K | ||||||||
Part No. | Item No. | Description | Page No. | |||||||
I
|
1 | Business | 3 | |||||||
1A | Risk Factors | 13 | ||||||||
1B | Unresolved Staff Comments | 19 | ||||||||
2 | Properties | 19 | ||||||||
3 | Legal Proceedings | 20 | ||||||||
4 | Submission of Matters to a Vote of Security Holders | 20 | ||||||||
II
|
5 | Market for Registrants Common Equity, Related Stockholder Matters And Issuer Purchases of Equity Securities | 21 | |||||||
6 | Selected Financial Data | 23 | ||||||||
7 | Managements Discussion and Analysis of Financial Condition and Results of Operation | 24 | ||||||||
7A | Quantitative and Qualitative Disclosures About Market Risk | 32 | ||||||||
8 | Financial Statements and Supplementary Data | 32 | ||||||||
9 | Changes in and Disagreements with Accountants On Accounting and Financial Disclosure | 32 | ||||||||
9A | Controls and Procedures | 33 | ||||||||
9B | Other Information | 35 | ||||||||
III
|
10 | Directors, Executive Officers and Corporate Governance | 35 | |||||||
11 | Executive Compensation | 35 | ||||||||
12 | Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters | 35 | ||||||||
13 | Certain Relationships and Related Transactions, and Director Independence | 35 | ||||||||
14 | Principal Accountant Fees and Services | 35 | ||||||||
IV
|
15 | Exhibits and Financial Statement Schedules | 36 | |||||||
Signatures | 40 | |||||||||
Audited Consolidated Financial Statements | F-1 |
1
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
This report contains certain forward-looking statements within the meaning of Section 27A of the
Securities Exchange Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934,
as amended. Forward-looking statements also may be included in other statements that we make. All
statements that are not descriptions of historical facts are forward-looking statements. These
statements can generally be identified by the use of forward-looking terminology such as
believes, expects, intends, may, will, should, or anticipates or similar terminology.
These forward-looking statements include, among others, statements regarding the timing of our
clinical trials, our cash position and future expenses, and our future revenues.
Our forward-looking statements are based on information available to us today, and we will not
update these statements. Although we believe that the expectations reflected in such
forward-looking statements are reasonable as of the date thereof, actual results could differ
materially from those currently anticipated due to a number of factors, including risks relating to
the early stage of our product candidates under development operating losses and anticipated future
losses; the value of our common stock; our need for additional capital; intense competition and
rapid technological change in the biopharmaceutical
industry; uncertainties relating to our patent and proprietary rights; uncertainties relating to
clinical trials: estimated clinical trial commencement date; government regulation; and
uncertainties of obtaining regulatory approval on a timely basis or at all. Additional information
about the factors and risks that could affect our business, financial condition and results of
operations, are contained in our filings with the U.S. Securities and Exchange Commission (SEC),
which are available at www.sec.gov.
2
PART I
ITEM 1. BUSINESS.
OVERVIEW
EntreMed, Inc. (EntreMed or the Company) (Nasdaq: ENMD) is a clinical-stage pharmaceutical
company focused on developing multi-mechanism oncology drugs that target disease cells directly and
the blood vessels that nourish them. EntreMed is focused on developing drugs that we believe are
safe and convenient, and provide the potential for improved patient outcomes.
EntreMeds goal is to develop and commercialize therapeutics based on the Companys scientific
expertise in angiogenesis, cell cycle regulation and inflammation processes vital to the
progression of cancer and other diseases. The Companys three clinical product candidates are
based on these mechanisms. The Companys expertise has also led to the identification of new
molecules, including new chemical entities derived from 2ME2 (2-methoxyestradiol), as well as new
chemical entities associated with multi-kinase inhibition and HDAC inhibition, important targets in
the treatment of oncology.
Panzem® (2-methoxyestradiol or 2ME2), one of the Companys two lead drug
candidates, is currently being tested as a cancer therapeutic in four Phase 2 clinical trials, and
has been granted U.S. Food and Drug Administration (FDA) Orphan Drug designation in three cancer
indications, including glioblastoma multiforme (GBM), multiple myeloma, and ovarian cancer. Our
second clinical stage compound is MKC-1, a novel cell cycle inhibitor, which is in Phase 2 clinical
trials for cancer. In May 2006, the Company commenced clinical studies with its third
clinical-stage compound, ENMD-1198, in patients with advanced cancer.
EntreMed is developing compounds that have broad therapeutic and commercial potential in
oncology. In order to further advance its commercial objectives, EntreMed may seek strategic
alliances, licensing relationships and co-development partnerships with other companies to develop
compounds for both oncology and non-oncology therapeutic areas.
We were incorporated under Delaware law in 1991. Our principal executive offices are located
at 9640 Medical Center Drive, Rockville, Maryland 20850, and our telephone number is (240)
864-2600.
MANAGEMENT
EntreMeds management team has aligned the Companys business strategy with its core
scientific strengths, while maintaining prudent resource management, fiscal responsibility and
accountability. Since 2004, the team has redirected EntreMeds financial resources and R&D
strategy to focus on small molecule drug candidates with broad therapeutic potential, manageable
development costs, and significant commercial opportunity. Under its senior leadership, EntreMed
is moving various small molecule compounds from discovery to clinical trials, including its two
lead candidates, Panzem® NCD and MKC-1.
SCIENTIFIC FOUNDATION
EntreMed developed its initial drug pipeline based on comprehensive research into the
relationship between malignancy and angiogenesis (the growth of new blood vessels). This research
led to a focus on drug candidates that act on the cellular pathways that affect biological
processes important in multiple diseases, specifically angiogenesis, inflammation and cell cycle
regulation. EntreMeds drug candidates have potential applications in oncology and other diseases
involved with one or more of these pathways:
3
Angiogenesis. Angiogenesis is a multi-step process in which preexisting blood vessels send
out capillary sprouts to produce new blood vessels. This tightly regulated process involves the
migration, proliferation and
differentiation of endothelial cells. In normal physiology, angiogenesis is a necessary
component of the menstrual cycle and wound healing, where the process is regulated through
appropriate shifts in the balance of pro-angiogenic and anti-angiogenic signals. This tight
regulation of angiogenesis in normal physiology is absent or aberrant in multiple disease settings
that are characterized by persistent, inappropriate blood vessel development.
Angiogenesis occurs in more than 80 diseases, particularly in various cancers where the growth
of new blood vessels is necessary to sustain tumor growth, as well as arthritis, where inflammation
triggers new blood vessel growth and joint erosion. EntreMed scientists, who have studied the
process of angiogenesis in-depth for over a decade, are developing drug candidates to inhibit blood
vessel formation and, in turn, control or stop diseases resulting from inappropriate blood vessel
growth.
Cell Cycle Regulation. Cell cycle regulation is the replication, differentiation and death of
cells. One specific aspect of cell cycle regulation is the programmed control of cell death
(apoptosis). In certain diseases, such as cancer, the balance between cell proliferation and cell
death is altered, resulting in inappropriate cell growth. EntreMeds compounds impact biochemical
pathways in cells that result in their death via apoptosis. The Company believes that the
selective induction of apoptosis through drugs that block cell cycle activities can either
stabilize or cause the regression of cancer, inflammation and other disease processes characterized
by inappropriate cell growth. EntreMeds preclinical studies have demonstrated induction of
endothelial cell and tumor cell apoptosis.
Inflammation. Inflammation is the process involving the reaction of tissue to injury or
disease. The condition may be either local or systemic and can be divided into acute (immediate)
and chronic (prolonged) patterns. The endothelial cell and angiogenesis (formation of new blood
vessels) are involved in inflammatory diseases. In contrast to acute inflammation, which is
defined by vascular changes, edema, and white blood cell accumulation (neutrophils), chronic
inflammation is characterized by additional white blood cell changes (macrophages and lymphocytes),
tissue destruction, angiogenesis, and scarring. As a result, the cellular pathways involved in
acute and chronic inflammation can be overlapping or distinct. Inflammation is a process that is
associated with many diseases, including cancer and arthritis. Many of EntreMeds compounds have
demonstrated both anti-inflammatory and anti-tumor properties in preclinical models.
Kinase Inhibition. Kinases are enzymes that are primary regulators of many essential
processes in living cells. There are approximately 500 different kinases encoded in the human
genome, and these proteins act together in intricate communication networks and pathways to control
virtually every aspect of cellular function. The reliance of the cell on kinases to regulate
function can be disastrous when kinase signaling becomes aberrant. Many human diseases have been
linked to these enzymes including all forms of cancer, arthritis, inflammation, diabetes, and
cardiovascular disease. The inhibition of kinases as a targeted therapeutic approach has now been
validated by several drugs that have advanced successfully through clinical trials to the
marketplace. The integral role kinases play in angiogenesis and cell cycle regulation has led
EntreMed to develop inhibitors to key kinases involved in these processes. EntreMeds current lead
kinase inhibitor ENMD-981693 has dual activity towards both angiogenesis and the cell cycle.
MULTI-MECHANISM PIPELINE
We believe EntreMeds pipeline offers promising and unique product candidates for continued
development and commercialization for the following reasons:
Multiple Mechanisms of Action. EntreMed compounds work through multiple mechanisms of action
(MOA). Therefore, a single compound can attack a disease through multiple cellular pathways, as
well as impact different diseases. For example, 2ME2s MOAs include the inhibition of: 1)
angiogenesis; 2) microtubule (cell structure) formation; and 3) hypoxia inducible factor-1 alpha
(HIF-1a), a protein required for angiogenesis and cell survival under stress. Apoptosis (cell
death) can also be induced by 2ME2. Working through multiple mechanisms of action, 2ME2 has the
potential to attack cancer cells through multiple pathways that affect the formation and
replication of tumor cells, and can interrupt the formation of blood vessels that nourish tumor
cells and sustain tumor growth.
4
Versatility. EntreMeds compounds have versatile potential therapeutic applications. While
the Companys preclinical and clinical efforts continue to focus on oncology, EntreMed believes
that other diseases characterized by angiogenesis represent future opportunities. However, at the
present time, the Companys efforts are focused entirely on our core therapeutic programs in
oncology and inflammation. Non-core programs will be evaluated on a case-by-case basis, and then
only in the context of external license or development alliances.
Convenient Dosing. EntreMed is developing drug candidates that will be easy to use with
minimal interruption to the patients daily routine as compared to other modes of drug
administration. The Company is focusing specifically on oral drug delivery technologies, as well as
other convenient administration routes.
Intellectual Property Position. All EntreMed pipeline programs are backed by strong
intellectual property rights. Each product candidate is covered by issued or pending composition,
method and use patents. The Company owns, or has licensed on an exclusive basis, a total of 49
issued patents and patent applications in the United States for our product candidates. The Company
has a total of 136 issued patents and pending patent applications in the United States and other
countries.
The compounds in EntreMeds pipeline were either discovered internally or licensed from third
parties. Panzem® (2ME2) is licensed from Childrens Medical Center Corporation, the
tubulin inhibitor program is licensed from Celgene Corporation, and MKC-1 is licensed from Roche.
Other compounds were discovered and developed internally and, as a result, are EntreMeds sole
property. EntreMed has retained commercial rights to all compounds, including our in-licensed
compounds.
DEVELOPMENT PIPELINE
EntreMeds pipeline contains a balanced portfolio of clinical product candidates and promising
preclinical compounds. The portfolio contains compounds that work primarily through multiple
mechanisms-of-action and have demonstrated potential in both oncology and inflammatory diseases.
The Companys pipeline consists of two product candidates (Panzem® NCD and MKC-1)
in multiple Phase 2 oncology studies, a Phase 1 oncology product candidate (ENMD-1198), plus
late-stage preclinical programs for a multi-kinase inhibitor for the treatment of cancer, and 2ME2
in the treatment of rheumatoid arthritis.
5
CLINICAL PROGRAMS
PanzemÒ. PanzemÒ is one of two lead clinical candidates.
2ME2 has multiple mechanisms of action (MOA), including inhibiting angiogenesis, disrupting
microtubule (cell structure) formation, down-regulating hypoxia inducible factor-one alpha (HIF-1a,
a survival protein), and inducing apoptosis (cell death). The 2ME2 mechanisms that are
particularly relevant to the treatment of cancer involve inhibiting endothelial cell growth
(anti-angiogenic activity) and killing tumor cells directly (pro-apoptotic activity).
Preclinical data has also shown that 2ME2 has activity in cell lines that are resistant to
various chemotherapy agents including taxanes (microtubule stabilizing agents), etoposide,
adriamycin and methotrexate (DNA synthesis interfering agents), and tamoxifen (anti-estrogen
agent). Preclinical data has also shown that 2ME2 has an additive or synergistic effect when used
in combination with approved cytotoxic agents, such as paclitaxel and temozolomide. Additionally,
preclinical models show that 2ME2 has potential therapeutic applications in inflammatory diseases
such as rheumatoid arthritis.
PanzemÒ NCD. EntreMed has formulated 2ME2 as an orally-administered liquid
suspension (Panzem® NCD) using Elan Drug Deliverys (Elan) NanoCrystalÒ
Colloidal Dispersion (NCD) technology to enhance 2ME2s bioavailability. NCD is Elans proprietary
technology that is used currently in multiple marketed pharmaceuticals. The NCD technology
produces nanometer-sized particles, which are up to 500 times smaller than particles manufactured
by conventional milling techniques. While Phase 1 and 2 clinical trials in 171 patients with a
prior capsule formulation showed evidence of biological activity, the newer formulation increased
bioavailability 5-10 fold to levels where optimum anti-tumor activity was observed in preclinical
studies.
6
PanzemÒ
Clinical Development Program Overview in Cancer Patients
Clinical Development Program Overview in Cancer Patients
# | ||||||||||||
PANZEM | OF | |||||||||||
TRIAL TYPE | FORMULATION | INDICATION | PTS | STATUS | COMMENTS | |||||||
Phase 2 (single agent)
|
NCD | Ovarian Cancer | 17 | Enrolling | Assess safety and efficacy. | |||||||
Phase 2 (single agent)
|
NCD | Hormone Refractory Prostate Cancer |
50 | Enrolling | Assess safety and efficacy. | |||||||
Phase 2 (single agent)
|
NCD | Glioblastoma | 32 | Enrolling | Assess safety, pharmacokinetics and efficacy. | |||||||
Phase 2 in
combination with Avastin® |
NCD | Carcinoid Cancer | 30 | Enrolling | Assess safety and efficacy. | |||||||
Phase 1b in combination with paclitaxel (Taxol®)
|
NCD | Metastatic Breast Cancer | 15 | Enrolling | Assess safety, pharmacokinetics and efficacy. | |||||||
Phase 1b Part B (single agent)
|
NCD | Advanced Cancers | 16 | Enrolling | Assess safety, food effect, and modified schedule. | |||||||
Phase 1b Part A (single agent)
|
NCD | Advanced Cancers | 16 | Closed | Well tolerated. Steady state 2ME2 levels achieved. Phase 2 dose determined. | |||||||
Phase 2 (single agent)
|
Capsule | Multiple Myeloma | 60 | Closed | Well tolerated; some patients with stable disease extending 18-60+ months. |
Since January 2006, the Company has commenced five additional clinical studies with
Panzem® NCD. These studies include: 1) a Phase 2 clinical trial in glioblastoma
multiforme (GBM) patients at the Duke University Medical Center Brain Tumor Center; 2) a Phase 1b
study of Panzem® NCD in combination with paclitaxel (Taxol®) in patients
with metastatic breast cancer, also being conducted at the Duke University Medical Center; 3) a
Phase 2 multi-site study in combination with Avastin® in metastatic carcinoid tumor
patients; 4) a multi-center Phase 2 study in patients with hormone refractory prostate cancer; and
5) a multi-center Phase 2 study in patients with recurrent or resistant epithelial ovarian cancer.
Additional Phase 2 studies under consideration include renal cell cancers and 2ME2 in combination
with temozolomide (Temodar®) for the treatment of GBM patients.
MKC-1. MKC-1 is an orally-active, small molecule, cell cycle inhibitor with a unique
mechanism of action. Specifically, MKC-1 arrests cellular mitosis by inhibiting a novel
intracellular target important in cellular trafficking that has been shown to be involved in cell
division. Since January 2006, the Company has commenced three clinical studies with MKC-1. These
studies include: 1) a Phase 2 clinical trial of MKC-1 in metastatic breast cancer patients;
2) a Phase 1 study in hematological cancers; and 3) a Phase 2 study of MKC-1 in combination
with pemetrexed (Alimta®) in patients with non-small cell lung cancer.
7
MKC-1
Clinical Development Program Overview in Cancer Patients
Clinical Development Program Overview in Cancer Patients
# | ||||||||||
OF | ||||||||||
TRIAL TYPE | INDICATION | PTS | STATUS | COMMENTS | ||||||
Phase 2 (single agent)
|
Metastatic Breast Cancer |
60 | Enrolling | Assess safety and efficacy. | ||||||
Phase 2 in combination with
Alimta ®
|
Advanced Cancer and Non-Small Cell Lung Cancer (NSCLC) | 60 | Enrolling | Assess safety and efficacy. | ||||||
Phase 1 (single agent)
|
Hematological Malignancies |
24 | Enrolling | Assess safety and efficacy. |
ENMD-1198. EntreMed discovered a New Chemical Entity (NCE) that inhibits tumor growth based
on modifying the chemical structure of 2-methoxyestradiol (2ME2) to increase its anti-tumor and
anti-angiogenic properties, as well as decrease its rate of metabolism. The lead compound from this
program, ENMD-1198, demonstrated improved pharmacokinetic parameters and improved metabolism while
maintaining 2ME2s multiple mechanisms of action.
ENMD-1198 has shown excellent anti-tumor activity in several preclinical animal models.
Preclinical data demonstrated that oral administration of ENMD-1198 leads to pronounced in vivo
anti-tumor activity in cancer models, resulting in a reduction of tumor burden and/or an increase
in survival when compared to controls. Oral daily treatment with ENMD-1198 in an orthotopic animal
model of human breast cancer led to the disruption of microtubules within tumor cells and a
substantial decrease in tumor cell proliferation and angiogenesis. In May 2006, the Company
initiated a Phase 1 trial to evaluate the safety, tolerability, pharmacokinetics, and clinical
benefit of ENMD-1198 in patients with advanced cancer.
PRECLINCAL PIPELINE
EntreMed has a portfolio of preclinical compounds and programs that are based on the
Companys scientific expertise in angiogenesis, cell cycle regulation and inflammation.
The Companys strategy is to continue adding value to its
pipeline by advancing its best preclinical assets forward into
clinical development, while selectively exploring strategic alliances and co-development
partners. EntreMed expects to submit INDs in 2007 for two
late-stage preclinical programs 2ME2 for rheumatoid arthritis and
ENMD-981693 for oncology.
2ME2 for Rheumatoid Arthritis. The mechanisms ascribed to 2ME2, namely anti-angiogenesis,
pro-apoptosis, down regulation of HIF-1a, and inhibition of bone resorption, have implicated its
use in diseases with inflammatory components, such as rheumatoid arthritis. EntreMed and its
collaborators have now established the dose-dependent, anti-arthritic activity of 2ME2 following
oral administration in four distinct animal models of rheumatoid arthritis. This activity has been
manifested as an inhibition in 1) the infiltration of inflammatory cells, 2) pannus formation, 3)
cartilage lesions, and 4) bone resorption.
Treatment with 2ME2 has resulted in a dose-dependent decrease in the severity of RA disease in
preclinical models, strongly suggesting disease-modifying anti-rheumatic drug (DMARD) activity
the potential to treat the underlying pathology of rheumatoid arthritis, rather than merely
treating symptoms such as pain. Based on these results, EntreMed has initiated IND-enabling
toxicology studies for 2ME2 in rheumatoid arthritis. The use of PanzemÒ for
rheumatoid arthritis opens the possibility to cross over with 2ME2 into a second therapeutic area
with a large, still underserved market.
8
Aurora Kinase Inhibitors. Aurora kinases are key regulators of the process of mitosis, or
cell division, and are often over-expressed in human cancers. Specifically, one of these compounds,
ENMD-981693, is a multi-target kinase inhibitor with a unique selectivity profile and multiple
mechanisms of action, including antiproliferative activity and the inhibition of angiogenesis.
IND-directed studies are currently underway, with the filing of an IND anticipated in the second
half of 2007.
Tubulin Inhibitors. Tubulin inhibitors comprise a broad family of compounds that bind to
tubulin and disrupt microtubules, resulting in programmed cell death (apoptosis). In March 2005,
the Company in-licensed Celgenes tubulin inhibitor program. The Company has obtained an exclusive
worldwide license to a broad grouping of these compounds for oncology and assumed responsibility
for the preclinical and clinical development of the tubulin inhibitors for oncology applications.
Results from in vitro and in vivo studies have shown that Celgenes tubulin inhibitors prevent
tumor cell proliferation in a dose-dependent manner and, based on in vitro studies, inhibit
angiogenesis.
HDAC Inhibitors. A histone deacetylase (HDAC) inhibitor program is currently in preclinical
evaluation. HDAC inhibitors have been shown to arrest cancer cell growth and/or induce
apoptosis both in vivo and in vitro.
BUSINESS DEVELOPMENT STRATEGY
Oncology is EntreMeds principal clinical and commercial focus, although recent data support
further development of our compounds in certain non-oncology applications, such as rheumatoid
arthritis. As a result, EntreMeds strategy is to continue developing compounds for oncology and
inflammatory diseases, while selectively exploring strategic alliances for its compounds in other
therapeutic areas. The Company may pursue co-development partners for its core pipeline product
candidates to help accelerate their development and strengthen the development program with
complementary expertise. Likewise, EntreMed can provide its co-development partners with
substantial know-how relating to small molecules that inhibit angiogenesis and inflammation, as
well as regulate cell cycle pathways.
Oncology Focus with Multi-Therapeutic Potential. EntreMed is focused on oncology.
PanzemÒ NCD and MKC-1, our two lead oncology product candidates, are currently in
Phase 2 clinical studies in glioblastoma, carcinoid, prostate, ovarian, non-small cell lung, and
metastatic breast cancer patients. ENMD-1198 is currently in Phase 1b dose-escalation studies in
advanced cancer patients. These product candidates play to our strength in angiogenesis, cell cycle
regulation and inflammation.
Commercialization Goal. EntreMeds goal is to commercialize its pipeline, led by
PanzemÒ NCD, MKC-1, and ENMD-1198. The Company is committed to maintaining a
balanced portfolio of oncology compounds that can be co-developed with pharmaceutical and
biotechnology partners, or commercialized for the Companys own account. EntreMed is committed to
pursuing value-creating technologies and products, making sound financial decisions, and building
the financial capacity to develop its clinical portfolio.
EMPLOYEES
As of December 31, 2006, we had 57 employees, consisting of 56 full-time employees and 1
part-time employee. Forty employees work in our research and development department. Certain of
our activities, such as manufacturing and clinical trial operations, are outsourced at the present
time. We may hire additional personnel, in addition to utilizing part-time or temporary
consultants, on an as-needed basis. None of our employees are
represented by a labor union, and we believe our relations with our employees are
satisfactory.
9
RELATIONSHIPS CORPORATE AND NON-PROFIT
Corporate Transactions.
| Celgene. In March 2005, we in-licensed Celgenes tubulin inhibitor program. We have assumed the responsibility for the preclinical and clinical development of tubulin inhibitors for oncology applications under this program. Celgene is our largest shareholder. | ||
| Childrens Medical Center Corporation (CMCC). As part of our three-way agreement with Alchemgen Therapeutics, Inc. executed in February 2004, CMCC holds the licenses for Endostatin and Angiostatin for all markets outside of Asia. |
Contract Manufacturing. The manufacturing efforts for the production of our clinical trial
materials are performed by contract manufacturing organizations. Established relationships, coupled
with supply agreements, have secured the necessary resources to ensure adequate supply of clinical
materials to support our clinical development program. We believe that our current strategy of
outsourcing manufacturing is cost-effective and allows for the flexibility we require.
2ME2 drug substance is currently bulk manufactured by Akzo Nobel and PanzemÒ
NCD is currently manufactured by Elan Drug Delivery, Inc. We do not anticipate any challenges in
securing contract manufacturing capacity at either of these facilities to produce
PanzemÒ NCD.
Sponsored Research Agreements. To complement our in-house research and development efforts,
we have entered into sponsored research agreements with outside scientists to conduct specific
projects as outlined below. Under these agreements, we have secured the rights to intellectual
property and to develop under exclusive license any discoveries resulting from these
collaborations. The funds we provide in accordance with these agreements partially support the
scientists laboratory, research personnel and research supplies.
Cooperative Research and Development Agreements (CRADAs). EntreMed extended its existing
CRADA with the National Cancer Institute:
| Preclinical and Clinical Development of 2ME2 (PanzemÒ) (Expires April 2007). | ||
| 2-Methoxyestradiol (2ME2) and 2ME2 Analogs as Inhibitors of Hypoxia Inducible Factor-1 alpha (HIF-1a ) (Expires September 2008). |
Clinical Trial Centers. As of February 7, 2007, we are conducting clinical trials at the
following institutions:
| Dana-Farber Cancer Institute, Boston, MA | ||
| Duke University Medical Center, Durham, NC | ||
| Indiana University Cancer Center, Indianapolis, IN | ||
| Mayo Clinic, Rochester, MN | ||
| Wisconsin Comprehensive Cancer Center, Madison, WI | ||
| Johns Hopkins University, Baltimore, MD | ||
| MD Anderson Cancer Center, Houston, TX | ||
| The Don and Sybil Harrington Cancer Center, Amarillo, TX | ||
| University of Iowa, Iowa City, IA | ||
| University of Maryland, Baltimore, MD | ||
| University of Colorado Cancer Center, Aurora, CO | ||
| St. Vincent Hospital and Health Care Centers, Inc., Indianapolis, IN |
PATENTS, LICENSES AND PROPRIETARY RIGHTS
Our success will depend in part on our ability to obtain patent protection for our products,
both in the United States and abroad. The patent position of biotechnology and pharmaceutical
companies, in general, is highly uncertain and involves complex legal and factual questions.
10
Following the February 2004 transfer of the licenses for endostatin and angiostatin back to
Childrens Hospital, Boston, EntreMed, Inc. and its subsidiary, Miikana Therapeutics, Inc., own, or
have licensed on an exclusive basis, a total of 61 issued patents and patent applications in the
United States for our product candidates. EntreMed, Inc. and its subsidiary, Miikana Therapeutics,
Inc., have a total of 205 issued patents and pending patent applications in the United States and
other countries.
We have licensed technology exclusively from Childrens Hospital, Boston, which covers the use
of steroid-derived small molecular weight compounds such as PanzemÒ that are
antimitotic and antiangiogenic agents. A U.S. patent application has been issued covering purified
PanzemÒ as a composition of matter. There are eight pending United States patent
applications and fourteen allowed or issued United States patents covering PanzemÒ
technology. Patent applications also cover estrogen-related compounds with anti-fungal activity and
the treatment of localized atherosclerosis. The terms of the licenses for PanzemÒ
extend until the last underlying patent expires.
We have patent applications filed in both the U.S. and selected international jurisdictions
that cover the steroid-derived small molecule designated ENMD 1198 that is currently in the clinic.
In addition, we have patent applications and patents filed in both the U.S. and selected
international jurisdictions that cover the small molecule designated MKC-1 that is currently in the
clinic.
We own the technology associated with our 2ME2 analogs, PAR-2 inhibitors, TFPI peptides, and
NCEs for oncology and inflammation.
Many patent applications corresponding to the above-described United States patent
applications have been filed in Europe, Japan, Canada, Australia, and other selected countries.
EntreMed, Inc. and its subsidiary, Miikana Therapeutics, Inc. have registered the trademarks
ENTREMED, MIIKANA, PANZEM® and THE ANGIOGENESIS COMPANY in the U.S. Patent and Trademark
Office and have applied for registration of the marks in selected foreign countries.
GOVERNMENT REGULATION
Our development, manufacture, and potential sale of therapeutics are subject to extensive
regulation by United States and foreign governmental authorities.
In the United States, the Food and Drug Administration (FDA) will regulate our product
candidates currently being developed as drugs or biologics. New drugs are subject to regulation
under the Federal Food, Drug, and Cosmetic Act (FFDCA), and biological products, in addition to
being subject to certain provisions of that Act, are regulated under the Public Health Service Act
(PHSA). We believe that the FDA is likely to regulate the products currently being developed by us
or our collaborators as new drugs. Both the FFDCA and PHSA and corresponding regulations govern,
among other things, the testing, manufacturing, safety, efficacy, labeling, storage, recordkeeping,
advertising and other promotion of biologics or new drugs, as the case may be. FDA clearances or
approvals must be obtained before clinical testing, and before manufacturing and marketing of
biologics or drugs.
Preparing drug candidates for approval has historically been a costly and time-consuming
process. Generally, in order to gain FDA permission to test a new agent, a developer first must
conduct preclinical studies in the laboratory and in animal model systems to gain preliminary
information on an agents effectiveness and to identify any safety problems. The results of these
studies are submitted as a part of an Investigational New Drug (IND) application for a drug or
biologic, which the FDA must review before human clinical trials of an investigational drug can
begin. In addition to the known safety and effectiveness data on the drug or biologic, the
IND must include a detailed description of the clinical investigations proposed to be
undertaken. Based on the current FDA organizational structure, PanzemÒ, 2ME2
analogs, and other compounds in our small molecule programs are expected to be regulated as new
drugs by the FDAs Center for Drug Evaluation and Research (CDER). Generally, as new chemical
entities like our small molecules are discovered, formal IND-directed toxicology studies will be
required prior to initiating human testing. Clinical testing may begin 30 days after submission of
an IND to the FDA unless FDA objects to the initiation of the study, or at such earlier time as FDA
expressly permits.
11
In order to commercialize any drug or biological products, we or our collaborators must
sponsor and file an IND and conduct clinical studies to demonstrate the safety and effectiveness
necessary to obtain FDA approval of such products. For studies conducted under INDs sponsored by us
or our collaborators, we or our collaborators will be required to select qualified investigators
(usually physicians within medical institutions) to supervise the administration of the products,
test or otherwise assess patient results, and collect and maintain patient data; monitor the
investigations to ensure that they are conducted in accordance with applicable requirements,
including the requirements set forth in the general investigational plan and protocols contained
in the IND; and comply with applicable reporting and recordkeeping requirements.
Clinical trials of drugs or biologics are normally done in three phases, although the phases
may overlap. Phase 1 trials for agents to be used to treat cancer patients are concerned primarily
with the safety and preliminary effectiveness of the drug, involve a small group ranging from 15 -
40 subjects, and may take from six months to over one year to complete. Phase 2 trials normally
involve 30 200 patients and are designed primarily to demonstrate effectiveness in treating or
diagnosing the disease or condition for which the drug is intended, although short-term side
effects and risks in people whose health is impaired may also be examined. Phase 3 trials are
expanded clinical trials with larger numbers of patients which are intended to evaluate the overall
benefit-risk relationship of the drug and to gather additional information for proper dosage and
labeling of the drug. Phase III clinical trials generally take two to five years to complete, but
may take longer. The FDA receives reports on the progress of each phase of clinical testing, as
well as reports of unexpected adverse experiences occurring during the trial, and it may require
the modification, suspension, or termination of clinical trials, if it concludes that an
unwarranted risk is presented to patients, or, in Phase 2 and 3, if it concludes that the study
protocols are deficient in design to meet their stated objectives.
If clinical trials of a new product are completed successfully, the sponsor of the product may
seek FDA marketing approval. If the product is classified as a new drug, an applicant must file a
New Drug Application (NDA) with the FDA and receive approval before commercial marketing of the
drug. The NDA must include detailed information about the product and its manufacture and the
results of product development, preclinical studies and clinical trials.
The testing and approval processes require substantial time and effort and there can be no
assurance that any approval will be obtained on a timely basis, if at all. Although it is the
policy of the FDA to complete the review of the initial submission of NDAs within six to twelve
months, the entire FDA review process may take several years to receive approval. Notwithstanding
the submission of relevant data, the FDA may ultimately decide that the NDA does not satisfy its
regulatory criteria and deny the approval. Further, the FDA may require additional clinical
studies before making a decision on approval. In addition, the FDA may condition marketing approval
on the conduct of specific post-marketing studies to further evaluate safety and effectiveness.
Even if FDA regulatory clearances are obtained, a marketed product is subject to continuing
regulatory requirements and review relating to GMP, adverse event reporting, promotion and
advertising, and other matters. Discovery of previously unknown problems or failure to comply with
the applicable regulatory requirements may result in restrictions on the marketing of a product or
withdrawal of the product from the market, as well as possible civil or criminal sanctions.
COMPETITION
Competition in the pharmaceutical, biotechnology and biopharmaceutical industries is intense
and based significantly on scientific and technological factors, the availability of patent and
other protection for technology and products, the ability and length of time required to obtain
governmental approval for testing, manufacturing and marketing and the ability to commercialize
products in a timely fashion. Moreover, the biopharmaceutical industry
is characterized by rapidly evolving technology that could result in the technological
obsolescence of any products that we develop.
12
We compete with many specialized biopharmaceutical firms, as well as a growing number of large
pharmaceutical companies that are applying biotechnology to their operations. Many
biopharmaceutical companies have focused their development efforts in the human therapeutics area,
including oncology and inflammation, and many major pharmaceutical companies have developed or
acquired internal biotechnology capabilities or made commercial arrangements with other
biopharmaceutical companies. These companies, as well as academic institutions, governmental
agencies and private research organizations, also compete with us in recruiting and retaining
highly qualified scientific personnel and consultants.
Our competition will be determined in part by the potential indications for which our product
candidates may be developed and ultimately approved by regulatory authorities. We may rely on third
parties to commercialize our products, and accordingly, the success of these products will depend
in significant part on these third parties efforts and ability to compete in these markets. The
success of any collaboration will depend in part upon our collaborative partners own competitive,
marketing and strategic considerations, including the relative advantages of alternative products
being developed and marketed by our collaborative partners and our competitors.
Many of our existing or potential competitors have substantially greater financial, technical
and human resources than we do and may be better equipped to develop, manufacture and market
products. In addition, many of these competitors have extensive experience in preclinical testing
and human clinical trials and in obtaining regulatory approvals. The existence of competitive
products, including products or treatments of which we are not aware, or products or treatments
that may be developed in the future, may adversely affect the marketability of products that we may
develop.
Available Information
Through our website at www.entremed.com, we make available, free of charge, our filings with
the Securities and Exchange Commission (SEC), including our annual proxy statements, annual
reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, and all
amendments thereto, as soon as reasonably practicable after such reports are filed with or
furnished to the Securities and Exchange Commission. Our filings are also available through the
Securities and Exchange Commission via their website, http://www.sec.gov. You may also
read and copy any materials we file with the SEC at the SECs Public Reference Room at 100 F
Street, N.E., Washington, D.C. 20549. You may obtain information on the operation of the Public
Reference Room by calling the SEC at 1-800-SEC-0330. The information contained on our website is
not incorporated by reference in this annual report on Form 10-K and should not be considered a
part of this report.
ITEM 1A. RISK FACTORS.
We Have a History of Losses and Anticipate Future Losses
To date, we have been engaged primarily in research and development activities. Although we
have received license fees and research and development funding from a former collaborator, limited
revenues on royalties from sales of Thalomid® and certain research grants, we have not
derived significant revenues from operations.
At December 31, 2006, we had an accumulated deficit of approximately $311,637,000. Losses
have continued since December 31, 2006. We will also be required to conduct substantial research
and development and clinical testing activities for our proposed products. We expect that these
activities will result in operating losses for the foreseeable future before we commercialize any
products, if ever. In addition, to the extent we rely on others to develop and commercialize our
products, our ability to achieve profitability will depend upon the success of these other parties.
To support our research and development of certain product candidates, we also may rely on
cooperative agreements from governmental and other organizations as a source of support. If our
cooperative agreements were to be reduced to any substantial extent, it may impair our ability to
continue our research and development efforts. Even if we do achieve profitability, we may be
unable to sustain or increase it.
13
The Market Price of Our Common Stock May Be Highly Volatile or May Decline Regardless of Our
Operating Performance.
Our stock price has fluctuated from year-to-year and quarter-to-quarter and will likely
continue to be volatile. The valuations of many biotechnology companies without consistent product
revenues and earnings are extraordinarily high based on conventional valuation standards, such as
price to earnings and price to sales ratios. These trading prices and valuations may not be
sustained. In the future, our operating results in a particular period may not meet the
expectations of any securities analysts whose attention we may attract, or those of our investors,
which may result in a decline in the market price of our common stock. Any negative change in the
publics perception of the prospects of biotechnology companies could depress our stock price
regardless of our results of operations. These factors may materially and adversely affect the
market price of our common stock.
Development of Our Products is at an Early Stage and is Uncertain
Our proposed products and research programs are in the early stage of clinical development and
require significant, time-consuming and costly research and development, testing and regulatory
clearances. In developing our products, we are subject to risks of failure that are inherent in the
development of products and therapeutic procedures. For example, it is possible that any or all of
our proposed products will be ineffective or toxic, or otherwise will fail to receive necessary FDA
clearances. There is a risk that the proposed products will be uneconomical to manufacture or
market or will not achieve market acceptance. There is also a risk that third parties may hold
proprietary rights that preclude us from marketing our proposed products or that others will market
a superior or equivalent product. Further, our research and development activities might never
result in commercially viable products.
Our product candidates are at the clinical and preclinical stages of development. Although
several of our product candidates have demonstrated some promising results in early clinical
(human) trials and preclinical (animal) studies, they may not prove to be effective in humans. For
example, testing on animals may occur under different conditions than testing in humans and
therefore the results of animal studies may not accurately predict human experience. Likewise,
early clinical studies may not be predictive of eventual safety or effectiveness results in
larger-scale pivotal clinical trials.
There are many regulatory steps that must be taken before any of these product candidates will
be eligible for FDA approval and subsequent sale, including the completion of preclinical and
clinical trials. We do not expect that these product candidates will be commercially available for
several years, if ever.
Even If Panzem® is Approved, the Commercial Success of Our Oncology Business is Uncertain and We
May Not Be Able to Recover the Value of Our Investment.
Even if Panzem® is approved by the FDA, the market for oncology treatments is competitive and
complex. The commercial success of the product will be limited if we cannot successfully
manufacture, distribute and sell it in jurisdictions in which it is approved. There can be no
assurance that demand for our drugs will support a volume and price that will achieve a profit in
accordance with our expectations, or that our revenues for these products will exceed our cost of
goods.
Technological Developments By Competitors May Render Our Products Obsolete.
If competitors were to develop superior technologies, our technologies could be rendered
noncompetitive or obsolete, resulting in a material adverse effect to
our business. Developments in the biotechnology and pharmaceutical industries are
expected to continue at a rapid pace. Success depends upon achieving and maintaining a competitive
position in the development of products and technologies. Competition from other biotechnology and
pharmaceutical companies can be intense. Many competitors have substantially greater research and
development capabilities, marketing, financial and managerial
resources and experience in the industry. Even if a competitor creates a technology that
is not superior, we may not be able to compete with
such technology.
14
We are Uncertain Whether Additional Funding Will Be Available For Our Future Capital Needs and
Commitments, and If We Cannot Raise Additional Funding, We May Be Unable to Complete Development of
Our Product Candidates.
We will require substantial funds in addition to our existing working capital to develop our
product candidates and otherwise to meet our business objectives. We have never generated
sufficient revenue during any period since our inception to cover our expenses and have spent, and
expect to continue to spend, substantial funds to continue our research and development and
clinical programs. Any one of the following factors, among others, could cause us to require
additional funds or otherwise cause our cash requirements in the future to increase materially:
| results of research and development activities; | ||
| progress of our preclinical studies or clinical trials; | ||
| results of clinical trials; | ||
| changes in or terminations of our relationships with strategic partners; | ||
| changes in the focus, direction, or costs of our research and development programs; | ||
| competitive and technological advances; | ||
| establishment of marketing and sales capabilities; | ||
| manufacturing; | ||
| the regulatory approval process; or | ||
| product launch. |
At December 31, 2006, we had cash and cash equivalents and marketable securities of
$50,570,097. We currently have no commitments or arrangements for any financing. We may continue
to seek additional capital through public or private financing or collaborative agreements. If
adequate funds are not available to us as we need them, we may be required to curtail
significantly, or eliminate at least temporarily, one or more of our drug development programs.
We Must Show the Safety and Efficacy of Our Product Candidates Through Clinical Trials, the Results
of Which are Uncertain
Before obtaining regulatory approvals for the commercial sale of our products, we must
demonstrate, through preclinical studies (animal testing) and clinical trials (human testing), that
our proposed products are safe and effective for use in each target indication. Testing of our
product candidates will be required, and failure can occur at any stage of testing. Clinical trials
may not demonstrate sufficient safety and efficacy to obtain the required regulatory approvals or
result in marketable products. The failure to adequately demonstrate the safety and efficacy of a
product under development could delay or prevent regulatory approval of the potential product.
Clinical trials for the product candidates we are developing may be delayed by many factors,
including that potential patients for testing are limited in number. The failure of any clinical
trials to meet applicable regulatory standards could cause such trials to be delayed or terminated,
which could further delay the commercialization of any of our product candidates. Newly emerging
safety risks observed in animal or human studies also can result in delays of ongoing or proposed
clinical trials. Any such delays will increase our product development costs. If such delays are
significant, they could negatively affect our financial results and the commercial prospects for
our products.
15
The Independent Clinical Investigators and Contract Research Organizations That We Rely Upon to
Assist in the Conduct of Our Clinical Trials May Not Be Diligent, Careful or Timely, and May Make
Mistakes, in the Conduct of Our Trials.
We depend on independent clinical investigators and contract research organizations, or CROs,
to assist in the conduct of our clinical trials under their agreements with us. The investigators
are not our employees, and we cannot control the amount or timing of resources that they devote to
our programs. If independent investigators fail to devote sufficient time and resources to our drug
development programs, or if their performance is substandard, it will delay the approval of our FDA
applications and our introduction of new drugs. The CROs we contract with to assist with the
execution of our clinical trials play a significant role in the conduct of the trials and the
subsequent collection and analysis of data. Failure of the CROs to meet their obligations could
adversely affect clinical development of our products.
The Success of Our Business Depends Upon the Members of Our Senior Management Team, Our Scientific
Staff and Our Ability to Continue to Attract and Retain Qualified Scientific, Technical and
Business Personnel.
We are dependent on the principal members of our management team and scientific staff for our
business success. The loss of any of these people could impede the achievement of our development
and business objectives. We do not carry key man life insurance on the lives of any of our key
personnel. There is intense competition for human resources, including management, in the
scientific fields in which we operate and there can be no assurance that we will be able to attract
and retain qualified personnel necessary for the successful development of our product candidates,
and any expansion into areas and activities requiring additional expertise. In addition, there can
be no assurance that such personnel or resources will be available when needed. In addition, we
rely on a significant number of consultants to assist us in formulating our research and
development strategy and other business activities. All of our consultants may have commitments to,
or advisory or consulting agreements with, other entities that may limit their availability to us.
We May Need New Collaborative Partners to Further Develop and Commercialize Products, and if We
Enter Into Such Arrangements, We May Give Up Control Over the Development and Approval Process and
Decrease our Potential Revenue
We plan to develop and commercialize our product candidates both with and without corporate
alliances and partners. Nonetheless, we intend to explore opportunities for new corporate alliances
and partners to help us develop, commercialize and market our product candidates. We expect to
grant to our partners certain rights to commercialize any products developed under these
agreements, and we may rely on our partners to conduct research and development efforts and
clinical trials on, obtain regulatory approvals for, and manufacture and market any products
licensed to them. Each individual partner will seek to control the amount and timing of resources
devoted to these activities generally. We anticipate obtaining revenues from our strategic partners
under such relationships in the form of research and development payments and payments upon
achievement of certain milestones. Since we generally expect to obtain a royalty for sales or a
percentage of profits of products licensed to third parties, our revenues may be less than if we
retained all commercialization rights and marketed products directly. In addition, there is a risk
that our corporate partners will pursue alternative technologies or develop competitive products as
a means for developing treatments for the diseases targeted by our programs.
We may not be successful in establishing any collaborative arrangements. Even if we do
establish such collaborations, we may not successfully commercialize any products under or derive
any revenues from these
arrangements. Our strategy also involves entering into multiple, concurrent strategic alliances to
pursue commercialization of our core technologies. There is a risk that we will be unable to manage
simultaneous programs successfully. With respect to existing and potential future strategic
alliances and collaborative arrangements, we will depend on the expertise and dedication of
sufficient resources by these outside parties to develop, manufacture, or market products. If a
strategic alliance or collaborative partner fails to develop or commercialize a product to which it
has rights, we may not recognize any revenues on that particular product.
16
We Have No Current Manufacturing or Marketing Capacity and Rely on Only One Supplier For Some of
Our Products
We do not expect to manufacture or market products in the near term, but we may try to do so
in certain cases. We do not currently have the capacity to manufacture or market products and we
have limited experience in these activities. If we elect to perform these functions, we will be
required to either develop these capacities, or contract with others to perform some or all of
these tasks. We may be dependent to a significant extent on corporate partners, licensees, or other
entities for manufacturing and marketing of products. If we engage directly in manufacturing or
marketing, we will require substantial additional funds and personnel and will be required to
comply with extensive regulations. We may be unable to develop or contract for these capacities
when required to do so in connection with our business.
We are currently manufacturing products for clinical trials on a contract basis.
Panzem® NCD, our lead small molecule clinical drug candidate, is currently manufactured
by Elan. We do not have arrangements in place with alternative suppliers if our current supplier
Elan was unable to deliver the product in necessary quantities.
We depend on our third-party manufacturers to perform their obligations effectively and on a
timely basis. These third parties may not meet their obligations and any such non-performance may
delay clinical development or submission of products for regulatory approval, or otherwise impair
our competitive position. Any significant problem experienced by one of our suppliers could result
in a delay or interruption in the supply of materials to us until such supplier resolves the
problem or an alternative source of supply is located. Any delay or interruption would likely lead
to a delay or interruption of manufacturing operations, which could negatively affect our
operations. Although we have identified alternative suppliers for our product candidates, we have
not entered into contractual or other arrangements with them. If we needed to use an alternate
supplier for any product, we would experience delays while we negotiated an agreement with them for
the manufacture of such product. In addition, we may be unable to negotiate manufacturing terms
with a new supplier that are as favorable as the terms we have with our current suppliers.
Problems with any manufacturing processes could result in product defects, which could require
us to delay shipment of products or recall products previously shipped. In addition, any prolonged
interruption in the operations of the manufacturing facilities of one of our sole-source suppliers
could result in the cancellation of shipments. A number of factors could cause interruptions,
including equipment malfunctions or failures, or damage to a facility due to natural disasters or
otherwise. Because our manufacturing processes are or are expected to be highly complex and subject
to a lengthy FDA approval process, alternative qualified production capacity may not be available
on a timely basis or at all. Difficulties or delays in our manufacturing could increase our costs
and damage our reputation.
The manufacture of pharmaceutical products can be an expensive, time consuming, and complex
process. Manufacturers often encounter difficulties in scaling-up production of new products,
including quality control and assurance and shortages of personnel. Delays in formulation and
scale-up to commercial quantities could result in additional expense and delays in our clinical
trials, regulatory submissions, and commercialization.
Failure of Manufacturing Facilities Producing Our Product Candidates to Maintain Regulatory
Approval Could Delay or Otherwise Hinder Our Ability to Market Our Product Candidates
Any manufacturer of our product candidates will be subject to applicable Good Manufacturing
Practices (GMP) prescribed by the FDA or other rules and regulations prescribed by foreign
regulatory authorities. We and any of our collaborators may be unable to enter into or maintain
relationships either domestically or abroad with manufacturers whose facilities and procedures
comply or will continue to comply with GMP and who are able to
produce our small molecules in accordance with applicable regulatory standards. Failure by a
manufacturer of our products to comply with GMP could result in significant time delays or our
inability to obtain marketing approval or, should we have market approval, for such approval to
continue. Changes in our manufacturers could require new product testing and facility compliance
inspections. In the United States, failure to comply with GMP or other applicable legal
requirements can lead to federal seizure of violated products, injunctive actions brought by the
federal government, inability to export product, and potential criminal and civil liability on the
part of a company and its officers and employees.
17
Manufacturing Our Product Candidates May Not Be Commercially Feasible
The manufacturing processes for several of the small molecules we are developing have not yet
been tested at commercial levels, and it may not be possible to manufacture these materials in a
cost-effective manner.
We Depend on Patents and Other Proprietary Rights, Some of Which are Uncertain
Our success will depend in part on our ability to obtain patents for our products, both in the
United States and abroad. The patent position of biotechnology and pharmaceutical companies in
general is highly uncertain and involves complex legal and factual questions. Risks that relate to
patenting our products include the following:
| our failure to obtain additional patents; | ||
| challenge, invalidation, or circumvention of patents already issued to us; | ||
| failure of the rights granted under our patents to provide sufficient protection; | ||
| independent development of similar products by third parties; or | ||
| ability of third parties to design around patents issued to our collaborators or us. |
For several of the products that we are developing, including Panzem®, composition
of matter patents is not available because the compounds are in the public domain. In these cases,
only patents covering the use of the product are available. In general, patents covering a new
use for a known compound can be more difficult to enforce against infringers of the use claims in
the patent.
Our potential products may conflict with patents that have been or may be granted to
competitors, universities or others. As the biotechnology industry expands and more patents are
issued, the risk increases that our potential products may give rise to claims that may infringe
the patents of others. Such other persons could bring legal actions against us claiming damages and
seeking to enjoin clinical testing, manufacturing and marketing of the affected products. Any such
litigation could result in substantial cost to us and diversion of effort by our management and
technical personnel. If any of these actions are successful, in addition to any potential liability
for damages, we could be required to obtain a license in order to continue to manufacture or market
the affected products. We may not prevail in any action and any license required under any needed
patent might not be made available on acceptable terms, if at all.
We are a party to sponsored research agreements and license agreements that require us to make
milestone payments upon attainment of certain regulatory milestones. Failure to meet such
milestones could result in the loss of certain rights to compounds covered under such license
agreements.
We also rely on trade secret protection for our confidential and proprietary information.
However, trade secrets are difficult to protect and others may independently develop substantially
equivalent proprietary information and techniques and gain access to our trade secrets and disclose
our technology. We may be unable to meaningfully protect our rights to unpatented trade secrets. We
require our employees to complete confidentiality training that specifically addresses trade
secrets. All employees, consultants, and advisors are required to execute a confidentiality
agreement when beginning an employment or a consulting relationship with us. The agreements
generally provide that all trade secrets and inventions conceived by the individual and all
confidential information developed or made known to the individual during the term of the
relationship automatically become our exclusive property. Employees and consultants must keep such
information confidential and may not disclose such information to third parties except in specified
circumstances. However, these agreements may not provide meaningful protection for our proprietary
information in the event of unauthorized use or disclosure of such information.
18
To the extent that consultants, key employees, or other third parties apply technological
information independently developed by them or by others to our proposed projects, disputes may
arise as to the proprietary rights to such information. Any such disputes may not be resolved in
our favor. Certain of our consultants are employed by or have consulting agreements with other
companies and any inventions discovered by them generally will not become our property.
Our Potential Products Are Subject to Government Regulatory Requirements and an Extensive Approval
Process
Our research, development, preclinical and clinical trials, manufacturing, and marketing of
most of our product candidates are subject to an extensive regulatory approval process by the FDA
and other regulatory agencies in the United States and abroad. The process of obtaining FDA and
other required regulatory approvals for drug and biologic products, including required preclinical
and clinical testing, is time consuming and expensive. Even after spending time and money, we may
not receive regulatory approvals for clinical testing or for the manufacturing or marketing of any
products. Our collaborators or we may encounter significant delays or costs in the effort to secure
necessary approvals or licenses. Even if we obtain regulatory clearance for a product, that product
will be subject to continuing review. Later discovery of previously unknown defects or failure to
comply with the applicable regulatory requirements may result in restrictions on a products
marketing or withdrawal of the product from the market, as well as possible civil or criminal
penalties.
Potential Products May Subject Us to Product Liability for Which Insurance May Not Be Available
The use of our potential products in clinical trials and the marketing of any pharmaceutical
products may expose us to product liability claims. We have obtained a level of liability insurance
coverage that we believe is adequate in scope and coverage for our current stage of development.
However, our present insurance coverage may not be adequate to protect us from liabilities we might
incur. In addition, our existing coverage will not be adequate as we further develop products and,
in the future, adequate insurance coverage and indemnification by collaborative partners may not be
available in sufficient amounts or at a reasonable cost. If a product liability claim or series of
claims are brought against us for uninsured liabilities, or in excess of our insurance coverage,
the payment of such liabilities could have a negative effect on our business and financial
condition.
We Have Engaged In and May Continue to Engage in Acquisitions, Which Could Negatively Affect Our
Business and Earnings
In January 2006, we acquired Miikana Therapeutics, Inc., a clinical-stage biopharmaceutical
company. We intend to continue to be opportunistic in acquiring companies that we believe are a
strategic fit with our business or complement our existing product candidates. There are risks
associated with such activities. These risks include, among others, incorrectly assessing the asset
quality of a prospective merger partner, encountering greater than anticipated costs in integrating
acquired businesses and being unable to profitably deploy assets acquired in the transaction, such
as drug candidates. Further, acquisitions may place additional constraints on our resources by
diverting the attention of our management from our business operations. To the extent we issue
securities in connection with additional transactions, these transactions and related issuances may
have a dilutive effect on earnings per share and our ownership. Our earnings, financial condition,
and prospects after an acquisition depend in part on our ability to successfully integrate the
operations of the acquired business or technologies. We may be unable to integrate operations
successfully or to achieve expected cost savings. Any cost savings which are realized may be
offset by losses in revenues or other charges to earnings.
ITEM 1B. UNRESOLVED STAFF COMMENTS.
None.
ITEM 2. PROPERTIES.
We currently lease approximately 46,000 square feet of space (approximately 32,000 square feet
of which is laboratory space) in Rockville, Maryland. The lease expires in February 2009. We
believe that our existing facilities will be adequate to accommodate the implementation of our
current business plan.
19
ITEM 3. LEGAL PROCEEDINGS.
EntreMed is subject in the normal course of business to various legal proceedings in which
claims for monetary or other damages may be asserted. Management does not believe such legal
proceedings, except as otherwise disclosed herein, are material.
ITEM 4. SUBMISSION OF MATTERS TO A VOTE OF SECURITY HOLDERS.
Not applicable.
20
PART II
ITEM 5. MARKET FOR REGISTRANTS COMMON EQUITY RELATED STOCKHOLDER
MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES.
Our common stock began trading publicly on the Nasdaq National Market under the symbol ENMD
on June 12, 1996. The following table sets forth the high and low closing price for our common
stock by quarter, as reported by the Nasdaq National Market, for the periods indicated:
HIGH | LOW | |||||||
2005: |
||||||||
First Quarter |
$ | 4.64 | $ | 2.10 | ||||
Second Quarter |
3.11 | 2.19 | ||||||
Third Quarter |
3.31 | 2.30 | ||||||
Fourth Quarter |
2.52 | 1.88 | ||||||
2006: |
||||||||
First Quarter |
$ | 2.87 | $ | 1.99 | ||||
Second Quarter |
2.54 | 1.51 | ||||||
Third Quarter |
1.93 | 1.45 | ||||||
Fourth Quarter |
2.20 | 1.52 |
On February 28, 2007, the closing price of our common stock, as reported by the Nasdaq
National Market, was $1.56 per share. As of February 28, 2007 there were approximately 965 holders
of record of our common stock.
Since our initial public offering in 1996, we have not paid cash dividends on our common
stock. We currently anticipate that any earnings will be retained for the continued development of
our business and we do not anticipate paying any cash dividends on our common stock in the
foreseeable future.
Options under Employee Benefit Plans
The following table discloses certain information about the options issued and available for
issuance under all outstanding Company option plans, as of December 31, 2006.
(a) | (b) | (c) | ||||||||||
Number of securities | ||||||||||||
Number of securities | remaining available for | |||||||||||
to be issued upon | Weighted-average | future issuance under equity | ||||||||||
exercise of | exercise price of | compensation plans | ||||||||||
outstanding options, | outstanding options, | [excluding securities | ||||||||||
Plan category | warrants and rights | warrants and rights | reflected in column (a)] | |||||||||
Equity compensation
plans approved by
security holders |
8,111,086 | $ | 7.87 | 788,097 | ||||||||
Equity compensation
plans not approved
by security holders |
142,370 | $ | 4.00 | 0 | ||||||||
Total |
8,253,456 | $ | 7.80 | 788,097 | ||||||||
Warrants issued under the unauthorized plans represent compensation for consulting services
rendered by the holders.
21
STOCK PRICE PERFORMANCE PRESENTATION
The following chart compares the cumulative total stockholder return on the Companys Shares with
the cumulative total stockholder return of the NASDAQ Stock Market U. S. Index, and the NASDAQ
Pharmaceuticals Index.
12/31/01 | 12/31/02 | 12/31/03 | 12/31/04 | 12/31/05 | 12/31/06 | |||||||||||||||||||
ENTREMED, INC. |
100.000 | 10.178 | 39.290 | 38.343 | 22.959 | 18.698 | ||||||||||||||||||
NASDAQ STOCK MARKET US |
100.000 | 69.131 | 103.365 | 112.489 | 114.881 | 126.216 | ||||||||||||||||||
NASDAQ PHARMACEUTICALS |
100.000 | 64.616 | 94.718 | 100.885 | 111.093 | 108.753 | ||||||||||||||||||
(1) | Assumes $100 invested on December 31, 2001 and assumes dividends are reinvested. Measurement points begin with the date of the assumed investment and include the last day of each of the subsequent 5 years through and including December 31, 2006. The material in this chart is not soliciting material, is not deemed filed with the SEC and is not incorporated by reference in any filing of the Company under the Securities Act of 1933, as amended, (the 1933 Act) or the 1934 Act, whether made before or after the date of this proxy statement and irrespective of any general incorporation language in such filing. |
22
ITEM 6. SELECTED FINANCIAL DATA.
The following selected consolidated financial data set forth below has been derived from our
audited consolidated financial statements. The data should be read in conjunction with the
consolidated financial statements and related notes, Managements Discussion and Analysis of
Financial Condition and Results of Operations in Item 7 and other financial information included
elsewhere in this annual report on Form 10-K.
Year Ended December 31, | ||||||||||||||||||||
2006 | 2005 | 2004 | 2003 | 2002 | ||||||||||||||||
STATEMENTS OF OPERATIONS DATA: |
||||||||||||||||||||
Revenues |
||||||||||||||||||||
Collaborative research
and development |
$ | | $ | | $ | | $ | 667,796 | $ | 835,493 | ||||||||||
License fees |
| 590,992 | 495,496 | 310,496 | 115,496 | |||||||||||||||
Grant revenues |
| | | 508,243 | 131,681 | |||||||||||||||
Royalty revenues |
6,881,799 | 5,310,439 | 5,918 | 2,705 | 38,790 | |||||||||||||||
Other |
12,559 | 16,624 | 12,581 | 86,306 | 55,030 | |||||||||||||||
Total revenues |
6,894,358 | 5,918,055 | 513,995 | 1,575,546 | 1,176,490 | |||||||||||||||
Expenses: |
||||||||||||||||||||
Research and development |
21,671,117 | 17,325,048 | 10,523,252 | 14,252,196 | 31,308,427 | |||||||||||||||
General and administrative |
7,393,722 | 5,920,455 | 6,570,664 | 7,022,986 | 13,932,133 | |||||||||||||||
Acquired In-Process R&D |
29,481,894 | | | | | |||||||||||||||
Interest expense |
156,787 | | | | 390,941 | |||||||||||||||
Investment income |
(1,867,204 | ) | (1,010,771 | ) | (313,940 | ) | (205,580 | ) | (317,910 | ) | ||||||||||
Gain on discharge of liabilities |
| | | | (2,174,765 | ) | ||||||||||||||
Gain on sale of asset |
(52,901 | ) | (3,420 | ) | (124,083 | ) | | (2,940,184 | ) | |||||||||||
Gain on sale of securities |
| | (520,000 | ) | | | ||||||||||||||
Gain on sale of royalty interest |
| | (3,000,000 | ) | | | ||||||||||||||
Net loss |
$ | (49,889,057 | ) | $ | (16,313,257 | ) | $ | (12,621,898 | ) | $ | (19,494,056 | ) | $ | (39,022,152 | ) | |||||
Dividends on Series A convertible preferred
stock |
(1,005,000 | ) | (1,005,000 | ) | (1,005,000 | ) | (1,005,000 | ) | | |||||||||||
Net loss attributable to common shareholders |
$ | (50,894,057 | ) | $ | (17,318,257 | ) | $ | (13,626,898 | ) | $ | (20,499,056 | ) | $ | (39,022,152 | ) | |||||
Net loss per share |
$ | (0.71 | ) | $ | (0.36 | ) | $ | (0.37 | ) | $ | (0.68 | ) | $ | (1.78 | ) | |||||
Weighted average number of
shares outstanding |
71,873,734 | 48,176,914 | 37,170,544 | 29,943,161 | 21,892,520 |
As of December 31, | ||||||||||||||||||||
2006 | 2005 | 2004 | 2003 | 2002 | ||||||||||||||||
BALANCE SHEET DATA: |
||||||||||||||||||||
Cash and cash equivalents
and short-term investments |
$ | 50,570,097 | $ | 30,082,388 | $ | 34,539,516 | $ | 36,941,430 | $ | 24,067,045 | ||||||||||
Working capital |
46,268,554 | 28,510,176 | 34,979,936 | 33,405,818 | 7,716,002 | |||||||||||||||
Total assets |
55,719,534 | 36,431,885 | 39,404,002 | 40,153,764 | 27,810,212 | |||||||||||||||
Deferred revenue, less
current portion |
| | 95,496 | 192,993 | 286,488 | |||||||||||||||
Accumulated deficit |
(311,636,886 | ) | (261,747,829 | ) | (245,434,572 | ) | (232,812,674 | ) | (213,318,618 | ) | ||||||||||
Total stockholders equity |
46,963,219 | 29,369,190 | 35,704,754 | 34,858,883 | 10,493,646 |
23
ITEM 7. MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS.
The following discussion should be read in conjunction with the Consolidated Financial
Statements and Notes thereto appearing elsewhere in this report. See Risk Factors.
OVERVIEW
We are a clinical-stage pharmaceutical company focused on developing next generation
multi-mechanism oncology and anti-inflammatory drugs that target disease cells directly and the
blood vessels that nourish them. We are focused on developing drugs that are safe and convenient,
and provide the potential for improved patient outcomes. Panzem® (2-methoxyestradiol or
2ME2), one of our lead drug candidates, is currently in Phase 2 clinical trials for cancer, as well
as in preclinical development for rheumatoid arthritis. MKC-1, a novel cell cycle inhibitor, is
also in Phase 2 clinical trials for cancer. ENMD-1198, a novel tubulin binding agent discovered by
EntreMed, is currently in a Phase 1 clinical trial for cancer. As our research and development
efforts have shifted to a more clinical focus, expenditures have increased and will continue to
increase as we secure material to support on-going and planned trials for our three clinical-stage
candidates.
In January 2006, we acquired Miikana Therapeutics, Inc., a clinical-stage biopharmaceutical
company with research laboratories in Toronto, Canada. As a result of the transaction, we enhanced
our pipeline with the addition of a Phase 2 drug candidate, MKC-1, and two preclinical programs,
one in aurora kinase inhibition and one in HDAC inhibition, both for the treatment of cancer.
Our goal is to develop and commercialize drugs based on our scientific expertise in
angiogenesis, cell cycle regulation and inflammation processes vital to the progression of
cancer and other diseases. Our three product candidates are based on these mechanisms.
In order to further advance our commercial objectives, we may seek strategic alliances,
licensing relationships and co-development partnerships with other companies to develop compounds
for both oncology and non-oncology therapeutic areas.
CRITICAL ACCOUNTING POLICIES AND THE USE OF ESTIMATES
The preparation of our financial statements in conformity with accounting principles generally
accepted in the U.S. requires management to make estimates and assumptions that affect the amounts
reported in our consolidated financial statements and accompanying notes. Actual results could
differ materially from those estimates. Our critical accounting policies, including the items in
our financial statements requiring significant estimates and judgments, are as follows:
| Revenue Recognition We recognize revenue in accordance with the provisions of Staff Accounting Bulletin No. 104, Revenue Recognition, whereby revenue is not recognized until it is realized or realizable and earned. Revenue is recognized when all of the following criteria are met: persuasive evidence of an arrangement exists, delivery has occurred or services have been rendered, the price to the buyer is fixed and determinable and collectibility is reasonably assured. |
| Royalty Revenue Royalties from licenses are based on third-party sales and recorded as earned in accordance with contract terms, when third-party results are reliably measured and collectibility is reasonably assured. The majority of our 2006 revenues were from royalties on the sale of Thalomid®, which we began to recognize in the third quarter. In 2004 certain provisions of a purchase agreement dated June 14, 2001 by and between Bioventure Investments kft (Bioventure) and the Company were satisfied, and, as a result, beginning in 2005 we became entitled to share in the royalty payments received by Royalty Pharma Finance Trust, successor to Bioventure, on annual Thalomid® sales above a certain threshold. Based on the licensing agreement royalty formula, annual royalty sharing commences with Thalomid® annual sales of approximately $225 million. We are also eligible to receive royalty payments under a February 2004 agreement with Childrens Medical Center Corporation (CMCC) and Alchemgen Therapeutics. Under the agreement, Alchemgen received rights to market endostatin and angiostatin in Asia. We did not receive royalties under this agreement in 2006. In the future, royalty payments, if any, will be recorded as revenue when received and/or when collectibility is reasonably assured. |
24
| Research and Development Research and development expenses consist primarily of compensation and other expenses related to research and development personnel, research collaborations, costs associated with pre-clinical testing and clinical trials of our product candidates, including the costs of manufacturing the product candidates, and facilities expenses. Research and development costs are expensed as incurred. | ||
| Stock-Based Compensation Issued in December 2004, Statement of Financial Accounting Standards No. 123R (SFAS 123R) requires companies to recognize expense associated with share-based compensation arrangements, including employee stock options and stock purchase plans, using a fair value-based option pricing model, and eliminates the alternative to use the intrinsic value method of accounting for share-based payments. SFAS 123R is effective for our fiscal year beginning January 1, 2006. Adoption of the expense provisions of SFAS 123R has a material impact on our results of operations. We have applied the modified prospective transition method; accordingly, compensation expense is reflected in the financial statements beginning January 1, 2006 with no restatement of prior periods. Compensation expense is recognized for awards that are granted, modified, repurchased or cancelled on or after January 1, 2006, as well as for the portion of awards previously granted that have not vested as of January 1, 2006. For the adoption of SFAS 123R, we have selected the straight-line expense attribution method, whereas our previous expense attribution method was the graded-vesting method, an accelerated method, described by FIN 28. Our results of operations for fiscal 2006 were impacted by the recognition of non-cash expense related to the fair value of our share-based compensation awards. Share-based compensation expense recognized under SFAS 123R for the year ended December 31, 2006 totaled approximately $1,656,000. |
The determination of fair value of stock-based payment awards on the date of grant
using the Black-Scholes model is affected by our stock price, as well as the input of other
subjective assumptions. These assumptions include, but are not limited to, the expected
term of stock options and our expected stock price volatility over the term of the awards.
Changes in the assumptions can materially affect the fair value estimates.
Any future changes to our share-based compensation strategy or programs would likely
affect the amount of compensation expense recognized under SFAS 123R and the comparability
to our prior period footnote disclosures of pro forma net earnings and earnings per share.
RESULTS OF OPERATIONS
Years Ended December 31, 2006, 2005 and 2004.
Revenues. Revenues increased 16% in 2006 to $6,894,000 from $5,918,000 in 2005 after
increasing 1,051% in 2005 from $514,000 in 2004. The fluctuation between periods results from
changes in the revenue components and also from the manner and timing of when certain revenues are
recorded. The three years presented reflect the following revenue types: royalty revenues and
licensing revenues. The increase in revenues in 2006 results from increased royalty revenue earned
on sales of Thalomid®. Beginning in 2005, we are entitled to share in the royalty
payments received by Royalty Pharma Finance Trust on annual Thalomid® sales above
approximately $225 million. Thalomid® sales in 2005 and 2006 surpassed the sharing
point in the third quarter and we recorded estimated royalty revenues of $5,310,000 and $6,882,000,
respectively. No royalty revenues were recorded on Thalomid® sales in 2004.
We did not record any licensing revenues in 2006, versus $591,000 in 2005. The 2005
amount reflects the accelerated recognition of deferred licensing revenues from the
January 2002 agreement with Allergan, which was terminated in April 2005 by Allergan in
accordance with the terms of the agreement, and the recognition of a
$400,000 licensing payment from Alchemgen in May 2005. This amount was recorded as revenue
when collectibility was deemed to be reasonably assured. Licensing revenues of $495,000
were recorded in 2004. This amount included the recognition of amortized licensing revenues from
the February 2004 agreement with Alchemgen in addition to the revenues from the 2002 five-year
strategic alliance with Allergan.
25
Research and Development Expenses. Our 2006 research and development expenses, which
totaled $21,671,000, reflect our expanded clinical base including the cost of initiating and
supporting multiple trials for Panzem® NCD and MKC-1 and also a Phase 1 clinical trial
for ENMD-1198. The increase in our 2006 R&D expenses is primarily attributable to our January 2006
acquisition of Miikana Therapeutics, Inc. We recorded R&D expenses of $5,167,000 related to
initiating multiple MKC-1 clinical trials, advancement of two acquired pre-clinical programs and
supporting the Toronto based research group. Our 2006 R&D expenses also include $352,000 in
non-cash stock-based compensation, pursuant to the adoption of SFAS 123R. The 2006 amount reflects
direct project costs for Panzem® of $7,814,000, $2,085,000 for ENMD-1198 and $3,000,000
for MKC-1. In 2005 our research and development expenses totaled $17,325,000 which included direct
project costs of $7,594,000 for Panzem® and $3,237,000 related to ENMD-1198. Research and
development expenses were $10,523,000 in 2004, with project costs for Panzem® of
$3,558,000 and $2,135,000 for ENMD-1198. The 2005 and 2006 expenditures reflect an increase in
clinical and regulatory activity along with associated contract manufacturing activities.
Panzem® NCD moved into Phase 2 oncology trials in January 2006 and is currently being
studied in multiple Phase 1 and 2 clinical trials and is also being evaluated as an IND candidate
to treat rheumatoid arthritis. MKC-1 is being administered in two Phase 2 oncology trials and is
also currently in a Phase 1 study for hematological cancers. ENMD-1198, a tubulin binding agent,
commenced clinical development with the initiation of a Phase 1 clinical trial in oncology in early
2006. At December 31, 2006, accumulated direct project expenses for Panzem®, our lead
drug candidate, totaled $43,109,000 and for ENMD-1198, a tubulin binding agent that has entered
Phase 1 trials for cancer, totaled $7,457,000. The balance of our R&D expenditures includes
facilities costs and other departmental overhead, and expenditures related to the advancement of
our pre-clinical.programs.
The expenditures that will be necessary to execute our business plan are subject to numerous
uncertainties, which may adversely affect our liquidity and capital resources. As of December 31,
2006, we have three proprietary product candidates in clinical trials. We expect our R&D expenses
to trend higher as these compounds advance through the various stages of clinical development.
Completion of clinical trials may take several years or more, but the length of time generally
varies substantially according to the type, complexity, novelty and intended use of a product
candidate.
We estimate that clinical trials of the type we generally conduct are typically completed over
the following timelines:
ESTIMATED | ||||
COMPLETION | ||||
CLINICAL PHASE | PERIOD | |||
Phase I |
1 Year | |||
Phase II |
1-2 Years | |||
Phase III |
2-4 Years | |||
The duration and the cost of clinical trials may vary significantly over the life of a project
as a result of differences arising during the clinical trial protocol, including, among others, the
following:
- | the number of patients that ultimately participate in the trial; | ||
- | the duration of patient follow-up that seems appropriate in view of the results; | ||
- | the number of clinical sites included in the trials; and | ||
- | the length of time required to enroll suitable patient subjects. |
26
We test our potential product candidates in numerous pre-clinical studies to identify
indications for which they may be product candidates. We may conduct multiple clinical trials to
cover a variety of indications for each product candidate. As we obtain results from trials, we
may elect to discontinue clinical trials for certain product candidates or for certain indications
in order to focus our resources on more promising product candidates or indications.
Our proprietary product candidates also have not yet achieved FDA regulatory approval, which
is required before we can market them as therapeutic products. In order to proceed to subsequent
clinical trial stages and to ultimately achieve regulatory approval, the FDA must conclude that our
clinical data establish safety and efficacy. Historically, the results from preclinical testing and
early clinical trials have often not been predictive of results obtained in later clinical trials.
A number of new drugs and biologics have shown promising results in clinical trials, but
subsequently failed to establish sufficient safety and efficacy data to obtain necessary regulatory
approvals.
An important element of our business strategy is to pursue the research and development of a
range of product candidates for a variety of oncology and non-oncology indications. This allows us
to diversify the risks associated with our research and development expenditures. As a result, we
intend to pursue development of our existing product candidates internally or through development
partnerships, as well as through the acquisition and subsequent development of promising
candidates. The goal is to align our future capital requirements with multiple product candidates
and to increase the likelihood that our future financial success is not substantially dependent on
any one product candidate. To the extent we are unable to maintain a broad range of product
candidates, our dependence on the success of one or a few product candidates would increase.
Furthermore, our business strategy includes the option of entering into collaborative
arrangements with third parties to complete the development and commercialization of our products.
In the event that third parties take over the clinical trial process for one of our product
candidates, the estimated completion date would largely be under the control of that third party
rather than us. We cannot forecast with any degree of certainty which proprietary products or
indications, if any, will be subject to future collaborative arrangements, in whole or in part, and
how such arrangements would affect our capital requirements.
As a result of the uncertainties discussed above, among others, we are unable to estimate the
duration and completion costs of our research and development projects. Our inability to complete
our research and development projects in a timely manner or our failure to enter into collaborative
agreements, when appropriate, could significantly increase our capital requirements and could
adversely impact our liquidity. These uncertainties could force us to seek additional, external
sources of financing from time to time in order to continue with our business strategy. There can
be no assurance that we would be able to raise additional capital if needed. Our inability to
raise additional capital, or to do so on terms reasonably acceptable to us, would jeopardize the
future success of our business.
Research and development expenses consist primarily of compensation and other expenses related
to research and development personnel, research collaborations, costs associated with internal and
contract pre-clinical testing and clinical trials of our product candidates, including the costs of
manufacturing the product candidates, and facilities expenses. Overall research and development
expenses increased to approximately $21,671,000 in 2006 from $17,325,000 in 2005, also an increase
from $10,523,000 in 2004. The 2006 increase primarily results from our acquisition of Miikana in
Janaury 2006. Our 2006 expenditures include $5,167,000 for R&D activities associated with MKC-1,
two acquired pre-clinical programs and support for the Toronto-based research group. Reflected in
the 2006 increase is the companys continued shift to a more clinical focus resulting in the
advancement to Phase 2 trials for Panzem ® NCD, the initiation of clinical development in oncology
for ENMD-1198 and, through Miikana, the addition of MKC-1 a Phase 2 oncology clinical candidate.
The higher research and development expenditures in 2005 versus 2004 result from increased clinical
and regulatory activity along with associated contract manufacturing activities primarily related
to the reformulated Panzem®. In 2005 Panzem® NCD completed enrollment in two
Phase 1B oncology trials and moved into Phase 2 oncology trials in January 2006. IND-directed
toxicity studies for ENMD-1198 were conducted and an IND was submitted and accepted in late 2005.
ENMD-1198, a tubulin binding agent, commenced clinical development with the initiation of clinical
trials in oncology in early 2006. Increases in contract manufacturing expenses included material
to support the respective 2005 activities and also the acquisition of API to support
Panzem® NCD and ENMD-1198 clinical programs in 2006. In 2005 we also incurred
formulation
27
costs for finished drug product for both candidates including certain Panzem® NCD
contract manufacturing milestones triggered by clinical events. The 2005 amount also reflects
increased costs associated with further development of various drug candidates, including a $1
million upfront fee associated with the license of Celgenes small molecule tubulin inhibitor
compounds for the treatment of cancer and a $200,000 success fee to Ferghana Partners, Inc., a
related party, in connection with the license agreement. The increases in R&D expenses
reflected in 2006 and 2005 were specifically impacted by the following:
| Outside Services We utilize outsourcing to conduct our product development activities. Larger-scale small molecule synthesis, in vivo testing and data analysis are examples of the services that we outsource. We expended $3,621,000 in 2006, $2,399,000 in 2005 and $1,741,000 in 2004 on these activities. The 2006 and 2005 increases resulted from continued development work on our preclinical pipeline programs, including IND-directed toxicity studies for ENMD-1198 in 2005 and Panzem® NCD for rheumatoid arthritis in 2006. Additionally, through a series of pre-clinical studies we identified a lead compound for the acquired Aurora Kinase program and the compound, ENMD-981693, is headed into toxicology studies with the goal of filing an IND in 2007. The lower costs in 2004 reflect our then single clinical candidate status and our specific focus on reformulating and optimizing Panzem® and the selection of our lead 2ME2 analog candidate, ENMD-1198. | ||
| Collaborative Research Agreements We made payments to our collaborators of $231,000, $673,000 and $622,000 in years 2006, 2005 and 2004, respectively. Our collaborative efforts are primarily directed towards further exploration of 2ME2 mechanism-of-action (MOA) in-vivo testing of therapeutic combination studies, and PanzemÒ non-oncology applications. Sponsored research payments to academic collaborators include payments to Childrens Hospital of $225,000 in 2005 and $300,000 in 2004. | ||
| Clinical Trial Costs Clinical costs increased to $3,406,000 in 2006 from $1,090,000 in 2005, which was a small increase from $1,008,000 in 2004. The significant increase in clinical trial costs reflects the progression of our clinical candidates and also the addition of a second Phase 2 oncology clinical candidate, MKC-1, acquired with Miikana Therapeutics. The 2006 expenses include initiating and supporting multiple trials for Panzem® NCD, the initiation of a Phase 1 clinical trial for ENMD-1198 and the initiation of multiple trials for MKC-1. Our 2005 clinical expenses reflect two Phase 1b clinical trials for the reformulated PanzemÒ NCD. The 2004 amount supported a Phase 1a clinical trial to test various dosing approaches for reformulated PanzemÒ along with continuing clinical trials of the capsule Panzem® formulation. Costs of such trials include the clinical site fees, monitoring costs and data management costs. | ||
| Contract Manufacturing Costs The costs of manufacturing the material used in clinical trials for our product candidates is reflected in contract manufacturing. These costs include bulk manufacturing, formulation, encapsulation and fill finish services, product release costs and also payments to contract manufacturers for technology access or licensing fees. Contract manufacturing costs decreased slightly in 2006 to $5,595,000 from $5,606,000 in 2005. The 2006 expenses include $1,079,000 related to the manufacture of MKC-1. The balance of the manufacturing activities relate primarily to supporting our Phase 2 Panzem® NCD trials. Our 2005 expenses included material to support 2005 activities and also the acquisition of API for the PanzemÒ and ENMD-1198 clinical programs in 2006. In 2005, we also incurred formulation costs for finished drug product for both candidates including certain PanzemÒ NCD contract manufacturing milestones triggered by clinical events. Product manufacturing costs were $1,392,000 in 2004. The 2004 costs reflect expenditures for the preparation of Panzem® NCD for preclinical and clinical use and encapsulation runs for the capsule form to support our Phase 2 and NCI clinical trials. | ||
| Personnel Costs Personnel costs increased to $4,368,000 in 2006 from $2,864,000 in 2005. Included in the 2006 costs is $1,212,000 related to Miikana employees. Personnel costs were $3,020,000 in 2004. |
Also reflected in our 2006 research and development expenses are patent costs of $756,000,
facility and related expenses of $1,503,000, laboratory supplies and animal costs of $1,062,000,
consulting fees of $624,000 and travel expenses of $235,000. In 2005, these expenses totaled
$654,000, $1,351,000, $772,000, $296,000 and
$200,000, respectively, and in 2004, these expenses totaled $493,000, $1,551,000, $531,000,
$174,000 and $69,000, respectively. The 2006 increases relate primarily to supporting our broader
pipeline.
28
General and Administrative Expenses. General and administrative expenses include compensation
and other expenses related to finance, business development and administrative personnel,
professional services and facilities.
General and administrative expenses increased to approximately $7,394,000 in 2006 from
$5,920,000 in 2005. General and administrative expenses were $6,571,000 in 2004. The 2006
increase relates primarily to the recording of non-cash stock-based compensation, pursuant to the
adoption of SFAS 123R, in the amount of $1,303,000. The 2005 decrease primarily reflected a
reduced level of professional services related to compliance with provisions of the Sarbanes-Oxley
Act of 2002, as compared to the amount incurred in 2004, the first year we were required to comply
with these provisions.
Acquired In-Process R&D.
In January 2006, we acquired Miikana Therapeutics, a private
biotechnology company. Pursuant to the Merger Agreement, we acquired all of the
outstanding capital stock of Miikana Therapeutics, Inc. in exchange for 9.96 million shares of
common stock and the assumption of certain obligations. Miikana was a development stage company.
Accordingly, the acquisition of Miikana was treated as an asset purchase. In accordance with EITF
98-3 Determining Whether a Nonmonetary Transaction Involves Receipt of Productive Asset or of a
Business, and Statement 141 Business Combinations the $30.1 million purchase price was first
allocated to the tangible assets acquired ($600,000) based on the estimated fair values at the
acquisition date. The balance of the purchase price ($29,500,000) was allocated to intangible
assets and recorded as in-process research and development as the research and development projects
in Miikanas pipeline, as of the acquisition date, had not reached technological feasibility and
had no alternative use. We believe the fair values assigned to the assets acquired and liabilities
assumed are based upon reasonable assumptions given current available facts and circumstances. The
total purchase price allocated was $30.1 million, consisting of 9,964,000 shares of our common
stock with a fair value of $21.9 million, assumed debt of $1.5 million, assumed current liabilities
of $2.7 million, $1 million loaned to Miikana prior to the closing and acquisition costs of $3
million. The fair value of common stock was determined using the closing price at the date of
acquisition.
Interest expense. Interest
expense for the year ended December 31, 2006 was approximately
$157,000. We assumed certain interest-bearing debt when we acquired Miikana in January
2006 and had no interest-bearing debt during 2005 or 2004.
Investment income. Investment income increased by 85% in 2006 to $1,867,000 as a result of
higher yields on higher invested balances in interest-bearing cash accounts and investments.
Investment income was $1,011,000 in 2005, an increase of 222% from $314,000 in 2004.
Dividends on Series A convertible preferred stock. The Consolidated Statements of Operations
for the years ended December 31, 2006, 2005 and 2004 reflect dividends of $1,005,000 relating to
Series A Convertible Preferred Stock held by Celgene pursuant to a Securities Purchase Agreement
dated December 31, 2002. The holders of Series A Preferred Stock will accumulate dividends at a
rate of 6% and will participate in dividends declared and paid on the common stock, if any. All
accumulated dividends must be paid before any dividends may be declared or paid on the Common
Stock. We have no plans to pay any dividends in the foreseeable future.
Gain on sale of securities. The Consolidated Statement of Operations for the year ended
December 31, 2004 reflects a gain of $520,000 resulting from the sale of certain securities of an
independent private biotechnology company. The securities were acquired in 1996 through 1999 and
accounted for using the equity method. The cost of these securities was written off in prior
periods and we had no residual cost basis in the securities when sold. As such, we have recorded a
gain on the sale equal to the sale proceeds.
Gain on sale of royalty interest. The Consolidated Statement of Operations for the year
ended December 31, 2004 reflects a gain of $3,000,000, which represents a one-time sale price
adjustment pursuant to a purchase agreement dated August 6, 2001 by and between Bioventure and the
Company. The adjustment was triggered by
$800,000,000 in cumulative Thalomid® sales through December 31, 2004.
29
LIQUIDITY AND CAPITAL RESOURCES
To date, we have been engaged primarily in research and development activities. As a result,
we have incurred operating losses for 2006 and expect to continue to incur operating losses in the
foreseeable future before we commercialize any products. In
January 2006, we acquired
Miikana Therapeutics, a private biotechnology company. Pursuant to
the Merger Agreement, we acquired all of the outstanding capital stock of Miikana Therapeutics, Inc. in exchange for
9.96 million shares of common stock and the assumption of certain obligations. In addition, based
on the success of the acquired pre-clinical programs, we may pay up to an additional $18
million upon the achievement of certain clinical and regulatory milestones. Such additional
payments will be made in cash or shares of stock at our option. We expect that
the Aurora Kinase pre-clinical program will advance to a Phase 1 clinical trial in 2007. A dosing
of the first patient triggers a purchase price adjustment milestone of $2 million, which is
expected to be due (in cash or stock at the our discretion) in 2007. Through the
acquisition, we acquired rights to MKC-1, a Phase 2 clinical candidate licensed from
Hoffman-LaRoche, Inc. (Roche) by Miikana in April 2005. Under the terms of the agreement, Roche
may be entitled to receive future payments upon successful attainment of certain clinical,
regulatory and commercialization milestones, we do not expect to trigger any of these milestone
payments in 2007. Under the terms of the license agreements for 2ME2 and Celgenes tubulin
inhibitor program, we must be diligent in bringing potential products to market and we may be
required to make future milestone payments totaling approximately $500,000 and $25.25 million,
respectively. As a result of progress on these licensed clinical and preclinical programs,
milestones requiring payments totaling $250,000 could be reached in 2007. If we fail to comply
with the milestones or fail to make any required sponsored research or milestone payment, we could
face the termination of the relevant license agreement.
At December 31, 2006, we had cash and short-term investments of $50,570,097 with working
capital of $46,268,554. We invest our capital resources with the primary objective of capital
preservation. As a result of trends in interest rates in 2006, we have invested in some securities
with maturity dates of more than 90 days to enhance our investment yields. As such, some of our
invested balances are classified as short-term investments rather than cash equivalents in our
consolidated financial statements at December 31, 2006.
In February 2006, we completed a private placement to institutional investors of units
consisting of our common stock and warrants. We issued 12,972,966 shares of stock and warrants
that are currently exercisable and remain exercisable until February 7, 2011 at an exercise price
of $2.50 per share. We received net proceeds from the financing of approximately $27.9 million.
In December 2006, we completed a registered direct offering of 10,727,500 shares of our common
stock at a price of $1.60 per share, for net proceeds of $15.9 million, after transaction-related
expenses.
To accomplish our business plans, we will be required to continue to conduct substantial
development activities for some or all of our proposed products. Under our current operating plans
in 2007 we expect to have four compounds under clinical investigation and we expect our 2007
results of operations to reflect a net loss of approximately $37,000,000, including non-cash
charges of approximately $4,700,000. In addition to the continued clinical development of Panzem®
NCD, MKC-1 and ENMD-1198 we plan to begin clinical evaluation for the treatment of rheumatoid
arthritis with Panzem® NCD and also anticipate initiating clinical evaluation in oncology of
ENMD-981693. We expect that the majority of our 2007 revenues will continue to be from royalties
on the sale of Thalomid®. Based on historical trend and analyst consensus for
Thalomid® sales in 2006, we expect to record royalty-sharing revenues in excess of $6.0
million in 2007; however, there can be no assurance in this regard. In addition, under our
licensing agreement with Oxford Biomedica, PLC and Oxford Biomedica (UK) Limited Oxford, we are
entitled to receive payments upon the achievement of certain milestones. However, we do not
control the drug development efforts of Oxford and have no control over when or whether such
milestones will be reached. We do not believe that we will receive any developmental milestone
payments under these agreements in 2007.
30
Based on our assessment of our current capital resources coupled with anticipated inflows, in
the absence
of additional financing, we believe that we will have adequate resources to fund planned
operations for more than twelve months from December 31, 2006. Our estimate may change, however,
based on our decisions with respect to future clinical trials related to our product candidates,
the timing of receipt of milestone payments, developments in our business including the acquisition
of additional intellectual property, other investments in new or complimentary technology, and our
success in executing our current business plan.
To address our long-term capital needs, we intend to continue to pursue strategic
relationships that will provide resources for the further development of our product candidates.
There can be no assurance, however, that these discussions will result in relationships or
additional funding. In addition, we may continue to seek capital through the public or private
sale of securities, if market conditions are favorable for doing so. If we are successful in
raising additional funds through the issuance of equity securities, stockholders will likely
experience substantial dilution, or the equity securities may have rights, preferences or
privileges senior to those of the holders of our common stock. If we raise funds through the
issuance of debt securities, those securities would have rights, preferences and privileges senior
to those of our common stock. There can be no assurance that we will be successful in seeking
additional capital.
INFLATION AND INTEREST RATE CHANGES
Management does not believe that our working capital needs are sensitive to inflation and
changes in interest rates.
CONTRACTUAL OBLIGATIONS
The table below sets forth our contractual obligations at December 31, 2006.
CONTRACTUAL OBLIGATIONS | PAYMENTS DUE BY PERIOD | |||||||||||||||||||
Total | Less than 1 | 1-3 years | 3 - 5 years | More than | ||||||||||||||||
year |
5
years |
|||||||||||||||||||
Operating Leases Obligations |
$ | 2,214,000 | $ | 1,013,000 | $ | 1,201,000 | $ | | $ | | ||||||||||
Loan Payable, including
interest |
848,000 | 848,000 | | | | |||||||||||||||
Purchase Obligations
|
||||||||||||||||||||
Clinical Trial Contracts |
5,516,000 | 4,591,000 | 855,000 | 70,000 | | |||||||||||||||
Contract Manufacturing |
638,000 | 638,000 | | | | |||||||||||||||
Outside Service Contracts |
337,000 | 337,000 | | | | |||||||||||||||
Other Contracts |
92,000 | 92,000 | | | | |||||||||||||||
Total Contractual Obligations |
$ | 9,645,000 | $ | 7,519,000 | $ | 2,056,000 | $ | 70,000 | $ | | ||||||||||
OFF-BALANCE-SHEET ARRANGEMENTS
We had no significant off-balance sheet arrangements during fiscal year 2006.
NEW ACCOUNTING PRONOUNCEMENTS
In May 2005, the FASB issued SFAS No. 154, Accounting Changes and Error Corrections a
replacement of APB Opinion No. 20 and FASB Statement No. 3 (SFAS 154). SFAS 154 replaces APB
Opinion No. 20, Accounting Changes and SFAS No. 3, Reporting Accounting Changes in Interim
Financial Statements, and changes the requirements for accounting for and reporting a change in
accounting principle. SFAS 154 requires restatement of prior period financial statements, unless
impracticable, for voluntary changes in accounting principle. The retroactive application of a
change in accounting principle should be limited to the direct effect of the change. Changes in
depreciation, amortization or depletion methods should be accounted for prospectively as a change
in accounting estimate. Corrections of accounting errors will be accounted for under the guidance
contained in APB Opinion No. 20. The effective date of this new pronouncement is for fiscal years
beginning after December 15, 2005
and prospective application is required. The adoption of SFAS 154 did not have a material
impact on our results of operations and financial condition.
31
On
January 1, 2006, we adopted Statement of Financial Accounting Standards No. 123R
Share Based Payment (SFAS 123R), which addresses the accounting for share-based payment
transactions in which we receive employee services in exchange for equity instruments.
The statement eliminates our ability to account for share-based compensation transactions
as prescribed by Accounting Principles Board Opinion No. 25, Accounting for Stock Issued to
Employees (APB No. 25), and generally requires that equity instruments issued in such
transactions be accounted for using a fair-value based method and the fair value of such equity
instruments be recognized as expenses in the consolidated statements of operations. The impact of
this statement is disclosed in footnotes 1 and 8.
In July 2006, the Financial Accounting Standards Board (FASB) issued FASB Interpretation No.
48, Accounting for Uncertainty in Income Taxes, an interpretation of FASB Statement No. 109 (FIN
48). FIN 48 clarifies the accounting for uncertainty in income taxes by prescribing the recognition
threshold a tax position is required to meet before being recognized in the financial statements.
It also provides guidance on derecognition, classification, interest and penalties, accounting in
interim periods, disclosure, and transition. FIN 48 is effective for fiscal years beginning after
December 15, 2006 and is required to be adopted by us in 2007. We do not expect the adoption of FIN
48 to have a material impact on our consolidated results of operations and financial condition.
In September 2006, the FASB issued SFAS No. 157, Fair Value Measurements (SFAS 157).
SFAS 157 provides guidance for using fair value to measure assets and liabilities. It also responds
to investors requests for expanded information about the extent to which companies measure assets
and liabilities at fair value, the information used to measure fair value, and the effect of fair
value measurements on earnings. SFAS 157 applies whenever other standards require (or permit)
assets or liabilities to be measured at fair value, and does not expand the use of fair value in
any new circumstances. SFAS 157 is effective for financial statements issued for fiscal years
beginning after November 15, 2007. We are currently evaluating the effect that the adoption of SFAS
157 will have on our consolidated results of operations and financial condition and are not yet in
a position to determine such effects.
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK.
The primary objective of our investment activities is to preserve our capital until it is
required to fund operations while at the same time maximizing the income we receive from our
investments without incurring investment market volatility risk. Our investment income is sensitive
to the general level of U.S. interest rates. In this regard, changes in the U.S. interest rates
affect the interest earned on our cash and cash equivalents. Due to the short-term nature of our
cash and cash equivalent holdings, a 10% movement in market interest rates would not materially
impact on the total fair market value of our portfolio as of December 31, 2006.
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA.
The response to this item is submitted in a separate section of this report. See Index to
Consolidated Financial Statements on Page F-1.
ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL
DISCLOSURE.
Not applicable.
32
ITEM 9A. CONTROLS AND PROCEDURES.
Evaluation of Disclosure Controls and Procedures
Under the supervision and with the participation of the Companys President and Chief
Executive Officer and its Chief Financial Officer (its principal executive officer and principal
financial officer), management has reviewed and evaluated the effectiveness of the design and
operation of the Companys disclosure controls and procedures. Based on that evaluation, the
President and Chief Executive Officer and the Chief Financial Officer have concluded that these
disclosure controls and procedures are effective as of December 31, 2006.
Changes in Internal Control Over Financial Reporting
During the quarter ended December 31, 2006, there were no changes in our internal control over
financial reporting that have materially affected, or are reasonably likely to materially affect,
our internal control over financial reporting except as described below.
Managements Report on Internal Control Over Financial Reporting
The management of EntreMed, Inc. is responsible for establishing and maintaining adequate
internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the
Securities Exchange Act of 1934, as amended). EntreMeds internal control over financial reporting
was designed to provide reasonable assurance to EntreMeds management and board of directors
regarding the reliability of financial reporting and the preparation of financial statements for
external purposes in accordance with generally accepted accounting principles. Any internal
control over financial reporting, no matter how well designed, has inherent limitations. As a
result of these inherent limitations, internal control over financial reporting may not prevent or
detect misstatements. Therefore, even those internal controls determined to be effective can
provide only reasonable assurance with respect to reliability of financial reporting and the
preparation of financial statements for external purposes in accordance with generally accepted
accounting principles.
EntreMeds management assessed the effectiveness of EntreMeds internal control over financial
reporting as of December 31, 2006 based on the criteria set forth by the Committee of Sponsoring
Organizations of the Treadway Commission (COSO) in Internal Control Integrated Framework.
Managements assessment included an evaluation of the design of EntreMeds internal control over
financial reporting and testing of the operational effectiveness of EntreMeds internal control
over financial reporting. Based on this assessment, EntreMeds management has concluded that our
internal control over financial reporting was effective as of December 31, 2006. Ernst & Young
LLP, the independent registered public accounting firm that audited the consolidated financial
statements included in this Annual Report on Form 10-K, has issued an attestation report on
managements assessment of the effectiveness of our internal control over financial reporting as of
December 31, 2006. This report which expresses an unqualified opinion on managements assessment
of and the effectiveness of our internal control over financial reporting as of December 31, 2006
is included herein.
33
Report of Independent Registered Public Accounting Firm
On Internal Control Over Financial Reporting
On Internal Control Over Financial Reporting
The Board of Directors and Stockholders of EntreMed, Inc.:
We have audited managements assessment, included in the accompanying Managements Report on
Internal Control Over Financial Reporting, that EntreMed, Inc. maintained effective internal
control over financial reporting as of December 31, 2006, based on criteria established in Internal
ControlIntegrated Framework issued by the Committee of Sponsoring Organizations of the Treadway
Commission (the COSO criteria). EntreMed, Inc.s management is responsible for maintaining
effective internal control over financial reporting and for its assessment of the effectiveness of
internal control over financial reporting. Our responsibility is to express an opinion on
managements assessment and an opinion on the effectiveness of the companys internal control over
financial reporting based on our audit.
We conducted our audit in accordance with the standards of the Public Company Accounting Oversight
Board (United States). Those standards require that we plan and perform the audit to obtain
reasonable assurance about whether effective internal control over financial reporting was
maintained in all material respects. Our audit included obtaining an understanding of internal
control over financial reporting, evaluating managements assessment, testing and evaluating the
design and operating effectiveness of internal control, and performing such other procedures as we
considered necessary in the circumstances. We believe that our audit provides a reasonable basis
for our opinion.
A companys internal control over financial reporting is a process designed to provide reasonable
assurance regarding the reliability of financial reporting and the preparation of financial
statements for external purposes in accordance with generally accepted accounting principles. A
companys internal control over financial reporting includes those policies and procedures that (1)
pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the
transactions and dispositions of the assets of the company; (2) provide reasonable assurance that
transactions are recorded as necessary to permit preparation of financial statements in accordance
with generally accepted accounting principles, and that receipts and expenditures of the company
are being made only in accordance with authorizations of management and directors of the company;
and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized
acquisition, use, or disposition of the companys assets that could have a material effect on the
financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or
detect misstatements. Also, projections of any evaluation of effectiveness to future periods are
subject to the risk that controls may become inadequate because of changes in conditions, or that
the degree of compliance with the policies or procedures may deteriorate.
In our opinion, managements assessment that EntreMed, Inc. maintained effective internal control
over financial reporting as of December 31, 2006, is fairly stated, in all material respects, based
on the COSO criteria. Also, in our opinion, EntreMed, Inc. maintained, in all material respects,
effective internal control over financial reporting as of December 31, 2006, based on the COSO
criteria.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight
Board (United States), the consolidated balance sheets as of December 31, 2006 and 2005 and the
related consolidated statements of operations, stockholders equity, and cash flows for each of the
three years in the period ended December 31, 2006 of EntreMed, Inc. and our report dated March 8,
2007, expressed an unqualified opinion thereon.
/s/ Ernst & Young LLP
McLean, Virginia
March 8, 2007
March 8, 2007
34
ITEM 9B. | OTHER INFORMATION |
None.
PART III
ITEM 10. | DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE |
Information required by this item will be contained in our Definitive Proxy Statement for our
2007 Annual Meeting of Stockholders, to be filed pursuant to Regulation 14A with the Securities and
Exchange Commission within 120 days of December 31, 2006. Such information is incorporated herein
by reference.
We have adopted a Code of Ethics, as defined in applicable SEC and NASD rules, that applies to
directors, officers and employees, including our principal executive officer and principal
financial and accounting officer. The Code of Ethics is available on the Companys website at
www.entremed.com.
ITEM 11. | EXECUTIVE COMPENSATION |
Information required by this item will be contained in our Definitive Proxy Statement for our
2007 Annual Meeting of Stockholders, to be filed pursuant to Regulation 14A with the Securities and
Exchange Commission within 120 days of December 31, 2006. Such information is incorporated herein
by reference.
ITEM 12. | SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS |
Information required by this item will be contained in our Definitive Proxy Statement for our
2007 Annual Meeting of Stockholders, to be filed pursuant to Regulation 14A with the Securities and
Exchange Commission within 120 days of December 31, 2006. Such information is incorporated herein
by reference.
ITEM 13. | CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE. |
Information required by this item will be contained in our Definitive Proxy Statement for our
2007 Annual Meeting of Stockholders, to be filed pursuant to Regulation 14A with the Securities and
Exchange Commission within 120 days of December 31, 2006. Such information is incorporated herein
by reference.
ITEM 14. | PRINCIPAL ACCOUNTANT FEES AND SERVICES. |
Information required by this item will be contained in our Definitive Proxy Statement for our
2007 Annual Meeting of Stockholders, to be filed pursuant to Regulation 14A with the Securities and
Exchange Commission within 120 days of December 31, 2006. Such information is incorporated herein
by reference.
35
PART IV
ITEM 15. EXHIBITS, FINANCIAL STATEMENT SCHEDULES.
(a) 1. FINANCIAL STATEMENTS See index to Consolidated Financial Statements.
2. Schedules
All financial statement schedules are omitted because they are not applicable, not required
under the instructions or all the information required is set forth in the financial statements or
notes thereto.
3. Exhibits
2.1(19)
|
Agreement and Plan of Merger, dated as of December 22, 2005 among EntreMed, Inc., E.M.K. Sub, Inc., Miikana Therapeutics, Inc., and Andrew Schwab | |
3.1
|
Amended and Restated Certificate of Incorporation of EntreMed, Inc. (incorporated by reference from our Form 10-K for the year ended December 31, 2002 previously filed with the Securities and Exchange Commission) | |
3.2(1)
|
By-laws of EntreMed, Inc. | |
4.1
|
Certificate of Designations of the Series A Convertible Preferred Stock (incorporated by reference to Exhibit 99.4 of our Form 8-K dated December 31, 2002, and filed with the Commission on January 15, 2003) | |
4.2
|
Warrant to Purchase Common Stock, dated January 13, 2003, issued by EntreMed, Inc. in favor of Celgene Corporation (incorporated by reference to Exhibit 99.5 of our Form 8-K dated December 31, 2002, and filed with the Commission on January 15, 2003) | |
10.1(1)
|
1992 Stock Incentive Plan* | |
10.2(1)
|
Amended and Restated 1996 Stock Option Plan* | |
10.3(1)
|
Form of Stock Option Agreement, under Amended and Restated 1996 Stock Option Plan* | |
10.4(2)
|
License Agreement between Childrens Hospital Medical Center Corporation and EntreMed, Inc. signed December 20, 1996 regarding Estrogenic Compounds as Anti-Mitotic Agents | |
10.5(3)
|
Amendment to the 1996 Stock Option Plan* | |
10.6(4)
|
License Agreement between Celgene Corporation and EntreMed, Inc. signed December 9, 1998 regarding thalidomide intellectual property | |
10.7(4)
|
Lease Agreement between EntreMed, Inc. and Red Gate III Limited Partnership, dated June 10, 1998 | |
10.8(5)
|
1999 Long-Term Incentive Plan* | |
10.9(6)
|
EntreMed, Inc. 2001 Long-Term Incentive Plan* | |
10. 10.1(7)
|
Purchase Agreement between Bioventure Investments kft and EntreMed, Inc., dated June 15, 2001+ | |
10.10.2(7)
|
Amendment 1 to Purchase Agreement between Bioventure Investments kft and EntreMed, Inc., dated July 13, 2001 |
36
10.10.3(7)
|
Amendment 2 to Purchase Agreement between Bioventure Investments kft and EntreMed, Inc., dated July 30, 2001 | |
10.10.4(7)
|
Amendment 3 to Purchase Agreement between Bioventure Investments kft and EntreMed, Inc., dated August 3, 2001 | |
10.11(8)
|
Board Service Agreement, dated February 5, 2003, between Michael M. Tarnow and EntreMed, Inc. * | |
10.12(9)
|
Securities Purchase Agreement by and among EntreMed, Inc., and Celgene Corporation, dated as of December 31, 2002 | |
10.13(9)
|
Investor and Registration Rights Agreement by and between EntreMed, Inc. and Celgene Corporation, dated as of December 31, 2002 | |
10.14(10)
|
Employment Agreement between EntreMed and James S. Burns effective June 15, 2004* | |
10.15(11)
|
Employment Agreement between EntreMed and Dane Saglio effective July 1, 2004* | |
10.19(12)
|
Employment Agreement between EntreMed and Carolyn F. Sidor, M.D. effective December 1, 2004* | |
10.20(13)
|
Securities Purchase Agreement by and among EntreMed and Certain Institutional Investors, dated as of December 23, 2004 | |
10.21(14)
|
EntreMed, Inc. 2001 Long Term Incentive Plan Non-Qualified Stock Option Grant Agreement (Director)* | |
10.22(14)
|
EntreMed, Inc. 2001 Long Term Incentive Plan Non-Qualified Stock Option Grant Agreement (Non-Director Employee)* | |
10.23(15)
|
Form of Letter Agreement between EntreMed and James S. Burns* | |
10.24(15)
|
Form of Restricted Stock Award under EntreMed, Inc. 2001 Long Term Incentive Plan* | |
10.18(16)
|
Letter Agreement between EntreMed and Dane Saglio dated May 20, 2005* | |
10.25(16)
|
Employment Agreement by and between EntreMed and Marc Corrado, dated as of May 20, 2005* | |
10.26(17)
|
License Agreement between EntreMed and Celgene Corporation signed March 24, 2005 regarding the development and commercialization of Celgenes small molecule tubulin inhibitor compounds for the treatment of cancer+ | |
10.27(18)
|
Description of Compensation of Directors* | |
10.28(20)
|
Employment Agreement by and between EntreMed and Cynthia Wong, dated as of June 1, 2006* | |
10.29(21)
|
Letter Agreement between EntreMed and Dane Saglio dated June 21, 2006* | |
10.30(22)
|
License Agreement, dated January 9, 2006, by and between Elan Pharma International Limited and EntreMed, Inc. + | |
10.31(22)
|
Research, Development and Commercialization Agreement, dated as of April 20, 2005, by and between Hoffman-La Roche Inc. and F. Hoffman La Roche Ltd. (together, Roche), and Miikana Therapeutics Inc.+ | |
23.1
|
Consent of Independent Registered Public Accounting Firm |
37
31.1
|
Rule 13a-14(a) Certification of President and CEO | |
31.2
|
Rule 13a-14(a) Certification of Chief Financial Officer | |
32.1
|
Rule 13a-14(b) Certification by President and CEO | |
32.2
|
Rule 13a-14(b) Certification by Chief Financial Officer |
*
|
Compensatory Plan, Contract or Arrangement. | |
+
|
Certain portions of this exhibit have been omitted based upon a request for confidential treatment. The omitted portions have been filed with the Commission pursuant to our application for confidential treatment. | |
(1)
|
Incorporated by reference from our Registration Statement on Form S-1 (File No. 333-3536) declared effective by the Securities and Exchange Commission on June 11, 1996. | |
(2)
|
Incorporated by reference from our Form 10-K for the year ended December 31, 1996 previously filed with the Securities and Exchange Commission. | |
(3)
|
Incorporated by reference from our Form 10-K for the year ended December 31, 1997 previously filed with the Securities and Exchange Commission. | |
(4)
|
Incorporated by reference from our Form 10-K for the year ended December 31, 1998 previously filed with the Securities and Exchange Commission. | |
(5)
|
Incorporated by reference from our Form 10-Q for the quarter ended June 30, 1999 previously filed with the Securities and Exchange Commission. | |
(6)
|
Incorporated by reference from Exhibit A to our definitive proxy statement filed with the Securities and Exchange Commission on June 27, 2005. | |
(7)
|
Incorporated by reference from our Form 10-Q for the quarter ended June 30, 2001 previously filed with the Securities and Exchange Commission. | |
(8)
|
Incorporated by reference from our Form 10-K/A for the year ended December 31, 2002 previously filed with the Securities and Exchange Commission. | |
(9)
|
Incorporated by reference from our Form 8-K dated December 31, 2002 filed with the Securities and Exchange Commission on January 15, 2003. | |
(10)
|
Incorporated by reference from our Form 10-Q for the quarter ended June 30, 2004 previously filed with the Securities and Exchange Commission. | |
(11)
|
Incorporated by reference from our Form 10-Q for the quarter ended September 30, 2004 previously filed with the Securities and Exchange Commission. | |
(12)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on December 6, 2004. | |
(13)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on December 29, 2004. |
38
(14)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on February 23, 2005. | |
(15)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on March 11, 2005. | |
(16)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on May 24, 2005. | |
(17)
|
Incorporated by reference from our Form 10-Q for the quarter ended March 31, 2005 previously filed with the Securities and Exchange Commission. | |
(18)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on August 2, 2005. | |
(19)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on December 29, 2005. | |
(20)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on June 6, 2006. | |
(21)
|
Incorporated by reference from our Form 8-K filed with the Securities and Exchange Commission on June 22, 2006. | |
(22)
|
Incorporated by reference from our Form 10-Q for the quarter ended March 31, 2006 previously filed with the Securities and Exchange Commission. |
39
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934,
the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto
duly authorized.
ENTREMED, INC. | ||||||
By: | /s/ James S. Burns. | |||||
James S. Burns | ||||||
President and Chief | ||||||
Executive Officer | ||||||
March 15, 2007 |
Pursuant to the requirements of the Securities Act of 1934, this report has been signed below
by the following persons in the capacities and on the dates indicated.
SIGNATURE | TITLE | DATE | ||
/s/ Michael M. Tarnow
|
Chairman of the Board | March 8, 2007 | ||
/s/ James S. Burns |
||||
President and Chief Executive Officer |
March 8, 2007 | |||
/s/ Dane R. Saglio
|
Chief Financial Officer (Principal Financial and Accounting Officer) |
March 8, 2007 | ||
/s/ Donald S. Brooks
|
Director | March 10, 2007 | ||
/s/ Dwight L. Bush
|
Director | March 8, 2007 | ||
/s/ Jennie C. Hunter-Cevera
|
Director | March 13, 2007 | ||
/s/ Mark C. M. Randall
|
Director | March 8, 2007 | ||
/s/ Ronald Cape
|
Director | March 8, 2007 | ||
/s/ Peter S. Knight
|
Director | March 8, 2007 |
40
The following consolidated financial statements of EntreMed, Inc. are included in Item
8:
Report of Independent Registered Public Accounting Firm |
F-2 | |||
Consolidated Balance Sheets as of December 31, 2006 and 2005 |
F-3 | |||
Consolidated Statements of Operations for the years ended December 31, 2006, 2005 and 2004 |
F-4 | |||
Consolidated Statements of Stockholders Equity for the years ended December 31, 2006, 2005 and 2004 |
F-5 | |||
Consolidated Statements of Cash Flows for the years ended December 31, 2006, 2005 and 2004 |
F-6 | |||
Notes to Consolidated Financial Statements |
F-7 |
F-1
Report of Independent Registered Public Accounting Firm
To the Board of Directors and Stockholders of EntreMed, Inc.:
We have audited the accompanying consolidated balance sheets of EntreMed, Inc. and subsidiaries as
of December 31, 2006 and 2005, and the related consolidated statements of operations, stockholders
equity, and cash flows for each of the three years in the period ended December 31, 2006. These
financial statements are the responsibility of the Companys management. Our responsibility is to
express an opinion on these financial statements based on our audits.
We conducted our audits in accordance with the standards of the Public Company Accounting Oversight
Board (United States). Those standards require that we plan and perform the audit to obtain
reasonable assurance about whether the financial statements are free of material misstatement. An
audit includes examining, on a test basis, evidence supporting the amounts and disclosures in the
financial statements. An audit also includes assessing the accounting principles used and
significant estimates made by management, as well as evaluating the overall financial statement
presentation. We believe that our audits provide a reasonable basis for our opinion.
In our opinion, the financial statements referred to above present fairly, in all material
respects, the consolidated financial position of EntreMed, Inc. and its subsidiaries, at December
31, 2006 and 2005, and the consolidated results of their operations and their cash flows for each
of the three years in the period ended December 31, 2006, in conformity with U.S. generally
accepted accounting principles.
As discussed in Note 1 to the consolidated financial statements, effective January 1, 2006 the
Company changed its accounting for stock-based compensation in connection with the adoption of FASB
Statement No. 123(R), Share-Based Payment.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight
Board (United States), the effectiveness of EntreMed, Inc.s internal control over financial
reporting as of December 31, 2006, based on criteria established in Internal Control-Integrated
Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission and our
report dated March 8, 2007, expressed an unqualified opinion thereon.
/s/ Ernst & Young LLP
McLean, Virginia
March 8, 2007
March 8, 2007
F-2
EntreMed, Inc.
Consolidated Balance Sheets
Consolidated Balance Sheets
DECEMBER 31, | ||||||||
2006 | 2005 | |||||||
ASSETS |
||||||||
Current assets: |
||||||||
Cash and cash equivalents |
$ | 20,896,141 | $ | 11,407,652 | ||||
Short-term investments |
29,673,956 | 18,674,736 | ||||||
Accounts receivable |
3,845,000 | 3,723,433 | ||||||
Note receivable |
| 1,000,000 | ||||||
Interest receivable |
73,895 | 181,231 | ||||||
Prepaid expenses and other |
377,871 | 338,462 | ||||||
Total current assets |
54,866,863 | 35,325,514 | ||||||
Property and equipment, net |
847,561 | 915,337 | ||||||
Other assets |
5,110 | 191,034 | ||||||
Total assets |
$ | 55,719,534 | $ | 36,431,885 | ||||
LIABILITIES AND STOCKHOLDERS EQUITY |
||||||||
Current liabilities: |
||||||||
Accounts payable |
$ | 5,909,317 | $ | 5,487,014 | ||||
Payable to related parties |
37,535 | 228,380 | ||||||
Accrued liabilities |
1,810,515 | 1,038,975 | ||||||
Current portion of deferred rent |
89,849 | 60,969 | ||||||
Loan payable |
751,093 | | ||||||
Total current liabilities |
8,598,309 | 6,815,338 | ||||||
Deferred rent, less current portion |
140,357 | 230,206 | ||||||
Minority interest |
17,649 | 17,151 | ||||||
Stockholders equity: |
||||||||
Convertible preferred stock, $1.00 par value;
5,000,000 shares authorized and 3,350,000 shares issued and
outstanding at December 31, 2006 and 2005 (liquidation
value $33,500,000 at December 31, 2006 and 2005) |
3,350,000 | 3,350,000 | ||||||
Common stock, $.01 par value: |
||||||||
170,000,000 and 120,000,000 shares authorized;
84,839,585 and 51,106,857 shares issued and outstanding
at December 31, 2006 and 2005, respectively |
848,400 | 511,069 | ||||||
Additional paid-in capital |
362,318,737 | 295,392,194 | ||||||
Deferred stock-based compensation |
| (102,000 | ) | |||||
Treasury stock, at cost: 874,999 shares held at
December 31, 2006 and 2005 |
(8,034,244 | ) | (8,034,244 | ) | ||||
Accumulated other comprehensive income |
117,212 | | ||||||
Accumulated deficit |
(311,636,886 | ) | (261,747,829 | ) | ||||
Total stockholders equity |
46,963,219 | 29,369,190 | ||||||
Total liabilities and stockholders equity |
$ | 55,719,534 | $ | 36,431,885 | ||||
See accompanying notes.
F-3
EntreMed, Inc.
Consolidated Statements of Operations
Consolidated Statements of Operations
YEAR ENDED DECEMBER 31, | ||||||||||||
2006 | 2005 | 2004 | ||||||||||
Revenues: |
||||||||||||
Licensing |
$ | | $ | 590,992 | $ | 495,496 | ||||||
Royalties |
6,881,799 | 5,310,439 | 5,918 | |||||||||
Other |
12,559 | 16,624 | 12,581 | |||||||||
6,894,358 | 5,918,055 | 513,995 | ||||||||||
Costs and expenses: |
||||||||||||
Research and development |
21,671,117 | 17,325,048 | 10,523,252 | |||||||||
General and administrative |
7,393,722 | 5,920,455 | 6,570,664 | |||||||||
Acquired In-Process R&D |
29,481,894 | | | |||||||||
58,546,733 | 23,245,503 | 17,093,916 | ||||||||||
Investment income |
1,867,204 | 1,010,771 | 313,940 | |||||||||
Interest expense |
(156,787 | ) | | | ||||||||
Gain on sale of assets |
52,901 | 3,420 | 124,083 | |||||||||
Gain on sale of securities ( Note 2) |
| | 520,000 | |||||||||
Gain on sale of royalty interest (Note 4) |
| | 3,000,000 | |||||||||
Net loss |
(49,889,057 | ) | (16,313,257 | ) | (12,621,898 | ) | ||||||
Dividends on Series A convertible preferred stock |
(1,005,000 | ) | (1,005,000 | ) | (1,005,000 | ) | ||||||
Net loss attributable to common shareholders |
$ | (50,894,057 | ) | $ | (17,318,257 | ) | $ | (13,626,898 | ) | |||
Net loss per share (basic and diluted) |
$ | (0.71 | ) | $ | (0.36 | ) | $ | (0.37 | ) | |||
Weighted average number of shares outstanding (basic and
diluted) |
71,873,734 | 48,176,914 | 37,170,544 | |||||||||
See accompanying notes.
F-4
ENTREMED, INC.
CONSOLIDATED STATEMENTS OF STOCKHOLDERS EQUITY
YEARS ENDED DECEMBER 31, 2006, 2005 and 2004
YEARS ENDED DECEMBER 31, 2006, 2005 and 2004
Accumulated | ||||||||||||||||||||||||||||||||||||||||
Additional | Deferred | Other | ||||||||||||||||||||||||||||||||||||||
Preferred Stock | Common Stock | Treasury | Paid-in | Stock | Comprehensive | Accumulated | ||||||||||||||||||||||||||||||||||
Shares | Amount | Shares | Amount | Stock | Capital | Compensation | Income | Deficit | Total | |||||||||||||||||||||||||||||||
Balance at December 31, 2003 |
3,350,000 | $ | 3,350,000 | 36,973,012 | $ | 378,480 | $ | (8,034,244 | ) | $ | 271,977,321 | $ | | $ | | $ | (232,812,674 | ) | $ | 34,858,883 | ||||||||||||||||||||
Issuance of common stock for options
and warrants exercised |
| | 208,946 | 2,090 | | 5,677 | | | | 7,767 | ||||||||||||||||||||||||||||||
Sale of common stock
at $2.55 per share |
| | 5,490,198 | 54,902 | | 10,781,472 | | | | 10,836,374 | ||||||||||||||||||||||||||||||
Recognition of non cash stock compensation |
| | 81,018 | 810 | | 174,189 | | | | 174,999 | ||||||||||||||||||||||||||||||
Fair value of warrants issued |
| | | | | 2,448,629 | | | | 2,448,629 | ||||||||||||||||||||||||||||||
Net loss |
| | | | | | | | (12,621,898 | ) | (12,621,898 | ) | ||||||||||||||||||||||||||||
Balance at December 31, 2004 |
3,350,000 | $ | 3,350,000 | 42,753,174 | $ | 436,282 | $ | (8,034,244 | ) | $ | 285,387,288 | $ | | $ | | $ | (245,434,572 | ) | $ | 35,704,754 | ||||||||||||||||||||
Issuance of common stock for options
exercised |
| | 67,070 | 671 | | 80,685 | | | | 81,356 | ||||||||||||||||||||||||||||||
Issuance of common stock for warrants
exercised |
| | 7,355,166 | 73,552 | | 9,826,448 | | | | 9,900,000 | ||||||||||||||||||||||||||||||
Stock issuance costs |
| | | | | (76,651 | ) | | | (76,651 | ) | |||||||||||||||||||||||||||||
Deferred stock-based compensation |
| | 56,448 | 564 | | 174,424 | (174,989 | ) | | | | |||||||||||||||||||||||||||||
Amortization of deferred stock-based compensation |
| 72,989 | | 72,989 | ||||||||||||||||||||||||||||||||||||
Net loss |
| | | | | | | | (16,313,257 | ) | (16,313,257 | ) | ||||||||||||||||||||||||||||
Balance at December 31, 2005 |
3,350,000 | $ | 3,350,000 | 50,231,858 | $ | 511,069 | $ | (8,034,244 | ) | $ | 295,392,194 | $ | (102,000 | ) | $ | | $ | (261,747,829 | ) | $ | 29,369,191 | |||||||||||||||||||
Issuance of common stock for options
exercised |
| | 7,500 | 75 | | 8,100 | | | | 8,175 | ||||||||||||||||||||||||||||||
Issuance of common stock for acquisition |
| | 9,964,000 | 99,640 | | 21,821,160 | | | | 21,920,800 | ||||||||||||||||||||||||||||||
Sale of common stock at $2.31 per share
of Miikana, net of stock issuance costs |
| | 12,972,966 | 129,730 | | 16,580,322 | | | | 16,710,052 | ||||||||||||||||||||||||||||||
Fair value of warrants issued |
| | | | | 11,156,752 | | | | 11,156,752 | ||||||||||||||||||||||||||||||
Sale of common stock at $1.60 per share,
net of stock issuance costs |
| | 10,727,500 | 107,275 | | 15,807,148 | | | | 15,914,423 | ||||||||||||||||||||||||||||||
Restricted stock grants |
| | 60,762 | 611 | | 94,178 | | | | 94,789 | ||||||||||||||||||||||||||||||
Amortization of deferred stock-based compensation |
| | | | | | 102,000 | | | 102,000 | ||||||||||||||||||||||||||||||
Stock-based compensation expense, net of forfeitures |
| | | | | 1,458,883 | | | | 1,458,883 | ||||||||||||||||||||||||||||||
Comprehensive loss: |
||||||||||||||||||||||||||||||||||||||||
Net loss |
| | | | | | | | (49,889,057 | ) | (49,889,057 | ) | ||||||||||||||||||||||||||||
Unrealized gain on investments |
| | | | | | | 117,212 | | 117,212 | ||||||||||||||||||||||||||||||
Comprehensive loss |
| | | | | | | | | (49,771,845 | ) | |||||||||||||||||||||||||||||
Balance at December 31, 2006 |
3,350,000 | $ | 3,350,000 | 83,964,586 | $ | 848,400 | $ | (8,034,244 | ) | $ | 362,318,737 | $ | | $ | 117,212 | $ | (311,636,886 | ) | $ | 46,963,219 | ||||||||||||||||||||
See accompanying notes.
F-5
EntreMed, Inc.
Consolidated Statements of Cash Flows
Consolidated Statements of Cash Flows
YEAR ENDED DECEMBER 31, | ||||||||||||
2006 | 2005 | 2004 | ||||||||||
CASH FLOWS FROM OPERATING ACTIVITIES |
||||||||||||
Net loss |
$ | (49,889,057 | ) | $ | (16,313,257 | ) | $ | (12,621,898 | ) | |||
Adjustments to reconcile net loss to net cash used in operating
activities: |
||||||||||||
Depreciation and amortization |
444,680 | 475,848 | 773,775 | |||||||||
Write-off of in-process R&D |
29,481,894 | | | |||||||||
Gain on sale of assets |
(52,901 | ) | (3,420 | ) | (124,083 | ) | ||||||
Gain on sale of securities |
| | (520,000 | ) | ||||||||
Gain on sale of royalty interest |
| | (3,000,000 | ) | ||||||||
Stock-based compensation expense |
1,553,672 | | | |||||||||
Amortization of deferred stock-based compensation |
102,000 | 72,988 | 174,999 | |||||||||
Amortization of premium on short-term investments |
(1,015,815 | ) | (393,815 | ) | (15,447 | ) | ||||||
Minority interest |
498 | 178 | (127 | ) | ||||||||
Changes in operating assets and liabilities: |
||||||||||||
Accounts receivable |
(72,285 | ) | (472,650 | ) | 178,196 | |||||||
Note receivable |
| (1,000,000 | ) | | ||||||||
Interest receivable |
107,336 | (96,142 | ) | 177,103 | ||||||||
Prepaid expenses and other |
7,705 | (150,969 | ) | 151,120 | ||||||||
Accounts payable |
346,672 | 3,936,601 | (2,248,891 | ) | ||||||||
Payable to related parties |
(190,845 | ) | 28,059 | 47,108 | ||||||||
Accrued liabilities |
(1,537,523 | ) | (377,469 | ) | 709,483 | |||||||
Deferred rent |
(60,969 | ) | (32,931 | ) | (5,709 | ) | ||||||
Deferred revenue |
| (190,992 | ) | (97,496 | ) | |||||||
Net cash used in operating activities |
(20,774,938 | ) | (14,517,971 | ) | (16,421,867 | ) | ||||||
CASH FLOWS FROM INVESTING ACTIVITIES |
||||||||||||
Proceeds from sale of property and equipment, net |
52,901 | 11,000 | 355,275 | |||||||||
Proceeds from sale of securities |
| | 520,000 | |||||||||
Acquisition, net of cash received |
(2,906,218 | ) | | | ||||||||
Purchases of short term investments |
(72,786,954 | ) | (51,491,900 | ) | (37,718,991 | ) | ||||||
Maturities of short term investments |
62,920,760 | 47,325,000 | 25,750,000 | |||||||||
Purchases of furniture and equipment |
(227,435 | ) | (248,677 | ) | (163,539 | ) | ||||||
Net cash used in investing activities |
(12,946,946 | ) | (4,404,577 | ) | (11,257,255 | ) | ||||||
CASH FLOWS FROM FINANCING ACTIVITIES |
||||||||||||
Net proceeds from sale of common stock |
43,907,403 | 9,904,705 | 13,292,770 | |||||||||
Repayment of loan |
(697,030 | ) | | | ||||||||
Net cash provided by financing activities |
43,210,373 | 9,904,705 | 13,292,770 | |||||||||
Net increase (decrease) in cash and cash equivalents |
9,488,489 | (9,017,843 | ) | (14,386,352 | ) | |||||||
Cash and cash equivalents at beginning of year |
11,407,652 | 20,425,495 | 34,811,847 | |||||||||
Cash and cash equivalents at end of year |
$ | 20,896,141 | $ | 11,407,652 | $ | 20,425,495 | ||||||
Supplemental disclosure of cash flow information: |
||||||||||||
Cash paid during the year for interest |
$ | 156,787 | $ | | $ | | ||||||
Non-cash investing activity: |
||||||||||||
Stock issued in connection with the acquisition of Miikana |
$ | 21,920,800 | $ | | $ | |
F-6
EntreMed, Inc.
Notes to Consolidated Financial Statements
December 31,2006
December 31,2006
1. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES
DESCRIPTION OF BUSINESS AND BASIS OF PRESENTATION
EntreMed, Inc. (EntreMed or the Company) is a clinical-stage pharmaceutical company focused on
developing next generation multi-mechanism oncology and antiinflammatory drugs that target disease
cells directly and the blood vessels that nourish them. EntreMed is focused on developing drugs
that are safe and convenient, and provide the potential for improved patient outcomes.
Panzem® (2-methoxyestradiol or 2ME2), one of the Companys lead drug candidates, is
currently being tested as a cancer therapeutic in four Phase 2 clinical trials, and has been
granted U.S. Food and Drug Administration (FDA) Orphan Drug designation in three cancer
indications, including glioblastoma multiforme (GBM), multiple myeloma, and ovarian cancer. MKC-1,
a novel cell cycle inhibitor, is also in Phase 2 clinical trials for cancer. In May 2006, the
Company commenced clinical studies with its third clinical-stage compound, ENMD-1198, in patients
with advanced cancer.
EntreMeds goal is to develop and commercialize therapeutics based on the Companys scientific
expertise in angiogenesis, cell cycle regulation and inflammation processes vital to the
progression of cancer and other diseases. The Companys three clinical product candidates are
based on these mechanisms.
In order to further advance its commercial objectives, EntreMed may seek strategic alliances,
licensing relationships and co-development partnerships with other companies to develop compounds
for both oncology and non-oncology therapeutic areas.
The accompanying consolidated financial statements include the accounts of the Companys
controlled subsidiaries, Miikana Therapeutics, Inc. (Miikana) and Cytokine Sciences, Inc. All
intercompany balances and transactions have been eliminated in consolidation. The Company refers
to EntreMed and its consolidated subsidiaries.
To date, the Company has been engaged primarily in research and development activities. As a
result, the Company has incurred operating losses through 2006 and expects to continue to incur
operating losses for 2007 and the foreseeable future before commercialization of any products.
To accomplish the Companys business plans, EntreMed will be required to continue to conduct
substantial development activities for all proposed products. The Company intends to continue to
pursue strategic relationships to provide resources for the further development of our product
candidates. There can be no assurance, however, that these discussions will result in relationships
or additional funding. In addition, the Company will continue to seek capital through the public
or private sale of securities. There can be no assurance that EntreMed will be
successful in seeking such additional capital.
SEGMENT INFORMATION
The Company currently operates in one business segment, which is the development of
therapeutics primarily for the treatment of cancer. The Company is managed and operated as one
business. A single management team that reports to the Companys President and Chief Executive
Officer comprehensively manages the entire business. The Company does not operate separate lines of
business with respect to its products or product candidates. Accordingly, the Company does not have
separately reportable segments as defined by FASB Statement No. 131, Disclosures about Segments of
an Enterprise and Related Information.
F-7
RESEARCH AND DEVELOPMENT
Research and development expenses consist primarily of compensation and other expenses related
to research and development personnel, research collaborations, costs associated with pre-clinical
testing and clinical trials of our product candidates, including the costs of manufacturing the
product candidates, and facilities expenses. Research and development costs are expensed as
incurred, including costs incurred in filing, defending and maintaining patents.
PROPERTY AND EQUIPMENT
Furniture and equipment and leasehold improvements are stated at cost and are depreciated over
their estimated useful lives of 5 to 10 years. Depreciation is determined on a straight-line basis.
Depreciation expense was $444,680, $475,848 and $773,775 in 2006, 2005 and 2004, respectively.
Property and equipment consists of the following:
DECEMBER 31 | ||||||||
2006 | 2005 | |||||||
Furniture and equipment |
$ | 4,673,562 | $ | 4,321,634 | ||||
Leasehold improvements |
1,288,791 | 1,288,791 | ||||||
5,962,353 | 5,610,425 | |||||||
Less: accumulated depreciation |
(5,114,792 | ) | (4,695,088 | ) | ||||
$ | 847,561 | $ | 915,337 | |||||
CASH AND CASH EQUIVALENTS
Cash and cash equivalents include cash and highly liquid investments with original maturities
of less than 90 days. Substantially all of the Companys cash equivalents are held in short-term
money market accounts of banks and brokerage houses.
SHORT-TERM INVESTMENTS
The Company accounts for short-term investments in accordance with Statement of Financial
Accounting Standards, No. 115, Accounting for Certain Investments in Debt and Equity Securities.
Short-term investments consist primarily of corporate debt securities, all of which mature within
one year. The Company has classified these investments as available for sale. Such securities are
carried at fair market value. The cost of securities sold is calculated using the specific
identification method. Unrealized gains and losses on these securities, if any, are reported as
accumulated other comprehensive income (loss), which is a separate component of stockholders
equity. Unrealized gains of $117,212 were recorded in 2006. No such amounts were recorded in 2005.
Realized gains and losses and declines in value judged to be other than temporary on securities
available for sale, if any, are included in operations. In 2006 and 2005, realized losses were
$24,272 and $97,384, respectively. Short-term investments are principally uninsured and subject to
normal credit risk. (See Note 2 for Gain on Sale of Securities)
ACCOUNTS RECEIVABLE
Accounts receivable are stated net of allowances for doubtful accounts. Allowances for
doubtful accounts are determined on a specific item basis. Management reviews the credit
worthiness of individual customers and past payment history to determine the allowance for doubtful
accounts. There is no allowance for doubtful accounts at December 31, 2006 and 2005.
As of December 31, 2006 and 2005, one individual customer represented 99% and 98%,
respectively, of the total accounts receivable.
NOTE RECEIVABLE
In December 2005, the Company loaned Miikana Therapeutics $1 million to repay certain
obligations. This is reflected as a note receivable in the accompanying December 31, 2005
consolidated balance sheet. Upon
F-8
consummation of the acquisition of Miikana Therapeutics (See Note 3), the note receivable was used
to pay a portion of the purchase price obligation.
LOAN PAYABLE
As of December 31.2006, the Company has a loan payable to Venture Lending & Leasing IV, Inc.
for approximately $751,000 at an interest rate of 13.4% payable in 2007.
INCOME TAXES
Income taxes have been provided using the liability method in accordance with Statement of
Financial Accounting Standards No. 109, Accounting for Income Taxes.
REVENUE RECOGNITION
The Company recognizes revenue in accordance with the provisions of Staff Accounting Bulletin
No. 104, Revenue Recognition, whereby revenue is not recognized until it is realized or realizable
and earned. Revenue is recognized when all of the following criteria are met: persuasive evidence
of an arrangement exists, delivery has occurred or services have been rendered, the price to the
buyer is fixed and determinable and collectibility is reasonably assured.
Royalty Revenue Royalties from licenses are based on third-party sales and recorded as
earned in accordance with contract terms, when third-party results are reliably measured and
collectibility is reasonably assured. The majority of the Companys 2006 and 2005 revenues were
from royalties on the sale of Thalomid®, which the Company began to recognize in the
third quarter of each year. In 2004, certain provisions of a purchase agreement dated June 14,
2001 by and between Bioventure Investments kft (Bioventure) and the Company were satisfied, and,
as a result, in 2005 the Company became entitled to share in the royalty payments received by
Royalty Pharma Finance Trust, successor to Bioventure, on annual Thalomid® sales above a
certain threshold. Based on the licensing agreement royalty formula, annual royalty sharing
commences with Thalomid® annual sales of approximately $225 million. The Company is
also eligible to receive royalty payments under a February 2004 agreement with Childrens Medical
Center Corporation (CMCC) and Alchemgen Therapeutics. Under the agreement, Alchemgen received
rights to market endostatin and angiostatin in Asia. Future royalty payments, if any, will be
recorded as revenue when received and/or when collectibility is reasonably assured.
Licensing Revenue The Company has recognized licensing revenues resulting from the January
2002 five-year strategic alliance with Allergan to develop and commercialize small molecule
angiogenic inhibitors for treatment and prevention of diseases and conditions of the eye. The
initial net fee was being amortized to revenue over the five-year license term. In April 2005,
Allergan terminated the license in accordance with its terms, which resulted in the accelerated
recognition of deferred revenue. In February 2004, the Company transferred rights to the proteins,
endostatin and angiostatin, in an agreement with Childrens Medical Center Corporation (CMCC) and
Alchemgen Therapeutics. Under the agreement, the Company received an upfront and a second cash
payment. The upfront licensing cash payment was fully amortized in 2004, as the Company had
completed its obligations to transfer data and material. Due to rights negotiations between the
licensee and CMCC, the second and final licensing cash payment in the amount of $400,000 was
received in May 2005. Management concluded collectibility was not reasonably assured until the
funds were received.
NET LOSS PER SHARE
Net loss per share (basic and diluted) was computed by dividing net loss available to common
stock by the weighted average number of shares of common stock outstanding. Common stock
equivalents, including Preferred Series A common stock equivalents, totaling 19,366,099 were
anti-dilutive and, therefore, were not included in the computation of weighted average shares used
in computing diluted loss per share.
F-9
COMPREHENSIVE LOSS
Under Financial Accounting Standard No. 130 (SFAS 130), Reporting Comprehensive Income, the
Company is required to display comprehensive loss and its components as part of the consolidated
financial statements. Comprehensive loss is comprised of net loss and unrealized gain on
investments as follows:
Years ended December 31, | ||||||||||||
2006 | 2005 | 2004 | ||||||||||
Net loss |
$ | (49,889,057 | ) | $ | (16,313,257 | ) | $ | (12,621,898 | ) | |||
Other comprehensive income |
117,212 | | | |||||||||
Comprehensive loss |
$ | (49,771,845 | ) | $ | (16,313,257 | ) | $ | (12,621,898 | ) |
SHARE-BASED COMPENSATION
Prior to January 1, 2006, the Company accounted for share-based compensation under the
recognition and measurement principles of Accounting Principles Board Opinion No. 25, Accounting
for Stock Issued to Employees (APB 25).
Effective January 1, 2006, the Company began recording compensation expense associated
with stock options and other equity-based compensation in accordance with provisions of Statement
123 (revised 2004) Share-Based Payment (SFAS 123R) and interpretative literature within SEC
Staff Accounting Bulletin No. 107, Share-Based Payment, (SAB 107), using the modified prospective
transition method and therefore has not restated results for prior periods. Under the modified
prospective transition method, share-based compensation expense for 2006 includes 1) compensation
expense for all share-based awards granted on or after January 1, 2006 as determined based on the
grant-date fair value estimated in accordance with the provisions of SFAS 123R and 2) compensation
expense for share-based compensation awards granted prior to, but not yet vested as of January 1,
2006, based on the grant date fair value estimated in accordance with the original provisions of
SFAS 123. The Company recognizes these compensation costs for stock options granted prior to
January 1, 2006 on an accelerated method, and for stock options granted after January 1, 2006, the
compensation costs are recognized based on a straight-line method over the requisite service
period, which is generally the option vesting term of three years.
For stock options granted prior to the adoption of SFAS 123R, the following table illustrates
the pro forma effect on net loss and net loss per share, as if the Company had applied the fair
value recognition provisions of SFAS 123 in determining stock-based compensation:
Years ended December 31, | ||||||||
2005 | 2004 | |||||||
Actual net loss |
$ | (16,313,257 | ) | $ | (12,621,898 | ) | ||
Deduct: Stock-based employee compensation expense if
SFAS No.123 had been applied to all awards |
(1,923,575 | ) | (6,664,579 | ) | ||||
Add: Stock-based employee compensation included in reported net loss |
72,988 | 174,999 | ||||||
Proforma net loss |
$ | (18,163,844 | ) | $ | (19,111,478 | ) | ||
Dividend on Series A convertible preferred stock |
(1,005,000 | ) | (1,005,000 | ) | ||||
Proforma net loss per share available to common shareholders |
$ | (19,168,844 | ) | $ | (20,116,478 | ) | ||
Net loss per share: |
||||||||
Basic and diluted as reported |
$ | (0.36 | ) | $ | (0.37 | ) | ||
Basic and diluted pro forma |
$ | (0.40 | ) | $ | (0.54 | ) |
F-10
NEW ACCOUNTING PRONOUNCEMENTS
In July 2006, the FASB issued FASB Interpretation No. 48,Accounting for Uncertainty in Income
Taxes, an interpretation of FASB Statement No. 109 (FIN 48). FIN 48 clarifies the accounting for
uncertainty in income taxes by prescribing the recognition threshold a tax position is required to
meet before being recognized in the financial statements. It also provides guidance on
derecognition, classification, interest and penalties, accounting in interim periods, disclosure,
and transition, FIN 48 is effective for fiscal years beginning after December 15, 2006 and is
required to be adopted by the Company in 2007. The Company does not expect the adoption of FIN 48
to have a material impact on its consolidated results of operations and financial condition.
In September 2006, the FASB issued SFAS No. 157, Fair Value Measurements (SFAS 157), which
defines fair value, establishes a framework for measuring fair value in accordance with generally
accepted accounting principles (GAAP) in the United States of America, and expands disclosures
about fair value measurements. SFAS 157 does not require any new fair value measurements under
GAAP and is effective for fiscal years beginning after November 17, 2007. The effects of adoption
will be determined by the types of instruments carried at fair value in our financial statements at
the time of adoption, as well as the method utilized to determine their fair values prior to
adoption. Based on our current use of fair value measurements, SFAS 157 is not expected to have a
material effect on our results of operations or financial position.
On January 1, 2006, the Company adopted Statement of Financial Accounting Standards No. 123R
Share Based Payment (SFAS 123R), which addresses the accounting for share-based payment
transactions in which the Company receives employee services in exchange for equity instruments.
The statement eliminates the Companys ability to account for share-based compensation transactions
as prescribed by Accounting Principles Board Opinion No. 25, Accounting for Stock Issued to
Employees (APB No. 25), and generally requires that equity instruments issued in such
transactions be accounted for using a fair-value based method and the fair value of such equity
instruments be recognized as expenses in the consolidated statements of operations. The impact of
this statement is disclosed in a preceding section of
footnote 1.
In May 2005, the FASB issued SFAS No. 154, Accounting Changes and Error Corrections a
replacement of APB Opinion No. 20 and FASB Statement No. 3 (SFAS 154). SFAS 154 replaces APB
Opinion No. 20, Accounting Changes and SFAS No. 3, Reporting Accounting Changes in Interim
Financial Statements, and changes the requirements for accounting for and reporting a change in
accounting principle. SFAS 154 requires restatement of prior period financial statements, unless
impracticable, for voluntary changes in accounting principle. The retroactive application of a
change in accounting principle should be limited to the direct effect of the change. Changes in
depreciation, amortization or depletion methods should be accounted for prospectively as a change
in accounting estimate. Corrections of accounting errors will be accounted for under the guidance
contained in APB Opinion No. 20. The effective date of this new pronouncement is for fiscal years
beginning after December 15, 2005 and prospective application is required. The adoption of SFAS 154
did not have a material impact on the Companys results of operations and financial condition.
In November 2005, the Financial Accounting Standards Board issued FASB Staff Position (FSP)
FAS 115-1, The Meaning of Other-Than-Temporary Impairment and Its Application to Certain
Investments (FSP FAS 115-1). FSP FAS 115-1, which is effective for reporting periods beginning
after December 15, 2005, provides guidance on other-than-temporary impairment models for marketable
debt and equity securities accounted for under SFAS No. 115 and non-marketable equity securities
accounted for under the cost method. FSP FAS 115-1 provides a basic three-step model to evaluate
whether an investment is other-than-temporarily impaired. Under FSP FAS 115-1, other than temporary
losses on short-term investments would be expensed rather than included in stockholders equity.
The Company currently does not have any investments scheduled to mature greater than one year. The
adoption of FSP FAS 115-1 did not have a material effect on the Companys results of operations,
financial condition or liquidity.
F-11
FINANCIAL INSTRUMENTS AND CONCENTRATIONS OF RISK
Financial instruments that potentially subject the Company to concentrations of credit
risk consist principally of cash and cash equivalents, short-term investments, accounts receivable
and note receivable. The Company maintains its cash and cash equivalents in bank deposit accounts,
which, at times, may exceed federally insured amounts. The Company believes it is not exposed to
any significant credit risk on cash and cash equivalents or short-term investments. The carrying
amount of current assets and liabilities approximates their fair values due to their short-term
maturities.
USE OF ESTIMATES
The preparation of consolidated financial statements in conformity with accounting principles
generally accepted in the United States requires management to make estimates and assumptions that
affect the amounts reported in the financial statements and accompanying notes. Actual results may
differ from those estimates, and such differences may be material to the consolidated financial
statements.
2. SALE OF SECURITIES
In September 2004, the Company sold certain securities of an independent private biotechnology
company. The securities were acquired in 1996 through 1999 and accounted for using the equity
method. Consistent with this approach, the cost of these securities was written down to $0 in
prior periods as the Company recorded its share of losses, and the Company had no residual cost
basis in the securities when sold. As such, the Company recorded a gain on the sale in 2004 equal
to the sale proceeds of $520,000.
3. ACQUISITION
In January 2006 the Company acquired Miikana Therapeutics, a private biotechnology company.
Pursuant to the Merger Agreement, the Company acquired all of the outstanding capital stock of
Miikana Therapeutics, Inc. in exchange for 9.96 million shares of common stock and the assumption
of certain obligations. In addition, based on the success of the acquired pre-clinical programs,
the Company may pay up to an additional $18 million upon the achievement of certain clinical and
regulatory milestones. Such additional payments will be made in cash or shares of stock at the
Companys option. The Company expects that the Aurora Kinase pre-clinical program will advance to
a Phase 1 clinical trial in 2007. A dosing of the first patient, expected in 2007, triggers a
purchase price adjustment milestone of $2 million. Through the acquisition, the Company acquired
rights to MKC-1, a Phase 2 clinical candidate licensed from Hoffman-LaRoche, Inc. (Roche) by
Miikana in April 2005. Under the terms of the agreement, Roche may be entitled to receive future
payments upon successful completion of developmental milestones. The Company does not anticipate
reaching any of these milestones in 2007. Roche is also eligible to receive royalties on sales and
certain one-time payments based on attainment of annual sales milestones.
Miikana purchase price allocation
Miikana is a development stage company, accordingly, the acquisition of Miikana is
treated as an asset purchase. In accordance with EITF 98-3 Determining Whether a
Nonmonetary Transaction Involves Receipt of Productive Asset or of a Business, and
Statement 141 Business Combinations the purchase price was first allocated to the
tangible assets acquired and liabilities assumed based on the estimated fair values at
the acquisition date. The balance of the purchase price was allocated to intangible
assets and recorded as in-process research and development as the research and
development projects in Miikanas pipeline, as of the acquisition date, had not reached
technological feasibility and had no alternative use.
We believe the fair values assigned to the assets acquired and liabilities assumed are based
upon reasonable assumptions given current available facts and circumstances.
F-12
The total purchase price allocated was $30.1 million, consisting of 9,964,000 shares of our
common stock with a fair value of $21.9 million, assumed debt of $1.5 million, assumed current
liabilities of $2.7 million, $1 million loaned to Miikana prior to the closing and acquisition
costs of $3 million. The fair value of common stock was determined using the closing price at the
date of acquisition.
The allocation is as follows:
Fair value of net tangible assets acquired |
$ | 600,000 | ||
In- process research and development |
29,500,000 | |||
Total |
$ | 30,100,000 | ||
4. LICENSE AGREEMENTS
Pursuant to a purchase agreement dated June 14, 2001 by and between Bioventure Investments kft
(Bioventure) and the Company, as amended July 13, 2001, July 30, 2001 and August 3, 2001 (the
Purchase Agreement), Bioventure purchased all of the Companys right, title and interest to the
net royalty payments payable by Celgene Corporation (Celgene) to the Company under the agreement
dated as of December 9, 1998 by and between the Company and Celgene (the Celgene Sublicense).
A provision of the Bioventure purchase agreement provided the potential for an adjustment in
the purchase price if cumulative sales of Thalomid® exceeded $800 million by December 31, 2004.
Based on Thalomid® sales reported publicly by Celgene, the Company concluded that cumulative
Thalomid® sales had reached this milestone by December 31, 2004. As such, the Company recorded a
gain on the sale of our royalty rights and a corresponding receivable of $3.0 million. The Company
received payment of this amount in March 2005. In addition to triggering this one-time adjustment
in the purchase price, exceeding the $800 million cumulative sales amount also triggers a royalty
sharing provision. Beginning the year after cumulative sales reach $800 million, EntreMed is
entitled to share in the royalty payments received by Royalty Pharma Finance Trust, successor to
Bioventure, on annual Thalomid® sales above a certain threshold. In 2006 and 2005
Thalomid® sales surpassed the royalty-sharing point and the Company recognized estimated
royalty revenues of $6,882,000 and $5,310,000, respectively. There can be no assurance that the
Company will receive additional material royalties under the royalty sharing provision in the
future.
In March 2005, the Company entered into an exclusive worldwide license agreement with Celgene
Corporation for the development and commercialization of Celgenes small molecule tubulin inhibitor
compounds for the treatment of cancer. Under the terms of the agreement, Celgene received an
upfront licensing fee and may receive additional payments upon successful completion of certain
clinical, regulatory and sales milestones. No such milestones have been reached through December
31, 2006. EntreMed will assume responsibility for preclinical and clinical development of the
tubulin inhibitors for oncology applications. The upfront license fee of $1,000,000 was recorded as
a component of research and development expense in the Consolidated Statement of Operations for the
year ended December 31, 2005.
In January 2006, the Company entered into a License Agreement with Elan Corporation, plc in
which the Company has been granted rights to utilize Elans proprietary NanoCrystal Technology to
develop the oncology product candidate, Panzem® NCD. Under the terms of the License
Agreement, Elan is eligible to receive payments upon the achievement of certain clinical,
manufacturing, and regulatory milestones. Milestones related to the initiation of Phase 2 clinical
trials have been paid and there are no additional milestones achieved as of December 31, 2006.
Additionally, Elan will receive royalty payments based on sales of Panzem® NCD. Under
the License Agreement and corresponding Services Agreement, Elan will manufacture EntreMeds
Panzem® NCD, a NanoCrystal Technology formulation with improved
bioavailability and absorption.
F-13
5. RELATED PARTY TRANSACTIONS
Until September 2006, the Company received legal services from a law firm with which one of
the Companys former officers was associated. Total expenses for service from this law firm were
$686,000, $1,180,000 and $1,015,000 in 2006, 2005 and 2004, respectively. The amounts reflected as
research and development, of $551,000, $779,000 and $628,000 in 2006, 2005 and 2004, respectively,
in the table below primarily represent patent work. The amounts reflected as general and
administrative, of $119,000, $351,000 and $387,000 in 2006, 2005 and 2004, respectively, represent
legal services. Also paid in 2006 are costs related to the Miikana acquisition of $16,000.
In 2005 and 2004 the Company also received financial advisory services from Ferghana Partners,
Inc., a provider of corporate financial advice to firms in the Life Sciences field. Until December
2006, the Companys chairman and CEO both held a de minimis ownership interest in Ferghana
Partners, Inc. They no longer have an ownership interest. Pursuant to a series of business
transactions, the Company paid $785,000 and $100,000 in fees to Ferghana Partners, Inc. in 2005 and
2004, respectively. The 2005 amount includes financial advisory fees of $60,000, a $200,000 fee
associated with the March 2005 Celgene license agreement and a $525,000 fee resulting from
Celgenes March 2005 exercise of a warrant, issued as part of the 2002 transaction for 7,000,000
shares of common stock. The $60,000 paid in advisory fees were recorded as general and
administrative costs, the $200,000 fee was recorded as research and development expense. The
balance of the 2005 fees paid to Ferghana and all of the fees paid to Ferghana in 2004 were
recorded as offsets against gross equity transaction proceeds and, as such, are not reflected as
expenses in the current period.
The Company completed two sales of securities during 2006. In February 2006, the Company sold
common stock and warrants to institutional investors. Celgene Corporation, the Companys largest
shareholder, acquired 864,864 shares of common stock and 432,432 warrants convertible into shares
of common stock in the transaction (see footnote 7), on the same terms and conditions as the other
purchasers in the transaction. In December 2006, Celgene also acquired 2,500,000 shares of the
Companys common stock on the same terms and conditions as the other purchasers in a separate sale
to institutional investors. The 2005 research and development amount also includes a $1 million
upfront licensing fee paid to Celgene pursuant to our license of Celgenes tubulin inhibitor
program.
Expenses from related parties are included in the following accounts within the consolidated
financial statements, $37,535, $228,380 and $200,321 of which are included in accounts payable at
December 31, 2006, 2005 and 2004, respectively:
2006 | 2005 | 2004 | ||||||||||
Research and development |
$ | 551,000 | $ | 1,979,000 | $ | 628,000 | ||||||
General and administrative |
119,000 | 411,000 | 387,000 | |||||||||
Additional paid in capital |
| 525,000 | 100,000 | |||||||||
Acquisition costs |
16,000 | 50,000 | | |||||||||
$ | 686,000 | $ | 2,965,000 | $ | 1,115,000 | |||||||
6. INCOME TAXES
The Company has net operating loss carryforwards for income tax purposes of approximately
$290,457,000 at December 31, 2006 ($261,541,000 at December 31, 2005) that expire in years 2007
through 2026. The Company also has research and development tax credit carryforwards of
approximately $11,005,000 as of December 31, 2006 that expire in years 2007 through 2025. These net
operating loss carryforwards include approximately $20,000,000, related to exercises of stock
options for which the income tax benefit, if realized, would increase additional paid-in capital.
The utilization of the net operating loss and research and development carryforwards may be limited
in future years due to changes in ownership of the Company pursuant to Internal Revenue Code
Section 382. For financial reporting purposes, a valuation allowance has been recognized to reduce
the net deferred tax assets to zero due to uncertainties with respect to the Companys ability to
generate taxable income in the future sufficient to realize the benefit of deferred income tax assets.
F-14
Deferred income taxes reflect the net effect of temporary differences between the carrying
amounts of assets and liabilities for financial reporting purposes and the amounts used for income
tax purposes. Significant components of the Companys deferred income tax assets and liabilities
as of December 31, 2006 and 2005 are as follows:
DECEMBER 31, | ||||||||
2006 | 2005 | |||||||
Deferred income tax assets (liabilities): |
||||||||
Net operating loss carryforwards |
$ | 112,174,000 | $ | 101,005,000 | ||||
Research and development credit carryforward |
11,005,000 | 10,616,000 | ||||||
Equity investment |
70,000 | 70,000 | ||||||
Other |
2,812,000 | 735,000 | ||||||
Depreciation |
301,000 | 161,000 | ||||||
Valuation allowance for deferred income tax assets |
(126,362,000 | ) | (112,587,000 | ) | ||||
Net deferred income tax assets |
$ | | $ | | ||||
A reconciliation of the provision for income taxes to the federal statutory rate is as
follows:
2006 | 2005 | 2004 | ||||||||||
Tax benefit at statutory rate |
$ | (16,963,000 | ) | $ | (5,547,000 | ) | $ | (4,291,000 | ) | |||
State taxes |
(942,000 | ) | (754,000 | ) | (505,000 | ) | ||||||
Other |
66,000 | 273,000 | 383,000 | |||||||||
Permanent M-1s |
10,027,000 | 29,000 | 6,000 | |||||||||
Change in valuation allowance |
7,944,000 | 7,565,000 | 4,407,000 | |||||||||
Change in estimated effective rate |
| (1,566,000 | ) | | ||||||||
$ | | $ | | $ | | |||||||
During 2006, the valuation allowance increased by $5,831,000 related to Miikana deferred
tax assets fully reserved as of the date of acquisition.
7. STOCKHOLDERS EQUITY
In 2002, the Company issued 3,350,000 shares of Series A Preferred Stock to Celgene.
The Series A Preferred Stock is convertible, at the option of Celgene, at any time, into common
stock at an initial per common share conversion price of $1.00 (1 share of preferred converts into
5 shares of common). The value of the common stock at the date the Series A Preferred Stock was
issued was $0.86. The conversion price is subject to change for certain dilutive events, as
defined. The Company may cause the Series A Preferred Stock to convert automatically provided all
of the following conditions are met:
(i) | As of the conversion date, the common stock is traded and was traded during the 60 trading days preceding the conversion date, on a national securities exchange; | ||
(ii) | The average per share closing price of the common stock is greater than $5.00 over a 60-trading day period ending on the conversion date, and | ||
(iii) | A registration statement with respect to resale of the common stock issuable in the conversion to the holders of the Series A Preferred Stock has been filed with the SEC, such registration statement is effective and the Company has agreed to maintain the effectiveness of the registration statement for at least 180 consecutive days beginning with the conversion date. |
The Series A Preferred Stock accrues and accumulates dividends at a rate of 6% and will
participate in dividends declared and paid on the common stock, if any. At December 31, 2006,
cumulative unpaid preferred stock dividends totaled $4,020,000 or $1.20 per share. All unpaid
preferred stock dividends must be paid before any dividends may be declared or paid on the Common
Stock, and will be added to the liquidation preference of the Series A Preferred Stock payable upon
the liquidation, dissolution or winding up of the Company. The liquidation preference is equal to
the greater of:
(i) | Two times the original per share purchase price plus accrued and unpaid dividends or | ||
(ii) | The amount per share that would be payable to a holder of shares of the Series A Preferred Stock had all of the shares been converted to common stock immediately prior to a liquidation event. |
F-15
The liquidation preference of the Series A Preferred Stock on a converted basis at December
31, 2006 totaled approximately $33,500,000, excluding cumulative unpaid preferred stock dividends
as discussed above. This value is calculated based on the contractual liquidation preference
articulated in the Series A Preferred Stock agreement. There can be no assurance what impact the
conversion of the Series A Preferred to common stock would have on the trading value of the
Companys common stock.
Holders of the Series A Preferred Stock generally vote together with the holders of common
stock, with each share of Series A Preferred Stock representing the number of votes equal to that
number of shares of common stock into which it is then convertible.
In December 2004, the Company completed a private placement of 5,490,198 shares of its common
stock and warrants to purchase a total of 1,098,040 shares of common stock at an exercise price of
$3.67, resulting in gross proceeds, prior to the deduction of fees and commissions of approximately
$14.0 million (net proceeds of $13.3 million).
In March 2005, the Company issued 7,000,000 shares of its common stock pursuant to the
exercise of a warrant held by Celgene Corporation. The warrant, exercisable at $1.50 per share was
issued to Celgene as part of the 2002 transaction and resulted in gross proceeds, prior to the
deduction of fees and commissions of $10.5 million (net proceeds of $9.9 million).
In January 2006, the Company acquired Miikana Therapeutics, a private biotechnology company.
Pursuant to the merger Agreement, the Company acquired all of the outstanding capital stock of
Miikana Thereapeutics, Inc. in exchange for 9.96 million shares of common stock and the assumption
of certain obligations.
In February 2006, the Company completed a private placement of 12,972,966 shares of its common
stock and warrants to purchase a total of 6,486,484 shares of common stock at an exercise price of
$2.50, resulting in gross proceeds, prior to the deduction of fees and commissions, of
approximately $30 million (net proceeds of approximately $27.9 million). The fair value of
warrants issued was $11,156,752, calculated using a Black-Scholes value of $1.72 with an expected
life of 5 years with no dividend yield. We assumed volatility was 103.84%, and used a risk free
interest rate of 4.52%.
In December 2006, the Company completed a registered direct offering of 10,727,500 shares of
its common stock resulting in gross proceeds, prior to the deduction of fees and commissions, of
approximately $17 million (net proceeds of approximately $15.9 million).
8. SHARE-BASED COMPENSATION
The Company has adopted incentive and nonqualified stock option plans whereby 11,983,333
shares of the Companys common stock were reserved for grants to various executive, scientific and
administrative personnel of the Company as well as outside directors and consultants, of which
788,097 shares remain available for grant under the Companys 2001 Long-term Incentive Plan as of
December 31, 2006. These options vest over periods varying from immediately to three years and
generally expire 10 years from the date of grant.
The Company recorded non-cash compensation charges of $197,000, $73,000 and $175,000 in 2006,
2005 and 2004, respectively, related to the issuance of restricted stock to members of our Board of
Directors, as each non-employee director receives an annual retainer fee of $25,000 that is payable
in restricted stock. As of December 31, 2006, $80,000 represents the non-vested restricted stock
compensation awards expected to vest and be recognized in 2007.
Prior to the adoption of SFAS 123R, the Company recorded share-based compensation under
Accounting Principles Board (APB) Opinion No. 25, Accounting for Stock Issued to Employees
(APB 25). Accordingly, no share-based compensation expense for such options is reflected in net
loss for the years ended December 31, 2005 and 2004, as exercise price equals fair market value of
stock on date of grant.
F-16
As a result of the adoption of SFAS 123R, the Companys net loss for the year ended December
31, 2006 includes $1,655,672 of compensation expense related to the Companys share-based
compensation awards. The compensation expense related to the Companys share-based compensation
arrangements is recorded as components
of general and administrative expense and research and development expense, as follows:
Research and development |
$ | 352,280 | ||
General and administrative |
1,303,392 | |||
Share-based compensation expense |
$ | 1,655,672 | ||
Net share-based compensation expense, per common share: |
||||
Basic and diluted |
$ | 0.023 | ||
Stock Options. The Company uses the Black-Scholes-Merton valuation model to estimate the fair
value of stock options granted to employees. Option valuation models, including
Black-Scholes-Merton, require the input of highly subjective assumptions, and changes in the
assumptions used can materially affect the grant date fair value of an award. These assumptions
include the risk free rate of interest, expected dividend yield, expected volatility, and the
expected life of the award.
Expected VolatilityVolatility is a measure of the amount by which a financial variable such
as a share price has fluctuated (historical volatility) or is expected to fluctuate (expected
volatility) during a period. The Company uses the historical volatility based on the weekly price
observations of its common stock during the period immediately preceding the share-based award
grant that is equal in length to the awards expected term (up to a maximum of five years).
EntreMed believes that historical volatility within the last five years represents the best
estimate of future long term volatility.
Risk-Free Interest RateThis is the average interest rate consistent with the yield available
on a U.S. Treasury note (with a term equal to the expected term of the underlying grants) at the
date the option was granted.
Expected Term of OptionsThis is the period of time that the options granted are expected to
remain outstanding. EntreMed adopted SAB 107s simplified method for estimating the expected term
of share-based awards granted during the year ended December 31, 2006.
Expected Dividend YieldEntreMed has never declared or paid dividends on its common stock and
does not anticipate paying any dividends in the foreseeable future. As such, the dividend yield
percentage is assumed to be zero.
Forfeiture RateThis is the estimated percentage of options granted that are expected to be
forfeited or cancelled on an annual basis before becoming fully vested. The Company estimates the
forfeiture rate based on historical forfeiture experience for similar levels of employees to whom
options were granted.
Following are the weighted-average assumptions used in valuing the stock options granted to
employees during the years ended December 31, 2006, 2005 and 2004:
Years ended December 31, | ||||||||||||
2006 | 2005 | 2004 | ||||||||||
Expected Volatility |
101.70 | % | 105.74 | % | 113.35 | % | ||||||
Risk free interest rate |
4.82 | % | 4.25 | % | 3.73 | % | ||||||
Expected term of option |
5 years | 5 years | 5 years | |||||||||
Forfeiture rate |
5.00 | % | N/A | N/A | ||||||||
Expected dividend yield |
| | |
The weighted average fair value of stock options granted was $1.25, $2.13 and $2.00 in 2006,
2005 and 2004, respectively.
Share-based compensation expense recognized in the Consolidated Statement of Operations for
the year ended December 31, 2006 is based on awards ultimately expected to vest, net of estimated
forfeitures. SFAS 123R requires forfeitures to be estimated at the time of grant and revised, if
necessary, in subsequent periods if actual forfeitures differ from those estimates.
F-17
A summary of the Companys stock option plans and of changes in options outstanding under the
plans during the years ended December 31, is as follows:
Weighted Average | ||||||||||||||||
Remaining | ||||||||||||||||
Weighted Average | Contractual Term | Aggregate Intrinsic | ||||||||||||||
Number of Options | Exercise Price | In years | Value | |||||||||||||
Outstanding at December 31, 2003 |
7,507,277 | $ | 10.48 | |||||||||||||
Exercised |
(7,125 | ) | $ | 1.09 | ||||||||||||
Granted |
1,176,728 | $ | 2.39 | |||||||||||||
Canceled |
(308,902 | ) | $ | 6.29 | ||||||||||||
Outstanding at December 31, 2004 |
8,367,978 | $ | 9.33 | |||||||||||||
Exercised |
(67,070 | ) | $ | 1.21 | ||||||||||||
Granted |
604,692 | $ | 2.68 | |||||||||||||
Canceled |
(943,582 | ) | $ | 12.66 | ||||||||||||
Outstanding at December 31, 2005 |
7,962,017 | $ | 9.05 | |||||||||||||
Exercised |
(7,500 | ) | $ | 1.09 | ||||||||||||
Granted |
1,022,132 | $ | 1.61 | |||||||||||||
Expired |
(855,563 | ) | $ | 11.56 | ||||||||||||
Forfeited |
(10,000 | ) | $ | 5.29 | ||||||||||||
Outstanding at December 31, 2006 |
8,111,086 | $ | 7.87 | 5.76 | $ | 543,508 | ||||||||||
Vested and expected to vest at
December 31, 2006 |
8,044,056 | $ | 7.92 | 5.66 | $ | 534,537 | ||||||||||
Exercisable at December 31, 2006 |
6,770,485 | $ | 9.02 | 5.12 | $ | 364,102 | ||||||||||
The aggregate intrinsic value is calculated as the difference between (i) the closing
price of the common stock at December 31, 2006 and (ii) the weighted average exercise price of the
underlying awards, multiplied by the number of options that had an exercise price less than the
closing price on the last trading day of 2006. The aggregate intrinsic value of options exercised
was $3,675, $48,961 and $15,319 for the years ended December 31, 2006, 2005 and 2004, respectively,
that had an exercise price less than the closing price on the last trading day of the respective
year.
Cash received from option exercises under all share-based payment arrangements for the years
ended December 31, 2006, 2005 and 2004, was $8,175, $81,356 and $7,767, respectively. Due to the
availability of net operating loss carryforwards and research tax credits, tax deductions for
option exercises were not recognized in the year ended December 31, 2006.
The following summarizes information about stock options granted to employees and directors
outstanding at December 31, 2006:
Options Outstanding | Options Exercisable | |||||||||||||||||||||||
Weighted | ||||||||||||||||||||||||
Average | Weighted | Weighted | ||||||||||||||||||||||
Number | Remaining | Average | Number | Average | ||||||||||||||||||||
Range of | Outstanding | Contractual | Exercise | Exercisable | Exercise | |||||||||||||||||||
Exercise Prices | at 12/31/06 | Life in Years | Price | at 12/31/06 | Price | |||||||||||||||||||
$0.00 $1.50 | 1,094,239 | 5.9 | $ | 1.11 | 1,084,149 | $ | 1.10 | |||||||||||||||||
$1.51 $3.00 | 2,465,970 | 8.4 | $ | 1.94 | 1,367,974 | $ | 2.08 | |||||||||||||||||
$3.01 $4.50 | 937,205 | 7.7 | $ | 3.49 | 704,690 | $ | 3.59 | |||||||||||||||||
$4.51 $6.00 | 216,272 | 5.8 | $ | 4.99 | 216,272 | $ | 4.99 | |||||||||||||||||
$6.01 $10.00 | 1,261,242 | 3.5 | $ | 9.13 | 1,261,242 | $ | 9.13 | |||||||||||||||||
$10.01 $15.00 | 634,977 | 3.1 | $ | 12.07 | 634,977 | $ | 12.07 | |||||||||||||||||
$15.01 $25.00 | 924,450 | 3.2 | $ | 19.27 | 924,450 | $ | 19.27 | |||||||||||||||||
$25.01 $35.00 | 554,608 | 3.1 | $ | 27.60 | 554,608 | $ | 27.60 | |||||||||||||||||
$35.01 $50.00 | 3,611 | 3.6 | $ | 44.82 | 3,611 | $ | 44.82 | |||||||||||||||||
$50.01 $65.00 | 18,512 | 3.3 | $ | 53.20 | 18,512 | $ | 53.20 | |||||||||||||||||
8,111,086 | 5.8 | $ | 7.87 | 6,770,485 | $ | 9.02 | ||||||||||||||||||
As of December 31, 2006, there was approximately $1,248,000 of total unrecognized
compensation cost related to nonvested employee stock options. That cost is expected to be
recognized over a weighted-average period of 1.6 years.
F-18
Warrants. Warrants granted generally expire after 5 years from the date of grant. Stock
warrant activity to non-employees is as follows:
Weighted Average | ||||||||
Number of Shares | Exercise Price | |||||||
Outstanding at December 31, 2003 |
12,047,581 | $ | 4.12 | |||||
Granted |
1,098,040 | $ | 3.67 | |||||
Exercised |
(337,500 | ) | $ | .94 | ||||
Expired |
(566,071 | ) | $ | 32.55 | ||||
Outstanding at December 31, 2004 |
12,242,050 | $ | 2.85 | |||||
Granted |
| | ||||||
Exercised |
(7,562,500 | ) | $ | 1.46 | ||||
Expired |
(74,672 | ) | $ | 6.60 | ||||
Outstanding at December 31, 2005 |
4,604,878 | $ | 5.06 | |||||
Granted |
6,486,484 | $ | 2.50 | |||||
Exercised |
| | ||||||
Expired |
(743,763 | ) | $ | 11.87 | ||||
Outstanding at December 31, 2006 |
10,347,599 | $ | 2.96 | |||||
Exercisable at December 31, 2006 |
10,347,599 | $ | 2.96 | |||||
9. COMMITMENTS AND CONTINGENCIES
Commitments
The Company entered into two license agreements with Childrens Hospital, Boston for the
exclusive, worldwide, royalty-bearing licenses to make, use and sell Endostatin and
2-methoxyestradiol (2ME2), both inhibitors of angiogenesis. In February 2004, the Company
transferred rights to Endostatin in an agreement with Childrens Medical Center Corporation and
Alchemgen Therapeutics. Therefore, the Company has no future milestone payment obligations related
to Endostatin. In consideration for retaining the 2ME2 rights, the Company must pay a royalty on
any sublicensing fees, as defined in the agreement, to Childrens Hospital, Boston. The agreement
obligates the Company to pay up to $1,000,000 upon the attainment of certain milestones. As of
December 31, 2006, the Company has paid $150,000 and accrued an additional $350,000 under this
agreement for the milestones that have been achieved to date.
In March 2005, the Company entered into an exclusive worldwide license agreement with Celgene
Corporation for the development and commercialization of Celgenes small molecule tubulin inhibitor
compounds for the treatment of cancer. Under the terms of the agreement, Celgene received an
upfront licensing fee of $1,000,000 and may receive additional payments up to approximately $25.25
million based upon the attainment of certain milestones. No such milestones have been reached
through December 31, 2006.
In January 2006, the Company entered into a License Agreement with Elan Corporation, plc in
which the Company has been granted rights to utilize Elans proprietary NanoCrystal Technology to
develop the oncology product candidate, Panzem® NCD. Under the terms of the License
Agreement, Elan is eligible to receive payments upon the achievement of certain clinical,
manufacturing, and regulatory milestones. Milestones related to the initiation of Phase 2 clinical
trials, totaling $500,000, were paid in 2005 and there are no additional milestones achieved as of
December 31, 2006. Additionally, Elan will receive royalty payments based on sales of
Panzem® NCD. Under the License Agreement and corresponding Services Agreement, Elan
will manufacture EntreMeds Panzem® NCD, a NanoCrystal Technology formulation
with improved bioavailability and absorption.
In January 2006, the Company acquired Miikana Therapeutics, a private biotechnology company.
Pursuant to the Merger Agreement, the Company acquired all of the outstanding capital stock of
Miikana Therapeutics, Inc. in exchange for 9.96 million shares of common stock and the assumption
of certain obligations. In addition, based on the success of the acquired pre-clinical programs,
the Company may pay up to an additional $18 million upon the achievement of certain clinical and
regulatory milestones. Such additional payments will be made in cash or shares of stock at the
Companys option. The Company expects that the Aurora Kinase pre-clinical program will advance to
a Phase 1 clinical trial in 2007. A dosing of the first patient, expected in 2007, triggers a
purchase price adjustment milestone of $2 million, payable in either stock or cash, at the
Companys discretion.. Through the acquisition, the Company acquired rights to MKC-1, a Phase 2
clinical candidate licensed from Hoffman-LaRoche, Inc. (Roche) by Miikana in April 2005. Under
the terms of the agreement, Roche may be
F-19
entitled to receive future payments upon successful completion of Phase 3 developmental
milestones. The Company does not anticipate reaching any of these milestones in 2007. Roche is
also eligible to receive royalties on sales and certain one-time payments based on attainment of
annual sales milestones. The Company is also obligated to make certain success fee payments to
ProPharma based on successful completion of developmental milestones under the Roche license
agreement.
The Company leases its primary facilities through February 2009. The lease agreement provides
for escalation of the lease payments over the term of the lease; however, rent expense is
recognized under the straight-line method. Additionally, the Company leases office equipment under
operating leases. The future minimum payments under its facilities and equipment leases as of
December 31, 2006 are as follows:
2007 |
1,013,211 | |||
2008 |
1,028,935 | |||
2009 |
171,644 | |||
Thereafter |
| |||
Total minimum payments |
$ | 2,213,790 | ||
Rental expense for the years ended December 31, 2006, 2005 and 2004 was $1,044,000,
$929,000, and $926,000, respectively.
Contingencies
EntreMed is subject in the normal course of business to various legal proceedings in which
claims for monetary or other damages may be asserted. Management does not believe such legal
proceedings, unless otherwise disclosed herein, are material.
10. EMPLOYEE RETIREMENT PLAN
The Company sponsors the EntreMed, Inc. 401(k) and Trust. The plan covers substantially all
employees and enables participants to contribute a portion of salary and wages on a tax-deferred
basis. Contributions to the plan by the Company are discretionary. Contributions by the Company
totaled $89,000, $77,000 and $87,000 in 2006, 2005 and 2004, respectively.
F-20
11. QUARTERLY FINANCIAL INFORMATION (UNAUDITED)
Summarized unaudited quarterly financial information for the years ended December 31, 2006 and
2005 is as follows:
QUARTER ENDED | ||||||||||||||||
MARCH 31, | JUNE 30, | SEPTEMBER 30, | DECEMBER 31, | |||||||||||||
2006 |
||||||||||||||||
Revenues |
$ | | $ | | $ | 3,023,185 | $ | 3,871,173 | ||||||||
Research and development costs |
4,011,100 | 4,258,206 | 5,544,134 | 7,857,677 | ||||||||||||
General and administrative expenses |
1,816,694 | 1,942,652 | 1,497,612 | 2,136,764 | ||||||||||||
Acquired In-Process R&D |
29,128,061 | 353,833 | | | ||||||||||||
34,955,855 | 6,554,691 | 7,041,746 | 9,994,441 | |||||||||||||
Investment income |
278,465 | 569,617 | 529,661 | 489,461 | ||||||||||||
Interest expense |
(48,713 | ) | (42,575 | ) | (36,098 | ) | (29,401 | ) | ||||||||
Gain on sale of assets |
15,400 | 1,925 | | 35,576 | ||||||||||||
Net loss |
(34,710,703 | ) | (6,025,724 | ) | (3,524,998 | ) | (5,627,632 | ) | ||||||||
Dividends on Series A convertible
preferred stock |
(251,250 | ) | (251,250 | ) | (251,250 | ) | (251,250 | ) | ||||||||
Net loss attributable to common
Shareholders |
(34,961,953 | ) | (6,276,974 | ) | (3,776,248 | ) | (5,878,882 | ) | ||||||||
Net loss per share (basic and diluted) |
$ | (0.53 | ) | $ | (0.09 | ) | $ | (0.05 | ) | $ | (0.08 | ) | ||||
2005 |
||||||||||||||||
Revenues |
$ | 25,249 | $ | 579,461 | $ | 1,249,600 | $ | 4,063,745 | ||||||||
Research and development costs |
4,379,356 | 3,812,353 | 4,128,756 | 5,004,583 | ||||||||||||
General and administrative expenses |
1,260,822 | 1,339,150 | 1,786,868 | 1,533,615 | ||||||||||||
5,640,178 | 5,151,503 | 5,915,624 | 6,538,198 | |||||||||||||
Investment income |
158,461 | 271,832 | 284,195 | 296,283 | ||||||||||||
Gain on sale of assets |
| | 2,000 | 1,420 | ||||||||||||
Net loss |
(5,456,468 | ) | (4,300,210 | ) | (4,379,829 | ) | (2,176,750 | ) | ||||||||
Dividends on Series A convertible
preferred stock |
(251,250 | ) | (251,250 | ) | (251,250 | ) | (251,250 | ) | ||||||||
Net loss attributable to common
Shareholders |
(5,707,718 | ) | (4,551,460 | ) | (4,631,079 | ) | (2,428,000 | ) | ||||||||
Net loss per share (basic and diluted) |
$ | (0.13 | ) | $ | (0.09 | ) | $ | (0.09 | ) | $ | (0.05 | ) |
F-21