ARCA biopharma, Inc. (ABIO)
10-K
Annual report pursuant to section 13 and 15(d)
Filed on 03/27/2012
Filed Period 12/31/2011
Table of Contents
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
þ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2011
or
¨ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to
Commission File Number: 000-22873
ARCA BIOPHARMA, INC.
(Exact Name of Registrant as Specified in Its Charter)
Delaware
(State or Other Jurisdiction of
Incorporation or Organization)
8001 Arista Place, Suite 430, Broomfield, CO
(Address of Principal Executive Offices)
36-3855489
(I.R.S. Employer
Identification No.)
80021
(Zip Code)
(720) 940-2200
(Registrant's telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Exchange Act:
Title of Each Class
Common Stock $0.001 par value
Name of Each Exchange on Which Registered
Nasdaq Capital Market
Securities registered pursuant to Section 12(g) of the Exchange Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in rule 405 of the Securities Act. Yes ¨ No þ
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 and Section 15(d) of the Act. Yes ¨ 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 ¨
Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Website, if any, every Interactive Data File
required to be submitted and posted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was
required to submit and post such files). Yes þ No ¨
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 registrant's 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, a non-accelerated filer or a smaller reporting company.
See the definitions of "large accelerated filer," "accelerated filer," and "small reporting company" in Rule 12b-2 of the Exchange Act.
Large accelerated filer ¨
Non-accelerated filer ¨ (Do not check if a smaller reporting company)
Accelerated filer ¨
Smaller reporting company þ
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ¨ No þ
The aggregate market value of the common stock held by non-affiliates of the Registrant on June 30, 2011, the last business day of the most recently
completed second fiscal quarter, was $14,193,288 based on the last sale price of the common stock as reported on that day by the Nasdaq Capital Market.
As of March 23, 2012 the Registrant had 12,182,999 shares of common stock outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the Registrant's Definitive Proxy Statement, which will be filed with the Commission pursuant to Section 14A in connection with the 2011
annual meeting of stockholders, are incorporated by reference into Part III of this Form 10-K.
Table of Contents
PART I
Item 1. Business
Item 1A. Risk Factors
Item 1B. Unresolved Staff Comments
Item 2. Properties
Item 3. Legal Proceedings
Item 4. Mine Safety Disclosures
PART II
TABLE OF CONTENTS
Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Item 6. Selected Financial Data
Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
Item 8. Financial Statements and Supplementary Data
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM, KPMG LLP
CONSOLIDATED BALANCE SHEETS
CONSOLIDATED STATEMENTS OF OPERATIONS
CONSOLIDATED STATEMENTS OF PREFERRED STOCK AND STOCKHOLDERS' EQUITY
CONSOLIDATED STATEMENTS OF CASH FLOWS
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Item 9A. Controls and Procedures
Item 9B. Other Information
PART III
Item 10. Directors, Executive Officers and Corporate Governance
Item 11. Executive Compensation
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Item 13. Certain Relationships and Related Transactions, and Director Independence
Item 14. Principal Accountant Fees and Services
PART IV
Item 15. Exhibits and Financial Statement Schedules
SIGNATURES
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Item 1.
Business
PART I
Some of the statements under "Business," "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations"
and elsewhere in this Annual Report constitute forward-looking statements. In some cases, you can identify forward-looking statements by the following
words: "may," "will," "could," "would," "should," "expect," "intend," "plan," "anticipate," "believe," "estimate," "predict," "project," "potential," "continue,"
"ongoing" or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. Examples of
these statements include, but are not limited to, statements regarding the following: the timing and results of any clinical trials, including the planned
Gencaro trial for the prevention of atrial fibrillation our ability to obtain additional funding or enter into a strategic or other transaction, the extent to which
our issued and pending patents may protect our products and technology, the potential of such product candidates to lead to the development of safe or
effective therapies, our ability to enter into collaborations, our ability to maintain listing of our common stock on a national exchange, our future operating
expenses, our future losses, our future expenditures, and the sufficiency of our cash resources to maintain operations. These statements involve known and
unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different
from the information expressed or implied by these forward-looking statements. While we believe that we have a reasonable basis for each forward-looking
statement contained in this Annual Report, we caution you that these statements are based on a combination of facts and factors currently known by us and
our projections of the future, about which we cannot be certain.
In addition, you should refer to the "Risk Factors" section of this Annual Report for a discussion of other important factors that may cause our actual
results to differ materially from those expressed or implied by our forward-looking statements. As a result of these factors, we cannot assure you that the
forward-looking statements in this Annual Report will prove to be accurate. Furthermore, if our forward-looking statements prove to be inaccurate, the
inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a
representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all.
We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. You
are advised, however, to consult any further disclosures we make on related subjects in our Quarterly Reports on Form 10-Q, Current Reports on Form 8-K,
and our website.
The terms "ARCA," "the Company," "we," "us," "our" and similar terms refer to ARCA biopharma, Inc.
Overview
We are a biopharmaceutical company whose principal focus is developing genetically-targeted therapies for cardiovascular diseases. Our lead product
candidate, GencaroTM(bucindolol hydrochloride), a pharmacologically unique beta-blocker and mild vasodilator, is being developed for the treatment of atrial
fibrillation, or AF, in patients with heart failure, or HF. We have identified common genetic variations in the cardiovascular system that we believe interact
with Gencaro's pharmacology and may predict patient response to the drug.
We have been granted patents in the U.S., Europe, and other jurisdictions for methods of treating AF and HF patients with Gencaro based on genetic
testing, which we believe will provide market exclusivity for these uses of Gencaro into at least 2026 in the U.S. and into 2025 in Europe. In addition, we
believe that if Gencaro is approved, the Gencaro patents will be eligible for patent term extension based on our current clinical trial plans which, if granted in
the U.S., may provide market exclusivity into 2029, and if granted in Europe may provide market exclusivity into 2030.
We are planning to initiate a Phase 3 clinical study of Gencaro in AF patients with HF and/or left ventricular dysfunction. We believe AF is an
attractive potential indication for Gencaro because data from the previously
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conducted Phase 3 HF trial of Gencaro in 2,708 HF patients, or the BEST HF trial, suggest that Gencaro may have a potentially significant effect in reducing
or preventing AF. Based on our analysis of data from the BEST HF trial, we believe that Gencaro's prevention of AF in HF patients is pharmacogenetically
regulated. We plan to enroll approximately 200-400 patients with persistent AF who have the genotype that appears to respond most favorably to Gencaro.
We anticipate that this trial could begin approximately 6 months after we obtain sufficient funding.
AF is a disorder in which the normally regular and coordinated contraction pattern of the heart's two small upper chambers (the atria) becomes irregular
and uncoordinated. The irregular contraction pattern associated with AF causes blood to pool in the atria, predisposing the formation of clots. These clots may
travel from the heart and become lodged in the arteries leading to the brain and other organs, thereby blocking necessary blood flow and potentially resulting
in stroke. AF is considered an epidemic cardiovascular disease that affects approximately 2-3 million Americans, making it one of the most common heart
rhythm disorders. The approved therapies for the treatment or prevention AF have certain disadvantages, such as toxic side effects. We believe there is an
unmet medical need for new AF treatments that have fewer side effects than currently available therapies and are more effective, particularly in patients with
HF where most of the approved drugs are contra-indicated or have warnings in their prescribing information.
The planned AF clinical trial is designed to be a multi-center, randomized, double-blind clinical trial to assess the safety and efficacy of Gencaro in AF
patients with HF and/or left ventricular dysfunction, with the primary endpoint being time to recurrent symptomatic AF after direct current cardioversion. This
AF trial is designed to compare Gencaro to the beta-blocker metoprolol CR/XL in the patient genotype we believe responds most favorably to Gencaro. The
therapeutic benefit of metoprolol CR/XL does not appear to be enhanced in patients with this genotype. We believe data from the BEST HF trial indicate that
Gencaro may have a potentially significant effect in reducing or preventing AF, and this effect may be one that is genetically regulated. The entire cohort of
patients in the BEST HF trial that were treated with Gencaro had a 41% reduction in the risk of new onset AF (time-to-event) compared to placebo (p =
0.0004), although because there was not a predetermined AF clinical endpoint in the BEST HF trial, the data is based on subsequent analysis of adverse
events and surveillance electrocardiograms (ECGs). In the DNA sub-study, patients with the most favorable genotype for Gencaro experienced a 74% (p =
0.0003) reduction in risk of AF, based on the same analysis. This most favorable genotype was present in about 47% of the patients in the sub-study, and we
estimate it is present in about 50% of the US general population. We believe the AF study would take approximately two and one half years from enrollment
of the first patient through completion.
We have exclusive patent rights to other product candidates that have potential indications in cardiovascular disease, oncology and other therapeutic
areas, some of which are in early stages of development and others of which are in later stages of development. We are seeking development partners to assist
us in the development of these product candidates or who may license rights to them. For example, we hold exclusive rights to rNAPc2, a recombinant protein
that is a potent, long acting tissue factor inhibitor with a unique mechanism of action. Previously, preclinical studies of rNAPc2 showed evidence of potential
efficacy against lethal hemorrhagic fever viruses.
To support the continued development of Gencaro, including the planned AF clinical trial and our ongoing operations, we will need to raise substantial
additional funding through public or private debt or equity transactions or a strategic combination or partnership, or government funding. We may seek
additional funding that could allow us to operate while we continue to pursue strategic combination, partnering, additional financing and licensing
opportunities. If we are delayed in obtaining funding or are unable to complete a strategic transaction, we may discontinue our development activities on
Gencaro or discontinue our operations. We believe our cash and cash equivalents balance as of December 31, 2011 will be sufficient to fund our operations, at
our current cost structure, through September 2012. We are unable to assert that our current cash and cash equivalents are sufficient to fund operations beyond
that date, and as a result, there is substantial doubt about our ability to continue as a going concern beyond September 2012. Changing circumstances may
cause us to
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consume capital significantly faster or slower than we currently anticipate. We have based these estimates on assumptions that may prove to be wrong, and we
could exhaust our available financial resources sooner than we currently anticipate.
On January 27, 2009, we completed a business combination (the "Merger") with ARCA Colorado in accordance with the terms of that Agreement and
Plan of Merger and Reorganization, dated September 24, 2008, and amended on October 28, 2008 (as amended, the "Merger Agreement"), in which a wholly-
owned subsidiary of Nuvelo, Inc. merged with and into ARCA Colorado, with ARCA Colorado continuing after the Merger as the surviving corporation and a
wholly-owned subsidiary of Nuvelo, Inc. Immediately following the Merger, we changed our name from Nuvelo, Inc. to ARCA biopharma, Inc., and our
common stock began trading on the Nasdaq Global Market under the symbol "ABIO" on January 28, 2009. On March 7, 2011, the listing of our common
stock was transferred from the Nasdaq Global Market to the Nasdaq Capital Market.
Our Strategy
Our mission is to become a leading biopharmaceutical company developing cardiovascular therapies with an emphasis on genetically-targeted
therapies. To achieve this goal, we are pursuing the following strategies:
•
•
•
•
Advance the development of Gencaro. We are planning to initiate a clinical study of Gencaro in AF patients with HF and/or left ventricular
dysfunction. Based on our analysis of data from the BEST HF trial we believe that Gencaro's prevention of AF in HF patients is genetically
regulated. We plan to enroll approximately 200-400 patients with persistent AF who have the genotype that appears to respond most favorably to
Gencaro. We anticipate that the trial could begin approximately 6 months after we obtain sufficient funding.
Raise substantial additional funding or complete a strategic transaction. To support the continued clinical development of Gencaro, including the
planned AF clinical trial, we are seeking to raise substantial additional funding, through the sale of public or private debt or equity securities,
government funding, or the completion of a strategic transaction.
Leverage our existing assets. We are pursuing opportunities to leverage certain of our development-stage product candidates. We are also
pursuing licensing transactions for certain of our other compounds which are in early stages of development for various indications. For example,
in 2011, we raised $2 million through the assignment of certain patent rights for one of these compounds to a large pharmaceutical company.
Build a cardiovascular pipeline. Our management and employees, including our chief executive officer, have extensive experience in
cardiovascular research, molecular genetics and clinical development of cardiovascular therapies. We are seeking to leverage this expertise to
identify, acquire and develop other cardiovascular products or candidates, with an emphasis on pharmacogenetic applications.
Atrial Fibrillation Market Background and Opportunity
AF is a disorder in which the normally regular and coordinated contraction pattern of the heart's two small upper chambers becomes irregular and
uncoordinated. The irregular contraction pattern associated with AF causes blood to pool in the atria, predisposing the formation of clots. These clots may
travel from the heart and become lodged in the arteries leading to the brain and other organs, thereby blocking necessary blood flow and potentially resulting
in stroke. AF is considered an epidemic cardiovascular disease based on the pace of increase in incidence in the U.S. and industrialized countries.
Approximately 2-3 million people in the U.S. have AF with one report estimating 160,000 new cases developing each year. Approximately 300,000-400,000
treated AF patients currently receive a form of beta-blocker as pharmaceutical intervention.
The goals of current medical therapy for AF are to maintain heart rhythm, also referred to as sinus rhythm, avoid the risk of complications and
minimize patient symptoms. Current treatments include pharmaceutical intervention and device intervention.
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There are several antiarrhythmic drugs approved by the FDA for the treatment and/or prevention of recurrent AF. However, these drugs all have safety and/or
administration concerns including contraindications, and all but one have contraindications or label warnings regarding their prescription in patients with HF.
Current device interventions for the treatment of AF include:
Electrical cardioversion which is used to restore normal heart rhythm with administration of a direct current shock;
Radiofrequency catheter ablation which can be effective in patients for whom medications are ineffective; and,
Atrial pacemakers which are implanted under the skin to regulate heart rhythm.
We are not aware of any beta-blocker approved for the indication of AF prevention but we believe beta-blockers may have mild efficacy in the
prevention of AF. In one reported analysis of data regarding placebo-controlled trials in HF beta-blockers were associated with a relative risk reduction in AF
onset of 27% in patients with heart failure. We also believe that Gencaro's prevention of AF in HF patients would provide this patient population a safer
treatment option than other treatments currently approved by the FDA.
Gencaro
Gencaro (bucindolol hydrochloride) is a pharmacologically unique beta-blocker and mild vasodilator being developed for the treatment of AF. Gencaro
is considered part of the beta-blocker class of compounds because of its property of blocking both beta-1, or ß1, and beta-2, or ß2, receptors in the cardiac
nervous system. The blocking of these receptors prevents binding with other molecules that serve to activate these receptors. We believe that Gencaro is well-
tolerated in cardiovascular patients because of its mild vasodilator effects. Originally developed by Bristol-Myers Squibb, or BMS, the active pharmaceutical
ingredient, or API, in Gencaro, bucindolol hydrochloride, has been tested clinically in approximately 4,500 patients. Gencaro was the subject of a Phase 3 HF
mortality trial of over 2,700 patients, mostly in the U.S., known as the "BEST" HF trial. The BEST HF trial included a DNA bank of over 1,000 patients,
which was used to evaluate the effect of genetic variation on patients' response to Gencaro.
At the time of the BEST HF trial, our founding scientists, Dr. Michael Bristow and Dr. Stephen Liggett, hypothesized that the unique pharmacologic
properties of Gencaro would interact with common genetic variations of ß1, and alpha2C, or a2C, receptors, which are important receptors that regulate cardiac
or sympathetic nerve function. They tested this hypothesis prospectively in a sub-study conducted using data from the BEST DNA bank. On the basis of this
study, Drs. Bristow and Liggett determined that patients with certain variations in these receptors had substantially improved outcomes on primary and certain
secondary clinical endpoints in the trial, such as mortality, HF progression, hospitalization and AF prevention, relative to the general patient population of the
BEST HF trial. We believe that these genetically determined receptor variations, which are detectable using standard genetic testing technology, can serve as
diagnostic markers for predicting enhanced therapeutic response to Gencaro, and potentially avoiding adverse events, in individual patients. We have patented
our methods for treating AF and HF patients with Gencaro in the U.S. and Europe based on genetic testing.
Pharmacology and Pharmacogenetics
Gencaro's pharmacology appears to be different from other compounds in the beta-blocker class in two fundamental respects. First, studies conducted
by our researchers indicate that in human myocardial preparations, Gencaro leads to inactivation of constitutively active (i.e. functional in the absence of
bound agonist) ß1 receptors through a mechanism separate from ß1-blockade, in addition to inhibiting the binding activity of the ß1 receptor like a typical beta-
blocker. Second, these same studies indicate that Gencaro lowers the systemic levels of the neurotransmitter norepinephrine, or NE, which is released by
cardiac and other sympathetic nerves. These two
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properties interact with common genetic variations in two cardiac receptors, the ß1 and a2C receptors, to produce the unique pharmacogenetic profile of
Gencaro. We believe that these two properties, and their pharmacogenetic implications, are unique to Gencaro.
Gencaro has an important interaction with the ß1 receptor found on muscle cells, or cardiac myocytes, of the heart. The general role of the ß1 receptor
and its downstream signaling cascades is to regulate the strength and rate of the heart's contractions. NE serves as an activator of the ß1 receptor, causing the
receptor to initiate signaling to the cardiac myocyte. Although this signaling may be beneficial to the failing heart in the short term, in chronic HF patients the
ß1 receptor also initiates harmful, or cardiomyopathic, signaling which, over time, exacerbates the heart's structural and functional decline. Beta-blockers
counteract this destructive process by reducing ß1 receptor signaling. They do this by binding to the receptor and blocking NE molecules from binding and
activating the signaling activity and, in Gencaro's case, by also inactivating certain ß1 receptors that are constitutively active (active in the absence of NE
stimulation).
There are two common genetic variations of the ß1 receptor, each of which we estimate is present in approximately 50% of the U.S. population. One of
these variations is known as the "ß1-389 Arg/Arg" genotype, or "ß1-389 Arg" receptor variant. Laboratory studies indicate that this variation results in a higher
functioning ß1 receptor, which has a greater ability to mediate the stimulatory effects of NE. In addition, this variation is also more likely to be constitutively
active and signal the cardiac myocyte to contract in the absence of NE. The ß1-389 Arg receptor also has much higher binding affinity for NE as compared to
the other variation, the "ß1-389 Gly carrier". The 389 Gly version, also present in about 50% of the U.S. population, results in a ß1 receptor that is much lower
functioning and, according to laboratory studies, has less probability of being in a constitutively active state compared to the ß1-389 Arg/Arg receptor.
We believe Gencaro has a powerful interaction with the higher-functioning ß1-389 Arg/Arg variation of the ß1 receptor. Laboratory studies show that
constitutively active receptors will continue to signal in the presence of standard beta-blockade. Laboratory studies in isolated human heart preparations also
show that Gencaro has the unusual ability of being able to stop the signaling of constitutively active receptors. We believe that individuals with the ß1-389
Arg/Arg genotype potentially will realize an enhanced therapeutic response to Gencaro because of the greater potential for active state, cardiomyopathic
signaling among individuals with this genotype, and the larger reduction in signaling that these individuals experience when taking Gencaro, relative to
individuals with the ß1-389 Gly carrier genotype. In addition, we believe the NE lowering properties of Gencaro will have selectively beneficial effect in
patients who have only ß1-389 Arg receptors because of the higher binding affinity of Arg receptors for NE.
The efficacy of Gencaro also appears to be influenced by the a2C receptor, located on the terminus of the sympathetic cardiac nerve, at its junction with
the cardiac myocyte. The role of this receptor is to modulate the amount of NE that is present at this junction, which in turn affects the activation of ß1
receptors and the heart's activity. There are two important genetic variations of this receptor that appear to affect the performance of Gencaro; the "a2C-wild
type", which is the normal functioning version of the receptor (approximately 87%-90% of the U.S. general population), and the "deletion variant", a version
of the receptor that functions poorly (approximately 10%-13% of the U.S. general population). The DNA sub-study of patients from the BEST HF trial,
conducted by Drs. Bristow and Liggett, indicated that these two variations of the a2C receptor appear to affect Gencaro efficacy in HF if the 389Gly carrier
variant of the ß1 receptor is also present, but not if the 389 Arg receptor variant of the ß1 receptor is present; in patients with the ß1-389 Gly carrier variant, the
wild type version of the a2C receptor appears to enhance efficacy, as compared to the deletion variant which appears to reduce efficacy. When the Arg version
of the ß1 receptor is present (ß1-389 Arg/Arg), the efficacy of Gencaro does not appear to depend on which version of the a2C receptor is present.
The DNA sub-study from the BEST HF trial indicated that the combinations of these receptor variations in individual patients appear to influence the
response to Gencaro with respect to significant clinical endpoints.
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However, the ß1-389 Arg/Arg variant appeared to have the most powerful effect on Gencaro response. While we believe that the ß1-389 Gly carrier patients
may respond favorably to Gencaro depending on their a2C variation type, we believe that all patients that possess the ß1-389 Arg/Arg variant may be
candidates for Gencaro. The ß1-389 Arg/Arg variant group, or "very favorable" group, constitutes an estimated 47-50% of the U.S. population. We believe
these individuals may have an enhanced therapeutic response to Gencaro because of its effect on this higher-functioning/constitutively active ß1 receptor
variant, and a favorable response to NE lowering, regardless of the patient's a2C receptor genotype. The planned AF clinical trial will enroll only patients that
possess this "very favorable" genotype.
The BEST HF trial
The BEST HF trial began in 1995. It was a double-blind, placebo-controlled, multi-center study of bucindolol's effect on reduction of mortality and
morbidity in an advanced chronic HF population. The primary endpoint of the BEST HF trial was all cause mortality (ACM) and the pre-specified main
secondary endpoint was progression of HF, defined as HF death, cardiac transplant, HF hospitalization, or emergency room visit for the treatment of
worsening HF not requiring hospitalization. The trial was planned to run four and one-half years, and enroll 2,800 patients. The trial enrolled a total of 2,708
chronic HF patients, who were mostly from the United States. Under the umbrella of the BEST HF trial sub-studies program, a DNA bank and sub-study was
created, and 1,040 of the BEST patients participated by providing blood for DNA analysis. The DNA bank provided data for the DNA sub-study of BEST
patients conducted by Drs. Bristow and Liggett.
In 1999, the BEST HF trial was terminated prior to the completion of follow-up, in response to a recommendation of the BEST HF trial Data and Safety
Monitoring Board. The primary reason for termination was loss of investigator equipoise; in other words, the fact that the BEST investigators were no longer
uncertain regarding the comparative therapeutic merits of giving a placebo versus giving a beta-blocker to a HF patient. Positive mortality results from two
other HF trials involving other beta-blockers had been reported, and a substantial number of BEST HF trial investigators concluded that it was unethical to
continue to give placebo to BEST HF trial participants. As a result, some investigators began to prescribe these other beta-blockers to patients in the trial,
which threatened to destroy the trial's integrity, therefore the trial was terminated early.
Clinical Results and the DNA Sub-study
Following termination, the preliminary results of the study were analyzed and published. The preliminary determination and general perception were
that the BEST HF trial had failed on the basis of not meeting its primary endpoint of ACM. The published values were a 10% risk reduction in mortality with
a p-value of 0.10. Subsequently, we reanalyzed the results from BEST, in accordance with the FDA approved, pre-specified statistical analysis plans, which
had not been performed by the sponsors of BEST when the trial was terminated. Our reanalysis appeared to show a 13% risk reduction on the primary
endpoint of all-cause mortality in the BEST HF trial with a p-value of 0.053.
In 2003 and 2004, the results of the DNA sub-study conducted by Drs. Bristow and Liggett began to be released and analyzed. The DNA sub-study
results indicated a significant enhancement of response on the major clinical endpoints from the BEST HF trial in patients with the "very favorable" genotype.
The HF risk reduction on clinical efficacy endpoints such as mortality and hospitalization ranged from approximately 34% to approximately 48% in this
genotype. In addition, in arrhythmia endpoints of atrial fibrillation or ventricular fibrillation, tracked by adverse events and surveillance ECGs, the risk
reduction by bucindolol in the "very favorable" genotype appeared to be even greater, ranging from 74% to 76%.
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Shown below are certain of the primary and secondary endpoint data from the BEST HF DNA sub-study results, by genotype:
BEST HF Trial Clinical Responses
1
by Genotype Groups
Endpoint
All Cause Mortality (ACM), TTE
Cardiovascular Mortality (CVM), TTE
ACM + transplantation
HF (HF) Progression
HF Hosp days/patient
AF prevention (from AE and ECG db)
VT/VF prevention (from AE db)
Very Favorable
patients
(47%)
Favorable
patients
(40%)
Unfavorable
patients
(13%)
i
i
i
i
i
i
i
38%*
48%*
43%*
34%**
48%**
74%**
76%**
i
i
i
i
i
i
i
25%
40%*
24%
20%
17%
6%
54%*
h
h
h
i
h
h
i
4%
11%
4%
1%
19%
33%
35%
1
*
Covariate adjusted, transplant censored analysis with 1 – hazard ratio estimates presented
p<0.05; **p<0.007; TTE: Time To Event; CRF: Case Report Form; Adj.: Adjudicated
Analysis of BEST HF trial for AF
Recently, the BEST HF study data was further analyzed focusing on AF.AF. According Although there was no pre-determined AF endpoint, including
reduction in risk of AF, in the BEST HF trial, according to our analysis of adverse events and surveillance ECG's during the trial, 8% of patients developed
new onset AF, with a greater incidence observed in the placebo group (10%) compared to the bucindolol group (6%). This corresponded to a 36% reduction in
the incidence of new onset AF (based on rates) for patients receiving bucindolol (p = 0.002). In a time to event analysis, the risk of new onset AF was reduced
by 41% (p = 0.0004) with bucindolol treatment.
As with the overall study cohort, most patients in the 1,040 patient DNA sub-study were in normal heart rhythm, also referred to as sinus rhythm, at
baseline. The proportion of patients in sinus rhythm at baseline was also similar in the two treatment groups for the overall DNA sub-study cohort, as well as
in the ß1-389 genotype subgroups. In the BEST DNA sub-study, the proportion of patients who developed new onset AF was similar compared to the overall
study cohort for both the placebo group (11% and 10%, respectively) and the Gencaro group in the DNA sub-study population compared to the overall study
cohort (7% and 6%, respectively). Also, there was a similar reduction in new onset AF observed in the bucindolol group compared to placebo (43% and 41%,
respectively, by time to event analysis). Therefore, the overall results from the genetic sub-study population are consistent with the results from the overall
study population.
The AF risk reduction we believe we observed in our analysis of adverse events and surveillance ECG's collected during the BEST HF trial was similar
to AF risk reductions observed in a meta analysis of data regarding seven placebo-controlled ß-blocker trials in HF patients. In this meta-analysis, ß-blockers
appeared to reduce the incidence of new onset AF in all but one trial, with an overall relative risk reduction of 27%. Despite the apparent efficacy signals for
the prevention of AF in HF trials, we are not aware of any ß-blocker that has FDA approval of use in this indication. The BEST HF trial data indicate that
Gencaro may have a robust effect on AF prevention in advanced HFREF patients and, factoring in differences in degree of clinical HF, Gencaro may have at
least as good an effect as other ß-blocking agents, even without pharmacogenetic targeting.
Clinical and Regulatory Strategy
The regulatory strategy for Gencaro is to obtain an AF approval in a genotype specific HF population. We will seek to enroll certain patients with the
Very Favorable genotype in our AF clinical trial since our analysis of AE's and ECGs from the BEST HF DNA sub-study indicated this group had a 74%
reduction in risk for new AF
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events. The FDA approval will be pursued through two Phase 3 trials. In the first trial, the design will include enrollment of 200-400 patients with persistent
AF who have the genotype that appears to respond most favorably to Gencaro. The trial will investigate Gencaro's superiority versus metoprolol CR/XL. If
successful, this first Phase 3 AF trial would be followed by a second Phase 3 trial to be conducted in the same target population with the objective of using
both trials to support a NDA for Gencaro as a therapy for AF in a genotype specific HF population. We believe if the first trial achieves a highly significant
finding of statistical significance of less than 0.01, this single trial, with supporting data from the BEST HF trial, may be sufficient for a Gencaro NDA
approval in an AF disease indication.
The Gencaro Test
If approved, we believe that Gencaro will be the first cardiovascular drug to be integrated with a companion diagnostic to predict enhanced efficacy.
We believe the drug label being sought for Gencaro would identify the patient receptor genotypes that can expect enhanced efficacy, as well as those with a
likelihood of a standard beta-blocker response and the small unfavorable subgroup with a low probability of benefit. The label being sought would
recommend receptor genotype testing prior to initiation of therapy. Accordingly, we collaborated with LabCorp to develop a receptor genotype diagnostic, the
Gencaro Test, and believe the test will be simple to administer and would be widely available. We currently intend to pursue a separate arrangement with
LabCorp or another third party to provide the diagnostic services of the Gencaro Test needed to support our planned AF trial.
Through our existing agreement with LabCorp we have collaborated to develop and commercialize the Gencaro Test for the treatment of patients with
HF. Under the terms of that collaboration, we licensed to LabCorp certain rights to commercialize a receptor genotype diagnostic for the ß1 and a2C
polymorphisms. In return, LabCorp agreed to develop the Gencaro Test and obtain FDA clearance or approval of the Gencaro Test for HF.
Licensing and Royalty Obligations
We have licensed worldwide rights to Gencaro, including all preclinical and clinical data from Cardiovascular Pharmacology and Engineering
Consultants, LLC, or CPEC, who has licensed rights in Gencaro from BMS. CPEC is a licensing entity which holds the rights of the biotechnology companies
that were the commercial sponsors of the BEST trial. If the FDA grants marketing approval for Gencaro, the license agreements require that we make a
milestone payment of $8.0 million, which is due within six months after FDA approval. Under the license agreements, we are required to make milestone
payments of up to $5.0 million in the aggregate upon regulatory marketing approval in Europe and Japan. Our royalty obligation under the licenses ranges
from 12.5% to 25% of revenue from the related product based on achievement of specified product sales levels including a 5% royalty that CPEC is obligated
to pay under its original license agreement for Gencaro. We have the right to buy down the royalties to a range of 12.5% to 17% by making a payment within
six months of regulatory approval.
We also have licensed worldwide rights to intellectual property covering the pharmacogenetic response of Gencaro based on the cardiac receptor
polymorphisms, which is owned by the University of Colorado. We have no material future financial obligations under this license. We also have an option to
license exclusive, worldwide rights to develop and commercialize diagnostics for these receptor polymorphisms, for the purpose of prescribing Gencaro, from
the licensee of these rights, the University of Cincinnati.
Development Pipeline
Our development activities are substantially focused on our lead product candidate, Gencaro, for the treatment of AF. We also believe, based upon data
from the BEST HF trial, that Gencaro may have additional potential for the treatment of HF and ventricular tachycardia/ventricular fibrillation. In 2008 we
submitted and the FDA accepted our NDA filing for Gencaro for the treatment of chronic HF. In 2009 the FDA issued a
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Complete Response Letter (CRL) in which the FDA stated that it could not approve the Gencaro NDA in its current form, and specified actions required for
approval of the NDA, including conducting an additional Phase 3 clinical trial of Gencaro in patients with HF. In 2010 we reached agreement with the FDA,
through the Special Protocol Assessment (SPA) process, on the design of a clinical trial to assess the safety and efficacy of Gencaro in approximately 3,200
patients with chronic HF who have the genotype that appears to respond most favorably to Gencaro. We do not expect to pursue development of Gencaro for
disease indications beyond AF without entering into a strategic partnership or collaboration for an HF clinical program. We believe Gencaro has potential to
address these additional indications, and that the clinical response of patients with these diseases may be genetically influenced, based on the same genetic
markers we have identified for our proposed treatment of AF with Gencaro.
We also have exclusive patent rights to other product candidates that have potential indications in cardiovascular disease, oncology and other
therapeutic areas, some of which are in early stages of development and others of which are in later stages of development. We are seeking partners to assist
us in the development of these candidates or who may license them. For example, we hold exclusive rights to rNAPc2, a potent, long acting, recombinant
protein anticoagulant with a unique mechanism of action involving inhibition of tissue factor, the protein responsible for initiating the extrinsic coagulation
pathway, the primary coagulation mechanism in humans. rNAPc2 was originally being developed as a cardiovascular therapy for thrombosis and other
indications. As a result, it has an extensive human clinical record, and has been safely tested in over 700 human patients in nine Phase 1 and Phase 2 clinical
trials. Previously, pilot studies of rNAPc2 conducted in non-human primates showed evidence of potential efficacy against lethal hemorrhagic fever viruses.
Competition
Current treatments include pharmaceutical intervention and device intervention. There are several antiarrhythmic drugs approved by the FDA for the
treatment and/or prevention of recurrent AF. However, these drugs all have safety and/or administration concerns, and all but one have contraindications or
label warnings regarding their prescription in patients with HF.
Current device interventions for the treatment of AF include:
Electrical cardioversion which is used to restore normal heart rhythm with administration of a direct current shock;
Radiofrequency catheter ablation which is can be effective in patients for whom medications are ineffective; and,
Atrial pacemakers, which are implanted under the skin to regulate heart rhythm.
Considering that most of the approved drugs and device interventions for the treatment or prevention AF have notable risks or adverse side effects, we
believe there is an unmet medical need for new AF treatments that have fewer side effects than currently available therapies and are more effective,
particularly in patients with HF where the approved drugs are contra-indicated or have warnings regarding their prescribing information. We believe that
Gencaro's prevention of AF in HF patients would provide this patient population a safer treatment option than other treatments currently approved by the
FDA.
The pharmaceutical industry is highly competitive. We face significant competition from pharmaceutical companies and biotechnology companies that
are researching and selling products designed to treat cardiovascular conditions. Most of these companies have significantly greater financial, product
development, manufacturing, and commercial resources than we have. In addition, our proposed prescribing information for Gencaro includes a
recommendation for genetic testing, which will add additional cost and procedures to the process of prescribing Gencaro, and which could make it more
difficult for us to compete against existing therapies.
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Manufacturing and Product Supply
Gencaro is a small molecule drug with an established manufacturing history. Multiple manufacturers of both the API and drug product have
successfully produced Gencaro for use in clinical trials over the course of its clinical development. We outsource all manufacturing and analytical testing of
the Gencaro API and drug product. We have selected third party contract manufacturing organizations on the basis of their technical and regulatory expertise.
Our approach with our contract manufacturing partners has been to replicate the manufacturing processes that were used to support the prior pivotal clinical
trial with Gencaro, and to minimize any changes from these baseline processes, thereby reducing technical and regulatory risk. We contracted with Groupe
Novasep to complete the drug substance registration batches required for the Gencaro NDA. These batches were successful, and the resulting drug substance
was used to supply the drug product registration campaign. Remaining inventory was placed in current Good Manufacturing Practice, or cGMP, storage to
provide a backup supply for the planned Phase 3 trial, and for use as an initial source of drug substance to support eventual product launch, if approved.
For drug product production, we have contracted with Patheon, Inc. to manufacture the Gencaro tablets. Gencaro is produced in a tablet form, utilizing
standard solid oral dosage processing techniques. Six separate dosage strengths are manufactured, with the maximum recommended dose of 50mg twice daily
for patient weighing 75kg or less and 100mg twice daily for patients weighing more than 75kg. Registration batches were successfully completed by Patheon,
Inc. and tablets from these runs have been placed in cGMP storage to supply the planned Phase 3 AF trial.
If sufficient funding is obtained, our manufacturing focus for 2012 will be to prepare the blinded clinical trial supplies for Gencaro and the comparator
compound, and to establish the appropriate packaging and clinical distribution channels necessary for the successful execution of the planned Phase 3 AF
trial.
Research and Development Expenses
Our research and development expenses totaled $2.3 million for the year ended December 31, 2011 as compared to $3.1 million for 2010, a decrease of
approximately $790,000. Our future R&D expenses are highly contingent upon our ability to raise substantial additional funding or complete a strategic
transaction. Should we receive funds from one or a combination of these sources, R&D expense in 2012 could be substantially higher than 2011 as we initiate
our planned AF clinical trial. Until substantial additional funding is obtained, R&D expenses in 2012 are expected to be comparable to 2011 levels.
Government Regulation
Governmental authorities in the U.S. at the federal, state, and local levels and foreign countries extensively regulate, among other things, the research,
development, testing, manufacture, labeling, promotion, advertising, marketing, distribution, sampling, and import and export of pharmaceutical and medical
device products.
Premarket Approval of Drugs
FDA approval is required before any new drug, dosage form, indication, or strength can be marketed in the U.S. We anticipate that all of our products
will require regulatory approval by governmental agencies prior to commercialization. The process of obtaining approval and the subsequent process of
maintaining compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial
resources. In addition, these statutes, rules, regulations and policies may change and our products may be subject to new legislation or regulations. There are
numerous FDA and other federal and state sanctions for non-compliance.
The steps required before new human therapeutic products are marketed in the U.S. and foreign countries include rigorous preclinical and clinical
testing and other approval requirements by regulatory agencies, such as the FDA and comparable agencies in foreign countries.
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Preclinical Phase. Preclinical studies are generally conducted in the laboratory to evaluate the potential efficacy and safety of a product candidate.
These studies include laboratory evaluation of product chemistry, formulation and stability, as well as studies to evaluate toxicity in animals. Preclinical
studies are governed by numerous regulations.
Clinical Phase. Before human clinical trials can commence, an Investigational New Drug, or IND, application, submitted to FDA, or a comparable
application submitted to a foreign country's agency, must become effective. The clinical phase of development involves the performance of human studies,
including adequate and well-controlled human clinical trials to establish the safety and efficacy of the product candidate for each proposed indication.
Typically, clinical evaluation involves three sequential phases, which may overlap. During Phase 1, clinical trials are conducted with a relatively small
number of subjects or patients to determine the early safety profile of a product candidate, as well as dose tolerance, absorption, and the pattern of drug
distribution and drug metabolism. Phase 2 trials are conducted with groups of patients afflicted by a specific target disease to determine preliminary efficacy,
optimal dosages and dosage tolerance and to identify possible adverse effects and safety risks. In Phase 3, larger-scale, multi- center trials are conducted with
patients afflicted with a specific target disease to provide data for the statistical proof of efficacy and safety as required by regulatory agencies. The conduct of
clinical trials is subject to extensive regulation.
NDA Submission. In the U.S., the results of preclinical and clinical testing along with chemistry, manufacturing and controls information, are submitted
to the FDA in the form of an NDA. Under the Prescription Drug User Fee Act, or PDUFA, after submission of an NDA and payment, or waiver, of the
required fee, the FDA's goal is to review most standard NDAs within 10 months from sponsor submission of the application by which time, the FDA must
issue a "complete response," or approve the NDA.
In responding to an NDA, the FDA may grant marketing approval or deny the application if the FDA determines that the application does not satisfy
the statutory and regulatory approval criteria. A denial may include a request for additional information, including additional clinical data and/or an additional
Phase 3 clinical trial. Data from clinical trials are not always conclusive and FDA may interpret data differently than we interpret data. Under the Food and
Drug Modernization Act of 1997, the FDA is authorized to approve a drug based on a single adequate and well-controlled study if such study and other
confirmatory data are sufficient to establish the drug's effectiveness. However, it has long been the FDA's general position that the standard of proof of a
drug's effectiveness generally requires at least two well-controlled and adequate Phase 3 clinical studies with p-values of less than 0.05 on the primary
endpoint.
In addition, in accordance with current FDA law and regulations, the FDA may refer a drug to an advisory committee for review prior to approval. In
some cases, FDA may require completion, within a specified time period, of additional clinical studies after approval, referred to as Phase 4 clinical studies, to
monitor the effect of a new product and may prevent or limit future marketing of the product based on the results of these post-marketing programs.
Furthermore, prior to granting approval, the FDA generally conducts an inspection of the facilities, including outsourced facilities that will be involved in the
manufacture, production, packaging, testing and control of the drug substance and finished drug product for compliance with current Good Manufacturing
Practice, or cGMP, requirements.
If the FDA approves the NDA, the sponsor is authorized to begin commercialization of the drug in accordance with the approval. Even if the FDA
approves the NDA, the FDA may decide later to suspend or withdraw product approval if compliance with regulatory standards is not maintained or if safety
problems are recognized after the product reaches the market. In addition, the FDA requires surveillance programs to monitor approved products that have
been commercialized, and the agency has the power to require additional clinical studies, to require changes in labeling or to prevent further marketing of a
product based on the results of these post-marketing programs. The FDA also has authority to request implementation of a risk evaluation and mitigation
strategy, or REMS, that could restrict distribution of Gencaro or require us to provide additional risk information to prescribers. Whether or not FDA approval
has been obtained, approval of a product candidate by
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comparable foreign regulatory authorities is necessary prior to the commencement of marketing of a product candidate in those countries. The approval
procedures vary among countries and can involve additional testing. The time required to obtain approval may differ from that required for FDA approval.
Although there are some centralized procedures for filings in the European Union countries, in general each country has its own procedures and requirements.
Post-approval Compliance. If regulatory approval for a drug or medical device is obtained, the product and the facilities manufacturing the product are
subject to periodic inspection and continued regulation by regulatory authorities, including compliance with cGMP, as well as labeling, advertising,
promotion, recordkeeping, and reporting requirements, including the reporting of adverse events. In addition, the FDA closely regulates the post-approval
marketing and promotion of drugs, including standards and regulations for direct-to-consumer advertising, off-label promotion, industry-sponsored scientific
and educational activities and promotional activities involving the Internet. Drugs may be marketed only for the approved indications and in accordance with
the provisions of the approved label. Companies are responsible for compliance with such requirements and would be responsible to ensure that all contract
manufacturing organizations who perform work for them also comply with such requirements. Failure to comply with these requirements can result in adverse
publicity, warning letters, corrective advertising and potential civil and criminal penalties.
Drug Price Competition and Patent Term Restoration Act of 1984. Under the Drug Price Competition and Patent Term Restoration Act of 1984, also
known as the Hatch-Waxman Act, Congress created an abbreviated FDA review process for generic versions of pioneer (brand name) drug products. The
Hatch-Waxman Act also provides for patent term restoration and the award, in certain circumstances, of non-patent marketing exclusivities.
Generic Drug Approval. The Hatch-Waxman Act established an abbreviated FDA review process for drugs that are shown to be equivalent to approved
pioneer drugs. Approval for a generic drug is obtained by filing an abbreviated NDA, or ANDA. Generic drug applications are "abbreviated" because they
generally do not include clinical data to demonstrate safety and effectiveness. Instead, an ANDA applicant must establish that its product is bioequivalent to
an approved drug and that it is the same as the approved drug with respect to active ingredient(s), route of administration, dosage form, strength and
recommended conditions of use (labeling). The FDA will approve the generic as suitable for an ANDA if it finds that the generic does not raise questions of
safety and effectiveness as compared to the pioneer drug. A drug is not eligible for ANDA approval if the FDA determines that it is not equivalent to the
pioneer drug or if it is intended for a different use. Any applicant who files an ANDA seeking approval of a generic version of an approved drug listed in
FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, or the Orange Book, before expiration of the patent(s) listed in the Orange Book
for that approved drug, must certify to the FDA for each patent that (i) no patent information on the drug has been submitted to the FDA; (ii) that such patent
has expired; (iii) the date on which such patent expires; or (iv) that such patent is invalid, unenforceable or will not be infringed by the manufacture, use or
sale of the generic drug. If the ANDA applicant makes a certification pursuant to (iv) above, or a Paragraph IV certification, and the NDA holder files an
infringement suit against the ANDA applicant within 45 days of receiving the Paragraph IV notification, the NDA owner is entitled to an automatic 30-month
stay of FDA's ability to approve the ANDA. This 30-month stay will end early upon any decision by a court that the patent is invalid, unenforceable or not
infringed by the generic drug.
Patent Term Restoration. The Hatch-Waxman Act provides for the restoration of a portion of the patent term lost during product development and FDA
review of an application. However, the maximum period of restoration cannot exceed five years, or restore the total remaining term of the patent to greater
than 14 years from the date of FDA approval of the product.
Patent Term Extension. While the term of a U.S. Patent is 20 years from the earliest priority date of a patent application (excluding a provisional patent
application) , a U.S. Patent that covers subject matter requiring regulatory approval to market is eligible for an extension of that patent term. Patent Term
Extension, or PTE,
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extends the term of an issued patent for generally 1) the length of the FDA approval process and 2) half of the time spent in clinical trials. However, there are
certain limitations to PTE, including the limitation that the term cannot be extended more than 14 years after approval has been obtained.
Under 35 U.S.C. § 156(a), a patent covering a method of using a product is eligible for PTE if the following conditions are met:
(1)
(2)
(3)
(4)
(5)
the patent has not yet expired;
the patent was not previously extended;
the patent owner submits an application for PTE that includes all necessary supporting information within 60 days of FDA approval;
the product was subject to regulatory review before its commercial marketing or use; and
the drug application is for the first permitted commercial marketing of the product.
We have obtained three U.S. patents (U.S. Patent Nos. 7,678,824,8,080,578, 8,093,286,), and have one pending U.S. patent application that generally
concern methods for treating patients with Gencaro based on the presence of certain polymorphisms in the ß1 and/or a2C adrenergic receptors. We believe that,
if approved by the FDA, one of the U.S. patents may be eligible for PTE, which could provide approximately 3 years or more of additional patent life based
on our current clinical trial plans.
Supplementary Protection Certificate, or SPC, is a form of patent term extension that is available for pharmaceutical products approved for marketing in
the European Union. We obtained a patent in Europe for use of Gencaro that is similar to the 824 patent (EP 1802775); this patent is in force in certain
countries in Europe, including the United Kingdom, France, Germany, Italy and Spain. We believe that this patent may be eligible for an SPC, if Gencaro is
approved for marketing in any European country in which the patent is in force, which could provide up to five years of additional patent life.
Non-Patent Marketing Exclusivities. Separate and apart from patent protection, the Hatch-Waxman Act entitles approved drugs to various periods of
non-patent statutory protection, known as marketing exclusivity. The Hatch-Waxman Act provides five years of "new chemical entity" marketing exclusivity
to the first applicant to gain approval of an NDA for a product that contains an active moiety not found in any other approved product. This exclusivity means
that another manufacturer cannot submit an ANDA or 505(b)(2) NDA until the marketing exclusivity period ends. This exclusivity protects the entire new
chemical entity franchise, including all products containing the active ingredient for any use and in any strength or dosage form, but will not prevent the
submission or approval of stand-alone NDAs where the applicants have conducted their own clinical studies to demonstrate safety and effectiveness. There is
an exception, however, for a competitor that seeks to challenge a patent with a Paragraph IV certification. Four years into the five-year exclusivity period, a
manufacturer who alleges that one or more of the patents listed with the NDA is invalid, unenforceable or not infringed may submit an ANDA or 505(b)(2)
NDA for a generic or modified version of the product.
The Hatch-Waxman Act also provides three years of "new use" marketing exclusivity for the approval of NDAs, and supplements, where those
applications contain the results of new clinical investigations (other than bioavailability studies) essential to the FDA's approval of the applications. Such
applications may be submitted for new indications, dosage forms, strengths, or new conditions of use of approved products. So long as the studies are
essential to the FDA's approval or were conducted by or for the applicant, this three-year exclusivity prohibits the final approval of ANDAs or 505(b)(2)
NDAs for products with the specific changes associated with those studies. It does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for other
products containing the same active ingredient, without those changes.
FDA Approval of Medical Devices
Unless an exemption applies, each medical device that a company wishes to market in the U.S. requires either approval of a PMA or 510(k) clearance
from the FDA. The FDA classifies medical devices into one of
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three classes. Devices deemed to pose lower risks are placed in either class I or II, which may require the manufacturer to submit to the FDA a 510(k)
requesting permission to commercially distribute the device. This process is generally known as 510(k) clearance. Some low risk devices are exempted from
this requirement. Devices deemed by the FDA to pose the greatest risks, or for which there is no predicate, are placed in class III, requiring approval of a
PMA.
PMA Pathway. Generally, a PMA must be supported by extensive data including, but not limited to, technical, preclinical, clinical trials, manufacturing
and labeling to demonstrate to the FDA's satisfaction a reasonable assurance of the safety and effectiveness of the device for its intended use. After a PMA is
sufficiently complete, the FDA will accept the application and begin an in-depth review of the submitted information and will generally conduct a pre-
approval inspection of the manufacturing facility or facilities to ensure compliance. By statute, the FDA has 180 days to review the "accepted application",
although, generally, review of the application can take between one and three years, but it may take significantly longer.
Clinical Trials. Clinical trials are generally required to support a PMA application and are sometimes required for 510(k) clearance.
Continuing Regulation. After a device is placed on the market, numerous regulatory requirements apply to the manufacturer, or holder of a PMA
approval. With respect to the Gencaro Test, we intend to seek a new or amended collaborative arrangement with a diagnostic company in which we could
license them certain rights to perform the diagnostic test for patients with AF. As part of such arrangement, we will seek to have the diagnostic company take
responsibility for compliance with the FDA's device approval and on-going regulatory requirements.
International Marketing Approvals. International sales of medical devices are subject to foreign government regulations, which vary substantially from
country to country and are subject to change. The time required to obtain approval by a foreign country may be longer or shorter than that required for FDA
clearance or approval, and the requirements may differ.
Other Regulatory Requirements. We are also subject to various federal, state and local laws, regulations and recommendations relating to safe working
conditions, laboratory and manufacturing practices, the experimental use of animals and the use and disposal of hazardous or potentially hazardous
substances, including radioactive compounds and infectious disease agents, used in connection with our work. The extent and character of governmental
regulation that might result from future legislation or administrative action cannot be accurately predicted.
Intellectual Property
The future success of our business will partly depend on our ability to maintain market exclusivity in the United States and important international
markets for Gencaro, and for other products or product candidates that we may acquire or develop. We will rely on statutory protection, patent protection,
trade secrets, know-how, and in-licensing of technology rights to maintain protection for our products.
We believe that both patent protection and data exclusivity statutes will give Gencaro market exclusivity in the U.S. and in major international markets.
If approved by the FDA or international regulatory agencies, Gencaro will qualify as a New Chemical Entity, or NCE, as it has never received regulatory
approval in any jurisdiction. As an NCE, Gencaro will enjoy market exclusivity in the United States and most international markets under data exclusivity
statutes. These laws provide for an exclusivity period beginning from regulatory approval, during which any generic competitor is barred from submitting an
application that relies on the data that has been submitted in connection with the approval of the NCE. In the U.S., the Hatch-Waxman Act provides for an
initial period of four or five years from approval of the NCE, during which a generic application attempting to rely on the data submitted for the NCE cannot
be filed with the FDA. This period can be extended under certain circumstances, and we believe that the maximum period of exclusivity under these
provisions is seven and one-half years from FDA approval, as discussed below.
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Many international markets have data exclusivity statutes that are analogous to Hatch-Waxman and often more protective. The analogous statute in the
European Medicines Evaluation Agency will, in general, provide Gencaro with a minimum of ten years of protection before such a generic application may be
approved. Protection under Hatch-Waxman and other data exclusivity statutes is sometimes considered superior to patent protection, as the generic cannot be
marketed during the period of exclusivity, thus eliminating the need to initiate patent infringement litigation with its accompanying risks and costs.
In addition to protection under data exclusivity statutes, we believe that Gencaro's patent portfolio provide alternative protection of market exclusivity.
We have been granted patents in the United States and Europe that claim the use of Gencaro with the genetic polymorphisms of the ß1 and a2C receptors that
predict Gencaro response. We believe that this patent strategy may effectively serve to exclude generic competition because of the threat of patent litigation.
Consequently, if our patent strategy is successful, we believe that the possibility of generic competition with Gencaro will be significantly reduced or
eliminated until at least the expiration of these patents, which would be no earlier than 2026 in the U.S and into 2025 in Europe. In addition, we believe that if
Gencaro is approved, the Gencaro patents will be eligible for patent term extension based on our current clinical trial plans which, if granted in the U.S., may
provide market exclusivity in the U.S. into 2029, and if granted in Europe could provide market exclusivity into 2030. We also believe that the initial period
of statutory exclusivity for Gencaro in the U.S. may be extended to seven and one-half years from approval, under a special Hatch-Waxman provision that
permits an automatic 30-month extension of the exclusivity period by pursuing litigation against any company attempting to enter the market with a generic
for a drug that is covered by a composition of matter or method of use patent.
We also own or have rights in a number of patents and patent applications relating to a number of pre-clinical and clinical candidate molecules,
including rNAPc2. We estimate that patents for rNAPc2 covering use as a treatment for hemorrhagic fever viruses will expire no earlier than 2023.
In some cases, certain of the U.S. patents may be entitled to an extension of their term and certain European patents may be entitled to supplemental
protection in one or more countries in Europe. The length of any such extension, if an extension is granted, will vary by country. We cannot predict whether
any such extensions will be granted.
Employees
As of December 31, 2011, we had 14 employees, of which 11 were full-time employees. Most of these employees operate out of the Broomfield,
Colorado location while one operates from a home-based office in another state. None of our employees are represented by any collective bargaining unit. We
believe that we maintain good relations with our employees.
Corporate Information
On January 27, 2009, we completed a business combination (the Merger) with ARCA Colorado in accordance with the terms of that Agreement and
Plan of Merger and Reorganization, dated September 24, 2008, and amended on October 28, 2008 in which a wholly-owned subsidiary of Nuvelo, Inc.
merged with and into ARCA Colorado, with ARCA Colorado continuing after the Merger as the surviving corporation and a wholly-owned subsidiary of
Nuvelo, Inc. Immediately following the Merger, we changed our name from Nuvelo, Inc. to ARCA biopharma, Inc. Nuvelo was originally incorporated as
Hyseq, Inc. in Illinois in 1992 and reincorporated in Nevada in 1993. On January 31, 2003, Nuvelo merged with Variagenics, Inc., a publicly traded Delaware
corporation based in Massachusetts, and, in connection with the merger, changed its name to Nuvelo, Inc. On March 25, 2004, Nuvelo was reincorporated
from Nevada to Delaware. On January 27, 2009, in connection with the Merger with ARCA Colorado described above, Nuvelo changed its name to ARCA
biopharma, Inc. Our principal offices are located in Broomfield, Colorado.
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We file our annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K pursuant to Section 13(a) or 15(d) of the
Securities Exchange Act of 1934 electronically with the SEC. The public may read or copy any materials that have been filed with the SEC at the SEC's
Public Reference Rooms at 100 F Street, N.E., Washington, D.C. 20549 on official business days during the hours of 10:00 a.m. and 3:00 p.m. The public
may obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330. The SEC maintains an Internet site that
contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC. The address of that site is
http://www.sec.gov.
You may obtain a free copy of our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to
those reports on our website at http://www.arcabiopharma.com on the earliest practicable date following the filing with the SEC or by contacting the Investor
Relations Department at our corporate office by calling (720) 940-2200. Information found on our website is not incorporated by reference into this report.
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Item 1A.
Risk Factors
An investment in ARCA's securities involves certain risks, including those set forth below and elsewhere in this report. In addition to the risks set forth
below and elsewhere in this report, other risks and uncertainties not known to ARCA, that are beyond its control or that ARCA deems to be immaterial may
also materially adversely affect ARCA's business operations. You should carefully consider the risks described below as well as other information and data
included in this report.
Risks Related to Our Business and Financial Condition
Our management and our independent registered public accountants, in their report on our financial statements as of and for the year ended
December 31, 2011, have concluded that due to our need for additional capital, and the uncertainties surrounding our ability to raise such funding,
substantial doubt exists as to our ability to continue as a going concern.
Our audited financial statements for the fiscal year ended December 31, 2011 were prepared assuming that we will continue as a going concern. The
going concern basis of presentation assumes that we will continue in operation for the foreseeable future and will be able to realize our assets and discharge
our liabilities and commitments in the normal course of business and do not include any adjustments to reflect the possible future effects on the recoverability
and classification of assets or the amounts and classification of liabilities that may result from our inability to continue as a going concern. Our management
and our independent registered public accountants have concluded that due to our need for additional capital, and the uncertainties surrounding our ability to
raise such funding, substantial doubt exists as to our ability to continue as a going concern. We may be forced to reduce our operating expenses and raise
additional funds to meet our working capital needs, principally through the additional sales of our securities or debt financings. However, we cannot guarantee
that will be able to obtain sufficient additional funds when needed or that such funds, if available, will be obtainable on terms satisfactory to us. If we are
unable to raise sufficient additional capital or complete a strategic transaction, we may be unable to continue to fund our operations, develop Gencaro or our
other product candidates, or realize value from our assets and discharge our liabilities in the normal course of business. These uncertainties raise substantial
doubt about our ability to continue as a going concern. If we become unable to continue as a going concern, we may have to liquidate our assets, and might
realize significantly less than the values at which they are carried on our financial statements, and stockholders may lose all or part of their investment in our
common stock.
We will need to raise substantial additional funds through the public or private debt and equity securities, from government funding or complete one or
more strategic transactions, to continue development of Gencaro. If we are unable to raise such financing or complete such a transaction, we may not be
able to continue operations.
In light of the expected development timeline to potentially obtain FDA approval for Gencaro, if at all, the substantial additional costs associated with
the development of Gencaro, including the costs associated with the planned AF clinical trial, the substantial cost of commercializing Gencaro, if it is
approved, we will need to raise substantial additional funding through public or private debt or equity transactions or a strategic combination or partnership, or
government funding. If we are delayed in obtaining funding or are unable to complete a strategic transaction, we may discontinue our development activities
on Gencaro or discontinue our operations. Even if we are able to fund continued development and Gencaro is approved, we expect that we will need to
complete a strategic transaction or raise substantial additional funding through public or private debt or equity securities to successfully commercialize
Gencaro.
We currently believe our cash and cash equivalents balance as of December 31, 2011 will be sufficient to fund our operations, at our current cost
structure through September 30, 2012. As a result of the significant additional required development of Gencaro, including the additional clinical trials, we
may not be able to raise sufficient capital on acceptable terms, or at all, to continue development of Gencaro or to continue operation and
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may not be able to execute any strategic transaction. We are unable to assert that our current cash and cash equivalents are sufficient to fund operations
beyond that date, and as a result, there is substantial doubt about our ability to continue as a going concern beyond September 30, 2012. Changing
circumstances may cause us to consume capital significantly faster or slower than we currently anticipate. We have based these estimates on assumptions that
may prove to be wrong, and we could exhaust our available financial resources sooner than we currently anticipate.
Our liquidity, and our ability to raise additional capital or complete any strategic transaction, depends on a number of factors, including, but not limited
to, the following:
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•
•
•
•
•
•
•
the costs and timing for additional clinical trials in order to gain possible FDA approval for Gencaro;
the market price of our stock and the availability and cost of additional equity capital from existing and potential new investors;
our ability to retain the listing of our common stock on the Nasdaq Capital Market;
general economic and industry conditions affecting the availability and cost of capital;
potential receipt of government or third party funding to further develop Gencaro or rNAPc2;
our ability to control costs associated with our operations;
the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; and
the terms and conditions of our existing collaborative and licensing agreements.
The sale of additional equity or convertible debt securities would likely result in substantial dilution to our stockholders. If we raise additional funds
through the incurrence of indebtedness, the obligations related to such indebtedness would be senior to rights of holders of our capital stock and could contain
covenants that would restrict our operations. We also cannot predict what consideration might be available, if any, to us or our stockholders, in connection
with any strategic transaction. Should strategic alternatives or additional capital not be available to us in the near term, or not be available on acceptable terms,
we may be unable to realize value from our assets and discharge our liabilities in the normal course of business which may, among other alternatives, cause us
to further delay, substantially reduce or discontinue operational activities to conserve our cash resources.
If we are not able to maintain the requirements for listing on the Nasdaq Capital Market, we could be delisted, which could have a materially adverse
effect on our ability to raise additional funds as well as the price and liquidity of our common stock.
Our common stock is currently listed on The NASDAQ Capital Market. To maintain the listing of our common stock on The NASDAQ Capital Market
we are required to meet certain listing requirements, including, among others, either: (i) a minimum closing bid price of $1.00 per share, a market value of
publicly held shares (excluding shares held by our executive officers, directors and 10% or more stockholders) of at least $1 million and stockholders' equity
of at least $2.5 million; or (ii) a minimum closing bid price of $1.00 per share, a market value of publicly held shares (excluding shares held by our executive
officers, directors and 10% or more stockholders) of at least $1 million and a total market value of listed securities of at least $35 million. As of March 23,
2011, the closing bid price of our common stock was $0.95 the total market value of our publicly held shares of our common stock (excluding shares held by
our executive officers, directors and 10% or more stockholders) was approximately $9.7 million and the total market value of our listed securities was
approximately $11.3 million. As of December 31, 2011, we had stockholders' equity of $5.7 million. In addition, as recently as March 7, 2012 the closing bid
price of our common stock has been as low as $0.91 per share. As of March 23, 2012 our stock has traded below the $1.00 threshold for 18 consecutive
trading days. If the closing bid price of our common stock is below $1.00 per share for 30 consecutive business days, we could be subject to delisting from
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The NASDAQ Capital Market may result in a decrease in the trading price of our common stock, lessen interest by institutions and individuals in investing in
our common stock, make it more difficult to obtain analyst coverage and make it more difficult for us to raise capital in the future.
Our failure to enter into a strategic transaction may materially and adversely affect our business.
Unless we are able to raise substantial additional funding through other means, we will need to complete a strategic transaction to continue the
development of Gencaro or our other operations. The strategic transactions that we may consider include a potential combination or partnership. Our board of
directors and management team has and will continue to devote substantial time and resources to the consideration and implementation of any such strategic
transaction. In addition, conditions in the financial markets may lead to an increased number of biotechnology companies that are also seeking to enter into
strategic transactions, which may limit our ability to negotiate favorable terms for any such transaction. Further, our current employees do not have experience
in the strategic transaction process, and our previous efforts to enter into a strategic transaction have not been successful. As a result of these and other factors,
there is substantial risk that we may not be able to complete a strategic transaction on favorable terms, or at all. The failure to complete a strategic transaction
may materially and adversely affect our business.
We may be limited in our ability to access sufficient funding through a private equity or convertible debt offering.
Nasdaq rules impose restrictions on our ability to raise funds through a private offering of our common stock, convertible debt or similar instruments
without obtaining stockholder approval. Under Nasdaq rules, an offering of more than 20% of our total shares outstanding for less than the greater of book or
market value requires stockholder approval unless the offering qualifies as a "public offering" for purposes of the Nasdaq rules. As of December 31, 2011, we
had 12,182,999 shares of common stock outstanding, 20% of which is 2,436,599 shares. To the extent we seek to raise funds through a private offering of
stock, convertible debt or similar instruments, we are limited in how much funding we could raise privately without requiring a stockholder vote.
In addition, we are currently subject to certain contractual rights of investors arising from our public and private equity financing transactions that limit
the nature and price of future public and private financing transactions that we may effect. For example, on April 18, 2011, we entered into separate
subscription agreements with certain institutional investors in connection with a registered direct public offering, pursuant to which we sold shares of our
common stock and warrants to purchase shares of our common stock to the investors. In connection with this transaction, we agreed that, subject to certain
exceptions, we would not, within the three year period following the closing of the offering, while the warrants are outstanding, effect or enter into an
agreement to effect any issuance of common stock or securities convertible into, exercisable for or exchangeable for common stock in a "variable rate
transaction," which means a transaction in which we issue or sell any convertible securities either (A) at a conversion price, exercise price or exchange rate or
other price that is based upon and/or varies with the trading prices of, or quotations for, the shares of common stock at any time after the initial issuance of
such convertible securities, or (B) with a conversion, exercise or exchange price that is subject to being reset at some future date after the initial issuance of
the convertible securities or upon the occurrence of the specified or contingent events directly or indirectly related to our business or the market for our
common stock. In addition, we agreed that, subject to certain exceptions, if we issue securities within one year following the closing of the offering, each
investor would have the right to purchase its pro rata share of a specified proportion of the securities in the future offering on the same terms, conditions and
price provided for in the proposed issuance of securities. In connection with this transaction we were also restricted from issuing or selling shares of our
common stock or securities convertible into our common stock for 90 days following the transaction.
Similarly, on December 21, 2011, we entered into separate subscription agreements with various institutional investors in connection with a private
placement of our common stock and warrants. We granted to
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these investors certain registration rights with respect to the shares of common stock (including common stock issuable upon exercise of the warrants). In
connection with this transaction, we agreed that, subject to certain exceptions, we would not, within the three year period following the closing of the offering,
enter into any variable rate transaction. In connection with this transaction we were also restricted from issuing or selling shares of our common stock or
securities convertible into our common stock for 45 days following the transaction.
The restrictions imposed by the terms of these offerings, and that could be imposed in future offerings, may limit our access to capital on agreeable
terms and delay or make impossible certain otherwise available equity financing opportunities and could severely restrict our access to the capital necessary to
conduct our business.
If we are not able to successfully develop, obtain FDA approval for and provide for the commercialization of Gencaro in a timely manner, we may not
be able to continue our business operations.
We currently have no products that have received regulatory approval for commercial sale. The process to develop, obtain regulatory approval for and
commercialize potential product candidates is long, complex and costly. In 2008 we submitted and the FDA accepted our NDA filing for Gencaro for the
treatment of chronic HF. In 2009 the FDA issued a CRL in which the FDA stated that it could not approve the Gencaro NDA in its current form, and specified
actions required for approval of the NDA, including conducting an additional Phase 3 clinical trial of Gencaro in patients with HF. In 2010 we reached
agreement with the FDA, through the SPA process, on the design of a clinical trial to assess the safety and efficacy of Gencaro in approximately 3,200
patients with chronic HF who have the genotype that appears to respond most favorably to Gencaro. We plan to conduct a clinical study of Gencaro in
approximately 200-400 HF patients with AF Clinical trials are typically lengthy, complex and expensive and we do not currently have the resources to fund
such a trial.
Failure to demonstrate that a product candidate, particularly Gencaro, is safe and effective, or significant delays in demonstrating such safety and
efficacy, would adversely affect our business. Failure to obtain marketing approval of Gencaro from appropriate regulatory authorities, or significant delays in
obtaining such approval, would also adversely affect our business and could, among other things, preclude us from completing a strategic transaction or
obtaining additional financing necessary to continue as a going concern.
Even if approved for sale, a product candidate must be successfully commercialized to generate value. We do not currently have the capital resources or
management expertise to commercialize Gencaro and, as a result, will need to complete a strategic transaction, or, alternatively, raise substantial additional
funds to enable commercialization of Gencaro, if it is approved. Failure to successfully provide for the commercialization of Gencaro, if it is approved, would
damage our business.
Our clinical trials for our product candidates may not yield results that will enable us to further develop our products and obtain the regulatory
approvals necessary to sell them.
We will only receive regulatory approval for our product candidates if we can demonstrate in carefully designed and conducted clinical trials that the
product candidate is safe and effective. We do not know whether any future clinical trials, including the planned AF clinical trial for Gencaro, will
demonstrate sufficient safety and efficacy to obtain the requisite regulatory approvals or will result in marketable products. Clinical trials are lengthy, complex
and expensive processes with uncertain results. We have spent, and expect to continue to spend, significant amounts of time and money in the clinical
development of our product candidates. We have never conducted a Phase 2 or Phase 3 clinical trial and do not currently have sufficient staff with the
requisite experience to do so, and we therefore expect that we will have to rely on contract research organizations to conduct certain of our clinical trials.
While certain of our employees have experience in designing and administering clinical trials, these employees have no such experience since being with us.
The results we obtain in preclinical testing and early clinical trials may not be predictive of results that are obtained in later studies. We may suffer
significant setbacks in advanced clinical trials, even after seeing promising results in earlier studies. Based on results at any stage of clinical trials, we may
decide to repeat or
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redesign a trial or discontinue development of one or more of our product candidates. If we fail to adequately demonstrate the safety and efficacy of our
products under development, we will not be able to obtain the required regulatory approvals to commercialize our product candidates, and our business,
results of operations and financial condition would be materially adversely affected.
Administering our product candidates to humans may produce undesirable side effects. These side effects could interrupt, delay or halt clinical trials of
our product candidates and could result in the FDA or other regulatory authorities denying approval of our product candidates for any or all targeted
indications.
If clinical trials for a product candidate are unsuccessful, we will be unable to commercialize the product candidate. If one or more of our clinical trials
are delayed, we will be unable to meet our anticipated development timelines. Either circumstance could cause the market price of our common stock to
decline.
We expect to rely on contract research organizations to conduct clinical trials, and as a result, will be unable to directly control the timing, conduct and
expense of clinical trials.
We expect that we, or any strategic partners, will rely primarily on third parties to conduct clinical trials, including the Gencaro AF clinical trial that we
plan to conduct. As a result, we will have less control over the conduct of the clinical trials, the timing and completion of the trials, the required reporting of
adverse events and the management of data developed through the trials than would be the case if we were relying entirely upon our own staff.
Communicating with outside parties can also be challenging, potentially leading to mistakes as well as difficulties in coordinating activities. Outside parties
may have staffing difficulties, may undergo changes in priorities or may become financially distressed, adversely affecting their willingness or ability to
conduct our trials. We may experience unexpected cost increases that are beyond our control. Problems with the timeliness or quality of the work of a contract
research organization may lead us or any strategic partner to seek to terminate the relationship and use an alternative service provider. However, making this
change may be costly and may delay ongoing trials, and contractual restrictions may make such a change difficult or impossible. Additionally, it may be
impossible to find a replacement organization that can conduct clinical trials in an acceptable manner and at an acceptable cost.
Even if we do use a contract research organization to conduct clinical trials, we will have to devote substantial resources and rely on the expertise of our
employees to manage the work being done by the contract research organization. We have never conducted a clinical trial and do not currently have sufficient
staff with the requisite experience to do so. The inability of our current staff to adequately manage any contract research organization that we hire may
exacerbate the risks associated with relying on a contract research organization.
If we encounter difficulties enrolling patients in our clinical trials, our trials could be delayed or otherwise adversely affected.
Clinical trials for our product candidates require that we identify and enroll a large number of patients with the disorder or condition under
investigation. We may not be able to enroll a sufficient number of patients to complete our clinical trials in a timely manner.
Patient enrollment is affected by factors including:
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•
•
design of the protocol;
the size of the patient population;
eligibility criteria for the study in question;
perceived risks and benefits of the drug under study;
availability of competing therapies, including the off-label use of therapies approved for related indications;
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efforts to facilitate timely enrollment in clinical trials;
the success of our personnel in making the arrangements with potential clinical trial sites necessary for those sites to begin enrolling patients;
patient referral practices of physicians;
availability of clinical trial sites; and
other clinical trials seeking to enroll subjects with similar profiles.
If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay or terminate ongoing or
planned clinical trials, either of which would have a negative effect on our business. Delays in enrolling patients in our clinical trials would also adversely
affect our ability to generate any product, milestone and royalty revenues under collaboration agreements, if any, and could impose significant additional costs
on us or on any future collaborators.
Our planned AF clinical trial will require the use of a third-party diagnostic services provider to administer the genetic test needed to identify the
patient receptor genotypes of clinical trial participants. We do not currently have a third-party diagnostic services provider identified to perform this work
for our planned AF clinical trial. If we have difficulty getting an arrangement for administering the Gencaro Test, the launch of our planned AF clinical
trial could be delayed.
The planned AF clinical trial we intend to conduct with Gencaro requires a companion test that identifies the patient's receptor genotype, or Gencaro
Test, and the trial will only enroll those patients with the receptor that has the potential for enhanced efficacy, the ß1 389 Arg/Arg receptor. Accordingly, the
planned AF clinical trial will require use of a third-party diagnostic service to perform the Gencaro Test. Previously we entered into a collaboration
arrangement with LabCorp to develop and commercials the Gencaro Test for the treatment of patients with HF. Under the terms of that collaboration, we
licensed to LabCorp certain rights to commercialize a receptor genotype diagnostic for the ß1 and a2Cpolymorphisms. We currently intend to pursue a separate
arrangement with LabCorp or another third party to provide the diagnostic services of the Gencaro Test needed to support our planned AF trial.
Obtaining an arrangement with a third party for developing or administering the Gencaro Test for the AF clinical trial could delay the launch of our
planned study.
Unless we are able to generate sufficient product revenue, we will continue to incur losses from operations and may not achieve or maintain
profitability. We are years away from commercializing a product and generating product revenue.
Our historical losses have had and will continue to have an adverse effect on our stockholders' equity and working capital, among other things. We are
years away from commercializing a product and generating any product revenue. As a result, we expect to continue to incur significant operating losses for
the foreseeable future. Even if we ultimately receive regulatory approval for Gencaro or our other product candidates, sales of such products may not generate
sufficient revenue for it to achieve or maintain profitability. Because of the numerous risks and uncertainties associated with developing therapeutic drugs, we
may experience larger than expected future losses and may never reach profitability.
We may not achieve our projected development goals in the time frames we announce and expect.
We set goals for, and make public statements regarding, the timing of certain accomplishments, such as commencement and completion of clinical
trials, the disclosure of trial results, the obtainment of regulatory approval and the sale of drug product, which we sometimes refer to as milestones. These
milestones may not be achieved, and the actual timing of these events can vary dramatically due to a number of factors such as delays or
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failures in our clinical trials, disagreements with current or future collaborative partners, the uncertainties inherent in the regulatory approval process and
manufacturing scale-up and delays in achieving manufacturing or marketing arrangements sufficient to commercialize our products. FDA approval of
Gencaro, if it occurs, is expected to require years of additional clinical development, including the completion of a new multi-year active comparator
superiority trial involving approximately 200-400 patients in a genotype-defined HF population with AF and additional clinical trials. There can be no
assurance that our clinical trials will be completed, or that we will make regulatory submissions or receive regulatory approvals as planned. If we fail to
achieve one or more of these milestones as planned, our business will be materially adversely affected.
Our product candidates are subject to extensive regulation, which can be costly and time-consuming, and unsuccessful or delayed regulatory approvals
could increase our future development costs or impair our future revenue.
The preclinical and clinical development, testing, manufacture, safety, efficacy, labeling, storage, recordkeeping, and subsequent advertising,
promotion, sale, marketing, and distribution, if approved, of our product candidates are subject to extensive regulation by the FDA and other regulatory
authorities in the United States and elsewhere. These regulations also vary in important, meaningful ways from country to country. We are not permitted to
market a potential drug in the United States until we receive approval of an NDA from the FDA. We have not received an NDA approval from the FDA for
Gencaro or any of our other product candidates. There can be no guarantees with respect to our product candidates that clinical studies will adequately support
an NDA, that the products will receive necessary regulatory approvals, or that they will prove to be commercially successful.
To receive regulatory approval for the commercial sale of any product candidates, we must demonstrate safety and efficacy in humans to the
satisfaction of regulatory authorities through preclinical studies and adequate and well-controlled clinical trials of the product candidates. This process is
expensive and can take many years, and failure can occur at any stage of the testing. Our failure to adequately demonstrate the safety and efficacy of our
product candidates will prevent regulatory approval and commercialization of such products. In 2008 we submitted and the FDA accepted our NDA filing for
Gencaro for the treatment of chronic HF. In 2009 the FDA issued a CRL in which the FDA stated that it could not approve the Gencaro NDA in its current
form, and specified actions required for approval of the NDA, including conducting an additional Phase 3 clinical trial of Gencaro in patients with HF. In
2010 we reached agreement with the FDA, through the SPA process, on the design of a clinical trial to assess the safety and efficacy of Gencaro in
approximately 3,200 patients with chronic HF who have the genotype that appears to respond most favorably to Gencaro. We are planning to conduct a
clinical study of Gencaro in approximately 200-400 HF patients with AF. This product candidate will require years of clinical development. Even if we
conduct additional studies in accordance with further FDA guidance and submit or file a new or amended NDA, the FDA may ultimately decide that the NDA
does not satisfy the criteria for approval.
In the event that we or our collaborators conduct preclinical studies that do not comply with Good Laboratory Practices or GLP or incorrectly design or
carry out human clinical trials in accordance with Good Clinical Practices or GCP or those clinical trials fail to demonstrate clinical significance, it is unlikely
that we will be able to obtain FDA approval for product development candidates. Our inability to successfully and effectively complete clinical trials for any
product candidate on schedule, or at all, will severely harm our business. Significant delays in clinical development could materially increase product
development costs or allow our competitors to bring products to market before we do, impairing our ability to effectively commercialize any future product
candidate. We do not know whether planned clinical trials will begin on time, will need to be redesigned or will be completed on schedule, if at all. Clinical
trials can be delayed for a variety of reasons, including:
•
delays or failures in obtaining regulatory authorization to commence a trial because of safety concerns of regulators relating to our product
candidates or similar product candidates of our competitors or failure to follow regulatory guidelines;
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delays or failures in obtaining clinical materials and manufacturing sufficient quantities of the product candidates for use in trials;
delays or failures in reaching agreement on acceptable terms with prospective study sites;
delays or failures in obtaining approval of our clinical trial protocol from an institutional review board, or IRB, to conduct a clinical trial at a
prospective study site;
delays in recruiting patients to participate in a clinical trial, which may be due to the size of the patient population, eligibility criteria, protocol
design, perceived risks and benefits of the drug, availability of other approved and standard of care therapies, availability of clinical trial sites;
other clinical trials seeking to enroll subjects with similar profile;
failure of our clinical trials and clinical investigators to be in compliance with the FDA's Good Clinical Practices;
unforeseen safety issues, including negative results from ongoing preclinical studies;
inability to monitor patients adequately during or after treatment;
difficulty monitoring multiple study sites; and
failure of our third-party contract research organizations, clinical site organizations and other clinical trial managers, to satisfy their contractual
duties, comply with regulations or meet expected deadlines.
In addition, any approvals we may obtain may not cover all of the clinical indications for which we seek approval or permit us to make claims of
superiority over currently marketed competitive products. Also, an approval might contain significant limitations in the form of narrow indications, warnings,
precautions or contraindications with respect to conditions of use. If the FDA determines that a risk evaluation and mitigation strategy, or REMS, is necessary
to ensure that the benefits of the drug outweigh the risks, we may be required to include as part of the NDA a proposed REMS that may include a package
insert directed to patients, a plan for communication with healthcare providers, restrictions on a drug's distribution, or a Medication Guide, to provide better
information to consumers about the drug's risks and benefits. Finally, an approval could be conditioned on our commitment to conduct further clinical trials,
which we may not have the resources to conduct or which may negatively impact our financial situation.
The manufacture and tableting of Gencaro is done by third party suppliers, who must also meet current Good Manufacturing Practices, or cGMP,
requirements and pass a pre-approval inspection of their facilities before we can obtain marketing approval.
All of our product candidates are prone to the risks of failure inherent in drug development. The results from preclinical animal testing and early human
clinical trials may not be predictive of results obtained in later human clinical trials. Further, although a new product may show promising results in
preclinical or early human clinical trials, it may subsequently prove unfeasible or impossible to generate sufficient safety and efficacy data to obtain necessary
regulatory approvals. The data obtained from preclinical and clinical studies are susceptible to varying interpretations that may delay, limit or prevent
regulatory approval, and the FDA and other regulatory authorities in the United States and elsewhere exercise substantial discretion in the drug approval
process. The numbers, size and design of preclinical studies and clinical trials that will be required for FDA or other regulatory approval will vary depending
on the product candidate, the disease or condition for which the product candidate is intended to be used and the regulations and guidance documents
applicable to any particular product candidate. The FDA or other regulators can delay, limit or deny approval of any product candidate for many reasons,
including, but not limited to:
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Side effects;
Safety and efficacy;
Defects in the design of clinical trials;
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•
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The fact that the FDA or other regulatory officials may not approve our or our third party manufacturer's processes or facilities; or
The fact that new regulations may be enacted by the FDA or other regulators may change their approval policies or adopt new regulations
requiring new or different evidence of safety and efficacy for the intended use of a product candidate.
In light of widely publicized events concerning the safety of certain drug products, regulatory authorities, members of Congress, the Government
Accountability Office, medical professionals and the general public have raised concerns about potential drug safety issues. These events have resulted in the
withdrawal of certain drug products, revisions to certain drug labeling that further limit use of the drug products and establishment of risk management
programs that may, for instance, restrict distribution of drug products. The increased attention to drug safety issues may result in a more cautious approach by
the FDA to clinical trials and approval. Data from clinical trials may receive greater scrutiny with respect to safety and the product's risk/benefit profile, which
may make the FDA or other regulatory authorities more likely to terminate clinical trials before completion, or require longer or additional clinical trials that
may result in substantial additional expense, and a delay or failure in obtaining approval or approval for a more limited indication than originally sought.
Aside from issues concerning the quality and sufficiency of submitted preclinical and clinical data, the FDA may be constrained by limited resources from
reviewing and determining the approvability of the Gencaro NDA in a timely manner.
In pursuing clinical development of Gencaro for an AF indication, we would likely be required to amend the Gencaro HF NDA or prepare a new NDA.
The FDA could approve Gencaro, but without including some or all of the prescribing information that we have requested. For instance, the FDA could
approve Gencaro for AF in a more limited patient population or included additional warnings in the drug's label. This, in turn, could substantially and
detrimentally impact our ability to successfully commercialize Gencaro and effectively protect our intellectual property rights in Gencaro.
If our product candidates receive regulatory approval, we would be subject to ongoing regulatory obligations and restrictions, which may result in
significant expenses and limit our ability to develop and commercialize other potential products.
If a product candidate of ours is approved by the FDA or by another regulatory authority, we would be held to extensive regulatory requirements over
product manufacturing, testing, distribution, labeling, packaging, adverse event reporting and other reporting to regulatory authorities, storage, advertising,
marketing, promotion, distribution, and record keeping. Regulatory approvals may also be subject to significant limitations on the indicated uses or marketing
of the product candidates. Potentially costly follow-up or post-marketing clinical studies may be required as a condition of approval to further substantiate
safety or efficacy, or to investigate specific issues of interest to the regulatory authority. Previously unknown problems with the product candidate, including
adverse events of unanticipated severity or frequency, may result in additional regulatory controls or restrictions on the marketing or use of the product or the
need for post marketing studies, and could include suspension or withdrawal of the products from the market.
Furthermore, our third-party manufacturers and the manufacturing facilities that they use to make our product candidates are regulated by the FDA.
Quality control and manufacturing procedures must continue to conform to cGMP after approval. Drug manufacturers and their subcontractors are required to
register their facilities and products manufactured annually with the FDA and certain state agencies and are subject to periodic unannounced inspections by
the FDA, state and/or other foreign authorities. Any subsequent discovery of problems with a product, or a manufacturing or laboratory facility used by us or
our collaborators, may result in restrictions on the product, or on the manufacturing or laboratory facility, including a withdrawal of the drug from the market
or suspension of manufacturing. Any changes to an approved product, including the way it is manufactured or promoted, often require FDA approval before
the product, as modified, can be marketed. We and our third-party manufacturers will also be subject to ongoing FDA requirements for submission of safety
and other post-market information.
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The marketing and advertising of our drug products by our collaborators or us will be regulated by the FDA, certain state agencies or foreign regulatory
authorities. Violations of these laws and regulations, including promotion of our products for unapproved uses or failing to disclose risk information, are
punishable by criminal and civil sanctions and may result in the issuance of enforcement letters or other enforcement action by the FDA, U.S. Department of
Justice, state agencies, or foreign regulatory authorities that could jeopardize our ability to market the product.
In addition to the FDA, state or foreign regulations, the marketing of our drug products by us or our collaborators will be regulated by federal, state or
foreign laws pertaining to health care "fraud and abuse," such as the federal anti-kickback law prohibiting bribes, kickbacks or other remuneration for the
order or recommendation of items or services reimbursed by federal health care programs. Many states have similar laws applicable to items or services
reimbursed by commercial insurers. Violations of these laws are punishable by criminal and civil sanctions, including, in some instances, imprisonment and
exclusion from participation in federal and state health care programs, including the Medicare, Medicaid and Veterans Affairs healthcare programs. Because
of the far-reaching nature of these laws, we may be required to discontinue one or more of our practices to be in compliance with these laws. Health care fraud
and abuse regulations are complex, and even minor irregularities can potentially give rise to claims that a statute or prohibition has been violated. Any
violations of these laws, or any action against us for violations of these laws, even if we successfully defend against it, could have a material adverse effect on
our business, financial condition and results of operations.
We could also become subject to false claims litigation under federal statutes, which can lead to civil money penalties, restitution, criminal fines and
imprisonment, and exclusion from participation in Medicare, Medicaid and other federal and state health care programs. These false claims statutes include
the False Claims Act, which allows any person to bring a suit on behalf of the federal government alleging submission of false or fraudulent claims, or
causing to present such false or fraudulent claims, under federal programs or contracts claims or other violations of the statute and to share in any amounts
paid by the entity to the government in fines or settlement. These suits against pharmaceutical companies have increased significantly in volume and breadth
in recent years. Some of these suits have been brought on the basis of certain sales practices promoting drug products for unapproved uses. This new growth
in litigation has increased the risk that a pharmaceutical company will have to defend a false claim action, pay fines or restitution, or be excluded from the
Medicare, Medicaid, Veterans Affairs and other federal and state healthcare programs as a result of an investigation arising out of such action. We may
become subject to such litigation and, if we are not successful in defending against such actions, those actions may have a material adverse effect on our
business, financial condition and results of operations. We could also become subject to false claims litigation and consumer protection claims under state
statutes, which also could lead to civil monetary penalties, restitution, criminal fines and imprisonment, and exclusion from participation in state health care
programs.
Of note, over the past few years there has been an increased focus on the sales and marketing practices of the pharmaceutical industry at both the
federal and state level. Additionally, the law or regulatory policies governing pharmaceuticals may change. New statutory requirements may be enacted or
additional regulations may be adopted that could prevent or delay regulatory approval of our product candidates or limit our ability to commercialize our
products. We cannot predict the likelihood, nature or extent of adverse government regulation that may arise from future legislation or administrative action,
either in the U.S. or elsewhere.
If we, our collaborators or our third-party manufacturers fail to comply with applicable continuing regulatory requirements, our business could be
seriously harmed because a regulatory agency may:
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issue untitled or warning letters;
suspend or withdraw our regulatory approval for approved products;
seize or detain products or recommend a product recall of a drug or medical device, or issue a mandatory recall of a medical device;
refuse to approve pending applications or supplements to approved applications filed by us;
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suspend our ongoing clinical trials;
restrict our operations, including costly new manufacturing requirements, or restrict the sale, marketing and/or distribution of our products;
seek an injunction;
pursue criminal prosecutions;
close the facilities of our contract manufacturers; or
impose civil or criminal penalties.
We are will need to establish a collaborative arrangement with a third-party diagnostics services provider to obtain marketing clearance or approval of
the companion Gencaro Test. There is no guarantee that the FDA will grant timely clearance or approval of the Gencaro Test, if at all, and failure to
obtain such timely clearance or approval would adversely affect our ability to market Gencaro.
The drug label we intend to seek for Gencaro would identify the patient receptor genotype for which the drug is approved. Accordingly, we believe
developing a Gencaro Test that is simple to administer and widely available will be critical to the successful commercialization of Gencaro and also to the
ability to conduct our planned AF clinical trial.
The Gencaro Test will be subject to regulation by the FDA and by comparable agencies in various foreign countries. The process of complying with the
requirements of the FDA and comparable agencies is costly, time consuming and burdensome.
Despite the time and expense expended, regulatory clearance or approval is never guaranteed. If regulatory clearance or approval is delayed, or if a
third-party diagnostic services provider is unable to obtain FDA approval of the Gencaro Test at all or in parallel with the approval of Gencaro, or is unable to
commercialize the test successfully and in a manner that effectively supports the commercial efforts for Gencaro, or if the information concerning the
differential response to Gencaro resulting from certain genetic variation is not included in the approval label for Gencaro, our planned AF clinical trial and the
commercial launch of Gencaro may be significantly and adversely affected.
Reliance on third parties to commercialize Gencaro could negatively impact our business. If we are required to establish a direct sales force in the U.S.
and are unable to do so, our business may be harmed.
Commercialization of Gencaro, particularly the establishment of a sales organization, will require substantial additional capital resources. We currently
intend to pursue a strategic partnership alternative for the commercialization of Gencaro, if it is approved, and we have suspended our efforts to build internal
sales, marketing and distribution capabilities. If we elect to rely on third parties to sell Gencaro and any other products, then we may receive less revenue than
if we sold such products directly. In addition, we may have little or no control over the sales efforts of those third parties.
If we are unable to complete a strategic transaction, we would be unable to commercialize Gencaro or any other product candidate without substantial
additional capital. Even if such capital were secured, we would be required to build internal sales, marketing and distribution capabilities to market Gencaro in
the U.S. None of our current employees have experience in establishing and managing a sales force.
In the event we are unable to sell Gencaro and other selected product candidates, either directly or through third parties via a strategic transaction, the
commercialization of Gencaro, if it is approved, may be delayed indefinitely.
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Future sales of Gencaro may suffer if its marketplace acceptance is negatively affected by the Gencaro Test.
The Gencaro Test is an important component of the commercial strategy for Gencaro in addition to being required to proceed with our planned AF trial.
We believe that the Gencaro Test helps predict patient response to Gencaro, and that this aspect of the drug is important to its ability to compete effectively
with current therapies. The Gencaro Test adds an additional step in the prescribing process, an additional cost for the patient and payors, the risk that the test
results may not be rapidly available and the possibility that it may not be available at all to hospitals and medical centers. Although we anticipate that
Gencaro, if approved in a timely manner, would be the first genetically-targeted cardiovascular drug, Gencaro will be one of a number of successful drugs in
the beta-blocker class currently on the market. Prescribers may be more familiar with these other beta-blockers, and may be resistant to prescribing Gencaro
as an AF or HF therapy. Any one of these factors could affect prescriber behavior, which in turn may substantially impede market acceptance of the Gencaro
Test, which could cause significant harm to Gencaro's ability to compete, and in turn harm our business.
We are dependent on our key personnel.
The success of our business is highly dependent on the principal members of our board of directors and executive management, including our Chairman
of the Board, Richard B. Brewer and our President and Chief Executive Officer, Michael R. Bristow. The loss of the services of any such individual might
seriously harm our product development, partnering and financing efforts. Recruiting and training personnel with the requisite skills is challenging and we
compete for talent with companies that are larger and have more financial resources.
We have no manufacturing capacity which puts us at risk of lengthy and costly delays of bringing our products to market.
We do not currently operate manufacturing facilities for clinical or commercial production of our product candidates, including their active
pharmaceutical ingredients, or API. We have no experience in drug formulation or manufacturing, and we lack the resources and the capabilities to
manufacture any of our product candidates on a clinical or commercial scale. We do not intend to develop facilities for the manufacture of product candidates
for clinical trials or commercial purposes in the foreseeable future.
We have contracted with Groupe Novasep to manufacture commercial quantities of the API for Gencaro. For drug production, we have contracted with
Patheon, Inc. to manufacture the Gencaro tablets. These contract manufacturers may not perform as agreed or may not remain in the contract manufacturing
business for the time required to successfully produce, store and distribute our products. In addition, these manufacturers may have staffing difficulties, may
not be able to manufacture our products on a timely basis or may become financially distressed. In the event of errors in forecasting production quantities
required to meet demand, natural disaster, equipment malfunctions or failures, technology malfunctions, strikes, lock-outs or work stoppages, regional power
outages, product tampering, war or terrorist activities, actions of regulatory authorities, business failure, strike or other difficulty, we may be unable to find an
alternative third-party manufacturer in a timely manner and the production of our product candidates would be interrupted, resulting in delays and additional
costs, which could impact our ability to commercialize and sell our product candidates.
We or our contract manufacturers may also fail to achieve and maintain required manufacturing standards, which could result in patient injury or death,
product recalls or withdrawals, an order by governmental authorities to halt production, delays or failures in product testing or delivery, cost overruns or other
problems that could seriously hurt our business. Contract manufacturers also often encounter difficulties involving production yields, quality control and
quality assurance, as well as shortages of qualified personnel. In addition, our contract manufacturers are subject to ongoing inspections and regulation by the
FDA, the U.S. Drug Enforcement Agency and corresponding foreign and state agencies and they may fail to meet these agencies' acceptable standards of
compliance. If our contract manufacturers fail to comply with applicable governmental regulations, such as quality control, quality assurance and the
maintenance of records and documentation, we may not be able to continue production of the API or finished product. If the safety of any API or product
supplied is compromised
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due to failure to adhere to applicable laws or for other reasons, this may jeopardize our regulatory approval for Gencaro and other product candidates, and we
may be held liable for any injuries sustained as a result.
Upon the occurrence of one of the aforementioned events, the ability to switch manufacturers may be difficult for a number of reasons, including:
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•
the number of potential manufacturers is limited and we may not be able to negotiate agreements with alternative manufacturers on commercially
reasonable terms, if at all;
long lead times are often needed to manufacture drugs;
the manufacturing process is complex and may require a significant learning curve; and
the FDA must approve any replacement prior to manufacturing, which requires new testing and compliance inspections.
If a third-party diagnostics provider responsible for the Gencaro Test or certain of its third-party suppliers fail to comply with ongoing FDA or other
foreign regulatory authority requirements, or if there are unanticipated problems with the Gencaro Test, these products could be subject to restrictions or
withdrawal from use in trial or from the market.
Any medical device for which a third-party diagnostics provider obtains clearance or approval, and the manufacturing processes, reporting
requirements, post-approval clinical data and promotional activities for such product, will be subject to continued regulatory review, oversight and periodic
inspections by the FDA and other domestic and foreign regulatory bodies. With respect to the Gencaro Test, to the extent applicable, any third-party
diagnostics provider and certain of its suppliers will be required to comply with the FDA's Quality System Regulation, or QSR, and International Standards
Organization, or ISO, requirements which cover the methods and documentation of the design, testing, production, control, quality assurance, labeling,
packaging, storage and shipping of any product for which clearance or approval is obtained. Regulatory bodies, such as the FDA, enforce the QSR and other
regulations through periodic inspections. The failure by a third-party diagnostics provider, or certain of its third-party manufacturers or suppliers, as the case
may be, to comply with applicable statutes and regulations administered by the FDA and other regulatory bodies, or the failure to timely and adequately
respond to any adverse inspectional observations or product safety issues, could result in, among other things, enforcement actions. If any of these actions
were to occur, it could harm our reputation and cause product sales and profitability of Gencaro to suffer and may prevent us from generating revenue or
utilizing the Gencaro Test further in any clinical trial.
Even if regulatory clearance or approval is granted, such clearance or approval may be subject to limitations on the intended uses for which the product
may be marketed and reduce our potential to successfully commercialize the product and generate revenue from the product.
A third-party diagnostics provider may need to conduct clinical trials to support current or future versions of the Gencaro Test. Delays or failures in
any such clinical trials may prevent a third-party diagnostics provider from commercializing any modified or new versions of the Gencaro Test and will
adversely affect our business, operating results and prospects.
Based on discussions with the FDA, we do not believe that additional clinical data are needed for the Gencaro Test submission. However, the FDA may
require clinical data for the Gencaro Test submission and/or future products. Initiating and completing clinical trials necessary to support 510(k)s or PMAs, if
required, for current or future products will be time consuming and expensive and the outcome uncertain. Moreover, the results of early clinical trials are not
necessarily predictive of future results, and any product we or our third party suppliers advance into clinical trials may not have favorable results in later
clinical trials.
Conducting successful clinical studies may require the enrollment of large numbers of patients, and suitable patients may be difficult to identify and
recruit. Patient enrollment in clinical trials and completion of patient
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participation and follow-up depends on many factors, including: the size of the patient population; the number of patients to be enrolled; the nature of the trial
protocol; the attractiveness of, or the discomforts and risks associated with, the treatments received by enrolled subjects; the availability of appropriate clinical
trial investigators, support staff, and proximity of patients to clinical sites; and the patients' ability to meet the eligibility and exclusion criteria for
participation in the clinical trial and patient compliance. For example, patients may be discouraged from enrolling in clinical trials if the trial protocol requires
them to undergo extensive post-treatment procedures or follow-up to assess the safety and effectiveness of our products or if they determine that the
treatments received under the trial protocol are not attractive or involve unacceptable risks or discomforts. In addition, patients participating in clinical trials
may die before completion of the trial or suffer adverse medical events unrelated to investigational products.
Development of sufficient and appropriate clinical protocols to demonstrate safety and efficacy are required, and we or the third-party diagnostics
provider may not adequately develop such protocols to support clearance and approval. The trials will require the submission and approval of an
investigational device exemption, or IDE, from the FDA. There is no guarantee that the FDA will approve the third-party diagnostics provider's or our future
IDE submissions. Further, the FDA may require them or us to submit data on a greater number of patients than originally anticipated and/or for a longer
follow-up period or change the data collection requirements or data analysis applicable to our clinical trials. Delays in patient enrollment or failure of patients
to continue to participate in a clinical trial may cause an increase in costs and delays in the approval and attempted commercialization of future products or
result in the failure of the clinical trial. In addition, despite considerable time and expense invested in such clinical trials, the FDA may not consider the data
to be adequate to demonstrate safety and efficacy. Such increased costs and delays or failures could adversely affect our or our third party suppliers' business,
operating results and prospects.
Transitioning from a developmental stage company will require successful completion of a number of steps, many of which are outside of our control
and, consequently, we can provide no assurance of our successful and timely transition from a developmental stage company.
We are a development stage biopharmaceutical company with a limited operating history. To date we have not generated any product revenue and have
historically funded our operations through investment capital. Our future growth depends on our ability to emerge from the developmental stage and
successfully commercialize or provide for the commercialization of Gencaro and our other product candidates, which in turn, will depend, among other
things, on our ability to:
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•
conduct additional clinical trials and develop and obtain regulatory approval for Gencaro or other product candidates;
successfully partner a companion genetic test with the commercial launch of Gencaro;
enter into a strategic transaction enabling the continued development and commercialization of Gencaro, or alternatively, raise significant
additional capital to enable these activities;
pursue additional indications for Gencaro and develop other product candidates, including other cardiovascular therapies; and
obtain commercial quantities of Gencaro or other product candidates at acceptable cost levels.
Any one of these factors or other factors discussed in this report could affect our ability to successfully commercialize Gencaro and other product
candidates, which could impact our ability to earn sufficient revenues to transition from a developmental stage company and continue our business.
If approved by the FDA, Gencaro will be entering a competitive marketplace and may not succeed.
Gencaro is a new type of beta-blocker and vasodilator being developed for AF. While we anticipate that this drug, if approved, would be the first
genetically-targeted cardiovascular drug, and potentially the only beta-blocker approved for AF, Gencaro will be one of a number of successful drugs in the
beta-blocker class currently
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on the market. For example, currently, there are three branded beta-blockers indicated for chronic HF in New York Health Association, or NYHA, class II-IV
patients: Toprol-XL (once-a-day formulation), Coreg and Coreg CR (once-a-day). Toprol-XL and Coreg have generic equivalents commercially available in
the U.S. (metoprolol succinate and carvedilol, respectively). The price of the generic forms of these drugs will be less than the anticipated price of Gencaro, if
approved. As a result, Gencaro may not be successful in competing against these existing drugs.
Our commercial opportunity may be reduced or eliminated if competitors develop and commercialize products that are safer, more effective, have fewer
side effects, are more convenient or are less expensive than Gencaro. If products with any of these properties are developed, or any of the existing products
are better marketed, then prescriptions of Gencaro by physicians and patient use of Gencaro could be significantly reduced or rendered obsolete and
noncompetitive. Further, public announcements regarding the development of any such competing drugs could adversely affect the market price of our
common stock and the value of our assets.
Future sales of our products may suffer if they are not accepted in the marketplace by physicians, patients and the medical community.
Gencaro or our other product candidates may not gain market acceptance among physicians, patients and the medical community. The degree of market
acceptance of Gencaro or our other product candidates will depend on a number of factors, such as its effectiveness and tolerability, as compared with
competitive drugs. Also, prevalence and severity of side-effects could negatively affect market acceptance of Gencaro or our other product candidates. Failure
to achieve market acceptance of Gencaro would significantly harm our business.
If we are unable to obtain acceptable prices or adequate reimbursement from third-party payors for Gencaro, or any other product candidates that we
may seek to commercialize, then our revenues and prospects for profitability will suffer.
Our or any strategic partner's ability to commercialize Gencaro, or any other product candidates that we may seek to commercialize, is highly
dependent on the extent to which coverage and reimbursement for these product candidates will be available from:
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governmental payors, such as Medicare and Medicaid;
private health insurers, including managed-care organizations; and
other third-party payors.
Many patients will not be capable of paying for our potential products themselves and will rely on third-party payors to pay for their medical needs. A
primary current trend in the U.S. health care industry is toward cost containment. Large private payors, managed-care organizations, group purchasing
organizations and similar organizations are exerting increasing influence on decisions regarding the use of, and reimbursement levels for, particular
treatments. Such third-party payors, including Medicare, are challenging the prices charged for medical products and services, and many third-party payors
limit reimbursement for newly approved health care products.
Cost-control initiatives could decrease the price we might establish for products, which could result in product revenues lower than anticipated. If the
prices for our product candidates decrease, or if governmental and other third-party payors do not provide adequate coverage and reimbursement levels, then
our revenue and prospects for profitability will suffer.
Health care reform measures could materially and adversely affect our business.
The business and financial condition of pharmaceutical and biotechnology companies are affected by the efforts of governmental and third-party payors
to contain or reduce the costs of health care. The U.S. Congress has
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enacted legislation to reform the health care system. While we anticipate that this legislation may, over time, increase the number of patients who have
insurance coverage for pharmaceutical products, it also imposes cost containment measures that may adversely affect the amount of reimbursement for
pharmaceutical products. These measures include increasing the minimum rebates for products covered by Medicaid programs and extending such rebates to
drugs dispensed to Medicaid beneficiaries enrolled in Medicaid managed care organizations as well as expansion of the 340(B) Public Health Services drug
discount program. In addition, such legislation contains a number of provisions designed to generate the revenues necessary to fund the coverage expansion,
including new fees or taxes on certain health-related industries, including medical device manufacturers. Beginning in 2013, each medical device
manufacturer will have to pay an excise tax (or sales tax) in an amount equal to 2.3% of the price for which such manufacturer sells its medical devices. Such
excise taxes may impact any potential sales of the Gencaro Test if it is approved for marketing. In foreign jurisdictions there have been, and we expect that
there will continue to be, a number of legislative and regulatory proposals aimed at changing the health care system. For example, in some countries other
than the United States, pricing of prescription drugs is subject to government control and we expect to see continued efforts to reduce healthcare costs in
international markets.
Some states are also considering legislation that would control the prices of drugs, and state Medicaid programs are increasingly requesting
manufacturers to pay supplemental rebates and requiring prior authorization by the state program for use of any drug for which supplemental rebates are not
being paid. Managed care organizations continue to seek price discounts and, in some cases, to impose restrictions on the coverage of particular drugs.
Government efforts to reduce Medicaid expenses may lead to increased use of managed care organizations by Medicaid programs. This may result in
managed care organizations influencing prescription decisions for a larger segment of the population and a corresponding constraint on prices and
reimbursement for drugs. It is likely that federal and state legislatures and health agencies will continue to focus on additional health care reform in the future
although we are unable to predict what additional legislation or regulation, if any, relating to the health care industry or third-party coverage and
reimbursement may be enacted in the future or what effect such legislation or regulation would have on our business. We or any strategic partner's ability to
commercialize Gencaro, or any other product candidates that we may seek to commercialize, is highly dependent on the extent to which coverage and
reimbursement for these product candidates will be available from government payors, such as Medicare and Medicaid, private health insurers, including
managed care organizations, and other third-party payors, and any change in reimbursement levels could materially and adversely affect our business. Further,
the pendency or approval of future proposals or reforms could result in a decrease in our stock price or limit our ability to raise capital or to obtain strategic
partnerships or licenses.
Our competitors may be better positioned in the marketplace and thereby may be more successful than us at developing, manufacturing and marketing
approved products.
Many of our competitors currently have significantly greater financial resources and expertise in conducting clinical trials, obtaining regulatory
approvals, managing manufacturing and marketing approved products than us. Other early-stage companies may also prove to be significant competitors,
particularly through collaborative arrangements with large and established companies. In addition, these third parties compete with us in recruiting and
retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring
therapies and therapy licenses complementary to our programs or advantageous to our business. We expect that our ability to compete effectively will depend
upon our ability to:
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successfully and rapidly complete clinical trials for any product candidates and obtain all requisite regulatory approvals in a cost-effective
manner;
build an adequate sales and marketing infrastructure, raise additional funding, or enter into strategic transactions enabling the commercialization
of our products;
develop competitive formulations of our product candidates;
attract and retain key personnel; and
identify and obtain other product candidates on commercially reasonable terms.
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If we fail to identify and license or acquire other products or product candidates, then we may be unable to expand our business, and the acquisition or
licensing of other products or product candidates may put a strain on our operations and will likely require us to seek additional financing.
One of our strategies is to license or acquire clinical-stage products or product candidates and further develop them for commercialization. The market
for licensing and acquiring products and product candidates is intensely competitive and many of our competitors may have greater resources than us. If we
undertake any additional acquisitions, whether of product candidates or other biopharmaceutical companies, the process of integrating an acquired product
candidate or complementary company into our business may put a strain on our operations, divert personnel, financial resources and management's attention.
In 2012, we expect our research and development activities will be dedicated to Gencaro. If we are not able to substantially expand our research and
development efforts, or identify, or license or acquire other products or product candidates or complete future acquisitions, then we will likely be unable
expand our pipeline of product candidates. In addition, any future acquisition would give rise to additional operating costs and will likely require us to seek
additional financing. Future acquisitions could result in additional issuances of equity securities that would dilute the ownership of existing stockholders.
Future acquisitions could also result in the incurrence of debt, contingent liabilities or the amortization of expenses related to other intangible assets, any of
which could adversely affect our operating results.
We would be subject to applicable regulatory approval requirements of the foreign countries in which we market our products, which are costly and
may prevent or delay us from marketing our products in those countries.
In addition to regulatory requirements in the United States, we would be subject to the regulatory approval requirements in each foreign country where
we market our products. In addition, we might be required to identify one or more collaborators in these foreign countries to develop, seek approval for and
manufacture our products and any companion genetic test for Gencaro. If we decide to pursue regulatory approvals and commercialization of our product
candidates internationally, we may not be able to obtain the required foreign regulatory approvals on a timely basis, if at all, and any failure to do so may
cause us to incur additional costs or prevent us from marketing our products in foreign countries, which may have a material adverse effect on our business,
financial condition and results of operations.
If our internal control over financial reporting is not considered effective, our business and stock price could be adversely affected.
Section 404 of the Sarbanes-Oxley Act of 2002 requires us to evaluate the effectiveness of our internal control over financial reporting as of the end of
each fiscal year, and to include a management report assessing the effectiveness of our internal control over financial reporting in our annual report on Form
10-K for that fiscal year. Our management, including our chief executive officer and chief financial officer, does not expect that our internal control over
financial reporting will prevent all error and all fraud. During the first quarter of 2011 there was a reduction in our workforce which included personnel
involved in financial reporting and our internal control processes. Though the process and design of our internal controls over financial reporting have not
been altered, the reduction in staff may have limited our ability to properly segregate internal control procedures which could result in deficiencies or material
weaknesses in our internal controls in the future. A control system, no matter how well designed and operated, can provide only reasonable, not absolute,
assurance that the control system's objectives will be met. Further, the design of a control system must reflect the fact that there are resource constraints, and
the benefits of controls must be considered relative to their costs. Because of the inherent limitations in all control systems, no evaluation of controls can
provide absolute assurance that all control issues and instances of fraud involving a company have been, or will be, detected. The design of any system of
controls is based in part on certain assumptions about the likelihood of future events, and we cannot assure you that any design will succeed in achieving its
stated goals under all potential future conditions. Over time, controls may become ineffective because of changes in conditions or deterioration in the degree
of compliance with policies or procedures. Because of the inherent limitations in a cost-effective control system, misstatements due to error or
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fraud may occur and not be detected. We cannot assure you that we or our independent registered public accounting firm will not identify a material weakness
in our internal control over financial reporting in the future. A material weakness in our internal control over financial reporting would require management to
consider our internal control over financial reporting as ineffective. If our internal control over financial reporting is not considered effective, we may
experience a loss of public confidence, which could have an adverse effect on our business and on the market price of our common stock.
Risks Related to Intellectual Property and Other Legal Matters
If product liability lawsuits are successfully brought against us, then we will incur substantial liabilities and may be required to limit
commercialization of Gencaro or other product candidates.
We face product liability exposure related to the testing of our product candidates in human clinical trials, and may face exposure to claims by an even
greater number of persons once we begin marketing and distributing our products commercially. If we cannot successfully defend against product liability
claims, then we will incur substantial liabilities.
Regardless of merit or eventual outcome, liability claims may result in:
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decreased demand for our products and product candidates;
injury to our reputation;
withdrawal of clinical trial participants;
costs of related litigation;
substantial monetary awards to patients and others;
loss of revenues; and
the inability to commercialize our products and product candidates.
We have obtained limited product liability insurance coverage. Such coverage, however, may not be adequate or may not continue to be available to us
in sufficient amounts or at an acceptable cost, or at all. We may not be able to obtain commercially reasonable product liability insurance for any product
candidate.
Defending against claims relating to improper handling, storage or disposal of hazardous chemicals, radioactive or biological materials could be time
consuming and expensive.
Our research and development of product candidates may involve the controlled use of hazardous materials, including chemicals, radioactive and
biological materials. We cannot eliminate the risk of accidental contamination or discharge and any resultant injury from the materials.
Various laws and regulations govern the use, manufacture, storage, handling and disposal of hazardous materials. We may be sued or be required to pay
fines for any injury or contamination that results from our use or the use by third parties of these materials. Compliance with environmental laws and
regulations may be expensive, and current or future environmental regulations may impair our research, development and production efforts.
The loss of any rights to market key products would significantly impair our operating results.
We have licensed from CPEC, who has licensed rights in Gencaro from Bristol Meyers Squibb (BMS) the exclusive rights to Gencaro for all
therapeutic and diagnostic uses in any country until the later of (i) 10 years from the first commercial sale of Gencaro in such country, or (ii) the termination
of our commercial exclusivity in such country. This license includes a sublicense to us from BMS. We are obligated to use commercially reasonable efforts to
develop and commercialize Gencaro, including obtaining regulatory approvals. Our ability to
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develop and commercialize Gencaro is dependent on numerous factors, including some factors that are outside of our control. CPEC has the right to terminate
our license if we materially breach our obligations under the license agreement and fail to cure any such breach within the terms of the license.
If our license agreement with CPEC is terminated for reasons related to non-payment of fees, or for any other breach, then we would have no further
rights to develop and commercialize Gencaro for any indication. The termination of this license, or of any other agreement which enables us to market a key
product or product candidate, could significantly and adversely affect our business.
Certain intellectual property licensed by us is the subject of additional licensing arrangements to which the party that has licensed rights to us is subject.
If such parties were to breach the terms of such licenses or such licenses were otherwise to terminate, our and our partners' rights to use such technology and
develop and commercialize their products such as the Gencaro Test may terminate and our business would be materially harmed.
Third parties may own or control patents or patent applications that we may be required to license to commercialize our product candidates or that
could result in litigation that would be costly and time consuming.
Our or any strategic partner's ability to commercialize Gencaro and other product candidates depends upon our ability to develop, manufacture, market
and sell these drugs without infringing the proprietary rights of third parties. A number of pharmaceutical and biotechnology companies, universities and
research institutions have or may be granted patents that cover technologies similar to the technologies owned by or licensed to us. We may choose to seek, or
be required to seek, licenses under third party patents, which would likely require the payment of license fees or royalties or both. We may also be unaware of
existing patents that may be infringed by Gencaro, the genetic testing we intend to use in connection with Gencaro or our other product candidates. Because
patent applications can take many years to issue, there may be other currently pending applications that may later result in issued patents that are infringed by
Gencaro or our other product candidates. Moreover, a license may not be available to us on commercially reasonable terms, or at all.
There is a substantial amount of litigation involving patent and other intellectual property rights in the biotechnology and biopharmaceutical industries
generally. If a third party claims that we are infringing on its technology, then our business and results of operations could be harmed by a number of factors,
including:
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infringement and other intellectual property claims, even if without merit, are expensive and time-consuming to litigate and can divert
management's attention from our core business;
monetary damage awards for past infringement can be substantial;
a court may prohibit us from selling or licensing product candidates unless the patent holder chooses to license the patent to us; and
if a license is available from a patent holder, we may have to pay substantial royalties.
We may also be forced to bring an infringement action if we believe that a competitor is infringing our protected intellectual property. Any such
litigation will be costly, time-consuming and divert management's attention, and the outcome of any such litigation may not be favorable to us.
Our intellectual property rights may not preclude competitors from developing competing products and our business may suffer.
Our competitive success will depend, in part, on our ability to obtain and maintain patent protection for our inventions, technologies and discoveries,
including intellectual property that we license. The patent positions of biotechnology companies involve complex legal and factual questions, and we cannot
be certain that our patents and licenses will successfully preclude others from using our technology. Consequently, we cannot be certain that
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any of our patents will provide significant market protection or will not be circumvented or challenged and found to be unenforceable or invalid. In some
cases, patent applications in the U.S. and certain other jurisdictions are maintained in secrecy until patents issue, and since publication of discoveries in the
scientific or patent literature often lags behind actual discoveries, we cannot be certain of the priority of inventions covered by pending patent applications.
Moreover, we may have to participate in interference proceedings declared by the U.S. Patent and Trademark Office to determine priority of invention or in
opposition proceedings in a foreign patent office, any of which could result in substantial cost to us, even if the eventual outcome is favorable. There can be
no assurance that a court of competent jurisdiction would hold any claims in any issued patent to be valid. An adverse outcome could subject us to significant
liabilities to third parties, require disputed rights to be licensed from third parties or require us to cease using such technology. Regardless of merit, the listing
of patents in the FDA Orange Book for Gencaro may be challenged as being improperly listed. We may have to defend against such claims and possible
associated antitrust issues. We could also incur substantial costs in seeking to enforce our proprietary rights against infringement.
While the composition of matter patents on the compound that comprises Gencaro have expired, we hold the intellectual property concerning the
interaction of Gencaro with the polymorphisms of the ß1 and 2Creceptors. We have obtained patents that claim methods involving Gencaro after a patient's
receptor genotype has been determined. Our NDA requested a label that will include a claim that efficacy varies based on receptor genotype and a
recommendation in the prescribing information that prospective patients be tested for their receptor genotype. We believe that under applicable law, a generic
bucindolol label would likely be required to include this recommendation as it pertains directly to the safe or efficacious use of the drug. Such a label may be
considered as inducing infringement, carrying the same liability as direct infringement. If the label with the genotype information for Gencaro is not approved,
or if generic labels are not required to copy the approved label, competitors could have an easier path to introduce competing products and our business may
suffer. The approved label may not contain language covered by the patents, or we may be unsuccessful in enforcing them.
We may not be able to effectively protect our intellectual property rights in some foreign countries, as our patents are limited by jurisdiction and many
countries do not offer the same level of legal protection for intellectual property as the U.S.
We require our employees, consultants, business partners and members of our scientific advisory board to execute confidentiality agreements upon the
commencement of employment, consulting or business relationships with us. These agreements provide that all confidential information developed or made
known during the course of the relationship with us be kept confidential and not disclosed to third parties except in specific circumstances. In the case of
employees, the agreements provide that all inventions resulting from work performed for us, utilizing the property or relating to our business and conceived or
completed by the individual during employment shall be our exclusive property to the extent permitted by applicable law.
Third parties may breach these and other agreements with us regarding our intellectual property and we may not have adequate remedies for the breach.
Third parties could also fail to take necessary steps to protect our licensed intellectual property, which could seriously harm our intellectual property position.
If we are not able to protect our proprietary technology, trade secrets and know-how, then our competitors may develop competing products. Any
issued patent may not be sufficient to prevent others from competing with us. Further, we have trade secrets relating to Gencaro, and such trade secrets may
become known or independently discovered. Our issued patents and those that may issue in the future, or those licensed to us, may be challenged, opposed,
invalidated or circumvented, which could allow competitors to market similar products or limit the patent protection term of our product candidates. All of
these factors may affect our competitive position.
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If the manufacture, use or sale of our products infringe on the intellectual property rights of others, we could face costly litigation, which could cause
us to pay substantial damages or licensing fees and limit our ability to sell some or all of our products.
Extensive litigation regarding patents and other intellectual property rights has been common in the biopharmaceutical industry. Litigation may be
necessary to assert infringement claims, enforce patent rights, protect trade secrets or know-how and determine the enforceability, scope and validity of
certain proprietary rights. Litigation may even be necessary to defend disputes of inventorship or ownership of proprietary rights. The defense and prosecution
of intellectual property lawsuits, U.S. Patent and Trademark Office interference proceedings, and related legal and administrative proceedings (e.g., a
reexamination) in the U.S. and internationally involve complex legal and factual questions. As a result, such proceedings are costly and time-consuming to
pursue, and their outcome is uncertain.
Regardless of merit or outcome, our involvement in any litigation, interference or other administrative proceedings could cause us to incur substantial
expense and could significantly divert the efforts of our technical and management personnel. Any public announcements related to litigation or interference
proceedings initiated or threatened against us could cause our stock price to decline. Adverse outcomes in patent litigation may potentially subject us to
antitrust litigation which, regardless of the outcome, would adversely affect our business. An adverse determination may subject us to the loss of our
proprietary position or to significant liabilities, or require us to seek licenses that may include substantial cost and ongoing royalties. Licenses may not be
available from third parties, or may not be obtainable on satisfactory terms. An adverse determination or a failure to obtain necessary licenses may restrict or
prevent us from manufacturing and selling our products, if any. These outcomes could materially harm our business, financial condition and results of
operations.
Risks Related to Stock Price Volatility
Our stock price is expected to be volatile.
Our common stock could be subject to significant fluctuations. Market prices for securities of early-stage pharmaceutical, biotechnology and other life
sciences companies have historically been particularly volatile. Some of the factors that may cause the market price of our common stock to fluctuate include:
•
•
•
•
•
•
•
•
•
•
•
the regulatory status of Gencaro and the Gencaro Test, and whether and when they are approved for sale, if at all, and the labeling or other
conditions of use imposed by the FDA;
our ability to secure substantial additional funding or complete a strategic transaction or to complete development of and commercialize Gencaro;
potential receipt of government or third party funding to further develop Gencaro or rNAPc2;
the results of our future clinical trials and any future NDAs of our current and future product candidates;
the entry into, or termination of, key agreements, including key strategic alliance agreements;
the results and timing of regulatory reviews relating to our product candidates;
failure of any of our product candidates, if approved, to achieve commercial success;
general and industry-specific economic conditions that may affect our research and development expenditures;
the results of clinical trials conducted by others on drugs that would compete with our product candidates;
issues in manufacturing our product candidates or any approved products;
the initiation of or material developments in or the conclusion of litigation to enforce or defend any of our intellectual property rights;
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•
•
•
•
•
•
•
the loss of key employees;
the introduction of technological innovations or new commercial products by our competitors;
changes in estimates or recommendations by securities analysts, if any, who cover our common stock;
future sales of our common stock;
changes in the structure of health care payment systems;
period-to-period fluctuations in our financial results; and
our ability to retain the listing of our common stock on the Nasdaq Capital Market.
Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual
companies. These broad market fluctuations may also adversely affect the trading price of our common stock.
In the past, following periods of volatility in the market price of a company's securities, stockholders have often instituted class action securities
litigation against those companies. Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which
could significantly harm our profitability and reputation.
Future sales or the possibility of future sales of our common stock may depress the market price of our common stock.
Sales in the public market of substantial amounts of our common stock could depress prevailing market prices of our common stock. As of
December 31, 2011, 12,182,999 shares of common stock were outstanding. All of these shares are freely transferable without restriction or further registration
under the Securities Act, except for shares held by our directors, officers and other affiliates and unregistered shares held by non-affiliates. The sale of these
additional shares, or the perception that such sales may occur, could depress the market price of our common stock.
As of December 31, 2011 approximately 2.8 million shares of our common stock were issuable upon the exercise of outstanding warrants, of which
1.5 million were exercisable as of that date and 1.25 million were issued pursuant to our private placement equity transaction completed in December 2011
and will become exercisable on June 22, 2012. Once a warrant is exercised, if the shares of our common stock issued upon the exercise of any such warrant
are not available for sale in the open market without further registration under the Securities Act, then the holder can arrange for the resale of shares either by
invoking any applicable registration rights, causing the shares to be registered under the Securities Act and thus freely transferable, or by relying on an
exemption to the Securities Act. If these registration rights, or similar registration rights that may apply to securities we may issue in the future, are exercised,
it could result in additional sales of our common stock in the market, which may have an adverse effect on our stock price.
As of December 31, 2011 there were approximately 864,000 shares of our common stock which may be issued upon exercise of outstanding stock
options. If and when these options are exercised, such shares will be available for sale in the open market without further registration under the Securities Act.
The existence of these outstanding options may negatively affect our ability to complete future equity financings at acceptable prices and on acceptable terms.
The exercise of those options, and the prompt resale of shares of our common stock received, may also result in downward pressure on the price of our
common stock.
In the absence of a significant strategic transaction, we will need to raise significant additional capital to finance our capital requirements, including the
research, development and commercialization of our drug products. If future securities offerings occur, they would dilute our current stockholders' equity
interests and could reduce the market price of our common stock.
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We do not expect to pay cash dividends, and accordingly, stockholders must rely on stock appreciation for any return on their investment.
We anticipate that we will retain our earnings, if any, for future growth and therefore do not anticipate paying cash dividends in the future. As a result,
only appreciation of the price of our common stock will provide a return to stockholders. Investors seeking cash dividends should not invest in our common
stock.
We have implemented anti-takeover provisions that could discourage, prevent or delay a takeover, even if the acquisition would be beneficial to our
stockholders.
Provisions of our certificate of incorporation and bylaws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire
us, even if doing so would benefit our stockholders. These provisions:
•
•
•
•
•
establish a classified board of directors so that not all members of our board may be elected at one time;
authorize the issuance of up to 5 million additional shares of preferred stock that could be issued by our board of directors to increase the number
of outstanding shares and hinder a takeover attempt;
limit who may call a special meeting of stockholders;
prohibit stockholder action by written consent, thereby requiring all stockholder actions to be taken at a meeting of our stockholders; and
establish advance notice requirements for nominations for election to our board of directors or for proposing matters that can be acted upon at a
stockholder meeting.
Specifically, our certificate of incorporation provides that all stockholder action must be effected at a duly called meeting and not by a written consent.
The bylaws provide, however, that our stockholders may call a special meeting of stockholders only upon a request of stockholders owning at least 50% of
our outstanding common stock. These provisions of our certificate of incorporation and bylaws could discourage potential acquisition proposals and could
delay or prevent a change in control. We designed these provisions to reduce our vulnerability to unsolicited acquisition proposals and to discourage certain
tactics that may be used in proxy fights. These provisions, however, could also have the effect of discouraging others from making tender offers for our
shares. As a consequence, they also may inhibit fluctuations in the market price of our shares that could result from actual or rumored takeover attempts. Such
provisions also may have the effect of preventing changes in our management.
We are permitted to issue shares of our preferred stock without stockholder approval upon such terms as our board of directors determines. Therefore,
the rights of the holders of our common stock are subject to, and may be adversely affected by, the rights of the holders of our preferred stock that may be
issued in the future. In addition, the issuance of preferred stock could have a dilutive effect on the holdings of our current stockholders.
We are subject to the Delaware anti-takeover laws regulating corporate takeovers. These anti-takeover laws prevent a Delaware corporation from
engaging in a merger or sale of more than 10% of its assets with any stockholder, including all affiliates and associates of the stockholder, who owns 15% or
more of the corporation's outstanding voting stock, for three years following the date that the stockholder acquired 15% or more of the corporation's stock
unless:
•
•
the board of directors approved the transaction where the stockholder acquired 15% or more of the corporation's stock;
after the transaction in which the stockholder acquired 15% or more of the corporation's stock, the stockholder owned at least 85% of the
corporation's outstanding voting stock, excluding shares owned by directors, officers and employee stock plans in which employee participants
do not have the right to determine confidentially whether shares held under the plan will be tendered in a tender or exchange offer; or
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•
on or after this date, the merger or sale is approved by the board of directors and the holders of at least two-thirds of the outstanding voting stock
that is not owned by the stockholder.
The provisions of our governing documents and current Delaware law may, collectively:
•
•
•
lengthen the time required for a person or entity to acquire control of us through a proxy contest for the election of a majority of our board of
directors;
discourage bids for our common stock at a premium over market price; and
generally deter efforts to obtain control of us.
Item 1B.
Unresolved Staff Comments
Not applicable.
Item 2.
Properties
Our headquarters facility consists of approximately 4,500 square feet of office space in Broomfield, Colorado, which is leased until June 2013. We
believe that this facility is adequate to meet our current needs.
Item 3.
Legal Proceedings
Not applicable.
Item 4.
Mine Safety Disclosures
Not applicable.
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PART II
Item 5.
Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
As of March 7, 2011, our common stock began trading on the Nasdaq Capital Market under the symbol "ABIO", and was previously traded under the
same symbol on the Nasdaq Global Market. Prior to completion of the merger with Nuvelo, Nuvelo's common stock traded under the symbol "NUVO" on the
Nasdaq Global Market from January 31, 2003 to January 27, 2009 (except for the period between June 19, 2003 and March 19, 2004, where it temporarily
traded under the symbol "NUVOD").
The following table sets forth, for the periods indicated, the high and low sales prices for our common stock, as reported by the Nasdaq Global Market
in 2010 and 2011 and the Nasdaq Capital Market in 2011:
Year ended December 31, 2011
First quarter
Second quarter
Third quarter
Fourth quarter
Year ended December 31, 2010
First quarter
Second quarter
Third quarter
Fourth quarter
Stockholders
High
Low
$
$
$
$
$
$
$
$
3.34
2.64
1.68
2.45
9.23
6.06
4.31
4.38
$
$
$
$
$
$
$
$
2.25
1.41
1.00
0.95
2.60
3.38
3.01
3.00
As of March 23, 2012, we had approximately 129 stockholders of record of our common stock, and the last sale price reported on the Nasdaq Capital
Market for our common stock was $0.95 per share.
Dividend Policy
The holders of our common stock are entitled to dividends in such amounts and at such times, if any, as may be declared by our Board of Directors out
of legally available funds. We have not paid any dividends on our common stock and do not anticipate paying any cash dividends in the foreseeable future.
Securities Authorized for Issuance Under Equity Compensation Plans
Information relating to our equity compensation plans as of December 31, 2010, under which our equity securities were authorized for issuance, is
included in Item 12 of Part III of this Annual Report.
Unregistered Sales of Equity Securities and Use of Proceeds
On December 22, 2011 ARCA sold approximately $1.75 million of its common stock and warrants to six institutional investors in a private placement
transaction. ARCA issued an aggregate of approximately 1.67 million shares of common stock to investors together with warrants to purchase approximately
1.25 million shares of common stock. The net proceeds, after deducting the placement fee and other offering expenses, were approximately $1.4 million, and
these proceeds are being used solely for general working capital purposes.
Each unit, consisting of one share of common stock and a warrant to purchase 0.75 share of common stock, was sold at a purchase price of $1.05. The
warrants become exercisable on June 22, 2012, expire 5 years after becoming exercisable and have an exercise price of $1.485 per share.
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Pursuant to the terms of the Registration Rights Agreement (the Rights Agreement) entered into as part of the transactions, ARCA granted to the
investors certain registration rights related to the shares underlying the units sold in the private placement. ARCA filed a registration statement, in accordance
with the terms of the Rights Agreement, for the resale of the shares underlying the units sold in the private placement. That registration statement was
declared effective by the Securities and Exchange Commission on January 26, 2012.
The foregoing is only a brief description of the material terms of the private placement and the associated Purchase Agreements, the Rights Agreement
and the Warrants and does not purport to be a complete description of the rights and obligations of the parties hereunder. The foregoing is qualified in its
entirety by reference to the form of Purchase agreement the form of Rights Agreement and form of Warrants, which were filed as Exhibits to our report on
Form 8K filed December 22, 2011.
Issuer Purchases of Equity Securities
None.
Item 6.
Selected Financial Data
Not applicable.
Item 7.
Management's Discussion and Analysis of Financial Condition and Results of Operations
We have included or incorporated by reference into this Management's Discussion and Analysis of Financial Condition and Results of Operations and
elsewhere in this Annual Report on Form 10-K, and from time to time our management may make, statements that constitute "forward-looking statements"
within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act. Forward-looking statements may be identified by words
including "anticipate," "plan," "believe," "intend," "estimate," "expect," "should," "may," "potential" and similar expressions. These statements involve known
and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different
from the information expressed or implied by these forward-looking statements. While we believe that we have a reasonable basis for each forward-looking
statement contained in this Annual Report, we caution you that these statements are based on a combination of facts and factors currently known by us and
our projections of the future, about which we cannot be certain. We undertake no obligation to publicly update any forward-looking statements, whether as a
result of new information, future events or otherwise. You are advised, however, to consult any further disclosures we make on related subjects in our
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and our website.
Overview
We are a biopharmaceutical company whose principal focus is developing genetically-targeted therapies for cardiovascular diseases. Our lead product
candidate, GencaroTM (bucindolol hydrochloride), a pharmacologically unique beta-blocker and mild vasodilator, is being developed for the treatment of atrial
fibrillation, or AF, in patients with heart failure, or HF. We have identified common genetic variations in the cardiovascular system that we believe interact
with Gencaro's pharmacology and may predict patient response to the drug.
We have been granted patents in the U.S., Europe, and other jurisdictions for methods of treating AF and HF patients with Gencaro based on genetic
testing, which we believe will provide market exclusivity for these uses of Gencaro into at least 2026 in the U.S. and into 2025 in Europe. In addition, we
believe that if Gencaro is approved, the Gencaro patents will be eligible for patent term extension based our on current clinical trial plans which, if granted in
the U.S., may provide market exclusivity into 2029, and if granted in Europe may provide market exclusivity into 2030.
We are planning to initiate a Phase 3 clinical study of Gencaro in AF patients with HF and/or left ventricular dysfunction. We believe AF is an
attractive potential indication for Gencaro because data from the previously
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conducted Phase 3 HF trial of Gencaro in 2,708 HF patients, or the BEST HF trial, suggest that Gencaro may have a potentially significant effect in reducing
or preventing AF. Based on our analysis of data from the BEST HF trial, we believe that Gencaro's prevention of AF in HF patients is pharmacogenetically
regulated. We plan to enroll approximately 200-400 patients with persistent AF who have the genotype that appears to respond most favorably to Gencaro.
We anticipate that this trial could begin approximately 6 months after we obtain sufficient funding.
AF is a disorder in which the normally regular and coordinated contraction pattern of the heart's two small upper chambers (the atria) becomes irregular
and uncoordinated. The irregular contraction pattern associated with AF causes blood to pool in the atria, predisposing the formation of clots. These clots may
travel from the heart and become lodged in the arteries leading to the brain and other organs, thereby blocking necessary blood flow and potentially resulting
in stroke. AF is considered an epidemic cardiovascular disease that affects approximately 2-3 million Americans, making it one of the most common heart
rhythm disorders. The approved therapies for the treatment or prevention AF have certain disadvantages, such as toxic side effects. We believe there is an
unmet medical need for new AF treatments that have fewer side effects than currently available therapies and are more effective, particularly in patients with
HF where most of the approved drugs are contra-indicated or have warnings in their prescribing information.
The planned AF clinical trial is designed to be a multi-center, randomized, double-blind clinical trial to assess the safety and efficacy of Gencaro in AF
patients with HF and/or left ventricular dysfunction, with the primary endpoint being time to recurrent symptomatic AF after direct current cardioversion. This
AF trial is designed to compare Gencaro to the beta-blocker metoprolol CR/XL in the patient genotype we believe responds most favorably to Gencaro. The
therapeutic benefit of metoprolol CR/XL does not appear to be enhanced in patients with this genotype. We believe data from the BEST HF trial indicate that
Gencaro may have a potentially significant effect in reducing or preventing AF, and this effect may be one that is genetically regulated. The entire cohort of
patients in the BEST HF trial that were treated with Gencaro had a 41% reduction in the risk of new onset AF (time-to-event) compared to placebo (p =
0.0004), although because there was not a predetermined AF clinical endpoint in the BEST HF trial, the data is based on a subsequent analysis of adverse
events and surveillance electrocardiograms (ECGs). In the DNA sub study, patients with the most favorable genotype for Gencaro experienced a 74% (p =
0.0003) reduction in risk of AF, based on the same analysis. This most favorable genotype was present in about 47% of the patients in the sub study, and we
estimate it is present in about 50% of the US general population. We believe the AF study would take approximately two and one half years from enrollment
of the first patient through completion.
We have exclusive patent rights to other product candidates that have potential indications in cardiovascular disease, oncology and other therapeutic
areas, some of which are in early stages of development and others of which are in later stages of development. We are seeking development partners to assist
us in the development of these product candidates or who may license rights to them. For example, we hold exclusive rights to rNAPc2, a recombinant protein
that is a potent, long acting tissue factor inhibitor with a unique mechanism of action. Previously, preclinical studies of rNAPc2 showed evidence of potential
efficacy against lethal hemorrhagic fever viruses.
To support the continued development of Gencaro, including the planned AF clinical trial and our ongoing operations, we will need to raise substantial
additional funding through public or private debt or equity transactions or a strategic combination or partnership, or government funding. We may seek
additional funding that could allow us to operate while we continue to pursue strategic combination, partnering, additional financing and licensing
opportunities. If we are delayed in obtaining funding or are unable to complete a strategic transaction, we may discontinue our development activities on
Gencaro or discontinue our operations. We believe our cash and cash equivalents balance as of December 31, 2011 will be sufficient to fund our operations, at
our current cost structure, through September 2012. We are unable to assert that our current cash and cash equivalents are sufficient to fund operations beyond
that date, and as a result, there is substantial doubt about our ability to continue as a going concern beyond September 2012. Changing circumstances may
cause us to
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consume capital significantly faster or slower than we currently anticipate. We have based these estimates on assumptions that may prove to be wrong, and we
could exhaust our available financial resources sooner than we currently anticipate.
On January 27, 2009, we completed a business combination (the "Merger") with ARCA Colorado in accordance with the terms of that Agreement and
Plan of Merger and Reorganization, dated September 24, 2008, and amended on October 28, 2008 (as amended, the "Merger Agreement"), in which a wholly-
owned subsidiary of Nuvelo, Inc. merged with and into ARCA Colorado, with ARCA Colorado continuing after the Merger as the surviving corporation and a
wholly-owned subsidiary of Nuvelo, Inc. Immediately following the Merger, we changed our name from Nuvelo, Inc. to ARCA biopharma, Inc., and our
common stock began trading on the Nasdaq Global Market under the symbol "ABIO" on January 28, 2009. On March 7, 2011, the listing of our common
stock was transferred from the Nasdaq Global Market to the Nasdaq Capital Market.
Results of Operations
Research and Development Expenses
•
Research and development, or R&D, expense comprises research & development, regulatory, and manufacturing process development activities
and costs. During 2011, our R&D efforts and costs were almost entirely for the development of Gencaro. Research and Regulatory costs
decreased approximately $940,000 primarily due to reduced personnel costs from staff reductions completed in the first quarter of 2011, plus the
conclusion of certain pre-clinical studies and regulatory activities done in 2010 with no similar activities or costs in 2011. Manufacturing process
development costs increased approximately $149,000 for the year due to milestone costs for ongoing, long-term stability studies of Gencaro and
new costs for preliminary analysis and development of clinical trial materials for our planned AF clinical trial.
Our R&D expenses are highly contingent upon our ability to raise substantial additional funding or complete a strategic transaction. Should we receive
funds from one or a combination of these sources, R&D expense in 2012 could be substantially higher than 2011 as we initiate our planned AF clinical trial.
Until substantial additional funding is obtained, R&D expenses in 2012 are expected to be comparable to 2011 levels or may decrease further.
Selling, General and Administrative Expenses
Selling, general and administrative expenses, or SG&A, primarily consist of personnel costs, consulting and professional fees, insurance, facilities and
depreciation expenses, and various other administrative costs.
SG&A expenses were $5.0 million for the year ended December 31, 2011, compared to $6.1 million for 2010, a decrease of approximately $1.1
million. Cost decreases of approximately $1.3 million were primarily comprised of reduced personnel, consulting, legal and accounting expenses.
Approximately $433,000 of the decrease was attributable to our staff reductions completed in the first quarter of 2011 and the balance is due to our reduced
operations overall. There was an increase in depreciation expense in 2011 of approximately $272,000 over 2010. The increase is directly related to the
relocation of our corporate office to a smaller office suite during the fourth quarter of the year. The move necessitated additional depreciation of certain
leasehold improvements, furniture and equipment that were not useable in the new office suite.
SG&A expenses for 2012 are expected to be comparable to 2011 levels, or modestly lower but are s contingent upon our ability to raise substantial
additional funding or complete a strategic transaction. Should we receive funds from one or a combination of these sources, SG&A expense in 2012 could be
substantially higher than 2011 as we increase activities to support initiating our planned AF clinical trial.
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Gain on Assignment of Patent Rights
During the year ended December 31, 2011, we entered into an agreement in which we assigned certain patent rights to a large pharmaceutical company.
In exchange for the patent rights we received a $2.0 million non-recourse payment during the second quarter of 2011.
Interest and Other Income
Interest and other income was $2,000 for the year ended December 31, 2011, as compared to $763,000 for 2010, representing a decrease of $761,000.
The decrease is comprised of grants totaling $489,000 under the Qualifying Therapeutic Discovery Project, provided under section 48D of the Internal
Revenue Code and realized gains of $263,000 on the sale of marketable securities. Both of these events occurred in and were exclusive to 2010. Interest
income was nominal in 2011 due to low investment yields and declining cash balances. We expect interest income to continue to be nominal in 2012.
Interest and Other Expense
Interest and other expense was $5,000 for the year ended December 31, 2011, as compared to $8,000 for 2010. The amounts and related change
between years are nominal to our overall operations. Based on our current capital structure, interest expense for 2012 is expected to be comparable to 2011.
Liquidity and Capital Resources
Cash and Cash Equivalents
Cash and cash equivalents
December 31,
2011
December 31,
2010
$
5,943
$
7,025
As of December 31, 2011, we had total cash and cash equivalents of $5.9 million, as compared to $7.0 million as of December 31, 2010. The net
decrease of $1.1 million is primarily due to $7.0 million of cash used for operating activities, offset by $2 million of cash from the assignment of certain
patent rights, plus approximately $4.0 million of net proceeds received from the sale of our common stock through two equity offerings.
Cash Flows from Operating, Investing and Financing Activities
Net cash (used in) provided by:
Operating activities
Investing activities
Financing activities
Net (decrease) increase in cash and cash equivalents
Year Ended
December 31,
2011
2010
$
$
(6,959)
2,006
3,871
(1,082)
$
$
(8,324)
265
7,321
(738)
Net cash used in operating activities for the year ended December 31, 2011 decreased $1.4 million compared with the 2010 period due to decreased
R&D and SG&A expenses discussed above.
Net cash flows provided by investing activities for the year ended December 31, 2011 was primarily due to $2 million of cash received from the
assignment of patent rights during 2011. Net cash provided by financing activities of approximately $3.9 million for the year ended December 31, 2011 is
comprised of $4.0 million of
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net proceeds from the sales of our common stock, less $146,000 in payments made on a vendor financing arrangement. For the year ended December 31,
2010, net cash provided by financing activities was $7.2 million of net proceeds from the sale of our common stock pursuant to an equity distribution
agreement and $139,000 of proceeds received from exercises of stock options.
Sources and Uses of Capital
Our primary sources of liquidity to date have been capital raised from issuances of shares of our common and preferred stock, issuance of convertible
promissory notes, and funds provided by the Merger. The primary uses of our capital resources to date have been to fund operating activities, including
research, clinical development and drug manufacturing expenses, license payments, and spending on capital items.
Considering the substantial additional time and costs associated with the development of Gencaro and our need to raise a significant amount of capital
on acceptable terms to finance the planned clinical trial and our ongoing operations, we are evaluating strategic alternatives for funding our continued
operations and development programs. We will need to raise substantial additional funding through public or private debt or equity transactions or a strategic
combination or partnership, or government funding to support the continued clinical development of Gencaro, including planned clinical trial. In evaluating
the substantial costs associated with development of rNAPc2 and our limited financial resources, further development of rNAPc2 will be dependent upon
receipt of government or third party funding, which may not be available.
On December 8, 2009, we entered into an equity distribution agreement, or the Agreement, with Wedbush Securities Inc., or the Agent, under which we
could, from time to time, offer and sell its common stock through the Agent. On April 30, 2010, we amended the Agreement to permit us to sell up to an
aggregate of $20 million in shares, which were registered on a registration statement on Form S-3 (File No. 333-148288). In the year ended December 31,
2010, we sold 1,164,600 shares of our common stock under this Agreement and realized $7.2 million of net proceeds. On May 23, 2011 the Company
terminated this agreement. No shares of common stock were sold during 2011 under this agreement.
On April 18, 2011, we entered into a placement agency agreement with Roth Capital Partners, LLC, pursuant to which it agreed to use its reasonable
efforts to arrange for the sale of up to 1,680,672 shares of ARCA's common stock and warrants to purchase up to 1,176,471 shares of ARCA's common stock
in a registered direct public offering. We paid the placement agent an aggregate fee equal to 7% of the gross proceeds received in the offering and reimbursed
the Placement Agent for its expenses incurred in connection with the offering, with a maximum expense reimbursement that, when aggregated with the 7%
fee, did not exceed 8% of our gross proceeds.
On April 18, 2011, we also entered into separate subscription agreements with certain institutional investors in connection with the offering, pursuant to
which we sold an aggregate of 1,680,672 shares of our common stock and warrants to purchase a total of 1,176,471 shares of our common stock to the
investors for aggregate gross proceeds, before deducting fees to the placement agent and other offering expenses payable by us, of approximately $3.0
million. Our net proceeds after deducting placement agent fees and offering expenses were approximately $2.5 million and the offering closed on April 21,
2011.
The common stock and warrants were sold in units, with each unit consisting of one share of our common stock and a warrant to purchase 0.7 shares of
our common stock. The purchase price per unit was $1.785. Subject to certain ownership limitations, the warrants are exercisable as of October 21, 2011 and
will remain exercisable for five years thereafter at an exercise price of $2.52 per share.
On December 21, 2011, we entered into separate Subscription Agreements (the "Purchase Agreements") with various institutional investors in
connection with a private placement of our common stock and warrants. Pursuant to the Purchase Agreements, we agreed to sell and issue an aggregate of
1,666,666 shares of our
48
Table of Contents
common stock and warrants to purchase up to an additional 1,250,000 shares of our common stock at a total purchase price of $1.05 per unit. The investors in
the private placement received warrants to purchase 0.75 shares of common stock for each share of common stock purchased.
The warrants issued pursuant to the Purchase Agreements (the "Warrants") are exercisable for a period of five years from the six month anniversary of
the closing date of the private placement and have an exercise price of $1.485 per share, equal to 110% of the closing sales price of ARCA's common stock on
the NASDAQ Capital Market on December 21, 2011.
We raised gross proceeds of approximately $1.75 million in connection with the private placement. The net proceeds, after deducting the payment of a
fee of approximately $100,000 to Roth Capital Partners, as placement agent, and other offering expenses, were approximately $1.4 million. We agreed to use
the net proceeds from the private placement solely for general working capital purposes. The private placement transaction closed that same day.
Pursuant to the terms of a Registration Rights Agreement (the "Rights Agreement") to be entered into at the closing of the transactions, we granted to
the investors certain registration rights related to the shares of common stock to be sold in the private placement and the shares of common stock underlying
the Warrants to be issued. We filed a registration statement, in accordance with the terms of the Rights Agreement, for the resale of the shares of common
stock to be issued pursuant to the Purchase Agreements and the shares of common stock underlying the Warrants. The registration statement was declared
effective by the Securities and Exchange Commission on January 26, 2012.
In addition to the proceeds of the stock sales, we may seek more interim funding that will allow us to continue operations while we pursue a strategic
combination, partnering, financing and licensing opportunities. We believe our cash and cash equivalents balance as of December 31, 2011 will be sufficient
to fund our operations, at our current cost structure, through September 30, 2012. However, we are unable to assert that these funds are sufficient to fund
operations beyond that date, and as a result, there is substantial doubt about our ability to continue as a going concern beyond September 30, 2012. The
consolidated financial statements contained in this report have been prepared with the assumption that we will continue as a going concern and will be able to
realize our assets and discharge our liabilities in the normal course of business and do not include any adjustments to reflect the possible future effects on the
recoverability and classification of assets or the amounts and classification of liabilities that may result from our inability to continue as a going concern. We
may not be able to raise sufficient capital on acceptable terms or at all to continue development of Gencaro or to continue operations and may not be able to
execute any strategic transaction.
Our liquidity, and ability to raise additional capital or complete any strategic transaction, depends on a number of factors, including, but not limited to,
the following:
•
•
•
•
•
•
•
•
the costs and timing for an additional clinical trial in order to gain possible FDA approval for Gencaro;
the market price of our stock and the availability and cost of additional equity capital from existing and potential new investors;
our ability to retain the listing of our common stock on the Nasdaq Capital Market;
general economic and industry conditions affecting the availability and cost of capital;
potential receipt of government or third party funding to further develop Gencaro or rNAPc2;
our ability to control costs associated with our operations;
the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; and
the terms and conditions of our existing collaborative and licensing agreements.
49
Table of Contents
The sale of additional equity or convertible debt securities would likely result in substantial additional dilution to our stockholders. If we raise
additional funds through the incurrence of indebtedness, the obligations related to such indebtedness would be senior to rights of holders of our capital stock
and could contain covenants that would restrict our operations. We also cannot predict what consideration might be available, if any, to us or our stockholders,
in connection with any strategic transaction. Should strategic alternatives or additional capital not be available to us in the near term, or not be available on
acceptable terms, we may be unable to realize value from our assets and discharge our liabilities in the normal course of business which may, among other
alternatives, cause us to further delay, substantially reduce or discontinue operational activities to conserve its cash resources.
Critical Accounting Policies and Estimates
A critical accounting policy is one that is both important to the portrayal of our financial condition and results of operation and requires management's
most difficult, subjective or complex judgments, often as a result of the need to make estimates about the effect of matters that are inherently uncertain. While
our significant accounting policies are described in Note 1 of "Notes to the Consolidated Financial Statements" included within Item 8 in this report, we
believe the following critical accounting policy affected our most significant judgments, assumptions, and estimates used in the preparation of our
consolidated financial statements and, therefore, is important in understanding our financial condition and results of operations.
Long-Lived Assets and Impairments
We review long-lived assets whenever events or changes in circumstances indicate that the carrying value of such assets may not be recoverable. As a
development stage company, we have not generated positive cash flows from operations, and such cash flows may not materialize for a significant period in
the future, if ever. Additionally, we may make changes to our business plan that would result in changes to expected cash flows from long-lived assets. It is
reasonably possible that future evaluations of long-lived assets, including changes from our current expected use of long-lived assets, may result in material
impairments.
Accrued Expenses
As part of the process of preparing our financial statements, we are required to estimate accrued expenses. This process involves identifying services
that third parties have performed on our behalf and estimating the level of service performed and the associated cost incurred for these services as of the
balance sheet date. Examples of estimated accrued expenses include contract service fees, such as fees payable to contract manufacturers in connection with
the production of materials related to our drug product, and professional service fees, such as attorneys, consultants, and clinical research organizations. We
develop estimates of liabilities using our judgment based upon the facts and circumstances known at the time.
Off-Balance Sheet Arrangements
We have not participated in any transactions with unconsolidated entities, such as special purpose entities, which would have been established for the
purpose of facilitating off-balance sheet arrangements.
Indemnifications
In the ordinary course of business, we enter into contractual arrangements under which we may agree to indemnify certain parties from any losses
incurred relating to the services they perform on our behalf or for losses arising from certain events as defined within the particular contract. Such
indemnification obligations may not be subject to maximum loss clauses. We have entered into indemnity agreements with each of our directors, officers and
certain employees. Such indemnity agreements contain provisions, which are in some respects broader than the specific indemnification provisions contained
in Delaware law. We also maintain an insurance policy for our directors and executive officers insuring against certain liabilities arising in their capacities as
such.
50
Table of Contents
Item 7A.
Quantitative and Qualitative Disclosures About Market Risk
Not applicable.
51
Table of Contents
Item 8.
Financial Statements and Supplementary Data
Report of Independent Registered Public Accounting Firm, KPMG LLP
Consolidated Balance Sheets as of December 31, 2011 and 2010
Consolidated Statements of Operations for the years ended December 31, 2011 and 2010 and for the period from December 17, 2001 (date of
inception) to December 31, 2011
Consolidated Statements of Preferred Stock and Stockholders' Equity for the years ended December 31, 2011 and 2010 and for the period
from December 17, 2001 (date of inception) to December 31, 2011
Consolidated Statements of Cash Flows for the years ended December 31, 2011 and 2010 and for the period from December 17, 2001 (date of
inception) to December 31, 2011
Notes to Consolidated Financial Statements
Page
53
54
55
56
59
60
52
Table of Contents
The Board of Directors and Stockholders
ARCA biopharma, Inc.:
Report of Independent Registered Public Accounting Firm
We have audited the accompanying consolidated balance sheets of ARCA biopharma, Inc. (a development stage enterprise) and subsidiaries (the Company)
as of December 31, 2011 and 2010, and the related consolidated statements of operations, preferred stock and stockholders' equity (deficit), and cash flows for
each of the years in the two-year period ended December 31, 2011 and for the period from December 17, 2001 (date of inception) to December 31, 2011.
These consolidated financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on these consolidated
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 consolidated financial statements referred to above present fairly, in all material respects, the financial position of ARCA biopharma, Inc.
(a development stage enterprise) and subsidiaries as of December 31, 2011 and 2010, and the results of their operations and their cash flows for each of the
years in the two-year period ended December 31, 2011 and for the period from December 17, 2001 (date of inception) to December 31, 2011, in conformity
with U.S. generally accepted accounting principles.
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in note 1
to the consolidated financial statements, the Company has suffered recurring losses from operations and is dependent upon raising additional funds from
strategic transactions, sales of equity, and/or issuance of debt. The Company's ability to consummate such transactions is uncertain. As a result, there is
substantial doubt about the Company's ability to continue as a going concern. Management's plans in regard to these matters are also described in note 1. The
consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.
Denver, Colorado
March 27, 2012
/s/ KPMG LLP
53
Table of Contents
Current assets:
Cash and cash equivalents
Other current assets
Total current assets
Property and equipment, net
Other assets
Total assets
ARCA BIOPHARMA, INC.
(a development stage enterprise)
CONSOLIDATED BALANCE SHEETS
ASSETS
LIABILITIES AND STOCKHOLDERS' EQUITY
Current liabilities:
Accounts payable
Accrued compensation and employee benefits
Accrued expenses and other liabilities
Deferred rent, current portion
Total current liabilities
Deferred rent, net of current portion
Total liabilities
Commitments and contingencies
Stockholders' equity:
Common stock, $0.001 par value; 100 million shares authorized at December 31, 2011 and December 31, 2010; 12,182,999
and 8,834,535 shares issued and outstanding at December 31, 2011 and December 31, 2010, respectively
Additional paid-in capital
Deficit accumulated during the development stage
Total stockholders' equity
Total liabilities and stockholders' equity
As of December 31,
2011
2010
(in thousands, except share
and per share amounts)
$
$
$
5,943 $
269
6,212
66
224
6,502 $
260 $
111
350
33
754
16
770
7,025
137
7,162
690
304
8,156
388
175
506
121
1,190
195
1,385
12
69,394
(63,674)
5,732
6,502 $
9
65,072
(58,310)
6,771
8,156
$
See accompanying Notes to Consolidated Financial Statements.
54
Table of Contents
ARCA BIOPHARMA, INC.
(a development stage enterprise)
CONSOLIDATED STATEMENTS OF OPERATIONS
Year Ended December 31,
Period from
December 17,
2001 (date of
inception) to
December 31,
2011
2010
(in thousands, except share and
per share amounts)
2011
Costs and expenses:
Research and development
Selling, general and administrative
Merger transaction costs
Restructuring expense, net
Loss on impairment of in-process research and development
Total costs and expenses
Loss from operations
Gain on assignment of patent rights
Gain on bargain purchase
Interest and other income
Interest and other expense
Loss before income taxes
Benefit from income taxes
Net loss
Less: Accretion of redeemable convertible preferred stock
Less: Deemed preferred stock dividend for additional common shares issuable under anti-dilution provisions
Net loss available to common stockholders
Net loss available to common stockholders per share:
Basic and diluted
Weighted average shares outstanding:
Basic and diluted
$
$
$
$
2,315 $
5,046
—
—
—
7,361
(7,361)
2,000
—
2
(5)
(5,364)
—
(5,364) $
—
—
(5,364) $
3,106 $
6,069
—
—
—
9,175
(9,175)
—
—
763
(8)
(8,420)
—
(8,420) $
—
—
(8,420) $
41,585
39,356
5,470
2,413
6,000
94,824
(94,824)
2,000
25,282
2,026
(439)
(65,955)
2,281
(63,674)
(245)
(781)
(64,700)
(0.53) $
(0.99)
10,038,243 8,506,320
See accompanying Notes to Consolidated Financial Statements.
55
Table of Contents
CONSOLIDATED STATEMENTS OF PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)
ARCA BIOPHARMA, INC.
(a development stage enterprise)
Preferred Stock
Stockholders' Equity (Deficit)
Series A
Redeemable
Convertible
Series B
Redeemable
Convertible
Additional
Paid In
Preferred Stock
Preferred Stock Common stock
Shares Amount Shares Amount Shares Amount
Capital
(in thousands, except share and per share amounts)
Deficit
Accumulated
During the
Development
Stage
Total
Balance, December 17, 2001 (date of inception)
Issuance of common stock to founders on December 31, 2002, for cash, at $0.06 per
share
Net loss
Balance, December 31, 2003
Issuance of common stock on September 30, 2004, for cash, at $0.06 per share
Net loss
Balance, December 31, 2004
Issuance of common stock on January 3, 2005, for cash, at $0.06 per share
Issuance of common stock on January 3, 2005, upon conversion of notes payable
and related accrued interest at $0.06 per share
Issuance of common stock on October 14, 2005, for intellectual property license
rights, at $8.14 per share
Issuance of common stock on October 14, 2005, upon conversion of notes payable
and related accrued interest
Net loss
Balance, December 31, 2005
Issuance of common stock on February 21, 2006, for intellectual property license
rights, at $0.72 per share
Issuance of Series A on February 22, 2006, for cash, at $1.6265 per share
Issuance of Series A on February 22, 2006, upon conversion of notes payable and
related accrued interest, at $1.6265 per share
Issuance of common stock upon exercise of stock options, for cash
Issuance of common stock on February 22, 2006, for intellectual property and
product license rights, at $0.72 per share
Issuance of common stock on June 23, 2006, for intellectual property license rights,
at $0.90 per share
Issuance of common stock on November 7, 2006, for intellectual property license
rights, at $0.90 per share
Issuance of Series A on December 8, 2006, for cash, at $1.6265 per share
Series A offering costs
Share-based compensation
Accretion of offering costs of redeemable convertible preferred stock
Net loss
Balance, December 31, 2006
Issuance of Series B convertible redeemable preferred stock, on May 31, 2007 for
$2.439 per share
Issuance of Series B convertible redeemable preferred stock, on December 28, 2007
for $3.253 per share
Series B offering Costs
Accretion of Series A offering costs
Accretion of Series B offering costs
— $ —
— $ — — $ — $
— $
— $ —
— —
— —
— —
— —
— —
— —
— —
— — 15,529 —
— — — —
— — 15,529 —
— — 118,319 —
— — — —
— — 133,848 —
— — 17,533 —
— —
— — 17,867 —
1
—
1
7
—
8
1
1
—
(116)
(116)
—
(511)
(627)
—
1
(116)
(115)
7
(511)
(619)
1
—
1
— —
— —
5,419 —
44
—
44
— —
— —
— — 186,571 —
— — — —
1,354
—
— 1,354
(1,459) (1,459)
— —
— — 361,238 —
1,408
(2,086)
(678)
— —
9,316
5,727,354
— — 104,229 —
— — — —
420,817
684
— —
— — — —
— — 48,111 —
— —
— — 83,443
1
— —
— — 15,028 —
— —
5,000
3,074,086
—
(98)
— —
—
17
— —
— —
229 —
— — — —
— — — —
— — — —
— — — —
— — — —
75
—
—
3
59
15
—
—
—
39
(17)
—
—
75
— —
— —
3
—
—
—
60
15
— —
— —
— —
39
—
(17)
—
(5,241) (5,241)
9,222,257 14,919
— — 612,278
1
1,582
(7,327) (5,744)
— — 3,688,902
9,000 — —
9,000 — —
— — 2,766,677
—
— —
(147) — —
— — — —
19
—
18 — —
—
— —
—
—
—
(19)
(18)
— —
— —
— —
(19)
—
(18)
—
56
Table of Contents
ARCA BIOPHARMA, INC.
(a development stage enterprise)
CONSOLIDATED STATEMENTS OF PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)—(Continued)
Preferred Stock
Stockholders' Equity (Deficit)
Series A
Redeemable
Convertible
Preferred Stock
Shares
Amount Shares
Series B
Redeemable
Convertible
Additional
Paid In
Preferred Stock Common stock
Amount Shares Amount
Capital
(in thousands, except share and per share amounts)
Deficit
Accumulated
During the
Development
Stage
Total
Issuance of common stock for intellectual property license rights, on
January 18, 2007 at $1.68 per share
Issuance of common stock for intellectual property license rights, on June 30,
2007 at $1.80 per share
Issuance of common stock for commercial license rights, on July 19, 2007,
vests upon achievement of specified criteria
Share-based compensation
Issuance of shares to executive on February 19, 2007, vesting upon
achievement of specified criteria, subject to repurchase
Issuance of common stock upon exercise of stock options for cash
Net loss
Balance, December 31, 2007
Accretion of Series A offering costs
Accretion of Series B offering costs
Share-based compensation
Estimated fair value of warrants issued in connection with convertible notes
payable
Issuance of common stock upon exercise of stock options, for cash
Net loss
Balance, December 31, 2008
Adjustment for fractional shares on common conversion
Deemed preferred stock dividend for additional common shares issuable under
anti-dilution provision
Accretion of Series A offering costs
Accretion of Series B offering costs
Conversion of preferred stock
Restricted stock release from restriction
Conversion of convertible notes and related accrued interest
Conversion of warrants for preferred stock
Merger with Nuvelo, Inc.
Adjustment for fractional shares
Share-based compensation
Issuance of common stock upon exercise of stock options for cash
Issuance of common stock under employee stock purchase plan and upon
vesting of restricted stock units
Estimated fair value of warrants issued in connection with lease termination
Net loss
Balance, December 31, 2009
Issuance of common stock for cash, net of offering costs
Issuance of common stock upon exercise of stock options for cash
Share-based compensation
Net loss
Balance, December 31, 2010
— —
— —
7,817 —
— —
— —
3,852 —
— —
— —
— —
— —
16,698 —
— —
— —
— —
— —
— —
— —
— —
83,490 —
13,359 —
— —
9,222,257 14,938 6,455,579 17,871 737,494
20
—
— —
— —
— —
— —
— —
— —
—
36
— —
1
— —
— —
— —
— —
— —
— — 216,926 —
— —
— —
9,222,257 14,958 6,455,579 17,907 954,420
1
(39) —
— —
— —
— —
42
—
— —
—
781
— —
93
—
(9,222,257) (15,000) (6,455,579) (18,781) 3,042,740
— —
— —
— —
3
— —
1
— —
3
(609) —
— —
63,123 —
— —
— — 872,792
— —
— — 2,686,957
— —
— —
— —
— —
— —
— —
1,064 —
— —
— —
— — 7,620,448
— — 1,164,600
— —
— —
— —
8
1
49,487 —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
— —
13
7
—
50
—
16
—
1,631
(20)
(36)
545
399
54
—
2,573
—
(781)
(42)
(93)
33,778
75
8,500
36
11,910
—
845
114
2
377
—
57,294
7,181
139
458
—
—
—
13
7
— —
50
—
— —
16
—
(13,994) (13,994)
(21,321) (19,689)
(20)
(36)
545
—
—
—
—
—
399
54
(19,431) (19,431)
(40,752) (38,178)
— —
(781)
—
(42)
—
—
(93)
— 33,781
75
—
—
8,501
36
—
— 11,913
— —
845
—
114
—
—
—
(9,138)
(49,890)
—
—
—
(8,420)
2
377
(9,138)
7,412
7,182
139
458
(8,420)
— $ —
— $ — 8,834,535 $
9 $
65,072 $
(58,310) $ 6,771
57
Table of Contents
ARCA BIOPHARMA, INC.
(a development stage enterprise)
CONSOLIDATED STATEMENTS OF PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)—(Continued)
Preferred Stock
Stockholders' Equity (Deficit)
Series A
Redeemable
Convertible
Preferred Stock
Series B
Redeemable
Convertible
Shares
Amount Shares
Preferred Stock
Amount
Additional
Paid In
Common stock
Shares
Amount
Capital
(in thousands, except share and per share amounts)
3,347,338
1,126
—
—
—
—
—
—
3
—
—
4,014
—
308
—
— —
— —
— —
— —
Deficit
Accumulated
During the
Development
Stage
Total
— 4,017
— —
308
—
(5,364) (5,364)
Issuance of common stock for cash, net of offering costs
Issuance of common stock upon exercise of stock options for cash
Share-based compensation
Net loss
—
—
—
—
Balance, December 31, 2011
— $ — — $ — 12,182,999 $
12 $
69,394 $
(63,674) $ 5,732
See accompanying Notes to Consolidated Financial Statements.
58
Table of Contents
ARCA BIOPHARMA, INC.
(a development stage enterprise)
CONSOLIDATED STATEMENTS OF CASH FLOWS
Cash flows used in operating activities:
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
Gain on patent rights assignment
Gain on bargain purchase
Depreciation and amortization
Non-cash interest expense
Share-based compensation
Issuance of warrants for lease termination
Accretion of liabilities
Impairment of property and equipment
Impairment of in-process research and development
Write-off of deferred tax liability
Gain on marketable securities available for sale
(Gain) loss from disposal of property and equipment
Other, net
Change in operating assets and liabilities (net of amounts acquired):
Other current assets
Other assets
Accounts payable
Accrued expenses and other liabilities
Deferred rent
Net cash used in operating activities
Cash flows provided by investing activities:
Cash received from Merger
Payment of deferred transaction costs
Purchase of property and equipment
Proceeds from sale of marketable securities
Proceeds from sale of property and equipment
Proceeds from patent rights assignment
Net cash provided by investing activities
Cash flows provided by (used in) financing activities:
Proceeds from issuance of convertible notes payable and related warrants for common stock
Proceeds from issuance of bank note payable
Proceeds from stock subject to repurchase
Proceeds from the issuance of preferred stock
Preferred stock offering costs
Proceeds from the issuance of common stock
Payment of offering costs
Repayment of principal on bank note payable
Repayment of principal on convertible notes payables
Repayment of principal on vendor finance agreement
Net cash provided by (used in) financing activities
Net (decrease) increase in cash and cash equivalents
Cash and cash equivalents, beginning of period
Cash and cash equivalents, end of period
Supplemental cash flow information:
Interest paid
Supplemental disclosure of noncash investing and financing transactions:
Accrued interest on notes payable converted to equity
Warrant issued in connection with credit facility
Accrued deferred transaction costs
Years Ended December 31,
2011
2010
(in thousands)
December 17,
2001 (date of
inception) to
December 31,
2011
$
(5,364)
$
(8,420) $
(63,674)
(2,000)
—
602
—
308
—
—
—
—
—
—
16
—
14
80
(128)
(220)
(267)
—
—
338
—
458
—
—
—
—
—
(263)
(4)
—
58
84
(145)
(316)
(114)
(6,959)
(8,324)
—
—
(19)
—
25
2,000
2,006
—
—
—
—
—
4,726
(709)
—
—
(146)
3,871
(1,082)
7,025
5,943
5
—
—
—
$
$
$
$
$
—
—
(4)
263
6
—
265
—
—
—
—
—
7,659
(338)
—
—
7,321
(738)
7,763
7,025 $
— $
— $
— $
— $
$
$
$
$
$
(2,000)
(25,282)
1,737
211
2,282
377
152
125
6,000
(2,281)
(263)
83
267
2,542
7,246
(1,930)
(18,984)
49
(93,343)
30,392
(1,186)
(1,879)
15,369
358
2,000
45,054
10,841
4,000
38
32,316
(246)
12,581
(1,047)
(4,000)
(105)
(146)
54,232
5,943
—
5,943
112
163
111
482
See accompanying Notes to Consolidated Financial Statements.
59
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ARCA BIOPHARMA, INC.
(a development stage enterprise)
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(1) The Company and Summary of Significant Accounting Policies
Description of Business
ARCA biopharma, Inc., or the Company or ARCA, a Delaware corporation, is headquartered in Broomfield, Colorado and is a biopharmaceutical
company principally focused on developing genetically-targeted therapies for cardiovascular diseases. The Company's lead product candidate, GencaroTM
(bucindolol hydrochloride), a pharmacologically unique beta-blocker and mild vasodilator, is being developed for the treatment and the prevention of atrial
fibrillation, or AF, in patients with heart failure, or HF. The Company has identified common genetic variations in the cardiovascular system that it believes
interact with Gencaro's pharmacology and may predict patient response to Gencaro treatment. The Company has been granted patents in the U.S., Europe, and
other jurisdictions for methods of treating AF and HF patients with Gencaro based on genetic testing, which it believes will provide market exclusivity for
these uses of Gencaro into at least 2026 in the U.S. and into 2025 in Europe. In addition, the Company believes that if Gencaro is approved, the Gencaro
patents will be eligible for patent term extension based on our current clinical trial plans which, if granted in the U.S., may provide market exclusivity in the
U.S. into 2029, and if granted in Europe may provide market exclusivity into 2030.
The Company is planning to initiate a Phase 3 clinical study of Gencaro in AF patients with HF and/or left ventricular dysfunction. The Company
believes AF is an attractive indication for Gencaro because data from the previously conducted Phase 3 HF trial of Gencaro in 2,708 HF patients, or the BEST
HF trial, suggest that Gencaro may have a potentially significant effect in reducing or preventing AF. Based on the BEST HF trial, the Company believes that
Gencaro's prevention of AF in HF patients is pharmacogenetically regulated. The Company plans to enroll approximately 200-400 patients with persistent AF
who have the genotype that appears to respond most favorably to Gencaro. The Company anticipates that the AF trial could begin approximately 6 months
after the Company obtains sufficient funding.
To support the continued development of Gencaro, including the planned AF clinical trial and ongoing operations, the Company will need to raise
substantial additional funding through public or private debt or equity transactions or a strategic combination or partnership, or government funding.
ARCA also holds exclusive patent rights to other product candidates that have potential indications in cardiovascular disease, oncology and other
therapeutic areas, some of which are in early stages of development and others of which are in later stages of development. The Company is seeking partners
to assist it in the development of these candidates or who may license them. For example, ARCA holds exclusive rights to rNAPc2, a recombinant protein that
is a potent, long acting tissue factor inhibitor with a unique mechanism of action. Previously, preclinical studies of rNAPc2 showed evidence of potential
efficacy against lethal hemorrhagic fever viruses.
Development Stage Risks, Liquidity and Going Concern
The Company is in the development stage and devotes substantially all of its efforts towards obtaining regulatory approval, exploring strategic
alternatives for further developing Gencaro, and raising capital necessary to fund its operations. The Company has not generated revenue to date and is subject
to a number of risks similar to those of other development stage companies, including dependence on key individuals, the development of and regulatory
approval of commercially viable products, the need to raise adequate additional financing necessary to fund the development and commercialization of its
products, and competition from larger companies. The Company has historically funded its operations through issuances of convertible promissory notes and
shares of its common and preferred stock, as well as through the business combination with Nuvelo, Inc, or Nuvelo.
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Since ARCA was founded on December 17, 2001, or Inception, the Company has incurred substantial losses and negative cash flows from operations.
Since Inception, the Company incurred a loss from operations of $94.8 million and had negative cash flows from operations of $93.3 million.
In light of the substantial additional time and costs associated with the development of Gencaro and the need to raise a significant amount of capital on
acceptable terms to finance the additional clinical trial and the Company's ongoing operations, the Company is evaluating strategic alternatives for funding
continued operations and development programs. The Company will need to complete a strategic transaction, such as a strategic combination or partnership,
or raise substantial additional funding through public or private debt or equity securities, or government funding to support the continued development of
Gencaro, including the additional clinical trial. In 2011, the Company raised $4.0 million, net of offering costs, through the sales of our common stock and
may seek additional funding that could allow it to operate while it continues to pursue strategic combination, partnering, additional financing and licensing
opportunities. If the Company is delayed in completing or is unable to complete additional funding and/or a strategic transaction, the Company may
discontinue its development activities or discontinue its operations. The Company currently believes its cash and cash equivalents balance as of December 31,
2011 will be sufficient to fund its operations through September 30, 2012. The Company is unable to assert that its current cash and cash equivalents are
sufficient to fund operations beyond that date, and as a result, there is substantial doubt about the Company's ability to continue as a going concern beyond
September 30, 2012. These consolidated financial statements have been prepared with the assumption that the Company will continue as a going concern and
will be able to realize its assets and discharge its liabilities in the normal course of business and do not include any adjustments to reflect the possible future
effects on the recoverability and classification of assets or the amounts and classification of liabilities that may result from the inability of the Company to
continue as a going concern. The Company may not be able to raise sufficient capital on acceptable terms, or at all, to continue development of Gencaro or to
otherwise continue operations and may not be able to execute any strategic transaction.
The Company's liquidity, and its ability to raise additional capital or complete any strategic transaction, depends on a number of factors, including, but
not limited to, the following:
•
•
•
•
•
•
•
the costs and timing for the planned AF clinical trial in order to gain possible FDA approval for Gencaro;
the market price of the Company's stock and the availability and cost of additional equity capital from existing and potential new investors;
the Company's ability to retain the listing of its common stock on the Nasdaq Capital Market;
general economic and industry conditions affecting the availability and cost of capital;
the Company's ability to control costs associated with its operations;
the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; and
the terms and conditions of the Company's existing collaborative and licensing agreements.
The sale of additional equity or convertible debt securities would likely result in substantial additional dilution to the Company's stockholders. If the
Company raises additional funds through the incurrence of indebtedness, the obligations related to such indebtedness would be senior to rights of holders of
the Company's capital stock and could contain covenants that would restrict the Company's operations. The Company also cannot predict what consideration
might be available, if any, to the Company or its stockholders, in connection with any strategic transaction. Should strategic alternatives or additional capital
not be available to the Company in the near term, or not be available on acceptable terms, the Company may be unable to realize value from its assets and
discharge its liabilities in the normal course of business which may, among other alternatives, cause the Company to further delay, substantially reduce or
discontinue operational activities to conserve its cash resources.
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Merger with Nuvelo, Inc.
On January 27, 2009, the Company completed a business combination, or the Merger, with ARCA Colorado in accordance with the terms of that
Agreement and Plan of Merger and Reorganization, dated September 24, 2008, and amended on October 28, 2008 (as amended, the "Merger Agreement"), in
which a wholly-owned subsidiary of Nuvelo merged with and into ARCA Colorado, with ARCA Colorado continuing after the Merger as the surviving
corporation and a wholly-owned subsidiary of Nuvelo. Immediately following the Merger, the Company changed its name from Nuvelo, Inc. to ARCA
biopharma, Inc. The business combination is treated as a reverse merger for accounting purposes, and ARCA Colorado is the accounting acquirer, and the
entity formerly known as Nuvelo, Inc. is the acquired company ("Nuvelo"). Pursuant to the rules and regulations of the United States Securities and Exchange
Commission, or the SEC, the historical financial statements of ARCA Colorado replaced the historical financial statements of the acquired company, and the
disclosures in this report relating to the pre-Merger business of the Company, unless noted as being the business of Nuvelo prior to the Merger, pertain to the
business of ARCA Colorado prior to the Merger. See Note 3 for further discussion of the Merger.
Merger Exchange Ratio and Reverse Stock Split
In conjunction with and immediately prior to the Merger, Nuvelo effected a 1 for 20 reverse stock split. As a result, and in accordance with the Merger
Agreement, each outstanding common share and warrant or option to purchase ARCA Colorado's common stock prior to the Merger was converted into the
right to receive or purchase 0.16698070, or the Exchange Ratio, shares of the Company's common stock, which Exchange Ratio incorporates the effect of the
reverse stock split. All common shares, options and warrants to purchase common shares and per common share amounts for all periods presented in the
accompanying financial statements and notes have been adjusted retroactively to reflect the effect of the Exchange Ratio, except for the par value per share
and the number of shares authorized, which are not affected by the Exchange Ratio. The accompanying consolidated financial statements and notes have not
been adjusted to retroactively reflect the effect of the Exchange Ratio on preferred shares, warrants to purchase preferred shares, and per preferred share
amounts.
Basis of Presentation
The Company has generated no revenue to date and its activities have consisted of seeking regulatory approval, research and development, exploring
strategic alternatives for further developing and commercializing Gencaro, and raising capital. Accordingly, the Company is considered to be in the
development stage at December 31, 2011.
Accounting Estimates in the Preparation of Financial Statements
The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America requires
management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at
the date of the financial statements and the reported amounts of expenses during the reporting period. The Company bases estimates on various assumptions
that are believed to be reasonable under the circumstances. The Company believes significant judgment was involved in estimating the fair value of assets
acquired and liabilities assumed in the Merger, including in-process research and development, facility exit costs, clinical trial accruals, and in estimating
other accrued liabilities, stock-based compensation, and income taxes. Additionally, significant estimates and judgment are required in the evaluation of in-
process research and development for impairment. Management is continually evaluating and updating these estimates, and it is possible that these estimates
will change in the future or that actual results may differ from these estimates.
Cash Equivalents
Cash equivalents generally consist of money market funds and debt securities with maturities of 90 days or less at the time of purchase. The Company
invests its excess cash in securities with strong ratings and has established guidelines relative to diversification and maturity with the objective of maintaining
safety of principal and liquidity.
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The Company classifies all cash equivalents as available-for-sale securities, and records investments at fair value. Unrealized holding gains and losses
on available-for-sale securities, net of any tax effect, are excluded from earnings and are reported in accumulated other comprehensive income (loss), a
separate component of stockholders' equity, until realized. The specific identification method is utilized to calculate the cost to determine realized gains and
losses from the sale of available-for-sale securities. Realized gains and losses are included in interest income in the consolidated statements of operations.
Concentrations of Credit Risk
Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash and cash equivalents and
other receivables. The Company has no off-balance-sheet concentrations of credit risk, such as foreign exchange contracts, option contracts, or foreign
currency hedging arrangements. The Company maintains cash and cash equivalent balances in the form of bank demand deposits, money market fund
accounts and debt securities with financial institutions that management believes are creditworthy. Such balances may at times exceed the insured amount.
Property and Equipment
Property and equipment are stated at cost less accumulated depreciation and amortization. Cost includes expenditures for equipment, leasehold
improvements, replacements, and renewals. Maintenance and repairs are charged to expense as incurred. When assets are sold, retired, or otherwise disposed
of, the cost and accumulated depreciation are removed from the accounts and any resulting gain or loss is reflected in operations. The cost of property and
equipment is depreciated using the straight-line method over the estimated useful lives of the related assets. Leasehold improvements are amortized over the
shorter of the life of the lease or the estimated useful life of the assets. Property and equipment acquired in the Merger were recorded at the estimated fair
value as of the date of the Merger, and are subsequently depreciated using the straight-line method over the estimated remaining useful lives of the related
assets.
Long-Lived Assets and Impairments
The Company reviews long-lived assets whenever events or changes in circumstances indicate that the carrying value of such assets may not be
recoverable. As a development stage company, the Company has not generated positive cash flows from operations, and such cash flows may not materialize
for a significant period in the future, if ever. Additionally, the Company may make changes to its business plan that would result in changes to expected cash
flows from long-lived assets. It is reasonably possible that future evaluations of long-lived assets, including changes from the Company's current expected use
of long-lived assets, may result in material impairments.
Accrued Expenses
As part of the process of preparing its financial statements, the Company is required to estimate accrued expenses. This process involves identifying
services that third parties have performed on the Company's behalf and estimating the level of service performed and the associated cost incurred for these
services as of the balance sheet date. Examples of estimated accrued expenses include contract service fees, such as fees payable to contract manufacturers in
connection with the production of materials related to the Company's drug product, and professional service fees, such as attorneys, consultants, and clinical
research organizations. The Company develops estimates of liabilities using its judgment based upon the facts and circumstances known at the time.
Segments
The Company operates in one segment. Management uses one measure of profitability and does not segment its business for internal reporting.
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Research and Development
Research and development costs are expensed as incurred. These consist primarily of salaries, contract services, and supplies.
Costs related to clinical trial and drug manufacturing activities are based upon estimates of the services received and related expenses incurred by
contract research organizations, or CROs, clinical study sites, drug manufacturers, collaboration partners, laboratories, consultants, or otherwise. Related
contracts vary significantly in length, and could be for a fixed amount, a variable amount based on actual costs incurred, capped at a certain limit, or for a
combination of these elements. Activity levels are monitored through communications with the vendors, including detailed invoices and task completion
review, analysis of expenses against budgeted amounts, and pre-approval of any changes in scope of the services to be performed. Certain significant vendors
may also provide an estimate of costs incurred but not invoiced on a periodic basis. Expenses related to the CROs and clinical studies are primarily based on
progress made against specified milestones or targets in each period.
Stock-Based Compensation
The Company's stock-based compensation cost recognized includes: (a) compensation costs for current period vesting of all share-based awards granted
prior to January 1, 2006, based on the intrinsic value method, and (b) compensation cost for current period vesting of all share-based awards granted or
modified subsequent to January 1, 2006, based on the estimated grant date fair value. The Company recognizes compensation costs for its share-based awards
on a straight-line basis over the requisite service period for the entire award, as adjusted for expected forfeitures.
From Inception through December 31, 2005, the Company accounted for issuances of stock-based compensation under the intrinsic-value-based
method of accounting. Under this method, compensation expense is generally recorded on the date of grant only if the estimated fair value of the underlying
stock exceeds the exercise price.
Income Taxes
The current provision for income taxes represents actual or estimated amounts payable or refundable on tax returns filed or to be filed each year.
Deferred tax assets and liabilities are recognized for the estimated future tax consequences attributable to differences between the financial statement carrying
amounts of existing assets and liabilities and their respective tax bases and operating loss and tax credit carryforwards. The effect on deferred tax assets and
liabilities of a change in tax rates is recognized in the period that includes the enactment date. The overall change in deferred tax assets and liabilities for the
period measures the deferred tax expense or benefit for the period. The measurement of deferred tax assets may be reduced by a valuation allowance based on
judgmental assessment of available evidence if deemed more likely than not that some or all of the deferred tax assets will not be realized. The Company has
recorded a valuation allowance against its deferred tax assets, as management has concluded that it is more likely than not that the net deferred tax asset will
not be realized through future taxable income, based primarily on the Company's history of operating losses. As a result of the Merger, a change of ownership
of Nuvelo per Internal Revenue Code Section 382 occurred, and accordingly, the Company's ability to utilize Nuvelo's pre-Merger net operating loss
carryforwards has been substantially reduced.
(2) Earnings (Loss) Per Share
The Company calculates basic earnings per share by dividing (loss) earnings attributable to common stockholders by the weighted average common
shares outstanding during the period, excluding common stock subject to vesting provisions. Diluted earnings per share is computed by dividing (loss)
attributable to common stockholders by the weighted average number of common shares outstanding during the period increased to include, if dilutive, the
number of additional common shares that would have been outstanding if the potential common shares had been issued. The Company's potentially dilutive
shares include options and warrants.
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Table of Contents
A reconciliation of the numerator and denominator used in the calculation of basic and diluted loss per share follows:
(In thousands, except shares and per share data)
Net loss
Net loss available to common shareholders
Weighted average shares of common stock outstanding
Less: Weighted-average shares of unvested common stock
Total weighted-average shares used in computing net loss per share attributed to common stockholders
Basic and diluted loss per share
$
$
Years Ended December 31,
2011
(5,364) $
(5,364) $
10,054,941
(16,698)
2010
(8,420)
(8,420)
8,523,018
(16,698)
10,038,243
(0.53) $
8,506,320
(0.99)
$
Potentially dilutive securities representing 2.1 million and 1.3 million weighted average shares of common stock were excluded for the years ended
December 31, 2011 and 2010, respectively, because including them would have an anti-dilutive effect on net loss attributable to common stockholders per
share.
(3) Merger with Nuvelo, Inc. on January 27, 2009
On January 27, 2009, the Company completed the Merger, with ARCA Colorado in accordance with the terms of the Merger Agreement, in which a
wholly-owned subsidiary of Nuvelo merged with and into ARCA Colorado, with ARCA Colorado continuing after the Merger as the surviving corporation
and a wholly-owned subsidiary of Nuvelo. Immediately following the Merger, the Company changed its name from Nuvelo, Inc. to ARCA biopharma, Inc.,
and its common stock began trading on the Nasdaq Global Market under the symbol "ABIO" on January 28, 2009. On March 7, 2011, the listing of the
Company's common stock was transferred from the Nasdaq Global Market to the Nasdaq Capital Market.
The Merger was treated as a reverse merger and accounted for as a business combination using the acquisition method of accounting in accordance with
ASC 805. For accounting purposes, ARCA Colorado was considered to have acquired Nuvelo in the Merger, as the stockholders of ARCA Colorado prior to
the Merger had a controlling interest in the combined company and the Company's management is the former management of ARCA Colorado. Pursuant to
the rules and regulations of the United States Securities and Exchange Commission, or the SEC, the historical financial statements of ARCA Colorado
replaced the historical financial statements of Nuvelo, and the disclosures in this report relating to the pre-Merger business of the Company, unless noted as
being the business of Nuvelo prior to the Merger, pertain to the business of ARCA Colorado prior to the Merger.
The estimated total acquisition consideration of $11.9 million to acquire Nuvelo was based on the market capitalization of Nuvelo as of January 27,
2009 and the estimated fair values of its vested stock options and warrants outstanding on that date, as this was deemed the most reliable measure of the
consideration effectively transferred to acquire Nuvelo on that date. The Company estimated the net assets acquired in the Merger to be $37.2 million,
including $45.5 million of cash, cash equivalents and marketable securities. In accordance with ASC 805, any excess of fair value of net assets acquired in a
business combination over the acquisition consideration results in a gain on bargain purchase, and as a result, the Company recorded a gain on bargain
purchase of $25.3 million.
(4) Financial Instruments
Fair value is defined as the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market
participants at the measurement date (exit price). Inputs used to measure fair value are classified into the following hierarchy:
•
Level 1—Unadjusted quoted prices in active markets for identical assets or liabilities
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•
•
Level 2—Unadjusted quoted prices in active markets for similar assets or liabilities; unadjusted quoted prices for identical or similar assets or
liabilities in markets that are not active; or inputs other than quoted prices that are observable for the asset or liability
Level 3—Unobservable inputs for the asset or liability
The Company's financial assets include $5.9 million at December 31, 2011 and $7.0 million at December 31, 2010, in money market funds, classified
as cash equivalents, which are measured at fair value based on Level 1 inputs on a recurring basis. There were no transfers between any fair value hierarchy
levels in 2011 or 2010.
Fair Value of Other Financial Instruments
The carrying amount of other financial instruments, including cash and accounts payable, approximated fair value due to their short maturities. As of
December 31, 2011 and 2010, the Company did not have any debt outstanding.
(5) Property and Equipment
Property and equipment consist of the following (in thousands):
Computer equipment
Lab equipment
Furniture and fixtures
Computer software
Leasehold improvements
Less accumulated depreciation and amortization
Estimated Life
3 years
5 years
5 years
3 years
Lesser of useful life or life of the lease
December 31,
2011
December 31,
2010
104 $
142
93
176
18
533
(467)
66 $
206
142
398
176
744
1,666
(976)
690
$
$
For the years ended December 31, 2011 and 2010, and for the period from Inception through December 31, 2011, depreciation and amortization
expense was $602,000, $338,000 and $1.7 million, respectively.
(6) Related Party Arrangements
Transactions with the Company's President and Chief Executive Officer
Effective July 1, 2011, the Company entered into an unrestricted research grant with its President and Chief Executive Officer's research laboratory, or
the Lab, for $160,000 for a one-year term for the advancement of research in cardiovascular disease. For the period from July 1, 2010 through June 30, 2011,
the Company provided funding to the Lab under another unrestricted research grant for $226,000. In the first half of 2011, the Company provided research
funding for the lab of approximately $92,000, in accordance with a similar unrestricted research grant arrangement. Funding of the unrestricted research
grants is contingent upon the Company's financial condition, and can be deferred or terminated at the Company's discretion. Total expense under these
arrangements for the years ended December 31, 2011 and 2010 was $155,000 and $255,000, respectively, and $1.4 million from Inception through
December 31, 2011.
The Company was a party to a materials transfer agreement with the University of Colorado, under which the Company paid $35,000 per year to
maintain the Heart Tissue Bank associated with the President and Chief Executive Officer's research lab at the University of Colorado. Total expense for the
year ended December 31, 2011 was $26,000 and was $227,000 from Inception through December 31, 2011.
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(7) Commitments and Contingencies
The Company has or is subject to the following commitments and contingencies:
Employment Agreements
The Company maintains employment agreements with several key executive employees. The agreements may be terminated at any time by the
Company with or without cause upon written notice to the employee, and entitle the employee to wages in lieu of notice for periods not exceeding one
calendar year from date of termination without cause or by the employee for good reason. Certain of these agreements also provide for payments to be made
under certain conditions related to a change in control of the Company.
Operating Leases
The Company is party to a lease agreement, dated February 8, 2008. The original lease provided for approximately 15,000 square feet of an office
facility in Broomfield, Colorado, which serves as the Company's primary business offices. The lease has a term of five years with rights to extend the term for
two additional three year periods. On June 14, 2011, the Company entered into a first amendment (the "Amendment") to the lease agreement. Under the terms
of the Amendment, the Company and its landlord mutually agreed for the Company to relocate from its previous office suite of approximately 15,000 square
feet, to another suite within the same building, comprising approximately 4,500 square feet. The office location continues to serve as the Company's primary
business office. The Amendment also modified the annual per square foot rate of rent and allows the Company to terminate with three months notice. As part
of the agreement, the Company made a one-time payment to the landlord of $200,000, which the landlord agreed to use for the landlord's improvements in the
new leased premises prior to the Company occupying the space. The original five year term of the Lease remains unchanged. Per the lease agreement, base
rent is subject to annual increases of approximately three percent per year. The rent expense for the lease is being recognized on a straight-line basis over the
lease term.
Under the original lease, the Company received tenant improvement reimbursements from the landlord totaling $593,000 which were recorded as
deferred rent and were amortized as reductions to rent expense. The $200,000 payment made to the landlord in conjunction with the Amendment was
recorded against the existing deferred rent balance. The net deferred rent balance is being amortized as reductions to rent expense over the remaining term of
the lease. The unamortized deferred rent balance as of December 31, 2011 was $49,000.
Rent expense under this lease for the years ended December 31, 2011 and 2010 was $150,000 and $123,000, respectively, and was $459,000 from
Inception through December 31, 2011.
Below is a summary of the future minimum lease payments committed under Company's facility in Broomfield, Colorado as of December 31, 2011 (in
thousands):
2012
2013
Total future minimum rental payments
University of Cincinnati
$
$
81
40
121
In April 2011, the Company entered into a license agreement with the University of Cincinnati to license exclusive worldwide rights to a portfolio of
U.S. and international patents, which includes certain U.S. and international diagnostic patents covering genetic markers for ARCA's lead drug candidate,
Gencaro. These patents provide the basis for exclusive worldwide development, use and commercialization of the genetic test which may indicate a patient's
likely response to Gencaro as a treatment for chronic HF, AF, and other
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indications. Under the terms of the agreement, ARCA agreed to pay the University of Cincinnati annual license fees and is obligated to future milestone
payments for each United States patent issued subsequent to the date of the agreement. The agreement also requires royalty payments on net sales from
genetic testing performed expressly for the purpose of prescribing bucindolol.
Laboratory Corporation of America
In February 2007, the Company entered into a commercialization and licensing agreement with Laboratory Corporation of America, or LabCorp, to
develop, make, market and sell diagnostic tests in connection with the medical prescription of the Company's lead compound, Gencaro. Under the agreement
the Company has licensed to LabCorp certain rights to commercialize a diagnostic test. The license agreement has a term of 10 years. LabCorp has the right to
cancel the agreement and give the rights to the diagnostic back to the Company. In addition, the Company granted to LabCorp 16,698 shares of common
stock. The shares are subject to a restricted stock agreement in which shares vest upon the attainment of certain regulatory approval and drug product sales
milestones.
Cardiovascular Pharmacology and Engineering Consultants, LLC, or CPEC
Under the terms of its strategic license agreement with CPEC, a licensing subsidiary of Indevus Pharmaceuticals Inc. (a wholly owned subsidiary of
Endo Pharmaceuticals), holding ownership rights to certain clinical trial data of Gencaro, the Company will incur milestone and royalty obligations upon the
occurrence of certain events. In August 2008, the Company paid CPEC a milestone payment of $500,000 based on the July 31, 2008 submission of its NDA
with the FDA. If the FDA grants marketing approval for Gencaro, the Company will owe CPEC another milestone payment of $8.0 million, which is due
within six months after FDA approval. The Company also has the obligation to make milestone payments of up to $5.0 million in the aggregate upon
regulatory marketing approval in Europe and Japan. The Company's royalty obligation ranges from 12.5% to 25% of revenue from the related product based
on achievement of specified product sales levels, including a 5% royalty that CPEC is obligated to pay under its original license agreement for Gencaro. The
Company has the right to buy down the royalties to a range of 12.5% to 17% by making a payment to CPEC within six months of regulatory approval.
Dendreon
In February 2004, Nuvelo obtained exclusive worldwide rights to all indications of rNAPc2 and all other rNAPc molecules owned by Dendreon
Corporation as a result of a licensing agreement entered into with them. Under the terms of the agreement, Nuvelo paid Dendreon an upfront fee of $4.0
million ($0.5 million in cash and $3.5 million in Nuvelo common stock) in 2004. Future milestone payments to Dendreon could reach as much as $2.5 million
if rNAPc2 is successfully developed and all commercialization milestones are achieved for the indication of treatment for Ebola virus infection. In addition,
such milestones could reach as much as $23.5 million if rNAPc2 is developed and commercialized for indications other than Ebola virus infection. ARCA
currently cannot predict if or when any of these milestones will be achieved. If rNAPc2 is commercialized, ARCA will be responsible for paying royalties to
Dendreon based on sales of rNAPc2.
(8) Collaborative Agreements
Archemix
In July 2006, Nuvelo entered into a collaboration agreement with Archemix Corporation, or Archemix. Under the agreement, Archemix was
responsible for the discovery of short-acting aptamers targeting the coagulation cascade for use in acute cardiovascular procedures, and the Company was
responsible for development and worldwide commercialization of these product candidates. In August 2006, Nuvelo made an upfront license fee payment to
Archemix of $4.0 million, and pursuant to the terms of the agreement committed
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to funding at least $5.25 million of Archemix's research over the first three years of the agreement. As of July 2009, this funding commitment had been
satisfied. Archemix had the right to receive payments totaling up to $35.0 million per development compound contingent upon the achievement of specified
development and regulatory milestones, along with potential royalty payments based on sales of licensed compounds. In February 2008, Nuvelo paid
Archemix a $1.0 million milestone fee that was accrued upon dosing of the first patient in the Phase 1 trial for NU172.
On April 20, 2010, the Company amended its collaboration agreement with Archemix for the discovery and development of novel aptamers with anti-
coagulation activities, or the Amended Agreement. In the Amended Agreement, the parties modified certain financial provisions and certain other provisions
to reflect the termination of the research and collaboration and limitation of the agreement to NU172. In summary, the agreement was amended, as follows:
•
•
•
•
Pursuant to the previous agreement, ARCA funded a research collaboration under which Archemix generated candidate aptamers for ARCA's
selection for further development and commercialization. In the Amended Agreement, ARCA is given sole control over the development,
manufacture and commercialization of NU172, and no further research or development collaboration is provided for.
Under the previous agreement, for each product resulting from the collaboration, ARCA had the obligation to fund the development and
commercialization of such product and pay milestones and royalties to Archemix on the net sales for such product. However, Archemix had the
option to share in 25% of the expenses incurred and profits obtained from the development and commercialization of such product, which
election Archemix could make after the inception of the Phase 3 clinical trial for the product. In the Amended Agreement, Archemix no longer
has such participation right, but will have the right to receive milestones and royalties on the net sales of NU172, if any, on the same terms and
conditions as those under the previous agreement.
The Amended Agreement revises the exclusivity provision to provide that Archemix will not, by itself or in collaboration with a third party,
develop, manufacture or commercialize short-acting aptamers that directly inhibit thrombin or are used as a treatment for viral or bacterial
infections, and in either case cause a therapeutically-useful level of anticoagulation.
Pursuant to the previous agreement, ARCA had the obligation to purchase Archemix common stock in an Archemix initial public offering under
certain conditions and subject to certain terms. In the Amended Agreement, this obligation is eliminated.
(9) Equity Distribution Agreement
In 2009 the Company entered into an equity distribution agreement, or the Agreement, with Wedbush Securities Inc., the Agent, under which the
Company could, from time to time, offer and sell its common stock through the Agent. On April 30, 2010, the Company amended the Agreement to permit it
to sell up to an aggregate of $20 million in shares, which were registered on a registration statement on Form S-3 (File No. 333-148288). In the year ended
December 31, 2010, the Company sold 1,164,600 shares of common stock under this Agreement and realized $7.2 million of proceeds, net of $338,000 of
offering costs. On May 23, 2011 the Company terminated this agreement. No shares of common stock were sold during 2011 under this agreement.
(10) Legal Matters
On February 9, 2007, Nuvelo and certain of Nuvelo's former and then current officers and directors were named as defendants in a purported securities
class action lawsuit filed in the United States District Court for the Southern District of New York. The suit alleged violations of the Securities Exchange Act
of 1934 related to the clinical trial results of alfimeprase, which Nuvelo announced on December 11, 2006, and the suit sought damages on behalf of
purchasers of Nuvelo's common stock during the period between January 5, 2006 and December 8,
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2006. On December 29, 2010, ARCA and the other defendants reached a settlement of the litigation with the plaintiffs, after participating in mediation, and on
February 25, 2011, the parties entered into a settlement agreement. ARCA's insurance carriers funded the settlement. On July 25, 2011 the order for final
settlement became effective and the suit was dismissed.
On or about December 6, 2001, Variagenics, Inc. was sued in a complaint filed in the United States District Court for the Southern District of New
York naming it and certain of its officers and underwriters as defendants. The complaint purportedly was filed on behalf of persons purchasing Variagenics'
stock between July 21, 2000 and December 6, 2000, and alleged violations of certain sections of the Securities Act of 1933, as amended, and the Securities
Exchange Act of 1934, as amended. The complaint alleged that, in connection with Variagenics' July 21, 2000 initial public offering, or IPO, the defendants
failed to disclose additional and excessive commissions purportedly solicited by and paid to the underwriter defendants in exchange for allocating shares of
Variagenics' stock to preferred customers and alleged agreements among the underwriter defendants and preferred customers tying the allocation of IPO
shares to agreements to make additional aftermarket purchases at predetermined prices. ARCA was involved in this litigation as a result of Nuvelo's merger
with Variagenics in January 2003. On April 1, 2009 the parties entered into a settlement agreement. On October 5, 2009, the Court approved the settlement
agreement. ARCA's share of the settlement was approximately $385,000 and was funded by ARCA's insurance carrier. Although the settlement was approved
by the Court, it had been appealed by members of the class. On January 9, 2012 the appeal was dismissed by the Court and the suit was settled.
(11) Stock-based Compensation
Warrants
As of December 31, 2011, warrants to purchase 2,750,151 shares of common stock were outstanding at exercise prices ranging from $1.485 to $19.48,
with a weighted average exercise price per share of $2.65. These warrants, which were granted as part of various financing and business agreements, expire at
various times between October 2013 and August 2018. Warrants were recorded in additional paid-in capital at their estimated fair market value at the date of
grant using the Black-Scholes option-pricing model.
Stock Plans
The Company's equity incentive plan was amended, as approved by shareholders on June 25, 2009, to (i) change the name of the plan from the
Amended and Restated Nuvelo, Inc. 2004 Equity Incentive Plan to the Amended and Restated ARCA biopharma, Inc. 2004 Equity Incentive Plan, or the
Equity Plan, (ii) increase the maximum number of shares issuable under the plan, revise the formula for determining the maximum number of shares issuable
under the plan and implement new share usage rules; and (iii) adjust the award limitations for stock options and stock appreciation rights. As a result of such
amendment, the maximum number of shares issuable under the Equity Plan was increased by 326,323 shares.
The Equity Plan provides for the granting of stock options (including indexed options), stock appreciation rights, restricted stock purchase rights,
restricted stock bonuses, restricted stock units, performance shares, performance units and deferred stock units. Under the Equity Plan, awards may be granted
to employees, directors and consultants of ARCA, except for incentive stock options, which may be granted only to employees. As of December 31, 2011,
options to purchase 393,345 shares were outstanding under the Equity Plan, and 506,908 shares were reserved for future awards.
In general, the Equity Plan authorizes the grant of stock options that vest at rates set by the Board of Directors or the Compensation Committee thereof.
Generally, stock options granted by ARCA under the equity incentive plans become exercisable ratably for a period of three to four years from the date of
grant and have a maximum term of ten years. The exercise prices of stock options under the equity incentive plan generally meet the following criteria: the
exercise price of incentive stock options must be at least 100% of the fair market value on the grant date and exercise price of options granted to 10% (or
greater) stockholders must be at least 110% of
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the fair market value on the grant date. ARCA's other stock plans under which options remained outstanding as of December 31, 2011 are the Non-Employee
Director Stock Option Plan. As of December 31, 2011, options to purchase 914 shares were outstanding under this stock plan.
In conjunction with the Merger, the Company discontinued grants under its 2004 Stock Option Plan effective January 27, 2009. As of December 31,
2011, options to purchase 469,979 shares with a weighted average exercise price of $2.38 per share were outstanding under this plan. Options and awards
outstanding under this plan will continue to vest according to the original terms of each grant. No new awards will be granted under this plan. Subsequent to
the Merger, the Company has granted stock-based compensation awards under the Equity Plan.
The Company granted options to purchase 164,700 and 128,170 shares of common stock in the years ended December 31, 2011 and 2010, respectively.
The fair values of employee stock options granted in the years ended December 31, 2011 and 2010 were estimated at the date of grant using the Black-Scholes
model with the following assumptions and had the following estimated weighted average grant date fair value per share:
Expected term
Expected volatility
Risk-free interest rate
Expected dividend yield
Weighted-average grant date fair value per share
Years Ended
December 31,
2011
5.8 years
2010
5.7 years
110%
2.20%
0%
1.83
$
86%
2.70%
0%
2.04
$
A summary of ARCA's stock option activities for the years ended December 31, 2011 and 2010, and related information as of December 31, 2011, is as
follows:
Options outstanding, beginning of period
Granted
Exercised
Forfeited and cancelled
Options outstanding, end of period
Options exercisable, end of period
Options vested and expected to vest
For the years ended December 31,
2011
2010
Weighted
Average
Exercise
Price
# of Options
Weighted
Average
Exercise
Price
# of Options
953,238
164,700
$
(1,126)
(252,574)
$
864,238
616,148
847,425
$
$
31.87
2.24
1.31
110.81
3.20
3.35
3.21
$
921,104
128,170
(49,487)
(46,549)
$
953,238
676,972
$
69.60
2.95
2.80
729.70
31.87
43.49
The total intrinsic value of options exercised for the years ended December 31, 2011 and 2010 was $1,000 and $208,000, respectively. As of
December 31, 2011, the unrecognized compensation expense related to unvested options, excluding estimated forfeitures, was $ 464,000, which compensation
expense is expected to be recognized over a weighted average period of 1.8 years. The Company recognizes compensation costs for its share-based awards on
a straight-line basis over the requisite service period for the entire award, as adjusted for expected forfeitures.
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The following table summarizes information about stock options outstanding and exercisable as of December 31, 2011:
Options Outstanding
Options Exercisable
Range of Exercise Prices
Number
Outstanding
$ 0.06 - $ 0.60
0.90 - 0.90
1.68 - 1.86
2.24 - 2.24
2.69 - 2.90
2.97 - 5.57
14.58 - 318.00
7,488
203,065
100,093
164,700
167,895
217,208
3,789
864,238
Weighted
Average
Remaining
Contractual
Term
(in years)
Weighted
Average
Exercise
Price
Number
Exercisable
Weighted
Average
Exercise
Price
3.42 $
4.83
5.90
9.38
6.93
7.26
4.00
6.82 $
0.52
0.90
1.83
2.24
2.82
4.63
143.19
3.20
7,488 $
203,065
95,829
32,017
109,765
164,195
3,789
616,148 $
0.52
0.90
1.83
2.24
2.83
4.74
143.19
3.35
For the years ended December 31, 2011 and 2010 and for the period from Inception through December 31, 2011, the Company recognized the
following non-cash, share-based compensation expense (in thousands):
Research and Development
Selling, General and Administrative
Restructuring Expense
Total
Years Ended
December 31,
2011
2010
$
$
117
191
—
308
$
$
128
330
—
458
$
$
Period from
December 17, 2001
(date of inception)
to December 31,
2011
496
1,399
387
2,282
Stock-based compensation expense related to non-employees was negligible in 2011 and 2010. ARCA did not recognize any tax benefit related to
employee stock-based compensation cost as a result of the full valuation allowance on its net deferred tax assets.
(12) Employee Benefit Plans
The Company has a 401(k) plan and makes a matching contribution equal to 100% of the employee's first 3% of the employee's contributions and 50%
of the employee's next 2% of contributions. The Company adopted the plan in 2006 and contributed $80,000 and $109,000 for the years ended December 31,
2011 and 2010, respectively, and has contributed $583,000 from Inception through December 31, 2011.
(13) Income Taxes
Effective June 1, 2005, the Company changed from an S-Corporation to a C-Corporation. As an S-Corporation, the net operating loss carryforwards
were distributed to the Company's stockholders; such amounts were not significant. Since June 2005 through December 31, 2011, for federal income tax
purposes, the Company has net operating loss carryforwards of approximately $94.0 million, and approximately $687,000 of research and development
credits that may be used to offset future taxable income. The net operating loss carryforwards will expire beginning 2025 through 2031. Utilization of net
operating losses and tax credits, including those acquired as a result of the Merger, will be subject to an annual limitation due to ownership change limitations
provided by IRC Section 382. The annual limitation may result in the expiration of the net operating losses and credits before utilization. As such, a portion of
the Company's net operating loss carryforwards may be limited.
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In assessing the realizability of deferred tax assets, management considers whether it is more likely than not that some portion or all of the deferred tax
assets will not be realized. The ultimate realization of deferred tax assets is dependent upon the generation of future taxable income during the period in which
those temporary differences become deductible. Management considers the scheduled reversal of deferred tax liabilities, projected future taxable income and
tax planning strategies in making this assessment. Due primarily to the Company's history of operating losses, management is unable to conclude that it is
more likely than not that the Company will realize the benefits of these deductible differences, and accordingly has provided a valuation allowance against the
entire net deferred tax asset of approximately $40.8 million at December 31, 2011, reflecting an increase of approximately $2.0 million from December 31,
2010. The deferred tax assets are primarily comprised of net operating loss carryforwards and research and experimentation credit carryforwards. As of
December 31, 2011 the Company has not performed a Section 382 limitation study. Depending on the outcome of such a study, the gross amount of net
operating losses recognizable in future tax periods could be limited. A limitation in the carryforwards would decrease the carrying amount of the gross amount
of the net operating loss carryforwards, with a corresponding decrease in the valuation allowance recorded against these gross deferred tax assets.
Income tax benefit attributable to our loss from operations before income taxes differs from the amounts computed by applying the U.S. federal
statutory income tax rate of 35%, as a result of the following (in thousands):
U.S. federal income tax benefit at statutory rates
State income tax benefit, net of federal benefit
Research and experimentation credits
Settlement of liabilities assumed in the Merger
Adjustment in tax basis of tangible and intangible assets acquired in the Merger
Other
Change in valuation allowance
Year ended December 31,
2011
2010
(1,877)
(161)
(71)
—
—
152
1,957
—
$
$
(2,947)
(253)
(53)
(5,273)
(1,816)
(54)
10,396
—
$
Without regard to the deferred tax liability on the impaired IPR&D, the Company has had no provision for income taxes since inception due to its S-
corporation status and its subsequent net operating losses.
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Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for financial reporting
and the amounts used for income tax purposes, as well as operating loss and tax credit carryforwards. The income tax effects of temporary differences and
carryforwards that give rise to significant portions of the Company's net deferred tax assets are as follows (in thousands):
Deferred tax assets:
Current deferred tax assets:
Vacation accrual
Total current deferred tax assets
Valuation allowance
Net current deferred tax assets
Noncurrent deferred tax assets:
Net operating loss carryforwards
Charitable contribution carryforwards
Research and experimentation credits
Capitalized intangibles
Stock based compensation
Depreciation and amortization
Other
Total noncurrent deferred tax assets
Valuation allowance
Net noncurrent deferred tax assets
Deferred tax liabilities:
Current deferred tax liabilities:
Depreciation and amortization
Total noncurrent deferred tax liabilities
Valuation allowance
Net deferred tax liabilities
Net noncurrent deferred tax assets
2011
2010
$
$
$
$
$
21
21
(21)
—
35,751
406
687
3,432
399
23
76
40,774
(40,774)
—
—
—
$
$
$
$
$
—
—
$
30
30
(30)
—
33,807
414
616
3,480
374
—
199
38,890
(38,890)
—
(82)
(82)
82
—
—
Since the Company is in a loss carryforward position, the Company is generally subject to U.S. federal and state income tax examinations by tax
authorities for all years for which a loss carryforward is available. Thus, the Company's open tax years extend back to 2005. The Company believes that its
tax filing positions and deductions related to tax periods subject to examination will be sustained upon audit and does not anticipate any adjustment will result
in a material adverse effect on the Company's financial condition, result of operations, or cash flow. For the years ended December 31, 2011 and 2010, the
Company has no reserve for uncertain tax positions. The Company does not expect that the total amounts of unrecognized tax benefits will significantly
increase or decrease within the subsequent twelve months. In the event the Company concludes it is subject to interest or penalties arising from uncertain tax
positions, the Company will record interest and penalties as a component of other income and expense. No amounts of interest or penalties were recognized in
the financial statements for the years ended December 31, 2011 and 2010.
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Item 9.
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Not applicable.
Item 9A.
Controls and Procedures
Evaluation of Disclosure Controls and Procedures
Under the supervision and with the participation of management, including our Chief Executive Officer and our Chief Financial Officer, we have
evaluated the effectiveness of the design and operation of our disclosure controls and procedures. Disclosure controls and procedures are controls and
procedures that are designed to ensure that information required to be disclosed in our reports filed or submitted under the Exchange Act is recorded,
processed, summarized and reported within the time periods specified in the SEC's rules and forms. Based on this evaluation, our Chief Executive Officer and
Chief Financial Officer have concluded that our disclosure controls and procedures were effective as of the end of the period covered by this annual report.
Management's Report on Internal Control over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting (as defined in Rules 13a-15(f) and
15(d)-15(f) under the Exchange Act). Our internal control system was designed to provide reasonable assurance to management and our board of directors
regarding the preparation and fair presentation of published 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.
Under the supervision and with the participation of management, including our Chief Executive Officer and Chief Financial Officer, we have assessed
the effectiveness of our internal control over financial reporting as of December 31, 2011. In making our assessment of internal control over financial
reporting, we used the criteria issued in the report Internal Control-Integrated Framework by the Committee of Sponsoring Organizations of the Treadway
Commission (COSO). We have concluded that our internal control over financial reporting was effective as of December 31, 2011 based on these criteria.
This annual report does not include an attestation report of our independent registered public accounting firm regarding internal control over financial
reporting. Management's report was not subject to attestation by our independent registered public accounting firm pursuant to the exemption from
Section 404(b) of the Sarbanes-Oxley Act for non-accelerated filers provided by the Dodd-Frank Wall Street Reform and Consumer Protection Act.
Changes in Internal Control over Financial Reporting
During the fourth quarter of 2011, 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.
Limitations on the Effectiveness of Controls
Our management, including the Chief Executive Officer and Chief Financial Officer, does not expect that our disclosure controls and procedures or our
internal control over financial reporting will prevent all errors and all fraud. A control system, no matter how well designed and operated, can provide only
reasonable, not absolute, assurance that the objectives of the control system are met. Because of the inherent limitations in all control systems, no evaluation
of controls can provide absolute assurance that all control issues and instances of fraud, if any, within our company have been detected.
Item 9B.
Other Information
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Item 10.
Directors, Executive Officers and Corporate Governance
PART III
The information required by this item is incorporated by reference to "Election of Board of Directors, " "Section 16(a) Beneficial Ownership Reporting
Compliance" and "Executive Officers" in our Definitive Proxy Statement to be filed pursuant to Regulation 14A under the Securities Exchange Act of 1934,
relating to our 2012 Annual Meeting of Stockholders.
Item 11.
Executive Compensation
The response to this item is incorporated by reference to "Executive Compensation" in our Definitive Proxy Statement to be filed pursuant to
Regulation 14A under the Exchange Act, relating to our 2012 Annual Meeting of Stockholders.
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The response to this item is incorporated by reference to "Equity Compensation Plan Information" and "Security Ownership of Certain Beneficial
Owners and Management" in our Definitive Proxy Statement to be filed pursuant to Regulation 14A under the Exchange Act, relating to our 2012 Annual
Meeting of Stockholders.
Item 13.
Certain Relationships and Related Transactions, and Director Independence
The response to this item is incorporated by reference to "Certain Relationships and Related Transactions" in our Definitive Proxy Statement to be filed
pursuant to Regulation 14A under the Securities Exchange Act of 1934, relating to our 2012 Annual Meeting of Stockholders.
Item 14.
Principal Accountant Fees and Services
The response to this item is incorporated by reference to "Ratification of Selection of Independent Auditors" in our Definitive Proxy Statement to be
filed pursuant to Regulation 14A under the Securities Exchange Act of 1934, relating to our 2012 Annual Meeting of Stockholders.
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Item 15.
Exhibits and Financial Statement Schedules
(a) The following documents are filed as part of this Report:
PART IV
Consolidated financial statements filed as part of this Report are listed under Part II, Item 8, page 47 of this Form 10-K.
No schedules are required because either the required information is not present or is not present in amounts sufficient to require
submission of the schedule, or because the information required is included in the consolidated financial statements or the notes thereto.
1.
2.
(b) Exhibits
The following documents are filed as part of this annual report on Form 10-K. We will furnish a copy of any exhibit listed to requesting stockholders
upon payment of our reasonable expenses in furnishing those materials.
Exhibit
Number
2.1
2.2
3.1
3.2
4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
4.10
4.11
Description
Agreement and Plan of Merger and Reorganization, dated September 24, 2008, among Nuvelo, Inc., Dawn Acquisition Sub, Inc. and ARCA
biopharma, Inc.(5)
Amendment No. 1 to Agreement and Plan of Merger and Reorganization, dated October 28, 2008, by and among Nuvelo, Inc., Dawn
Acquisition Sub, Inc. and ARCA biopharma, Inc.(6)
Amended and Restated Certificate of Incorporation of the Registrant, as amended.(8)
Second Amended and Restated Bylaws of the Registrant, as amended.(9)
Form of Common Stock Certificate.(7)
Certificate of Designations of Series A Junior Participating Preferred Stock. (included as part of Exhibit 3.1)
Warrant to Purchase Stock Agreement, dated July 17, 2007, by and between ARCA Discovery, Inc. and Silicon Valley Bank.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and SVB
Financial Group.(8)
Warrant to Purchase Stock Agreement, dated August 19, 2008, by and between ARCA biopharma, Inc. and Silicon Valley Bank.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and SVB
Financial Group.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Boulder Ventures IV, L.P.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Boulder
Ventures IV, L.P.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Boulder Ventures IV (Annex),
L.P.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Boulder
Ventures IV (Annex), L.P.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and InterWest Partners IX, LP.(8)
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Exhibit
Number
4.12
Description
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and InterWest
Partners IX, LP.(8)
4.13 Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Atlas Venture Fund VII, L.P.(8)
4.14
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Atlas Venture
Fund VII, L.P.(8)
4.15 Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and The Peierls Foundation, Inc.(8)
4.16
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and The Peierls
Foundation, Inc.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Skyline Venture Partners Qualified
Purchaser Fund IV, L.P.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Skyline
Venture Partners Qualified Purchaser Fund IV, L.P.(8)
4.17
4.18
4.19 Warrant to Purchase Stock Agreement, dated October 18, 2009, by and between ARCA biopharma, Inc. and BioMed Realty, L.P.(16)
4.20
4.21
10.1§
10.2§
Form of Common Stock Purchase Warrant.(23)
Form of Warrant to Purchase Common Stock.(27)
Amended and Restated Collaboration and License Agreement, dated July 31, 2006, by and between Nuvelo, Inc. and Archemix Corp.(2)
Second Amended and Restated Collaboration and License Agreement, dated April 20, 2010, by and between ARCA biopharma, Inc. and
Archemix Corp.(17)
Lease, dated February 8, 2008, by and between ARCA Discovery, Inc. and Arista Place, LLC.(8)
Loan and Security Agreement, dated July 17, 2007, by and between ARCA Discovery, Inc. and Silicon Valley Bank.(8)
First Amendment to Loan and Security Agreement, dated January 21, 2009, by and between ARCA biopharma, Inc. and Silicon Valley Bank.(8)
Second Amendment to Loan and Security Agreement, dated March 23, 2009, by and between ARCA biopharma Colorado, Inc. and Silicon
Valley Bank.(8)
Third Amendment to Loan and Security Agreement, dated April 6, 2009, by and between ARCA biopharma Colorado, Inc. and Silicon Valley
Bank(14)
Fourth Amendment to Assumption of Loan and Security Agreement, dated April 10, 2009, by and between ARCA biopharma, Inc., ARCA
biopharma Colorado, Inc. and Silicon Valley Bank(14)
License and Sublicense Agreement, dated October 28, 2003, by and between ARCA Discovery, Inc. and CPEC, L.L.C.(12)
Amendment to License and Sublicense Agreement, dated February 22, 2006, by and between ARCA Discovery, Inc. and CPEC L.L.C.(13)
Exclusive License Agreement, dated October 14, 2005, by and between ARCA Discovery, Inc. and the University of Colorado's License Equity
Holdings, Inc.(12)
10.3
10.4
10.5
10.6
10.7
10.8
10.9§
10.10§
10.11§
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Exhibit
Number
10.12§
10.13§
10.14
10.15§
10.16§
10.17§
Description
First Amendment to Exclusive License Agreement, dated June 23, 2006, by and between ARCA Discovery, Inc. and the University of Colorado's
License Equity Holdings, Inc.(12)
Second Amendment to Exclusive License Agreement, dated July 20, 2006, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Third Amendment to Exclusive License Agreement, dated July 19, 2007, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Fourth Amendment to Exclusive License Agreement, dated August 22, 2007, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Diagnostic, Collaboration and Option Agreement, dated June 23, 2006, by and between ARCA Discovery, Inc. and CardioDX, Inc.(12)
Amendment to Diagnostic, Collaboration and Option Agreement, dated October 1, 2007, by and between ARCA Discovery, Inc. and CardioDX,
Inc.(12)
10.18§ Manufacturing Agreement, dated September 11, 2006, by and between ARCA Discovery, Inc. and Patheon, Inc.(12)
10.19§
Development, Commercialization and Licensing Agreement, dated February 1, 2007, by and between ARCA Discovery, Inc. and Laboratory
Corporation of America Holdings, Inc.(13)
Amendment No. 1 to Development, Commercialization and Licensing Agreement, dated May 14, 2007, by and between ARCA Discovery, Inc.
and Laboratory Corporation of America Holdings, Inc.(12)
Amendment No. 2 to Development, Commercialization and Licensing Agreement, dated June 10, 2008, by and between ARCA Discovery, Inc.
and Laboratory Corporation of America Holdings, Inc.(12)
10.20
10.21§
10.22 Materials Transfer Agreement, dated October 14, 2005, by and between ARCA Discovery, Inc. and the University of Colorado.(12)
10.23
10.24
Lease Surrender and Termination Agreement, dated August 5, 2009, by and between ARCA biopharma, Inc. and The Irvine Company LLC.(9)
Lease Termination and Warrant Purchase Agreement, dated September 18, 2009, by and between ARCA biopharma, Inc., BMR-201 Industrial
Road LLC and BioMed Realty, L.P.(10)
Exclusive Option Agreement, dated December 2, 2009, by and between ARCA biopharma, Inc. and the University of Cincinnati.(16)
Agreement Term Extension Letter dated December 8, 2010, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and the
University of Cincinnati.(19)
Agreement Term Extension Letter dated December 21, 2010, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and the
University of Cincinnati.(20)
Agreement Term Extension Letter dated January 21, 2011, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and the
University of Cincinnati.(21)
ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 1 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 2 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 3 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
10.25§
10.26
10.27
10.28
10.29†
10.30†
10.31†
10.32†
79
Table of Contents
Exhibit
Number
10.33†
10.34†
10.35†
10.36†
10.37†
10.38†
10.39†
10.40†
10.41†
10.42†
10.43†
10.44†
10.45†
10.46†
10.47
10.48†
10.49
10.50†
10.51†
10.52†
10.53†
10.54†
10.55†
10.56
Description
Amendment No. 4 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 5 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 6 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
ARCA biopharma, Inc. 2004 Stock Incentive Plan, Form of Executive Incentive Stock Option Agreement.(7)
ARCA biopharma, Inc. 2004 Stock Incentive Plan, Form of Non-Executive Incentive Stock Option Agreement.(7)
ARCA biopharma, Inc. 2004 Stock Incentive Plan, Form of Nonqualified Stock Option Agreement.(7)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Partial Acceleration Stock Option
Agreement.(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of No Acceleration Stock Option
Agreement.(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Director Stock Option Agreement.
(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Notice of Grant of Stock Option.(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Notice of Director Grant of Stock
Option.(8)
Form of Indemnification Agreement between Nuvelo, Inc. and its directors and officers.(1)
Nuvelo, Inc. Amended Executive Change in Control and Severance Benefit Plan.(4)
Amended and Restated Employment and Retention Agreement, dated June 4, 2008, by and between ARCA biopharma, Inc. and Michael R.
Bristow.(8)
Assignment and Assumption Agreement, dated January 26, 2009, by and between ARCA biopharma, Inc. and ARCA biopharma Colorado, Inc.
(8)
Amended and Restated Employment Agreement, dated June 12, 2008, by and between ARCA biopharma, Inc. and Christopher D. Ozeroff.(8)
Assignment and Assumption Agreement, dated January 26, 2009, by and between ARCA biopharma, Inc. and ARCA biopharma Colorado, Inc.
(8)
Amended and Restated ARCA biopharma, Inc. 2004 Equity Incentive Plan(11)
ARCA biopharma, Inc. Employee Severance Benefit Plan(18)
ARCA biopharma, Inc. 2009 Reduction in Force Severance Benefit Plan(18)
Form of Option Amendment pursuant to ARCA biopharma, Inc. 2004 Equity Incentive Plan and ARCA biopharma, Inc. 2004 Stock Option Plan
(change of control)(18)
Form of Option Agreement and Grant Notice pursuant to ARCA biopharma, Inc. 2004 Equity Incentive Plan (NDA/change of control
acceleration)(18)
Employment Agreement, dated February 11, 2009, by and between ARCA biopharma, Inc. and Patrick Wheeler.(16)
Form of Indemnification Agreement between ARCA biopharma, Inc. and its directors and officers.(8)
80
Table of Contents
Exhibit
Number
10.57
Description
Agreement Term Extension Letter dated March 31, 2011, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and the
University of Cincinnati.(22)
10.61§
Form of Subscription Agreement.(23)
10.58
10.59§ License Agreement, dated April 15, 2011, by and between ARCA biopharma and the University of Cincinnati.(24)
10.60
First Amendment to Lease Agreement, dated June 14, 2011, by and between Arista Place, LLC and ARCA biopharma Inc., (f/k/a ARCA
Discovery, Inc.).(25)
Amended and Restated Exclusive License Agreement, dated August 12, 2011, by and between the Regents of the University of Colorado and
ARCA biopharma, Inc.(26)
10.62 Form of Subscription Agreement.(27)
10.63
14.1
16.1
23.1*
24.1*
31.1*
Form of Registration Rights Agreement.(27)
Code of Business Conduct and Ethics(9)
Letter from Ernst & Young LLP to the Securities and Exchange Commission, dated March 30, 2009.(15)
Consent of KPMG LLP, Independent Registered Public Accounting Firm.
Power of Attorney (included in the signature page hereto).
Certification of Chief Executive Officer pursuant to Rule 13a-14(a) or 15d-14(a) under the Securities Exchange Act of 1934, as adopted pursuant
to Section 302 of the Sarbanes-Oxley Act of 2002.
Certification of Chief Financial Officer pursuant to Rule 13a-14(a) or 15d-14(a) under the Securities Exchange Act of 1934, as adopted pursuant
to Section 302 of the Sarbanes-Oxley Act of 2002.
Certification of Chief Executive Officer and Chief Financial Officer pursuant to 18 U.S.C. sec. 1350, as adopted pursuant to Section 906 of the
Sarbanes-Oxley Act of 2002.
31.2*
32.1*
101.INS XBRL Instance Document (furnished electronically herewith)
101.SCH XBRL Taxonomy Extension Schema Document (furnished electronically herewith)
101.CAL XBRL Taxonomy Extension Calculation Linkbase Document (furnished electronically herewith)
101.LAB XBRL Taxonomy Extension Label Linkbase Document (furnished electronically herewith)
101.PRE XBRL Taxonomy Extension Presentation Linkbase Document (furnished electronically herewith)
101.DEF XBRL Taxonomy Extension Definition Linkbase Document (furnished electronically herewith)
*
†
§
(1)
(2)
Filed herewith.
Compensatory plan or agreement.
Confidential treatment has been requested for portions of this document, which are omitted and filed separately with the SEC.
XBRL (Extensible Business Reporting Language) information is furnished and not filed or a part of a registration statement or prospectus for purposes
of sections 11 or 12 of the Securities Act of 1933, as amended, is deemed not filed for purposes of section 18 of the Securities Exchange Act of 1934,
as amended, and otherwise is not subject to liability under these sections.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Hyseq, Inc.'s Form S-1, filed on June 12, 1997, as amended,
File No. 333-29091.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 10-Q, filed on November 8, 2006, File
No. 000-22873.
81
Table of Contents
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
Previously filed with the SEC as an Appendix to and incorporated herein by reference from Nuvelo, Inc.'s Proxy Statement on Schedule 14A, filed on
April 18, 2007, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 10-Q, filed on November 7, 2007, File
No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 8-K, filed on September 25, 2008, File
No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 8-K, filed on October 29, 2008, File No.
000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on January 28,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-K, filed on March 27,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on November 16,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on September 24,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q/A, filed on August 21,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on May 15, 2009,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q/A, filed on
November 6, 2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on April 10, 2009,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on March 30,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-K, filed on March 4,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on August 10,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on August 10,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on December 14,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on December 22,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on January 26,
2011, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on April 5, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K filed on April 18, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on May 16, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K filed on June 20, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on August 15,
2011, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K filed on December 22,
2011, File No. 000-22873.
82
Table of Contents
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) 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.
ARCA biopharma, Inc.
By:
Date: March 27, 2012
/s/ PATRICK M. WHEELER
Patrick M. Wheeler
Principal Accounting Officer
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Michael R. Bristow and
Patrick M. Wheeler, and each of them, as his true and lawful attorneys-in-fact and agents, with full power of substitution for him, and in his name in any and
all capacities, to sign any and all amendments to this Annual Report on Form 10-K, and to file the same, with exhibits thereto and other documents in
connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and
authority to do and perform each and every act and thing requisite and necessary to be done therewith, as fully to all intents and purposes as he might or could
do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, and any of them or his or her substitute or substitutes, may lawfully do
or cause to be done by virtue hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed by the following persons on behalf of ARCA
biopharma, Inc., in the capacities and on the dates indicated.
Signature
/s/ MICHAEL R. BRISTOW
Michael R. Bristow
/s/ PATRICK M. WHEELER
Patrick M. Wheeler
/s/ RICHARD B. BREWER
Richard B. Brewer
/s/ JEAN-FRANCOIS FORMELA
Jean-Francois Formela
/s/ LINDA GRAIS
Linda Grais
/s/ BURTON E. SOBEL
Burton E. Sobel
/s/ JOHN L. ZABRISKIE
John L. Zabriskie
President and Chief Executive Officer and Director (Principal Executive Officer)
Title
Chief Financial Officer (Principal Financial Officer and Principal Accounting Officer)
Director
Director
Director
Director
Director
83
Date
March 27, 2012
March 27, 2012
March 27, 2012
March 27, 2012
March 27, 2012
March 27, 2012
March 27, 2012
Table of Contents
EXHIBIT INDEX
Exhibit
Number
2.1
2.2
3.1
3.2
4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
4.10
4.11
4.12
4.13
4.14
4.15
4.16
4.17
Description
Agreement and Plan of Merger and Reorganization, dated September 24, 2008, among Nuvelo, Inc., Dawn Acquisition Sub, Inc. and ARCA
biopharma, Inc.(5)
Amendment No. 1 to Agreement and Plan of Merger and Reorganization, dated October 28, 2008, by and among Nuvelo, Inc., Dawn
Acquisition Sub, Inc. and ARCA biopharma, Inc.(6)
Amended and Restated Certificate of Incorporation of the Registrant, as amended.(8)
Second Amended and Restated Bylaws of the Registrant, as amended.(9)
Form of Common Stock Certificate.(7)
Certificate of Designations of Series A Junior Participating Preferred Stock. (included as part of Exhibit 3.1)
Warrant to Purchase Stock Agreement, dated July 17, 2007, by and between ARCA Discovery, Inc. and Silicon Valley Bank.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and SVB
Financial Group.(8)
Warrant to Purchase Stock Agreement, dated August 19, 2008, by and between ARCA biopharma, Inc. and Silicon Valley Bank.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and SVB
Financial Group.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Boulder Ventures IV, L.P.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Boulder
Ventures IV, L.P.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Boulder Ventures IV (Annex), L.P.
(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Boulder
Ventures IV (Annex), L.P.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and InterWest Partners IX, LP.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and InterWest
Partners IX, LP.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Atlas Venture Fund VII, L.P.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Atlas
Venture Fund VII, L.P.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and The Peierls Foundation, Inc.(8)
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and The Peierls
Foundation, Inc.(8)
Warrant to Purchase Stock Agreement, dated October 10, 2008, by and between ARCA biopharma, Inc. and Skyline Venture Partners Qualified
Purchaser Fund IV, L.P.(8)
84
Table of Contents
Exhibit
Number
4.18
4.19
4.20
4.21
10.1§
10.2§
10.3
10.4
10.5
10.6
10.7
10.8
10.9§
10.10§
10.11§
10.12§
10.13§
10.14
10.15§
10.16§
10.17§
Description
Amendment No. 1 to Warrant to Purchase Stock Agreement, dated February 19, 2009, by and between ARCA biopharma, Inc. and Skyline
Venture Partners Qualified Purchaser Fund IV, L.P.(8)
Warrant to Purchase Stock Agreement, dated October 18, 2009, by and between ARCA biopharma, Inc. and BioMed Realty, L.P.(16)
Form of Common Stock Purchase Warrant.(23)
Form of Warrant to Purchase Common Stock.(27)
Amended and Restated Collaboration and License Agreement, dated July 31, 2006, by and between Nuvelo, Inc. and Archemix Corp.(2)
Second Amended and Restated Collaboration and License Agreement, dated April 20, 2010, by and between ARCA biopharma, Inc. and
Archemix Corp.(17)
Lease, dated February 8, 2008, by and between ARCA Discovery, Inc. and Arista Place, LLC.(8)
Loan and Security Agreement, dated July 17, 2007, by and between ARCA Discovery, Inc. and Silicon Valley Bank.(8)
First Amendment to Loan and Security Agreement, dated January 21, 2009, by and between ARCA biopharma, Inc. and Silicon Valley Bank.
(8)
Second Amendment to Loan and Security Agreement, dated March 23, 2009, by and between ARCA biopharma Colorado, Inc. and Silicon
Valley Bank.(8)
Third Amendment to Loan and Security Agreement, dated April 6, 2009, by and between ARCA biopharma Colorado, Inc. and Silicon Valley
Bank(14)
Fourth Amendment to Assumption of Loan and Security Agreement, dated April 10, 2009, by and between ARCA biopharma, Inc., ARCA
biopharma Colorado, Inc. and Silicon Valley Bank(14)
License and Sublicense Agreement, dated October 28, 2003, by and between ARCA Discovery, Inc. and CPEC, L.L.C.(12)
Amendment to License and Sublicense Agreement, dated February 22, 2006, by and between ARCA Discovery, Inc. and CPEC L.L.C.(13)
Exclusive License Agreement, dated October 14, 2005, by and between ARCA Discovery, Inc. and the University of Colorado's License Equity
Holdings, Inc.(12)
First Amendment to Exclusive License Agreement, dated June 23, 2006, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Second Amendment to Exclusive License Agreement, dated July 20, 2006, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Third Amendment to Exclusive License Agreement, dated July 19, 2007, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Fourth Amendment to Exclusive License Agreement, dated August 22, 2007, by and between ARCA Discovery, Inc. and the University of
Colorado's License Equity Holdings, Inc.(12)
Diagnostic, Collaboration and Option Agreement, dated June 23, 2006, by and between ARCA Discovery, Inc. and CardioDX, Inc.(12)
Amendment to Diagnostic, Collaboration and Option Agreement, dated October 1, 2007, by and between ARCA Discovery, Inc. and
CardioDX, Inc.(12)
85
Table of Contents
Exhibit
Number
10.18§
10.19§
10.20
10.21§
10.22
10.23
10.24
10.25§
10.26
10.27
10.28
10.29†
10.30†
10.31†
10.32†
10.33†
10.34†
10.35†
10.36†
10.37†
10.38†
10.39†
10.40†
Description
Manufacturing Agreement, dated September 11, 2006, by and between ARCA Discovery, Inc. and Patheon, Inc.(12)
Development, Commercialization and Licensing Agreement, dated February 1, 2007, by and between ARCA Discovery, Inc. and Laboratory
Corporation of America Holdings, Inc.(13)
Amendment No. 1 to Development, Commercialization and Licensing Agreement, dated May 14, 2007, by and between ARCA Discovery, Inc.
and Laboratory Corporation of America Holdings, Inc.(12)
Amendment No. 2 to Development, Commercialization and Licensing Agreement, dated June 10, 2008, by and between ARCA Discovery, Inc.
and Laboratory Corporation of America Holdings, Inc.(12)
Materials Transfer Agreement, dated October 14, 2005, by and between ARCA Discovery, Inc. and the University of Colorado.(12)
Lease Surrender and Termination Agreement, dated August 5, 2009, by and between ARCA biopharma, Inc. and The Irvine Company LLC.(9)
Lease Termination and Warrant Purchase Agreement, dated September 18, 2009, by and between ARCA biopharma, Inc., BMR-201 Industrial
Road LLC and BioMed Realty, L.P.(10)
Exclusive Option Agreement, dated December 2, 2009, by and between ARCA biopharma, Inc. and the University of Cincinnati.(16)
Agreement Term Extension Letter dated December 8, 2010, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and
the University of Cincinnati.(19)
Agreement Term Extension Letter dated December 21, 2010, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and
the University of Cincinnati.(20)
Agreement Term Extension Letter dated January 21, 2011, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and the
University of Cincinnati.(21)
ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 1 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 2 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 3 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 4 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 5 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
Amendment No. 6 to the ARCA Discovery, Inc. 2004 Stock Incentive Plan.(7)
ARCA biopharma, Inc. 2004 Stock Incentive Plan, Form of Executive Incentive Stock Option Agreement.(7)
ARCA biopharma, Inc. 2004 Stock Incentive Plan, Form of Non-Executive Incentive Stock Option Agreement.(7)
ARCA biopharma, Inc. 2004 Stock Incentive Plan, Form of Nonqualified Stock Option Agreement.(7)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Partial Acceleration Stock Option
Agreement.(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of No Acceleration Stock Option
Agreement.(8)
86
Table of Contents
Exhibit
Number
10.41†
10.42†
10.43†
10.44†
10.45†
10.46†
10.47
10.48†
10.49
10.50†
10.51†
10.52†
10.53†
10.54†
10.55†
10.56
10.57
10.58
10.59§
10.60
10.61§
10.62
10.63
14.1
16.1
Description
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Director Stock Option Agreement.
(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Notice of Grant of Stock Option.
(8)
ARCA biopharma, Inc. 2004 Equity Incentive Plan (f/k/a Nuvelo, Inc. 2004 Equity Incentive Plan), Form of Notice of Director Grant of Stock
Option.(8)
Form of Indemnification Agreement between Nuvelo, Inc. and its directors and officers.(1)
Nuvelo, Inc. Amended Executive Change in Control and Severance Benefit Plan.(4)
Amended and Restated Employment and Retention Agreement, dated June 4, 2008, by and between ARCA biopharma, Inc. and Michael R.
Bristow.(8)
Assignment and Assumption Agreement, dated January 26, 2009, by and between ARCA biopharma, Inc. and ARCA biopharma Colorado, Inc.
(8)
Amended and Restated Employment Agreement, dated June 12, 2008, by and between ARCA biopharma, Inc. and Christopher D. Ozeroff.(8)
Assignment and Assumption Agreement, dated January 26, 2009, by and between ARCA biopharma, Inc. and ARCA biopharma Colorado, Inc.
(8)
Amended and Restated ARCA biopharma, Inc. 2004 Equity Incentive Plan(11)
ARCA biopharma, Inc. Employee Severance Benefit Plan(18)
ARCA biopharma, Inc. 2009 Reduction in Force Severance Benefit Plan(18)
Form of Option Amendment pursuant to ARCA biopharma, Inc. 2004 Equity Incentive Plan and ARCA biopharma, Inc. 2004 Stock Option
Plan (change of control)(18)
Form of Option Agreement and Grant Notice pursuant to ARCA biopharma, Inc. 2004 Equity Incentive Plan (NDA/change of control
acceleration)(18)
Employment Agreement, dated February 11, 2009, by and between ARCA biopharma, Inc. and Patrick Wheeler.(16)
Form of Indemnification Agreement between ARCA biopharma, Inc. and its directors and officers.(8)
Agreement Term Extension Letter dated March 31, 2011, of the Exclusive Option Agreement by and between ARCA biopharma, Inc. and the
University of Cincinnati.(22)
Form of Subscription Agreement.(23)
License Agreement, dated April 15, 2011, by and between ARCA biopharma and the University of Cincinnati.(24)
First Amendment to Lease Agreement, dated June 14, 2011, by and between Arista Place, LLC and ARCA biopharma Inc., (f/k/a ARCA
Discovery, Inc.).(25)
Amended and Restated Exclusive License Agreement, dated August 12, 2011, by and between the Regents of the University of Colorado and
ARCA biopharma, Inc.(26)
Form of Subscription Agreement.(27)
Form of Registration Rights Agreement.(27)
Code of Business Conduct and Ethics(9)
Letter from Ernst & Young LLP to the Securities and Exchange Commission, dated March 30, 2009.(15)
87
Table of Contents
Exhibit
Number
23.1*
24.1*
31.1*
31.2*
32.1*
101.INS
101.SCH
101.CAL
101.LAB
101.PRE
101.DEF
Description
Consent of KPMG LLP, Independent Registered Public Accounting Firm.
Power of Attorney (included in the signature page hereto).
Certification of Chief Executive Officer pursuant to Rule 13a-14(a) or 15d-14(a) under the Securities Exchange Act of 1934, as adopted
pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
Certification of Chief Financial Officer pursuant to Rule 13a-14(a) or 15d-14(a) under the Securities Exchange Act of 1934, as adopted
pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
Certification of Chief Executive Officer and Chief Financial Officer pursuant to 18 U.S.C. sec. 1350, as adopted pursuant to Section 906 of
the Sarbanes-Oxley Act of 2002.
XBRL Instance Document (furnished electronically herewith)
XBRL Taxonomy Extension Schema Document (furnished electronically herewith)
XBRL Taxonomy Extension Calculation Linkbase Document (furnished electronically herewith)
XBRL Taxonomy Extension Label Linkbase Document (furnished electronically herewith)
XBRL Taxonomy Extension Presentation Linkbase Document (furnished electronically herewith)
XBRL Taxonomy Extension Definition Linkbase Document (furnished electronically herewith)
*
†
§
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Filed herewith.
Compensatory plan or agreement.
Confidential treatment has been requested for portions of this document, which are omitted and filed separately with the SEC.
XBRL (Extensible Business Reporting Language) information is furnished and not filed or a part of a registration statement or prospectus for purposes
of sections 11 or 12 of the Securities Act of 1933, as amended, is deemed not filed for purposes of section 18 of the Securities Exchange Act of 1934,
as amended, and otherwise is not subject to liability under these sections.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Hyseq, Inc.'s Form S-1, filed on June 12, 1997, as amended,
File No. 333-29091.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 10-Q, filed on November 8, 2006, File
No. 000-22873.
Previously filed with the SEC as an Appendix to and incorporated herein by reference from Nuvelo, Inc.'s Proxy Statement on Schedule 14A, filed on
April 18, 2007, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 10-Q, filed on November 7, 2007, File
No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 8-K, filed on September 25, 2008, File
No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from Nuvelo, Inc.'s Form 8-K, filed on October 29, 2008, File No.
000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on January 28,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-K, filed on March 27,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on November 16,
2009, File No. 000-22873.
88
Table of Contents
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on September 24,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q/A, filed on August 21,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on May 15, 2009,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q/A, filed on
November 6, 2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on April 10, 2009,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on March 30,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-K, filed on March 4,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on August 10,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on August 10,
2009, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on December 14,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on December 22,
2010, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on January 26,
2011, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K, filed on April 5, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K filed on April 18, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on May 16, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K filed on June 20, 2011,
File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 10-Q, filed on August 15,
2011, File No. 000-22873.
Previously filed with the SEC as an Exhibit to and incorporated herein by reference from ARCA biopharma, Inc.'s Form 8-K filed on December 22,
2011, File No. 000-22873.
89
Consent of Independent Registered Public Accounting Firm
Exhibit 23.1
The Board of Directors
ARCA biopharma, Inc.:
We consent to the incorporation by reference in the registration statements (Nos. 333-161485, 333-146078, 333-134981, 333-126590, 333-115747,
333-108563, 333-103055, 333-101276, 333-96313, 333-68172, 333-68170, 333-53089, 333-53087, 333-41663, 333-39194, 333-08978, and 333-154839) on
Form S-8 and the registration statements on Form S-3 (Nos. 333-172686 and 333-178984) and the related prospectuses of ARCA biopharma, Inc. (the
Company) of our report dated March 27, 2012, with respect to the consolidated balance sheets of ARCA biopharma, Inc. as of December 31, 2011 and 2010,
and the related consolidated statements of operations, preferred stock and stockholders' equity (deficit), and cash flows for each of the years in the two-year
period ended December 31, 2011, and for the period from December 17, 2001 (date of inception) to December 31, 2011, which report appears in the
December 31, 2011 annual report on Form 10-K of ARCA biopharma, Inc.
Our report dated March 27, 2012 contains an explanatory paragraph that states that the Company's recurring losses from operations and its dependence upon
raising additional funds from strategic transactions, sales of equity, and/or issuance of debt raise substantial doubt about its ability to continue as a going
concern. The consolidated financial statements do not include any adjustments that might result from the outcome of that uncertainty.
Denver, Colorado
March 27, 2012
/s/ KPMG LLP
Exhibit 31.1
I, Michael R. Bristow, certify that:
CERTIFICATION
1.
2.
3.
4.
I have reviewed this annual report on Form 10-K of ARCA biopharma, Inc.;
Based on my knowledge, this annual report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make
the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this
annual report;
Based on my knowledge, the financial statements, and other financial information included in this annual report, fairly present in all material respects
the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this annual report;
The registrant's other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f))
for the registrant and have:
a)
b)
c)
d)
designed such disclosure controls and procedures or caused such disclosure controls and procedures to be designed under our supervision, to
ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those
entities, particularly during the period in which this annual report is being prepared;
designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, 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;
evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in the report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this annual report based on such evaluation;
disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent
fiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially
affect, the registrant's internal control over financial reporting; and
5.
The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the
registrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent functions):
a)
b)
all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably
likely to adversely affect the registrant's ability to record, process, summarize and report financial information; and
any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control
over financial reporting.
Date: March 27, 2012
/s/ Michael R. Bristow
Michael R. Bristow
President and Chief Executive Officer
Exhibit 31.2
I, Patrick M. Wheeler, certify that:
CERTIFICATION
1.
2.
3.
4.
I have reviewed this annual report on Form 10-K of ARCA biopharma, Inc.;
Based on my knowledge, this annual report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make
the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this
annual report;
Based on my knowledge, the financial statements, and other financial information included in this annual report, fairly present in all material respects
the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this annual report;
The registrant's other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f))
for the registrant and have:
a)
b)
c)
d)
designed such disclosure controls and procedures or caused such disclosure controls and procedures to be designed under our supervision, to
ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those
entities, particularly during the period in which this annual report is being prepared;
designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, 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;
evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in the report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this annual report based on such evaluation;
disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent
fiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially
affect, the registrant's internal control over financial reporting; and
5.
The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the
registrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent functions):
a)
b)
all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably
likely to adversely affect the registrant's ability to record, process, summarize and report financial information; and
any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control
over financial reporting.
Date: March 27, 2012
/s/ Patrick M. Wheeler
Patrick M. Wheeler
Chief Financial Officer
ARCA BIOPHARMA, INC.
CERTIFICATION PURSUANT TO
18 U.S.C. SEC. 1350
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
Pursuant to the requirement set forth in Rule 13a-14(b) of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), and Section 1350 of
Chapter 63 of Title 18 of the United States Code (18 U.S.C. §1350), Michael R. Bristow, Chief Executive Officer of ARCA biopharma, Inc. (the "Company"),
and Patrick M. Wheeler, Acting Chief Financial Officer of the Company, each hereby certifies that, to the best of his knowledge:
(1)
(2)
The Company's Annual Report on Form 10-K for the period ended December 31, 2011, to which this Certification is attached as Exhibit 32.1 (the
"Annual Report") fully complies with the requirements of Section 13(a) or Section 15(d) of the Exchange Act, and
The information contained in the Annual Report fairly presents, in all material respects, the financial condition and results of operations of the
Company.
In Witness Whereof, the undersigned have set their hands hereto as of the 27th day of March, 2012.
/s/ Michael R. Bristow
Michael R. Bristow
President and Chief Executive Officer
(Principal Executive Officer)
/s/ Patrick M. Wheeler
Patrick M. Wheeler
Chief Financial Officer
(Principal Financial Officer)
A signed original of this written statement required by Section 906 of the Public Company Accounting Reform and Investor Protection Act of 2002 (18
U.S.C. § 1350, as adopted) has been provided to the Company and will be retained by the Company and furnished to the Securities and Exchange
Commission or its staff upon request. This certification accompanies the Annual Report to which it relates, is not deemed filed with the Securities and
Exchange Commission and is not to be incorporated by reference into any filing of ARCA biopharma, Inc. under the Securities Act of 1933, as amended, or
the Securities Exchange Act of 1934, as amended (whether made before or after the date of the Annual Report), irrespective of any general incorporation
language contained in such filing.