S-1/A 1 ds1a.htm AMENDMENT NO.8 TO FORM S-1 Amendment No.8 to Form S-1
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As filed with the Securities and Exchange Commission on February 1, 2011

Registration No. 333-164574

 

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

AMENDMENT NO. 8

TO

FORM S-1

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

 

 

BG Medicine, Inc.

(Exact name of Registrant as specified in its charter)

 

Delaware   8071   04 3506204
(State or other jurisdiction of incorporation or organization)  

(Primary Standard Industrial

Classification Code Number)

 

(I.R.S. Employer

Identification Number)

610 Lincoln Street North

Waltham, Massachusetts 02451

(781) 890-1199

(Address, including zip code, and telephone number, including area code, of Registrant’s principal executive offices)

 

 

Pieter Muntendam, M.D.

President and Chief Executive Officer

BG Medicine, Inc.

610 Lincoln Street North

Waltham, Massachusetts 02451

(781) 890-1199

(Name, address, including zip code, and telephone number, including area code, of agent for service)

 

 

Copies to:

 

William T. Whelan, Esq.

Scott A. Samuels, Esq.

Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

One Financial Center

Boston, Massachusetts 02111

(617) 542-6000

  

Donald J. Murray, Esq.

Dewey & LeBoeuf LLP

1301 Avenue of the Americas

New York, New York 10019

(212) 259-8000

 

 

Approximate date of commencement of proposed sale to the public: As soon as practicable after this registration statement becomes effective.

If any of the securities being registered on this form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box.    ¨

If this form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.    ¨

If this form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.    ¨

If this form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.    ¨

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 “smaller reporting company” in Rule 12b-2 of the Exchange Act.

 

Large accelerated filer    ¨   Accelerated filer    ¨
Non-accelerated filer    x (Do not check if a smaller reporting company)   Smaller reporting company    ¨

The Registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the registration statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

 

 

 


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The information in this preliminary prospectus is not complete and may be changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This preliminary prospectus is not an offer to sell these securities and it is not soliciting an offer to buy these securities in any state or jurisdiction where the offer or sale is not permitted.

 

PROSPECTUS   SUBJECT TO COMPLETION, DATED FEBRUARY 1, 2011  

 

4,750,000 Shares

LOGO

Common Stock

 

 

BG Medicine, Inc. is offering 4,750,000 shares of common stock. This is our initial public offering, and no public market currently exists for our common stock. We anticipate that the initial public offering price will be $7.00 per share.

Our common stock has been approved for listing on The NASDAQ Global Market under the symbol “BGMD.”

Investing in our common stock involves risks. See “Risk factors” beginning on page 9 of this prospectus.

 

     Per share      Total  

Initial public offering price

   $                            $                        

Underwriting discounts and commissions

   $         $     

Proceeds, before expenses, to us

   $         $     

We have granted the underwriters an option for 30 days from the date of this prospectus to purchase up to 712,500 additional shares of our common stock at the public offering price, less the underwriting discounts and commissions, to cover over-allotments.

Certain of our principal stockholders and/or their affiliates have indicated an interest in purchasing up to an aggregate of $25.3 million of shares of common stock in this offering based upon the expected initial public offering price of $7.00 per share. However, because these potential indications of interest are not binding agreements or commitments to purchase, any or all of these stockholders may elect not to purchase any shares in this offering. Any such purchases, if completed, would be made on the same terms as the shares that are sold to the public generally. See “Prospectus summary — The offering.”

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The underwriters expect to deliver the shares of common stock on or about                     , 2011.

Sole Book-Running Manager

Lazard Capital Markets

 

Baird   Cowen and Company

The date of this prospectus is                     , 2011


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You should rely only on the information contained in this prospectus. We have not, and the underwriters have not, authorized any other person to provide you with different information. If anyone provides you with different or inconsistent information, you should not rely on it. We are not, and the underwriters are not, making an offer to sell these securities in any jurisdiction where the offer or sale is not permitted. You should assume that the information appearing in this prospectus is accurate only as of the date on the front cover of this prospectus. Our business, financial condition, results of operations and prospects may have changed since that date.

TABLE OF CONTENTS

 

 

     Page  

Prospectus summary

     1   

Risk factors

     9   

Special note regarding forward looking statements

     31   

Use of proceeds

     32   

Dividend policy

     33   

Capitalization

     34   

Dilution

     37   

Selected consolidated financial information

     39   

Management’s discussion and analysis of financial condition and results of operations

     41   

Business

     58   
     Page  

Management

     93   

Compensation

     100   

Principal stockholders

     123   

Certain relationships and related person transactions

     128   

Description of capital stock

     132   

Shares eligible for future sale

     137   

Underwriting

     140   

Where you can find more information

     145   

Legal matters

     145   

Experts

     145   

Index to consolidated financial statements

     F-1   

 

 

This prospectus contains market data and industry forecasts that were obtained from industry publications, third party market research and publicly available information. These publications generally state that the information contained therein has been obtained from sources believed to be reliable, but the accuracy and completeness of such information is not guaranteed. While we believe that the information from these publications is reliable, we have not independently verified, and make no representation as to the accuracy of, such information.

Through and including                     , 2011, all dealers that effect transactions in these securities, whether or not participating in this offering, may be required to deliver a prospectus. This requirement is in addition to the dealers’ obligation to deliver a prospectus when acting as underwriters and with respect to their unsold allotments or subscriptions.

 

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Prospectus summary

This summary provides an overview of selected information contained elsewhere in this prospectus and does not contain all of the information you should consider before investing in our common stock. You should carefully read this prospectus and the registration statement of which this prospectus is a part in their entirety before investing in our common stock, including the information discussed under “Risk factors” and our consolidated financial statements and notes thereto that appear elsewhere in this prospectus. Unless otherwise indicated herein, the terms “we,” “our,” “us,” or “the Company” refer to BG Medicine, Inc. and its subsidiary.

OUR COMPANY

We are a life sciences company focused on the discovery, development and commercialization of novel diagnostic tests based on biomarkers for high-value market opportunities in healthcare that we identify. We believe that our tests will provide clinicians with improved information to better detect and characterize disease states. We believe that this information may enable physicians to achieve better patient outcomes and contain healthcare costs. We focus on blood-based tests that we intend to sell, subject to regulatory clearance or approval, through various channels, including through leading diagnostic instrument manufacturers that will offer our tests as novel assays on their instruments.

Our lead product, the BGM Galectin-3 test for heart failure, measures galectin-3 levels in blood plasma or serum. Galectin-3 is a protein that has been shown to play an important role in heart failure, which is a leading cause of death. Heart failure is a heterogenous condition that is characterized by the heart’s inability to pump blood efficiently to meet the requirements of organs in the body. According to the American Heart Association, heart failure affects an estimated 5.8 million Americans and we believe similar numbers in Europe. We have measured galectin-3 in eight controlled studies involving over 5,300 patients with heart failure. In these studies, galectin-3 was found to be a strong independent predictor of mortality or hospitalization. We believe that the data from these studies indicate that heart failure patients with high levels of galectin-3 have a more progressive form of the disease, which we refer to as galectin-3-dependent heart failure. We believe that our galectin-3 test will provide physicians with meaningful information that may lead to more clinically- and cost-effective management of heart failure patients.

We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through Laboratory Corporation of America, or LabCorp. This test is indicated for use in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. In addition, we obtained CE Mark in the European Union for a manual galectin-3 test in October 2009 and have begun limited sales and marketing activities in certain countries in Europe, but, to date, we have recognized only a limited amount of product revenue.

Although our manual BGM Galectin-3 test is an important element of our commercialization strategy, we believe that automated instrument versions of our test will be required for us to achieve broad customer acceptance and clinical adoption. We have entered into worldwide development and commercialization agreements with Abbott Laboratories, Alere, bioMérieux and Siemens for the inclusion of our galectin-3 test on a variety of automated laboratory instruments, including point-of-care instruments. Under these agreements, we have the right to enter into one additional similar agreement with another diagnostic laboratory instrument manufacturer for use on its instruments. We believe that, subject to completion of development of the galectin-3 test on these instruments, one or more of these laboratory instrument manufacturers will be in a position to submit a 510(k) premarket notification to the FDA no later than the fourth quarter of 2011 in order to obtain regulatory clearance to market automated instrument versions of our galectin-3 test in the United States. Subject to clearance from the

 

 

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FDA, we expect an automated instrument version of this test to be available for commercial use through one or more of these instrument manufacturers in the first half of 2012. We believe that it will take considerably less time for laboratory instrument manufacturers to develop and obtain FDA regulatory clearance for an automated version of our galectin-3 test than it took for us to develop and receive FDA regulatory clearance for the manual version of the test, since only the method for performing the test will change. The automated version of the test will be designed in the same way and be indicated for the same use as the manual test, and the manual test will serve as the predicate device under the FDA’s 510(k) clearance requirements. As a result, we expect that the FDA will be able to rely on much of the data and information reviewed, and knowledge gained, during the clearance process for the manual version of our test, thereby reducing the time necessary to receive clearance for the automated version of the test. Notwithstanding these factors, the FDA may not clear the automated version of this test as and when we expect.

In May 2010, we entered into a license and supply agreement with LabCorp under which LabCorp began offering galectin-3 testing services to clinicians in the United States in January 2011. The galectin-3 testing services offered by LabCorp utilize the manual versions of our diagnostic test. Additionally, LabCorp has agreed to perform certain sales and marketing activities to promote galectin-3 testing, which are expected to commence in the first quarter of 2011.

We are also developing three other diagnostic product candidates for cardiovascular disease:

 

Ø  

a second indication of our galectin-3 test as a predictor of heart failure development in patients following heart attack or a related condition called unstable angina, a serious form of cardiac chest pain;

 

Ø  

AMIPredict to identify patients with a high risk of suffering a heart attack or stroke within the following two to four years, for which we are conducting validation studies that we expect to complete in the first half of 2011; and

 

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LipidDx, a novel protein biomarker, to aid in the management of common lipid disorders.

We will need to complete additional development activities for these other product candidates and submit these product candidates for regulatory clearance or approval prior to commercialization in each of the markets where we plan to introduce them. We currently plan to follow the same 510(k) regulatory pathway for these other product candidates in the United States that we followed for our galectin-3 test. We believe that the cardiovascular tests we are developing enable several promising new paradigms for the treatment of patients with cardiovascular disease.

As part of our strategy, we plan to use the patient samples and data generated from our existing and any new collaborations and initiatives to discover and advance the development and commercialization of our product candidates. For example, we initiated and are leading the HRP (“high-risk plaque”) initiative, for atherothrombotic cardiovascular disease, such as heart attack and stroke. This initiative, which we began in 2006, is sponsored by Abbott, AstraZeneca, Merck, Philips and Takeda. These sponsors have provided an aggregate of approximately $25 million to us to conduct studies that aim to discover and validate novel biomarkers that may be used to detect a patient’s risk for atherothrombosis. For example, one of the HRP-funded studies is a large prospective study known as the BioImage study. In consideration for leading the HRP initiative, we have acquired certain rights to use the samples collected in the BioImage study and the data generated from the study for our own product discovery and development studies, which we conduct using our proprietary biomarker discovery platform. In addition to the HRP initiative, in 2009, we partnered with the National Heart, Lung, and Blood Institute, or NHLBI, and Boston University to access samples and data from the Framingham Heart Study to conduct biomarker discovery studies.

 

 

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OUR SOLUTION

We believe that the current medical model has limitations in its ability to manage disease treatment, which often relies on a trial-and-error approach to medical management and characterization of disease based on signs and symptoms. We believe that our diagnostic tests can play a central role in the solution to this important medical challenge by better matching patients with appropriate treatments and enabling early detection and characterization of diseases, leading to more effective and often lower cost treatments. In order to facilitate market acceptance and broad adoption of our biomarker-based diagnostic tests, we plan to make them available to the laboratories that perform these tests on behalf of physicians and their patients in several ways. We are pursuing three distinct paths for commercialization of our diagnostic tests, including sales of manual versions of our diagnostic tests through laboratory service providers, sales by us through certified clinical laboratories and sales of automated versions of our diagnostic tests through leading diagnostic instrument manufacturers for use on their instruments.

We believe that our solution offers several important benefits over existing approaches in diagnostics by:

 

Ø  

Enabling us to structure a discovery process for high-value market opportunities. We believe that our proprietary technology platform offers us an opportunity to initiate a structured process for discovering biomarkers for high-value market opportunities that we identify.

 

Ø  

Providing novel tests for use on laboratory instruments. We are focused on discovering, developing and commercializing biomarker-based diagnostic tests that can be sold through leading diagnostic instrument manufacturers for use as novel assays on their extensive installed base of laboratory instruments.

 

Ø  

Selecting and developing the best commercialization model for each test. Many factors influence how diagnostic tests are commercialized, including their complexity and ability to be offered as simple first generation products, potential need for rapid turn-around, testing volume and reimbursement level, among others. Our multi-pronged commercialization strategy allows us to consider these factors and tailor our commercialization strategy for each product in a manner that best suits the particular test, whether it be manual or automated, offered as in vitro diagnostic test kits to clinical laboratories or as a testing service directly to physicians or patients.

 

Ø  

Improving characterization of disease process. We are developing diagnostic tests to identify disease during the subclinical stage, or before signs and symptoms are present. We believe that early detection and characterization of disease can help physicians better match patients with appropriate treatments, resulting in better clinical outcomes.

 

Ø  

Reducing healthcare costs. We are developing novel diagnostic tests for costly disease states that place tremendous demands on healthcare systems. We believe that our tests can help improve medical management and care outcomes, while reducing healthcare costs in our target markets.

 

Ø  

Involving stakeholders to plan our discoveries. We involve payors, leading scientists and other stakeholders in the selection and execution of our discovery and development projects so that our diagnostic tests may better address unmet medical needs. We believe our approach, in which we identify a significant unmet medical need then attempt to discover a solution to meet the need, provides us with a competitive advantage relative to the prevailing paradigm of attempting to find or establish a market after making an academic discovery.

OUR STRATEGY

Our objective is to become a leader in discovering, developing and commercializing diagnostic tests based on novel biomarkers that we discover or in-license. Key elements of our strategy are to:

 

Ø  

Obtain regulatory clearance or approval for and launch our product candidates.

 

 

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Use patient samples and data generated from our partnerships with third-party payors and government programs to discover clinically-relevant biomarkers for high-value market opportunities using our proprietary biomarker discovery platform.

 

Ø  

Partner with leading laboratory service providers to provide widespread access to our tests upon clearance or approval.

 

Ø  

Partner with leading diagnostic laboratory instrument manufacturers for the development and commercialization of diagnostic tests that can be sold through the manufacturers for use as novel assays on their automated or point-of-care instruments.

 

Ø  

Continue to use patient samples and data generated from existing and new collaborations to successfully advance the development and commercialization of our products candidates.

 

Ø  

Retain primary commercial responsibility for our biomarker tests to drive market penetration and clinical support for our products.

RISKS ASSOCIATED WITH OUR BUSINESS

Our business is subject to numerous risks that could prevent us from successfully implementing our business strategy. These and other risks are discussed more fully in “Risk factors” immediately following this prospectus summary and include the following:

 

Ø  

We are an early stage company with a history of losses, and we expect to incur losses for at least the next several years and we may never achieve profitability.

 

Ø  

Although we recently received FDA clearance for our manual BGM Galectin-3 test for heart failure, we may not obtain regulatory clearance for our other diagnostic product candidates when expected, if at all.

 

Ø  

If the marketplace does not accept our galectin-3 test or any other diagnostic products we might develop, we may be unable to generate sufficient revenue to sustain and grow our business.

 

Ø  

Our business is dependent on our ability to successfully develop and commercialize novel diagnostic products and services based on biomarkers. If we fail to develop and commercialize diagnostic products, we may be unable to execute our business plan.

 

Ø  

If third parties assert that we have infringed their patents and proprietary rights or challenge the validity of our patents and proprietary rights, we may become involved in intellectual property disputes and litigation that would be costly, time consuming and delay or prevent the development or commercialization of our product candidates.

 

Ø  

We expect to expand our development, clinical research and marketing capabilities, and as a result, we may encounter difficulties in managing our growth.

COMPANY INFORMATION

We were incorporated in Delaware in February 2000 and later that year chose the name Beyond Genomics, Inc. In October 2004, we changed our name to BG Medicine, Inc. We maintain our operations at 610 Lincoln Street North, Waltham, Massachusetts 02451, and our phone number is (781) 890-1199. Our website address is www.bg-medicine.com. The information contained in, or that can be accessed through, our website is not part of this prospectus.

“BG Medicine,” the BG Medicine logo and BGM Galectin-3 are trademarks and service marks of BG Medicine, Inc. All other trademarks, service marks, trade names, logos and brand names identified in this prospectus are the property of their respective owners.

 

 

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The offering

 

Common stock offered by us

4,750,000 shares

 

Common stock to be outstanding after this offering

18,143,607 shares

 

Over-allotment option

712,500 shares

 

Use of proceeds

We intend to use the net proceeds of this offering to fund: the commercial launch of our lead product, BGM Galectin-3, including establishing a commercial organization and infrastructure; the development, potential regulatory submission and potential commercial launch activities for our other diagnostic product candidates, including our galectin-3 test to identify patients at elevated risk for heart failure following a heart attack, AMIPredict and LipidDx; our biomarker discovery efforts and potential clinical development of additional novel diagnostic product candidates; possible acquisitions of technologies, products or businesses to complement our business; and other general corporate purposes. See “Use of proceeds” for a more complete description of our intended use of the net proceeds from this offering.

 

Risk factors

Investing in our common stock involves a high degree of risk. See “Risk factors” and the other information included in this prospectus for a discussion of factors you should carefully consider before investing in shares of our common stock.

 

NASDAQ Global Market symbol

BGMD

The number of shares of common stock to be outstanding after the offering is based on an aggregate of 13,393,607 shares of common stock outstanding as of September 30, 2010, after giving effect to the conversion of our outstanding preferred stock and the conversion of our outstanding bridge notes, each as discussed below. Unless otherwise indicated, the information contained in this prospectus, including the information above, excludes:

 

Ø  

2,442,662 shares of common stock issuable upon the exercise of outstanding options as of September 30, 2010, with a weighted-average exercise price of $4.37 per share;

 

Ø  

521,098 shares of common stock reserved for future issuance under our 2001 Stock Option and Incentive Plan, or our 2001 Stock Plan, as of September 30, 2010; provided, however, that immediately upon completion of this offering, our 2001 Stock Plan will terminate so that no further awards may be granted under our 2001 Stock Plan;

 

Ø  

an aggregate of up to 1,199,976 shares of common stock reserved for future issuance under our 2010 Employee, Director and Consultant Stock Plan, or our 2010 Stock Plan, which will become effective upon completion of the offering;

 

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1,217,197 shares of common stock issuable upon the exercise of outstanding warrants as of September 30, 2010, with a weighted-average exercise price of $0.54 per share;

 

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138,449 shares of common stock issuable upon the exercise of outstanding warrants issued on November 4, 2010, with an exercise price of $0.02 per share; and

 

 

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3,304 shares of common stock issuable upon the automatic net exercise of a warrant to purchase 14,018 shares of our common stock upon the completion of this offering at an exercise price of $5.35 per share and based upon the expected initial public offering price of $7.00 per share.

Unless otherwise indicated, the information we present in this prospectus, including the information above:

 

Ø  

reflects the conversion of all of our outstanding preferred stock into 9,541,931 shares of our common stock immediately prior to completion of this offering;

 

Ø  

reflects the issuance of 857,127 shares of our common stock upon the automatic conversion of $6.0 million in principal amount of outstanding bridge notes issued pursuant to the agreement described below based upon the expected initial public offering price of $7.00 per share;

 

Ø  

assumes no exercise of the underwriters’ over-allotment option to purchase up to an additional 712,500 shares of our common stock; and

 

Ø  

reflects the effectiveness of our restated certificate of incorporation and restated bylaws upon completion of this offering.

In addition, unless otherwise indicated, all information in this prospectus gives effect to a 1-for-1.6667 reverse split of our common stock effected on November 29, 2010.

On March 30, 2010, we entered into an agreement to issue up to an aggregate of $6.0 million principal amount of convertible promissory notes, or bridge notes, to certain of our principal stockholders. We refer to this financing as our bridge note financing. We issued $4.0 million of the bridge notes as of September 30, 2010 and the balance of $2.0 million in November 2010. Interest on the bridge notes accrues at the rate of 12% per year. The unpaid principal amount of the bridge notes, together with any interest accrued but unpaid thereon, will automatically convert upon the closing of this offering into a number of shares of our common stock equal to the quotient obtained by dividing the unpaid principal amount of the notes plus interest accrued but unpaid thereon by the initial public offering price. Based upon the expected initial public offering price of $7.00 per share, the $6.0 million principal amount of the outstanding bridge notes will convert into approximately 857,127 shares of our common stock. In connection with the bridge note financing, we issued warrants to purchase 415,347 shares of our common stock. The warrants will be exercisable at an exercise price of $0.02 per share.

If the actual initial public offering price is not equal to the expected initial public offering price of $7.00 per share, the number of shares of common stock into which the bridge notes will convert upon completion of this offering will differ from that set forth above. A $1.00 decrease in the expected initial public offering price of $7.00 per share would increase the number of shares of common stock issuable upon the conversion of bridge notes by an aggregate of 142,848 shares. A $1.00 increase in the expected initial public offering price of $7.00 per share would decrease the number of shares of common stock issuable upon the conversion of the bridge notes by an aggregate of 107,133 shares. Following the closing of this offering, the actual shares of common stock to be issued will be based on the amount of accrued interest then outstanding and the actual initial public offering price.

Certain of our principal stockholders and/or their affiliates, including Flagship Ventures, or Flagship, Gilde Europe Food & Agribusiness Fund B.V., or Gilde, General Electric Pension Trust, or GE, Legg Mason Capital Management Special Investment Trust, Inc., or Legg Mason, SMALLCAP World Fund, Inc., or SMALLCAP, and Stelios Papadopoulos, have indicated an interest in purchasing up to an aggregate of $25.3 million of shares of common stock in this offering based upon the expected initial public offering price of $7.00 per share. However, because these potential indications of interest are not binding agreements or commitments to purchase, any or all of these stockholders may elect not to purchase any shares in this offering. Any such purchases, if completed, would be made on the same terms as the shares that are sold to the public generally.

 

 

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Summary consolidated financial data

The following tables present a summary of our consolidated financial data for the periods, and as of the dates, indicated. Our summary consolidated statements of operations data for each of the three years in the period ended December 31, 2009 and the summary consolidated balance sheet data as of December 31, 2009 have been derived from our audited consolidated financial statements and related notes included elsewhere in this prospectus. The consolidated statement of operations data for the nine months ended September 30, 2009 and 2010, and the consolidated balance sheet data as of September 30, 2010, have been derived from our unaudited condensed consolidated financial statements included elsewhere in this prospectus. Our summary consolidated financial data should be read together with “Management’s discussion and analysis of financial condition and results of operations” and our consolidated financial statements and related notes included elsewhere in this prospectus. The report from our independent registered public accounting firm on our 2009 consolidated financial statements expresses an unqualified opinion on the consolidated financial statements and includes an explanatory paragraph relating to substantial doubt about our ability to continue as a going concern.

 

    Years ended December 31,     Nine months ended
September 30,
 
Consolidated statements of
operations data:
  2007     2008     2009     2009     2010  
    (in thousands, except share and per share amounts)  

Revenue

  $ 8,982      $ 14,580      $ 8,490      $ 8,117      $ 620   
                                       

Operating expenses:

         

Cost of revenue

    7,301        13,822        8,431        7,902        650   

Research and development

    5,832        6,858        8,527        6,502        5,596   

Selling, general and administrative

    3,820        4,475        7,520        5,541        6,224   

Costs related to abandoned stock offering

    3,154                               

Gain on sale of property and equipment

    (118                            
                                       

Total operating expenses

    19,989        25,155        24,478        19,945        12,470   
                                       

Loss from operations

    (11,007     (10,575     (15,988     (11,828     (11,850

Interest income

    302        422        121        102        4   

Interest expense(1)

    (689     (4,921     (244     (203     (1,964

Other income (expense)

                  (26     29        (29
                                       

Net loss

    (11,394     (15,074     (16,137     (11,900     (13,839

Accretion of redeemable convertible preferred stock

    (368     (872     (977     (727     (769
                                       

Net loss attributable to common stockholders

  $ (11,762   $ (15,946   $ (17,114   $ (12,627   $ (14,608
                                       

Net loss attributable to common stockholders per share — basic and diluted

  $ (4.14   $ (5.52   $ (5.84   $ (4.32   $ (4.93
                                       

Weighted-average common shares outstanding used in computing per share amounts — basic and diluted

    2,843,773        2,889,513        2,930,818        2,925,131        2,963,626   

Pro forma net loss attributable to common stockholders per share — basic and diluted(2)

      $ (1.29     $ (1.11
                     

Pro forma weighted-average common shares outstanding used in computing per share amounts — basic and diluted(2)

        12,472,749          12,505,557   

 

 

footnotes on following page

 

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(1)   Interest expense in 2008 and in the nine months ended September 30, 2010 includes non-cash charges of $4.0 million and $1.7 million, respectively, related to expense arising from the issuance of warrants issued in connection with convertible debt that were accounted for as debt discount and beneficial conversion features on convertible debt. Such amounts were immediately recognized as interest expense because the debt was due upon demand.

 

(2)   Net loss used in computing pro forma basic and diluted net loss per share and the number of weighted-average common shares used in computing pro forma basic and diluted net loss per share give effect to the automatic conversion of all of our outstanding convertible preferred stock into 9,541,931 shares of common stock upon the completion of this offering as if such conversion had occurred at the beginning of the period.

The following table sets forth consolidated balance sheet data as of September 30, 2010:

 

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on an actual basis;

 

Ø  

on an unaudited pro forma basis to give effect upon the completion of this offering to (i) the automatic conversion of all shares of our convertible preferred stock outstanding at September 30, 2010 into an aggregate of 9,541,931 shares of our common stock; (ii) the conversion of warrants to purchase 92,305 shares of our convertible preferred stock into warrants to purchase 55,381 shares of our common stock; (iii) the issuance in November 2010 of the remaining $2.0 million in principal amount of bridge notes and the issuance of warrants to purchase 138,449 shares of our common stock, which resulted in a charge to operations totaling approximately $650,000; and (iv) the issuance of 857,127 shares of our common stock upon the automatic conversion of $6.0 million in principal amount of outstanding bridge notes upon the completion of this offering based upon the expected initial public offering price of $7.00 per share;

 

Ø  

on an unaudited pro forma as adjusted basis to give effect to the pro forma adjustments described above and the receipt by us of $28.6 million from the sale of 4,750,000 shares of our common stock offerred by us in this offering based upon the expected initial public offering price of $7.00 per share after deducting underwriting discounts and commissions and estimated offering expenses paid or payable by us.

The unaudited pro forma and pro forma as adjusted consolidated balance sheet data is presented for informational purposes only and does not purport to represent what our consolidated financial position actually would have been had the transactions reflected occurred on the dates indicated or to project our financial condition as of any future date.

 

     As of September 30, 2010  
Consolidated balance sheet data:    Actual     Pro forma     Pro forma
as adjusted(1)
 
     (unaudited)  
     (in thousands)  

Cash, cash equivalents and marketable securities

   $ 2,855      $ 4,855      $ 34,948   

Deferred offering costs

     1,484        1,484        —     

Total assets

     5,969        7,969        36,578   

Warrant liability

     509        46        46   

Long-term debt, including current portion

     4,509        388        388   

Total liabilities

     9,008        4,424        4,424   

Redeemable convertible preferred stock

     71,828        —          —     

Convertible preferred stock

     1,708        —          —     

Accumulated deficit

     (92,415     (93,065     (93,065

Total stockholders’ (deficit) equity

     (74,867     3,545        32,154   

 

(1)   Each $1.00 increase or decrease in the expected initial public offering price of $7.00 per share would increase or decrease, as applicable, our pro forma as adjusted cash, cash equivalents and marketable securities, total assets and total stockholders’ (deficit) equity by approximately $4.4 million, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the underwriting discounts and commissions and estimated offering expenses paid or payable by us.

 

 

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Risk factors

Investing in our common stock involves a high degree of risk. You should carefully consider the risks described below and all of the other information set forth in this prospectus, including our consolidated financial statements and the related notes, before deciding to invest in our common stock. If any of the events or developments described below occurs, our business, financial condition or results of operations could be negatively affected. In that case, the market price of our common stock could decline, and you could lose all or part of your investment.

RISKS RELATED TO OUR BUSINESS AND STRATEGY

We are an early stage company with a history of losses, we expect to incur losses for at least the next several years, and we may never achieve profitability.

We have incurred substantial net losses since our inception in February 2000. For the years ended December 31, 2007, 2008 and 2009, we incurred net losses of $11.4 million, $15.1 million and $16.1 million, respectively, and for the nine months ended September 30, 2010, we incurred a net loss of $13.8 million. Our accumulated deficit was approximately $92.4 million at September 30, 2010. We expect to continue to incur substantial net losses for at least the next several years, and these losses are likely to increase in the near-term.

Historically, we have generated limited revenue from our biomarker discovery and analysis services agreements. Additionally, we have only recently begun limited marketing and sales activities in Europe relating to our first diagnostic test for galectin-3, and, to date, we have recognized only a limited amount of product revenue. As we continue the discovery and development of our diagnostic product candidates, our expenses are expected to increase significantly. Accordingly, we will need to generate significant revenue to achieve profitability. We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. Even as we begin selling this test and potentially other products, we expect our losses to continue as a result of ongoing research and development expenses, as well as increased manufacturing, sales and marketing expenses. These losses, among other things, have had and will continue to have an adverse effect on our working capital, total assets and stockholders’ equity. Because of the numerous risks and uncertainties associated with our product development and commercialization efforts, we are unable to predict when we will become profitable, and we may never become profitable. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. If we are unable to achieve and then maintain profitability, our business, financial condition and results of operations will be negatively affected and the market value of our common stock will decline.

We may not have sufficient resources to continue as a going concern without the proceeds from this offering.

We have received a report from our independent registered public accounting firm on the 2009 financial statements that contains an explanatory paragraph stating that our stockholders’ deficit, recurring net losses and history of negative cash flows from operations raise substantial doubt about our ability to continue as a going concern. We anticipate that our existing cash resources are not sufficient to fund our current business plans beyond the end of March 2011. We cannot be certain that additional financing will be available in sufficient amounts or on terms acceptable to us, if at all. We believe that the successful completion of this offering will allow us to meet our anticipated cash requirements through 2012. If we are unable to successfully complete this offering, we will need to obtain alternative financing and modify our operational plans in order to continue as a going concern.

 

 

 

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Our business is dependent on our ability to successfully develop and commercialize novel diagnostic products and services based on biomarkers. If we fail to develop and commercialize diagnostic products, we may be unable to execute our business plan.

Historically, we have generated revenue from initiatives, collaborations and biomarker discovery and analysis services agreements with pharmaceutical companies and healthcare organizations. Our current business strategy, however, focuses on discovering, developing and commercializing diagnostic products and services based on biomarkers, and we do not expect to continue to receive significant revenue from performing biomarker discovery and analysis services for third parties. The success of our business will depend on our ability to develop and commercialize diagnostic products based on the candidates that we currently have in our product pipeline, as well as others that we might develop internally or in-license in the future.

Prior to commercializing our diagnostic products, we are required to undertake time-consuming and costly development activities, sometimes including clinical studies, and to obtain regulatory clearance or approval, for which the outcome is uncertain. We have limited experience in taking biomarker discovery projects through the development and commercialization stages. There are considerable risks involved in these activities. The science and methods that we are employing are innovative and complex, and it is possible that our product development programs will ultimately not yield diagnostic tests for commercialization. Products that appear promising in early development may fail to be validated in subsequent studies, and even if we achieve positive results, we may still fail to obtain the necessary regulatory clearances or approvals. Few research and development projects result in commercial products, and perceived viability in early clinical studies often is not replicated in later studies. At any point, we may abandon development of a product candidate, or we may be required to expend considerable resources obtaining additional clinical and nonclinical data, which would adversely impact the timing for generating potential revenue from those product candidates. Further, our ability to develop and launch diagnostic tests is dependent on our receipt of substantial additional funding either through this offering or other financing transactions. If our discovery and development programs yield fewer commercial products than we expect, we may be unable to execute our business plan, and our business, financial condition and results of operations may be adversely affected.

We may not be able to successfully commercialize our galectin-3 test or complete our AMIPredict studies as described in this prospectus in the timeframes we expect.

We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. In addition, we are currently conducting additional validation studies using the automated version of our AMIPredict product candidate and expect to complete these validation studies in the first half of 2011. Commercial introduction of the automated version of our galectin-3 test and our AMIPredict product will require FDA clearance or approval. There are a variety of risks and uncertainties that may cause delays in, or prevent us from, successfully commercializing our galectin-3 test or achieving these development milestones in accordance with our planned timeline, or at all, which we explain in greater detail in the sections titled “Business — BGM galectin-3 in heart failure — Overview,” “Business — BGM galectin-3 in heart failure — Commercialization” and “Business — AMIPredict for acute atherothrombosis (cause of heart attack or stroke) — Additional studies planned.” Delays may result from unanticipated problems in product development, an inability to obtain regulatory clearance or approval on a timely basis, and an inability to successfully enter into partnerships with diagnostic laboratory instrument companies and other risks described elsewhere in this prospectus.

 

 

 

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We may never successfully commercialize our diagnostic tests. If we are unable to execute our commercialization strategy, we may be unable to generate sufficient revenue to sustain our business.

We are an early stage company and have engaged in only limited sales and marketing activities for our first product, the BGM Galectin-3 test for heart failure. To date, we have recognized only a limited amount of product revenue. We are in the process of transitioning into a commercial organization, and we have only very limited experience to date in conducting commercial activities.

We anticipate that a substantial portion of any future product revenue will come from sales of our galectin-3 test. We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. In addition, the test has obtained CE Mark in the European Union, but we have commenced only limited sales and marketing activities in the region.

Our success in commercializing our galectin-3 test and any other product candidates that we are able to develop will require that we expand or develop a wide variety of operational functions with which to date we have had little or no experience. We intend to retain worldwide marketing rights to our products, and we will be primarily responsible for generating demand, increasing market adoption, working with payors to make reimbursement and coverage determinations and ensuring that our biomarker-based tests realize their market potential. To accomplish this, we will need to create a commercial infrastructure that we do not currently have. We have hired a senior sales executive, but to execute our strategy we also plan to hire a limited number of professionals to form our specialty sales force. Sales professionals with the necessary technical and business qualifications we plan to hire are in high demand, and we may have difficulty hiring or retaining them. We plan to distribute and market our products initially through U.S. national and regional laboratory service providers, such as LabCorp, and through large diagnostic laboratory instrument manufacturers, such as Abbott Diagnostics, Alere Inc., or Alere, bioMérieux SA, or bioMérieux, and Siemens Healthcare Diagnostics Inc., or Siemens. Moreover, even if we are able to implement this strategy, we will be largely dependent on these third parties for the commercial success of our products. They may not deploy the resources we would like them to, and our revenue would then suffer. In addition, we could become embroiled in disputes with these parties regarding the terms of any agreements, their performance or intellectual property rights. Any dispute could disrupt the sales of our products and adversely affect our reputation and revenue. Our strategy to leverage the expertise, marketing resources and installed base of these potential partners may ultimately fail.

If the marketplace does not accept our galectin-3 test or any other diagnostic products we might develop, we may be unable to generate sufficient revenue to sustain and grow our business.

Even though we believe that the manual version of our BGM Galectin-3 test and our other diagnostic product candidates represent promising commercial opportunities, our products may never gain significant acceptance in the marketplace and therefore never generate substantial revenue or profits for us. As is the case with all novel biomarkers, we must establish a market for our galectin-3 test and build that market through physician education and awareness programs. We have built and launched an educational website for Europe supporting the clinical utility of our galectin-3 test for use in heart failure. Publication in peer review journals of results from studies using our products will be an important consideration in the adoption by physicians of our products. The process of publication in leading medical journals is subject to a peer review process. Peer reviewers may not consider the results of our galectin-3 studies sufficiently novel or worthy of publication. Failure to have our studies published in peer review journals may adversely affect adoption of our products.

 

 

 

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Under our collaboration agreements with Abbott, Alere, bioMérieux and Siemens for the commercialization of our galectin-3 test, we bear primary responsibility for validating the clinical utility of our galectin-3 test. We are also responsible for promoting the utility of the galectin-3 biomarker, including developing and executing plans to raise awareness of, and create demand for, our galectin-3 test among clinicians and payors, as well as developing and implementing a reimbursement strategy for our galectin-3 test. We have little experience in these types of activities. We may be unable to demonstrate that our galectin-3 test provides incremental benefits over currently available heart failure diagnostic tests sufficient to ensure adoption of our test. Our ability to successfully commercialize the diagnostic products that we may develop will depend on numerous factors, including:

 

Ø  

whether healthcare providers believe our galectin-3 test and any other diagnostic tests that we successfully develop provide sufficient incremental clinical utility;

 

Ø  

whether the medical community accepts that our diagnostic products have sufficient sensitivity and specificity to be meaningful in patient care and treatment decisions; and

 

Ø  

whether health insurers, government health programs and other third-party payors will cover and pay for our diagnostic tests and the amount they will reimburse.

These factors may present obstacles to commercial acceptance of our diagnostic product candidates. If these obstacles arise, we may need to devote substantial time and money to surmount these obstacles, and we might not be successful. Failure to achieve widespread market acceptance of our diagnostic products would materially harm our business, financial condition and results of operations.

Health insurers and other third-party payors may decide not to cover our diagnostic products or may provide inadequate reimbursement, which could jeopardize our commercial prospects.

In the United States, the regulatory process that allows diagnostic tests to be marketed is independent of any coverage determinations made by third-party payors. For new diagnostic tests, private and government payors decide whether to cover the test, the reimbursement amount for a covered test and the specific conditions for reimbursement. Physicians may order diagnostic tests that are not reimbursed by third-party payors, but coverage determinations and reimbursement levels and conditions are critical to the commercial success of a diagnostic product.

Each third-party payor makes its own decision about which tests it will cover and how much it will pay, although many payors will follow the lead of Medicare. As a result, the coverage determination process is often a time-consuming and costly process that requires us to provide scientific and clinical support for the use of each of our products to each payor separately, with no assurance that approval will be obtained. If third-party payors decide not to cover our diagnostic tests or if they offer inadequate payment amounts, our ability to generate revenue from our diagnostic tests could be limited. Even if one or more third-party payors decides to reimburse for our tests, a third-party payor may stop or lower payment at any time, which would reduce revenue. We intend to develop a strategy to advocate for desired coverage and payment levels, which will include aligning ourselves with third-party payors to encourage the acceptance of our products. However, we cannot predict whether third-party payors will cover our tests or offer adequate reimbursement. We also cannot predict the timing of such decisions. In addition, physicians or patients may decide not to order our tests if third-party payments are inadequate, especially if ordering the test could result in financial liability for the patient.

In the United States, the American Medical Association assigns specific Current Procedural Terminology, or CPT, codes, which are a medical nomenclature used to report medical procedures and services under public and private health insurance plans. Once the CPT code is established, the Centers for Medicare and Medicaid Services, or CMS, establishes reimbursement payment levels and coverage rules for Medicare, and

 

 

 

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private payors establish rates and coverage rules independently. We have initiated the process to obtain an analyte-specific CPT code for measuring galectin-3 in plasma or serum. Based on the AMA’s submission process, we expect to be eligible to obtain an analyte-specific CPT Code for galectin-3 testing on the 2013 Clinical Laboratory Fee Schedule or thereafter. However, we cannot guarantee that our galectin-3 test will receive its own analyte-specific CPT code and will be approved for reimbursement by Medicare or other third-party payors. Additionally, any or all of our diagnostic tests developed in the future may not be approved for reimbursement or may be approved at a level that limits our commercial success.

In addition, payment for diagnostic tests furnished to Medicare beneficiaries is made based on a fee schedule set by CMS in most instances. In recent years, payments under these fee schedules have decreased and may decrease more, which could jeopardize our commercial prospects. Reimbursement decisions in the European Union and in other jurisdictions outside of the United States vary by country and region and there can be no assurance that we will be successful in obtaining adequate reimbursement.

We expect to face intense competition, often from companies with greater resources and experience than us.

The diagnostics industry is highly competitive and subject to rapid change. The industry continues to expand and evolve as an increasing number of competitors and potential competitors enter the market. Many of these competitors and potential competitors have substantially greater financial, technological, managerial and research and development resources and experience than we do. Some of these competitors and potential competitors have more experience than we do in the development of diagnostic products, including validation procedures and regulatory matters. In addition, we expect that our diagnostic products, if successfully developed, will compete with product offerings from large and well-established companies that have greater marketing and sales experience and capabilities than we do. We are aware of other diagnostic tests under development, which, if successfully developed and commercialized, would compete with our products. Our competitors, some of whom we collaborate with and will rely on to commercialize our products, may include established diagnostics companies, such as Abbott, Beckman Coulter, Roche Diagnostics, General Electric, Alere, LabCorp, Ortho Clinical Diagnostics, Mitsubishi, Philips and Siemens. We may also compete with national laboratory services providers with extensive service networks for diagnostic tests, such as LabCorp and Quest Diagnostics, and specialized laboratories, such as Genzyme Genetics and Myriad Genetics. Companies that may compete with us in cardiovascular disease, immune disorders and central nervous system disorders include Athena Diagnostics, Atherotech, Celera Group, Dako, diaDexus, QIAGEN, Liposcience, Rules-Based Medicine and XDx. If we are unable to compete successfully, we may be unable to grow and sustain our revenue.

We are dependent on third parties for the patient samples that are essential to our biomarker discovery and diagnostics product development plans.

To pursue our biomarker discovery and diagnostics product development program, we will need access, over time, to thousands of patient samples, including blood, blood plasma and serum, urine and other fluids. We do not have direct access to a supply of patient samples. As a result, we have made arrangements with third parties, such as academic medical centers, government programs and payors such as Humana, that we believe will give us access to a significant number of patient samples over the coming years. Most of the institutions and physicians from which we obtain biological specimens that we use in our research and validation work are “Covered Entities” under the Health Insurance Portability and Accountability Act of 1996, or HIPAA. Under this law, these parties may have to obtain proper authorization from their patients for the subsequent use of those samples and associated clinical information. We are not presently a Covered Entity or a Business Associate of a Covered Entity subject to HIPAA; however, we may become a Covered Entity or a Business Associate of a Covered Entity in the future, if we provide clinical laboratory testing services. We may lose access to patient samples provided

 

 

 

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by such third parties, or have that access limited, because the third parties decrease the number of patient samples they provide, due to changes in privacy laws governing the use and disclosure of medical information or due to changes in the laws restricting our ability to obtain patient samples and associated information. In certain instances, we owe the party providing the samples for our research programs payments which may be related to the sales of products derived from those research programs. In addition, we may be forced to actively pursue patient samples from other sources for the diagnostic testing indications we pursue, which could be expensive and time consuming. If we fail to secure and maintain an adequate supply of patient samples, or if our existing supply arrangements are terminated or result in access to fewer samples than expected, our ability to pursue our biomarker discovery and development efforts may be slowed or halted, which could have a material adverse effect on our business, financial condition and results of operations.

We rely on third-party suppliers for some of our laboratory instruments and supplies used in biomarker discovery and development and we will rely on third-party suppliers for the commercialization of our products. If any of these supply arrangements are interrupted or terminated, we may not be able to find adequate replacements on a timely basis or at all.

We rely on mass spectrometry equipment and other advanced instruments from Applied Biosystems and other vendors to generate the vast majority of data for our biomarker discovery and development projects. In addition, we anticipate that we will rely on Abbott, Alere, bioMérieux, Siemens and other vendors to supply us with laboratory immunochemistry instruments and reagents for the development and future commercialization of the BGM Galectin-3 test for heart failure, AMIPredict and future diagnostic product candidates. If we were to lose any of these suppliers or if our suppliers were to become unwilling or unable to provide these materials in required quantities or on our required timelines, we would be required to identify new suppliers with similar instrumentation, reagents and software capable of supporting our discovery and development efforts based on our proprietary technologies, or possibly modify our discovery and development processes and procedures. If supplies for the BGM Galectin-3 test for heart failure, AMIPredict or any future diagnostic product candidates are interrupted or terminated, we may need to repeat some or all of our development studies for such products, and we may need to seek a new or amended FDA registration for such products. We may not be able to identify or contract with acceptable replacement sources on a timely basis, on acceptable terms, or at all. If we are able to identify other suppliers, there is no guarantee that we would be able to transfer our technologies to new instruments and equipment or substitute reagents or other materials with comparable results or on a timely basis. We may also become involved in disputes with our third-party suppliers or we may become party to disputes between these suppliers and other parties, which could be expensive and time consuming. Delays or difficulties experienced with these third-party suppliers would have a material adverse effect on our business, financial condition and results of operations.

We may need to raise additional capital in the future. If we are unable to secure adequate funds on terms acceptable to us, we may be unable to execute our business plan.

We expect to continue to incur substantial net losses for at least the next several years. We believe that our current cash, cash equivalents and marketable securities, together with the expected net proceeds from this offering, will be sufficient to meet our anticipated cash requirements through 2012. If we incur delays in commencing commercialization of our galectin-3 test or in achieving significant product revenue, or if we encounter other unforeseen adverse business developments, we may exhaust our capital resources prior to this time.

 

 

 

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We cannot be certain that additional capital will be available when needed or that our actual cash requirements will not be greater than anticipated. Financing opportunities may not be available to us, or if available, may not be on favorable terms. The availability of financing opportunities will depend on various factors, such as market conditions and our financial condition and outlook. In addition, if we raise additional funds through the issuance of equity or convertible debt securities, the percentage ownership of our stockholders could be significantly diluted, and these newly-issued securities may have rights, preferences or privileges senior to those of existing stockholders. If we obtain additional debt financing, a substantial portion of our operating cash flow may be dedicated to the payment of principal and interest on such indebtedness, and the terms of the debt securities issued could impose significant restrictions on our operations. If we raise additional funds through collaborations and licensing arrangements, we might be required to relinquish significant rights to our technologies or products, or grant licenses on terms that are not favorable to us. If we are unable to obtain financing on terms favorable to us, we may be unable to execute our business plan and we may be required to cease or reduce development or commercialization of our product candidates, sell some or all of our technology or assets or merge with another entity.

Declining general economic or business conditions may have a negative impact on our business.

Continuing concerns over U.S. healthcare reform legislation and energy costs, geopolitical issues, the availability and cost of credit and government stimulus programs in the United States and other countries have contributed to increased volatility and diminished expectations for the global economy. These factors, combined with low business and consumer confidence and high unemployment, precipitated an economic slowdown and recession. If the economic climate does not improve or continues to deteriorate, our business, including our access to patient samples and the addressable market for diagnostic tests that we may successfully develop, as well as the financial condition of our suppliers and our third-party payors, could be adversely affected, resulting in a negative impact on our business, financial condition and results of operations.

RISKS RELATED TO OUR INTELLECTUAL PROPERTY

If the combination of patents, trade secrets and contractual provisions that we rely on to protect our intellectual property proves inadequate, our ability to successfully commercialize our proposed products will be harmed and we may never be able to operate our business profitably.

Our success depends, in large part, on our ability to protect proprietary methods, discoveries and diagnostic tests that we develop under the patent and other intellectual property laws of the United States and other countries, so that we can seek to prevent others from unlawfully using our inventions and proprietary information. We rely on both patents and trade secrets to protect the proprietary aspects of our methods and discoveries. We have a non-exclusive license to practice and commercialize technology covered by two issued U.S. patents and their foreign counterparts that relate to our methods for discovering biomarkers. As of January 31, 2011, we had 20 pending patent applications filed either with the U.S. Patent and Trademark Office or under the Patent Cooperation Treaty, or PCT, and foreign counterparts of certain of these patent applications. A subset of the intellectual property that we own or license relates to our galectin-3 test for heart failure. This intellectual property includes U.S. Patent Application No. 10/575,745 exclusively licensed from ACS Biomarker B.V. and nine corresponding patent applications pending in the United States and abroad. We received an issue notification dated January 26, 2011, which indicates that U.S. Patent Application No. 10/575,745 will issue as a patent on February 15, 2011, and that the term of the patent is adjusted to expire in November 2026. We own a

 

 

 

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U.S. and a PCT application relating to a specific method and kit for detecting galectin-3. Any patent issuing from this U.S. application could expire as early as 2029. In addition, we own two U.S. patent applications related to methods for clinical evaluation of subjects and therapies based on galectin-3 measurements. For the diagnostic tests that we develop based on our biomarker discoveries, we expect to rely primarily on patent protection. We have filed or have license rights to a number of patent applications related to our proprietary methods and diagnostic tests, but we do not yet have any issued patents in the United States or Europe. Moreover, several of our owned and licensed patent applications are in an early stage of prosecution, and we cannot assure you that any of the pending patent applications will result in patents being issued. In addition, due to technological changes that may affect our proposed products or judicial interpretation of the scope of our patents, our proposed products might not, now or in the future, be adequately covered by our patents.

The patentability of biomarkers and of test methods and products based on biomarkers is well-established in most countries. However, the issue of any patent, including the patents for which we have applied, depends upon a detailed interpretation of the specific patent claims and prior art, and generally is highly uncertain because of the complex legal and factual considerations it involves. In recent years, patentability issues have been the subject of much litigation. The result of these legal developments may preclude or limit the patent protection available for our diagnostic tests, such as those we use to develop our proposed products. The patentability of claims currently pending, the validity and enforceability of issued or to be issued patent claims and the commercial value of our patent rights, therefore, are highly uncertain.

In addition, we cannot be certain that we hold the rights to the technology covered by pending patent applications or to other proprietary technology required for us to commercialize our proposed products. Rights in applications filed by us or our licensors may be affected adversely by patent applications filed by others which have not yet been published. For example, because certain U.S. patent applications are confidential until patents issue, such as applications filed prior to November 29, 2000, or applications filed after this date which will not be filed in foreign countries, third parties may have filed patent applications for technology covered by our pending patent applications without our being aware of those applications, and our patent applications may not have priority over those applications. For this and other reasons, we may be unable to secure desired patent rights, thereby losing desired exclusivity or co-exclusivity. It is also possible that one or more organizations will hold patent rights to which we will need a license. If those organizations refuse to grant us a license to such patent rights on reasonable terms, we will not be able to market our proposed products.

If third parties assert that we have infringed their patents and proprietary rights or challenge the validity of our patents and proprietary rights, we may become involved in intellectual property disputes and litigation that would be costly, time consuming, and delay or prevent the development or commercialization of our proposed products.

Our ability to commercialize our proposed products depends on our ability to develop, manufacture, market and sell our proposed products without infringing the proprietary rights of third parties. Third parties may allege that our proposed products or our methods or discoveries infringe their intellectual property rights. Numerous U.S. and foreign patents and pending patent applications, which are owned by third parties, exist in fields that relate to our proposed products and our underlying methodologies and discoveries, including patents and patent applications claiming methods for the discovery of biomarkers or biomarker sets and assay systems and methods designed to exploit them clinically in drug discovery efforts or in selection of patients.

A third party may sue us for infringing its patent rights. Likewise, we may need to resort to litigation to enforce a patent issued or licensed to us or to determine the scope and validity of third party proprietary rights. In addition, a third party may claim that we have improperly obtained or used its confidential or

 

 

 

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proprietary information. The cost to us of any litigation or other proceeding relating to intellectual property rights, even if resolved in our favor, could be substantial, and the litigation would divert our management’s attention from other aspects of our business. Some of our competitors may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources. Uncertainties resulting from the initiation and continuation of any litigation could limit our ability to continue our operations.

If we are found to infringe upon intellectual property rights of third parties, we might be forced to pay damages, potentially including treble damages, if we are found to have willfully infringed on such parties’ patent rights. In addition to any damages we might have to pay, a court could require us to stop the infringing activity or obtain a license. Any license required under any patent may not be made available on commercially acceptable terms, if at all. In addition, such licenses are likely to be non-exclusive and, therefore, our competitors may have access to the same technology licensed to us. If we fail to obtain a required license and are unable to design around a patent, we may be unable to effectively market some or all of our products, which could limit our ability to generate revenue or achieve profitability and possibly prevent us from generating revenue sufficient to sustain our operations. Moreover, we expect that a number of our collaborations will provide that royalties payable to us for licenses to our intellectual property may be offset by amounts paid by our collaborators to third parties who have competing or superior intellectual property positions in the relevant fields, which could result in significant reductions in our revenue from products developed through collaborations.

Many of our employees were previously employed at universities or other biotechnology, pharmaceutical or diagnostic products companies, including our competitors or potential competitors. While we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have inadvertently or otherwise used or disclosed the former employer’s intellectual property, trade secrets or other proprietary information. Litigation based on such allegations may be brought against us, and even if we are successful in defending ourselves, we could incur substantial costs and our management could be distracted. If we fail in defending such allegations, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.

If we are unable to protect our trade secrets, we may be unable to protect our interests in proprietary technology, processes and know-how that is not patentable or for which we have elected not to seek patent protection.

In addition to patented technology, we rely upon unpatented proprietary technology, processes and know-how, including particularly our biomarker discovery methodologies. In an effort to protect our unpatented proprietary technology, processes and know-how, we require our employees, consultants, collaborators, contract manufacturers and advisors to execute confidentiality agreements. These agreements, however, may not provide us with adequate protection against improper use or disclosure of confidential information, in particular as we are required to make such information available to a larger pool of people as we seek to expand our discovery and development efforts and commercialize our proposed products. These agreements may be breached, and we may not become aware of, or have adequate remedies in the event of, any such breach. In addition, in some situations, these agreements may conflict with, or be subject to, the rights of third parties with whom our employees and consultants have previous employment or consulting relationships. Also, others may independently develop substantially equivalent technology, processes and know-how or otherwise gain access to our trade secrets. If we are unable to protect the confidentiality of our proprietary technology, processes and know-how, competitors may be able to use this information to develop products that compete with our products, which could adversely impact our business.

 

 

 

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If we fail to comply with our obligations in the agreements under which we license development or commercialization rights to products or technology from third parties, we could lose license rights that are important to our business.

Several of our collaboration agreements provide for licenses to us of intellectual property or sharing of rights to intellectual property that is important to our business, and we may enter into additional agreements in the future that provide licenses to us of valuable technology. These licenses impose, and future licenses may impose, various commercialization, milestone and other obligations on us, including the obligation to terminate our use of patented subject matter under certain contingencies. If a licensor becomes entitled to, and exercises, termination rights under a license, we would lose valuable rights and our ability to develop our products. We may need to license other intellectual property to commercialize future products. Our business may suffer if any current or future licenses terminate, if the licensors fail to abide by the terms of the license or fail to prevent infringement by third parties, if the licensed patents or other rights are found to be invalid or if we are unable to enter into necessary licenses on acceptable terms.

RISKS RELATED TO THE GROWTH OF OUR MANAGEMENT TEAM, WORKFORCE, MANUFACTURING AND FACILITIES

Our future success depends on our ability to retain our chief executive officer and other key employees and to attract, retain and motivate qualified personnel.

Our success depends on our ability to attract, retain and motivate highly qualified management and scientific personnel. In particular, we are highly dependent on Pieter Muntendam, M.D., our President and Chief Executive Officer, and the other principal members of our executive team. All of the arrangements with the principal members of our executive and scientific teams may be terminated by us or the employee at any time without notice. The loss of any of these persons’ expertise would be difficult to replace and could have a material adverse effect on our ability to achieve our business goals. In addition, the loss of the services of any member of our senior management or our scientific staff may impede the achievement of our research, development and commercialization objectives by diverting management’s attention to transition matters and identification of suitable replacements, if any. There can be no assurance that we will be successful in hiring or retaining qualified personnel, and our failure to do so could have a material adverse effect on our business, financial condition and results of operations.

Recruiting and retaining qualified scientific personnel and, in the future, sales and marketing personnel will also be critical to our success. We may not be able to attract and retain these personnel on acceptable terms given the competition among pharmaceutical, biotechnology and diagnostic companies for similar personnel. We also experience competition for the hiring of scientific personnel from universities and research institutions. We do not maintain “key person” insurance on any of our employees. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us.

 

 

 

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We expect to expand our development, clinical research, and marketing capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.

To accommodate the commercial launch of any diagnostic products that we are able to develop successfully and the demands of being a public company, we expect to experience significant growth in the number of our employees and the scope of our operations. To manage our anticipated future growth, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities, and continue to recruit and train additional qualified personnel. Due to our limited resources, we may not be able to effectively manage the expansion of our operations or recruit and train additional qualified personnel. The expansion of our operations may lead to significant costs and may divert our management and business development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.

If our sole laboratory facility becomes damaged or inoperable, our ability to pursue our discovery and development efforts may be jeopardized.

We currently perform all of our biomarker discovery and development work in our laboratories at our headquarters in Waltham, Massachusetts. At the present time, we do not have redundant laboratory facilities. Our facilities could be harmed or rendered inoperable by natural or man-made disasters, including fire, flooding and power outages, which may render it difficult or impossible for us to perform our biomarker discovery and development work for some period of time. A key component of our discovery engine is our unique access to biological samples, and the resulting data sets and medical histories that form the foundation of our biomarker discovery and clinical validation. Access to suitable samples for discovery or validation is often an important gating factor for our discovery projects. If these biological samples or related data are damaged or compromised, our ability to pursue our discovery and development projects, as well as our reputation, may be jeopardized. In some cases, the samples are unique and irreplaceable. Furthermore, our facilities and the equipment we use to perform our discovery and development work could be costly and time-consuming to repair or replace. Although we maintain insurance for damage to our property and the disruption of our business, this insurance may not be sufficient to cover all of our potential losses and may not continue to be available to us on acceptable terms, or at all. If the patient samples to which we have obtained access are damaged or we lose operation of our laboratory facilities for any extended period of time, our discovery and development projects could be delayed, and our reputation and relationships with collaborators could be harmed. In order to establish a redundant laboratory facility, if necessary, we would be required to spend considerable time and money securing adequate space, constructing the facility, recruiting and training employees and establishing the additional operational and administrative infrastructure necessary to support a second facility.

Failure in our information technology and storage systems could significantly disrupt the operation of our proprietary technology platform and our ability to discover and validate biomarkers, which would adversely impact our development and commercialization efforts.

Our ability to execute our business plan depends, in part, on the continued and uninterrupted performance of our information technology systems, or IT systems, which support our discovery and development platform. Our platform integrates molecular measurement technologies based on specialized mass spectrometry, chromatography, nuclear magnetic resonance spectroscopy and multiplexed assay technologies. Due to the sophisticated nature of our proprietary technology platform, we are substantially dependent on our IT systems. IT systems are vulnerable to damage from a variety of sources, including telecommunications or network failures, malicious human acts and natural disasters. Moreover, despite network security and back-up measures, some of our servers are potentially vulnerable to physical or

 

 

 

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electronic break-ins, computer viruses and similar disruptive problems. Despite the precautionary measures we have taken to prevent unanticipated problems that could affect our IT systems, sustained or repeated system failures that interrupt our ability to generate and maintain data, and in particular to operate our proprietary technology platform, could adversely affect our ability to operate our business.

We rely on a single third party to manufacture and supply our product candidates. Any problems experienced by this vendor could result in a delay or interruption in the supply of our product candidates to us until this vendor cures the problem or until we locate and qualify an alternative source of supply.

The manufacture of our diagnostic product candidates requires specialized equipment and utilizes complicated production processes that would be difficult, time-consuming and costly to duplicate. Corgenix Medical Corporation is currently the third-party manufacturer of our galectin-3 test. Any prolonged disruption in the operations of our third-party manufacturer could have a significant negative impact on our ability to manufacture products on our own and would cause us to seek additional third-party manufacturing contracts, thereby increasing our development and any commercialization costs. We may suffer losses as a result of business interruptions that exceed coverage under our manufacturer’s insurance policies. Events beyond our control, such as natural disasters, fire, sabotage or business accidents could have a significant negative impact on our operations by disrupting our product candidate development and commercialization efforts until our third-party manufacturer can repair its facility or put in place third-party contract manufacturers to assume this manufacturing role, which we may not be able to do on reasonable terms, if at all. In addition, if we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines. The delays associated with the verification of a new manufacturer or the reverification of an existing manufacturer could negatively affect our ability to develop product candidates or produce approved products in a timely manner. Any delay or interruption in our clinical studies for the validation and commercialization of our product candidates could negatively affect our business.

In pursuing the first path of our commercialization strategy for our manual BGM Galectin-3 test for heart failure, we plan to rely initially on LabCorp to provide the majority of our manual galectin-3 testing services in the United States. Any disruptions in LabCorp’s operations could result in a delay or interruption of the galectin-3 testing service.

We are pursuing three distinct paths for the commercialization of our diagnostic tests, including sales of manual versions of our tests through laboratory service providers, sales by us through certified clinical laboratories and sales of automated versions of our tests through leading diagnostic instrument manufacturers for use on their instruments. In pursuing the first path of our commercialization strategy for our manual BGM Galectin-3 test for heart failure, we plan to rely initially on Labcorp to provide a majority of our manual galectin-3 testing services in the United States. We may suffer losses as a result of any business interruptions experienced by LabCorp. Events beyond our control, such as natural disasters, fire, sabotage or business accidents could have a significant negative impact on our operations. Any prolonged disruption in LabCorp’s operations could have a significant negative impact on our ability to successfully commercialize our galectin-3 test by selling manual versions of our galectin-3 test through laboratory service providers in the United States until LabCorp cures the problem or until alternate testing sites are established or arrangements have been made with alternate providers of laboratory testing services, which we may not be able to do on acceptable terms, if at all, and which may increase our commercialization costs. Additionally, the delays associated with identifying and setting up alternate laboratory service providers could negatively affect the adoption of galectin-3 testing by physicians.

 

 

 

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If we become subject to product liability claims, we may be required to pay damages that exceed our insurance coverage, and such claims may harm our business in other ways.

Our business exposes us to product liability claims that are inherent in the testing, production, marketing and sale of diagnostic products. Although we currently maintain limited product liability insurance, we anticipate needing to secure additional product liability insurance for the development and commercialization of our product candidates. We cannot be certain whether we will be able to secure such insurance on commercially reasonable terms, or at all. A product liability claim in excess of any insurance coverage we may obtain would have to be paid out of our cash reserves and could harm our business. In addition, any injunction or other restriction on our ability to sell against one of our product candidates could harm our business.

If we complete our development of any diagnostic tests, the marketing, sale and use of our tests could lead to the filing of product liability claims if someone were to allege that our product failed to perform as it was designed. A product liability claim could result in substantial damages and be costly and time consuming for us to defend. We cannot provide assurance that our product liability insurance would protect us from the financial impact of defending a product liability claim. Any product liability claim brought against us, with or without merit, could increase our insurance rates or prevent us from securing insurance coverage in the future. Additionally, any product liability lawsuit could cause injury to our reputation, result in the recall of our product candidates, or cause current collaborators to terminate existing agreements and potential collaborators to seek other partners, any of which could impact our results of operations.

Our activities involve hazardous materials and may subject us to environmental liability or other costs.

Certain activities of our businesses involve the controlled use of limited quantities of hazardous, biological and radioactive materials and may generate biological waste. We and our manufacturers are subject to laws and regulations governing the use, manufacture, storage, handling and disposal of these materials and certain waste products. We cannot eliminate the risk of accidental contamination or discharge and liability for any resultant injury from these materials. We may be sued for any injury or contamination that results from our use or the use by third parties of these materials. In the event of an accident or if we otherwise fail to comply with applicable regulations, we could lose our permits or approvals or be held liable for damages or penalized with fines. Although we currently maintain limited insurance to cover claims related to hazardous materials or environmental liability claims, any claims in excess of our insurance coverage would be required to be paid out of our cash reserves and could harm our business, financial condition and results of operations. Compliance with environmental laws and regulations may be expensive, and current or future environmental regulations may impair our research, development and production efforts.

RISKS RELATED TO REGULATORY APPROVAL AND OTHER GOVERNMENT REGULATIONS

Although we recently received FDA clearance for our manual BGM Galectin-3 test for heart failure, we may not obtain regulatory clearance for the automated version of this test or for our other diagnostic product candidates when expected, if at all.

In the United States, we intend to seek FDA clearance or approval for all of our products prior to their launch for clinical use, whether offered as a diagnostic kit or laboratory service. The FDA process can be lengthy and unpredictable. For example, for our first product, the BGM Galectin-3 test for heart failure, we initially submitted a 510(k) premarket notification to the FDA in March 2009. Upon review of our 510(k) application, the FDA determined that our device was not substantially equivalent to the legally

 

 

 

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marketed device to which we claimed substantial equivalence and therefore denied clearance. The FDA indicated that additional clinical and other data were required in support of our filing, and we re-submitted a 510(k) application in December 2009 with additional data. In February 2010, we received a letter from the FDA regarding our 510(k) application that requested additional clinical and statistical information to support our application and, after further contact with the FDA, we submitted our formal response to the FDA letter in August 2010. We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test.

Commercial introduction of the automated version of our galectin-3 test and our AMIPredict product will require FDA clearance or approval. If we submit a 510(k) application for any of our product candidates and the FDA denies our request, we may be required to seek and obtain premarket approval, or PMA. The PMA process is more complex, costly and time-consuming than the 510(k) process. A PMA must be supported by more detailed and comprehensive scientific evidence, including clinical data, to demonstrate the safety and efficacy of the medical device for its intended purpose. Any material delays in our receipt of regulatory clearance or approval for our automated galectin-3 test and our other product candidates in development, or our failure to obtain such clearances or approvals at all, would have a material adverse effect on our business, financial condition and results of operations.

To market our products in Europe, we must obtain CE mark and may, in some cases, need marketing approval from the European Medicines Agency. In October 2009, we obtained CE Mark in the European Union for our first product, our galectin-3 test for heart failure.

Changes in regulatory review procedures, approval requirements or enactment of additional regulatory approval requirements may delay or prevent us from marketing our proposed products. The process of obtaining regulatory clearances or approvals to market medical devices, including in vitro diagnostic test kits, from the FDA and similar regulatory authorities outside of the United States can be costly and time consuming, and there can be no assurance that such clearances or approvals will be granted on a timely basis or at all. Furthermore, each regulatory agency may impose its own requirements and may refuse to grant approval or may require additional data before granting marketing approval even if marketing approval has been granted by other agencies. For example, in seeking clearance from the FDA for our galectin-3 test, we relied on samples from previously concluded studies sponsored by other parties to determine the clinical utility of our galectin-3 test, and we may do so for our other product candidates. While the FDA accepted such data in support of our galectin-3 test, and we believe it has accepted such data in other cases, the FDA may require us to conduct our own prospective studies to support future product clearances or approvals, which would make the development and validation of our product candidates more costly and time-consuming.

Our manual BGM Galectin-3 test for heart failure and any future products cleared by the FDA will be subject to ongoing regulation by the FDA. Failure to comply with such regulation could cause a material adverse effect on our business, financial condition and results of operations.

After a device is placed on the market, numerous regulatory requirements apply. These include:

 

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compliance with QSR;

 

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labeling regulations, which prohibit the promotion of products for unapproved or “off-label” uses and impose other restrictions on marketing; and

 

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medical device reporting regulations, which require that manufacturers report to the FDA if their device may have caused or contributed to a death or serious injury or malfunctioned in a way that would likely cause or contribute to a death or serious injury if it were to recur.

 

 

 

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Failure to comply with applicable regulatory requirements can result in enforcement action by the FDA, which may include any of the following sanctions:

 

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warning letters;

 

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fines, injunctions, and civil penalties;

 

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recall or seizure of our products;

 

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operating restrictions, partial suspension or total shutdown of production;

 

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refusal to grant 510(k) clearance or PMAs of new products;

 

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withdrawal of 510(k) clearance or PMAs that are already granted; and

 

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criminal prosecution.

Being subject to any of these sanctions could adversely affect our business, financial condition and results of operations.

Even if we are successful in obtaining regulatory clearance or approval for our product candidates, we will be subject to regulations under additional federal and state laws.

If we develop diagnostic tests suitable for commercialization, and after receiving all necessary regulatory clearances and approvals, we will be subject to national, regional and local regulations. For example, in the United States, the regulations which we may be subject to include:

 

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the federal Food, Drug and Cosmetic Act and the rules, regulations, guidance documents and other interpretations thereunder relating to the manufacture and marketing of medical products;

 

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the federal Medicare and Medicaid Anti-kickback Law, and state anti-kickback prohibitions;

 

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the federal physician self-referral prohibition, commonly known as the Stark Law, and the state equivalents;

 

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the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA;

 

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the various state laws governing patient privacy; and

 

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the federal civil and criminal False Claims Act.

The risk of our being found in violation of these laws and regulations is increased by the fact that many of them have not been fully interpreted by the regulatory authorities or the courts, and their provisions are open to a variety of interpretations.

If in the future we decide to operate our own laboratory for our diagnostic tests, we will become subject to the Clinical Laboratory Improvement Amendments of 1988, or CLIA, a federal law that regulates clinical laboratories that perform testing on specimens derived from humans for the purpose of providing information for the diagnosis, prevention or treatment of disease. CLIA is intended to ensure the quality and reliability of clinical laboratories in the United States by mandating specific standards in the areas of personnel qualifications, administration, and participation in proficiency testing, patient test management, quality control, quality assurance and inspections. There can be no assurances that we will be able to obtain CLIA accreditation, or if we do, that we would be able to renew it. If we are unable to obtain CLIA accreditation, we may be limited in our ability to perform testing, which would limit our revenue and harm our business.

Any action brought against us for violation of these laws or regulations, even if we prevail, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business. If our operations are found to be in violation of any of these laws and regulations, we may be

 

 

 

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subject to any applicable penalty associated with the violation, including civil and criminal penalties, damages and fines. We could also be required to refund any improperly received payments, and we could be required to curtail or cease our operations. Any of the foregoing consequences could seriously harm our business, financial condition and results of operations.

If we or our third-party manufacturer fail to comply with the FDA’s quality system regulation, or if we are not successful in addressing the observations included in a Form FDA-483 that we recently received, the development and manufacture of our products could be delayed or interrupted and our products may be subject to product recalls.

We and our contract manufacturers are required to comply with the FDA’s quality system regulation, or QSR, and other regulations which cover, among other things, the methods and documentation of the design, testing, production, control, quality assurance, labeling, packaging, storage and shipping of our products. The FDA monitors compliance with QSR through periodic inspections. In November 2010, the FDA conducted an inspection of our facilities in Waltham, Massachusetts for the first time. Following that inspection, the FDA issued a Form FDA-483 listing three inspectional observations (variances from protocols or other deficiencies) with respect to our facilities. The first observation related to how we documented our procedures and findings for an in-use stability study. This study was designed to determine the conditions under which our test components may be stored for reuse once opened. In response to the FDA observations, we have repeated this study using our third-party manufacturer, Corgenix. The results from the Corgenix-run study corroborated the results from our earlier study, which confirmed that our test components are stable (and therefore reliable) under specified storage conditions, and therefore, no further action is required. The second observation related to our documentation and implementation of corrective and preventative action procedures. The third observation related to documentation and implementation of training programs for our staff. We have taken corrective actions and believe we have remediated the noted deficiencies. However, we cannot be sure that our remedial measures will be acceptable to the FDA or that the FDA will not cite further deficiencies in subsequent inspections. While it is our intention to outsource the commercial manufacturing of our galectin-3 test and our other products under development, we do intend to continue performing studies as part of our internal product development activities. The Form FDA-483 did not require us to cease manufacturing or any other activities, and we intend to continue our operations in the normal course. If the FDA determines that we or our contractors are not in compliance with applicable regulatory standards or that we did not adequately remediate the noted deficiencies, we could be prevented or forced to delay the development or manufacture of our products, which could have a material adverse effect on our business, financial condition and results of operations. Moreover, any failure to maintain QSR compliance could force us to cease the development or manufacture of our products and subject us to other enforcement sanctions, including withdrawal of our products from the U.S. or foreign markets, and delay or interrupt the development or manufacture of additional products.

Healthcare reform measures could hinder or prevent our product candidates’ commercial success.

The U.S. government and other governments have shown significant interest in pursuing healthcare reform. Any government-adopted reform measures could adversely impact the pricing of healthcare products, including our diagnostic products, and services in the U.S. or internationally and the amount of reimbursement available from governmental agencies or other third party payors. The continuing efforts of the U.S. and foreign governments, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce healthcare costs may adversely affect our ability to set prices we believe are fair for any diagnostic products we may develop and commercialize. Changes in

 

 

 

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healthcare policy, such as the creation of broad limits for diagnostic products, could substantially interrupt the sale of future diagnostic tests, increase costs, divert management’s attention and adversely affect our ability to generate revenues and achieve profitability.

New laws, regulations and judicial decisions, or new interpretations of existing laws, regulations and decisions, relating to healthcare availability, methods of delivery or payment for diagnostic products and services, or sales, marketing or pricing, may limit our potential revenue, and we may need to revise our research and development or commercialization programs. The pricing and reimbursement environment may change in the future and become more challenging due to several reasons, including policies advanced by the U.S. government, new healthcare legislation or fiscal challenges faced by government health administration authorities. Specifically, in both the U.S. and some foreign jurisdictions, there have been a number of legislative and regulatory proposals and initiatives to change the healthcare system in ways that could affect our ability to sell any diagnostic products we may develop and commercialize profitably. Some of these proposed and implemented reforms could result in reduced reimbursement rates for our diagnostic products, which would adversely affect our business strategy, operations and financial results. For example, in March 2010, President Obama signed into law a legislative overhaul of the U.S. healthcare system, known as the Patient Protection and Affordable Care Act of 2010, as amended by the Healthcare and Education Affordability Reconciliation Act of 2010, or the PPACA, which may have far reaching consequences for life science companies like us. As a result of this new legislation, substantial changes could be made to the current system for paying for healthcare in the United States, including changes made in order to extend medical benefits to those who currently lack insurance coverage. Extending coverage to a large population could substantially change the structure of the health insurance system and the methodology for reimbursing medical services, drugs and devices. These structural changes could entail modifications to the existing system of private payors and government programs, such as Medicare and Medicaid, the creation of a government-sponsored healthcare insurance source, or some combination of both, as well as other changes. Restructuring the coverage of medical care in the United States could impact the reimbursement for prescribed drugs, biopharmaceuticals, medical devices or our product candidates. If reimbursement for our approved product candidates, if any, is substantially less that we expect in the future, or rebate obligations associated with them are substantially increased, our business could be materially and adversely impacted. In addition, certain members of Congress have declared their intentions to effect the repeal of some or all of PPACA, adding further uncertainty to the law’s future impact on us.

Further federal and state proposals and healthcare reforms could limit the prices that can be charged for the product candidates that we develop and may further limit our commercial opportunity. Our results of operations could be materially adversely affected by the PPACA, by the Medicare prescription drug coverage legislation, by the possible effect of such current or future legislation on amounts that private insurers will pay and by other health care reforms that may be enacted or adopted in the future.

RISKS RELATED TO OUR COMMON STOCK AND THIS OFFERING

An active trading market for our common stock may not develop, and you may not be able to resell your shares at or above the initial public offering price.

Prior to this offering, there has been no public market for our common stock. Although our common stock has been approved for listing on The NASDAQ Global Market, an active trading market for our common stock may never develop or be sustained following this offering. If no trading market develops, securities analysts may not initiate or maintain research coverage of our company, which could further depress the market for our common stock.

 

 

 

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The initial public offering price of shares of our common stock is, or will be, determined by negotiation between us and the underwriters and may not be indicative of prices that will prevail following the completion of this offering. The market price of shares of our common stock may decline below the initial public offering price, and you may not be able to resell your shares of our common stock at or above the initial public offering price, or at all.

Certain of our existing stockholders and/or their affiliates have indicated an interest in purchasing up to 76.1% of the shares in this offering. These purchases would reduce the public float of our common stock after this offering from approximately 57.6% to approximately 36.5% of our outstanding shares of common stock, which could adversely affect the trading market for our common stock.

Certain of our principal stockholders and/or their affiliates have indicated an interest in purchasing, individually, up to an aggregate of $25.3 million of shares of common stock in this offering (or 76.1% of the shares we are offering), based upon the expected initial public offering price of $7.00 per share. If such stockholders purchase all shares they have indicated an interest in purchasing, the number of shares beneficially owned after this offering by all directors and executive officers as a group will increase to 11,432,879, and the percentage of common stock beneficially owned by them after this offering will increase to 55.7%. The purchase of shares by these affiliated entities in this offering will reduce the public float of our common stock after this offering from approximately 57.6% to approximately 36.5% of our outstanding shares of common stock, which could adversely affect the liquidity of the trading market for our common stock from what it would have been had these shares been purchased by unaffiliated investors, in as much as federal securities laws restrict sales of our shares by these stockholders. Reducing the public float and liquidity of our common stock can affect the market price of our common stock and make it more difficult to sell the shares purchased in this offering at current market prices, or at all. See “Principal stockholders” for more information regarding beneficial ownership of our common stock.

Our stock price is likely to be volatile, and the market price of our common stock after this offering may drop below the price you pay.

The initial public offering price may vary from the market price of our common stock after the offering. If an active market for our stock develops and continues, our stock price nevertheless may be volatile. Market prices for securities of early stage life sciences companies have historically been particularly volatile. As a result of this volatility, you may not be able to sell your common stock at or above the initial public offering price. Some of the many factors that may cause the market price of our common stock to fluctuate include:

 

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our ability to commercialize the products, if any, that we are able to develop;

 

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the progress and results of our biomarker discovery and product candidate development efforts;

 

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actions taken by regulatory authorities with respect to our product candidates, or our sales and marketing activities;

 

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regulatory developments in the United States, the European Union and other jurisdictions;

 

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the outcome of legal actions to which we may become a party;

 

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announcements concerning product development results or intellectual property rights of others;

 

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announcements of technological innovations or new products by us or our competitors;

 

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changes in financial estimates or recommendations by securities analysts;

 

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changes in our capital structure, such as future issuances of securities or the incurrence of additional debt;

 

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restatements of our financial results and/or material weaknesses in our internal controls;

 

 

 

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publication of research reports about us or the diagnostic products industry by securities or industry analysts;

 

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fluctuations in our operating results; and

 

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deviations in our operating results from the estimates of securities analysts or other analyst comments.

The stock markets, and the markets for medical diagnostics and biotechnology stocks in particular, have experienced volatility that has often been unrelated to the operating performance of particular companies. These broad market fluctuations may adversely affect the trading price of our common stock. Investors may not be able to sell when they desire due to insufficient buyer demand and may realize less than, or lose all of, their investment.

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 financial condition, operating results and reputation.

The requirements of being a public company will require greater resources, increase our costs and distract our management, and we may be unable to comply with these requirements in a timely or cost-effective manner.

As a public company with equity securities listed on The NASDAQ Global Market, we will incur significant legal, accounting and other expenses that we did not incur as a private company. We will need to comply with certain rules, regulations and requirements with which we were not required to comply prior to this offering. Complying with rules, regulations and requirements will require substantial effort on the part of our board of directors and management and will increase our costs and expenses. We will be required to:

 

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institute a more formalized function of internal control over financial reporting;

 

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prepare and distribute periodic and current public reports;

 

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formalize old and establish new internal policies, such as those relating to disclosure controls and procedures and insider trading;

 

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involve and retain to a greater degree outside counsel and accountants in the above activities; and

 

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establish and maintain an investor relations function, including the provision of certain information on our website.

Compliance with these rules and regulations will increase our legal and financial compliance costs and will make some activities more time-consuming and costly. For example, we expect these new rules and regulations to make it more difficult and more expensive for us to obtain director and officer liability insurance and we may be required to incur substantial costs to maintain the same or similar coverage.

The securities laws require, among other things, that we implement and maintain effective internal control for financial reporting and disclosure. In particular, under current regulations, commencing with our fiscal year ending December 31, 2011, we must begin to perform system and process evaluation and testing of our internal control over financial reporting to allow management and our independent registered public accounting firm to report on the effectiveness of our internal control over financial reporting. Our testing, or the subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal control over financial reporting that are deemed to be material weaknesses. We expect to incur significant expense and devote substantial management effort toward ensuring compliance with these requirements. Moreover, if we are not able to comply with these requirements in a timely manner, or if we or our independent registered public accounting firm identifies deficiencies in our internal control over

 

 

 

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financial reporting that are deemed to be material weaknesses, the market price of our common stock could decline and we could be subject to sanctions or investigations by The NASDAQ Stock Market, the Securities and Exchange Commission or other regulatory authorities, which would entail expenditure of additional financial and management resources.

The ownership of our common stock will continue to be highly concentrated and your interests may conflict with the interests of our existing stockholders.

Certain of our principal stockholders and/or their affiliates, including Flagship, Gilde, GE, Legg Mason, SMALLCAP and Stelios Papadopoulos, have indicated an interest in purchasing up to an aggregate of $25.3 million of shares of common stock in this offering based upon the expected initial public offering price of $7.00 per share. However, because these potential indications of interest are not binding agreements or commitments to purchase, any or all of these stockholders may elect not to purchase any shares in this offering. If these principal stockholders and/or their affiliates purchase all shares they have indicated interests in purchasing, the aggregate number of shares controlled by our executive officers, directors and current holders of more than 5% of our outstanding common stock, together with their affiliates and related persons, will represent approximately 86.8% of our outstanding common stock, or approximately 83.5% if the underwriters exercise their over-allotment option in full. If these principal stockholders and/or their affiliates do not purchase such shares in this offering, our executive officers, directors and current holders of more than 5% of our outstanding common stock, together with their affiliates and related persons, will control approximately 66.9% of our outstanding common stock after this offering, or approximately 64.4% if the underwriters exercise their over-allotment option in full. We have outstanding an aggregate of $6.0 million principal amount of bridge notes, which are held by certain of our principal stockholders. Based upon the expected initial public offering price of $7.00 per share, the $6.0 million in principal amount of outstanding bridge notes will convert into approximately 857,127 shares of our common stock, which are included in the percentages set forth above. In connection with the bridge note financing, we issued warrants to purchase 415,347 shares of our common stock at an exercise price of $0.02 per share.

Accordingly, these stockholders, if acting as a group, or Flagship, which alone would control approximately 37.2% of our outstanding common stock, assuming our principal stockholders and/or affiliates purchase the additional shares that they have indicated an interest in purchasing, based on 18,143,607 shares outstanding after this offering, will have control or substantial influence over the outcome of corporate actions requiring stockholder approval, including the election of directors and the approval of significant corporate transactions, and they may in some instances exercise this control or substantial influence in a manner that advances their best interests and not necessarily those of other stockholders. This concentration of ownership may have the effect of delaying, preventing or deterring a change of control, could deprive you of the opportunity to receive a premium for our common stock as part of a sale and could adversely affect the market price of our common stock.

Management will have broad discretion over the use of the net proceeds from the offering and may not apply the net proceeds effectively or in a manner that is consistent with the uses described in this prospectus.

Although we intend to use the net proceeds of this offering to, among other things, finance working capital needs, including the commercialization of our galectin-3 diagnostic test and the continued development of our product candidates, as well as to fund continuing operations, because of the number and variability of factors that will determine our use of these proceeds, we cannot specify with certainty the particular uses of the net proceeds that we will receive from this offering. We will have broad discretion in the application of the net proceeds, including for any of the purposes described in “Use of proceeds” in this prospectus. However, our plans may change, and we could use the net proceeds in ways with which stockholders do not agree, or for corporate purposes that may not result in a significant or

 

 

 

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any return on your investment. In addition, we may invest the net proceeds from this offering in a manner that does not produce income or that loses value.

A significant portion of our total outstanding shares of common stock is restricted from immediate resale but may be sold into the market in the near future. This could cause the market price of our common stock to drop significantly, even if our business is doing well.

Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares of common stock intend to sell shares, could reduce the market price of our common stock. As of September 30, 2010, our eight largest stockholders beneficially owned, collectively, approximately 90% of our outstanding common stock on an as-converted basis. If one or more of them were to sell a substantial portion of the shares they hold, it could cause our stock price to decline. Based on an aggregate of 13,393,607 shares outstanding as of September 30, 2010, upon completion of this offering, we will have 18,143,607 outstanding shares of common stock, assuming no exercise of the underwriters’ option to purchase additional shares. Holders of substantially all of the shares of our common stock are or will be subject to 180-day contractual lock-up agreements with the underwriters or us.

In addition, as of September 30, 2010, there were 2,442,662 shares subject to outstanding options that will become eligible for sale in the public market to the extent permitted by any applicable vesting requirements, the lock-up agreements and Rules 144 and 701 under the Securities Act of 1933, as amended. Moreover, after this offering, holders of an aggregate of approximately 13,723,450 shares of our common stock or securities exercisable for shares of our common stock will have rights, subject to some conditions, to require us to file registration statements covering their shares and to include their shares in registration statements that we may file for ourselves or other stockholders. Holders of warrants exercisable for approximately 55,381 additional shares of our common stock as of September 30, 2010, will have rights, subject to some conditions, to include their shares in registration statements that we may file for ourselves or other stockholders.

We also intend to register all shares of common stock that are issuable or reserved for grant under our stock plans. Once we register these shares, they can be freely sold in the public market upon issuance and once vested, subject to the 180-day lock-up period under the lock-up agreements described in the “Shares eligible for future sale” section of this prospectus.

If securities or industry analysts do not publish research or reports about our business, or if they change their recommendations regarding our common stock adversely, the price and trading volume of our common stock could decline.

The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our industry. If one or more of the analysts who cover us or our industry make unfavorable comments about our market opportunity or product candidates or downgrade our common stock, the market price of our common stock would likely decline. If one or more of these analysts ceases coverage of us or fails to regularly publish reports on us, we could lose visibility in the financial markets, which could cause the market price of our common stock or trading volume to decline.

Investors in this offering will pay a much higher price than the book value of our common stock and therefore you will incur immediate and substantial dilution of your investment.

If you purchase our common stock in this offering, you will pay more for our common stock than the amounts paid by existing stockholders for their shares. You will incur immediate and substantial dilution

 

 

 

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of $5.26 per share based upon the expected initial public offering price of $7.00 per share. Further, investors purchasing our common stock in this offering will contribute approximately 28.1% of the total amount invested by stockholders since our inception, but will only own approximately 26.2% of the shares of our common stock outstanding following the offering. In the past, we also issued options and warrants to acquire our common stock at prices significantly below the initial public offering price. To the extent these outstanding options or warrants are ultimately exercised, you will sustain further dilution. For further information, see “Dilution” elsewhere in this prospectus.

Because we do not intend to pay dividends for the foreseeable future, investors in the offering will benefit from their investment in shares only if our common stock appreciates in value.

We currently intend to retain our future earnings, if any, to finance the operation and growth of our business and do not expect to pay any dividends in the foreseeable future. In addition, the terms of our loan and security agreement with Silicon Valley Bank currently prohibit us from paying cash dividends on our common stock. As a result, the success of an investment in our common stock will depend upon any future appreciation in their value. There is no guarantee that our common stock will appreciate in value or even maintain the price at which investors in this offering have purchased their shares.

Provisions of our certificate of incorporation, our bylaws and Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove the current members of our board and management.

Certain provisions of our restated certificate of incorporation and restated bylaws that will be in effect upon the completion of this offering could discourage, delay or prevent a merger, acquisition or other change of control that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. Furthermore, these provisions could prevent or frustrate attempts by our stockholders to replace or remove members of our board of directors. These provisions also could limit the price that investors might be willing to pay in the future for our common stock, thereby depressing the market price of our common stock. Stockholders who wish to participate in these transactions may not have the opportunity to do so. These provisions:

 

Ø  

allow the authorized number of directors to be changed only by resolution of our board of directors;

 

Ø  

establish a classified board of directors, such that not all members of the board of directors may be elected at one time;

 

Ø  

authorize our board of directors to issue without stockholder approval preferred stock, the rights of which will be determined at the discretion of the board of directors that, if issued, could operate as a “poison pill” to dilute the stock ownership of a potential hostile acquirer to prevent an acquisition that is not approved by our board of directors;

 

Ø  

require that stockholder actions must be effected at a duly called stockholder meeting and prohibit stockholder action by written consent;

 

Ø  

establish advance notice requirements for stockholder nominations to our board of directors or for stockholder proposals that can be acted on at stockholder meetings;

 

Ø  

limit who may call stockholder meetings; and

 

Ø  

require the approval of the holders of 80% of the outstanding shares of our capital stock entitled to vote in order to amend certain provisions of our restated certificate of incorporation and restated bylaws.

In addition, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which may, unless certain criteria are met, prohibit large stockholders, in particular those owning 15% or more of the voting rights on our common stock, from merging or combining with us for a prescribed period of time.

 

 

 

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Special note regarding forward looking statements

This prospectus contains forward looking statements. These statements involve known and unknown risks, uncertainties and other important factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward looking statements. Forward looking statements include, but are not limited to, statements about:

 

Ø  

our estimates of future performance, including the expected timing of the launch of our products;

 

Ø  

our ability to conduct the clinical studies required for regulatory clearance or approval and to demonstrate the clinical benefits and cost-effectiveness to support commercial acceptance of our products;

 

Ø  

the timing, costs and other limitations involved in obtaining regulatory clearance or approval for any of our product candidates;

 

Ø  

the potential benefits of our product candidates over current medical practices or other diagnostics;

 

Ø  

our ability to market, commercialize and achieve market acceptance for any of our product candidates that we are developing or may develop in the future;

 

Ø  

willingness of third-party payors to reimburse for the cost of our tests;

 

Ø  

estimates of market sizes and anticipated uses of our product candidates;

 

Ø  

our ability to enter into collaboration agreements with respect to our product candidates and the performance of our collaborative partners under such agreements;

 

Ø  

our ability to protect our intellectual property and operate our business without infringing upon the intellectual property rights of others;

 

Ø  

the expected timing, progress or success of our research and development and any commercialization efforts;

 

Ø  

our ability to successfully obtain sufficient supplies of samples for our biomarker discovery and development efforts; and

 

Ø  

our estimates regarding anticipated operating losses, future revenue, expenses, capital requirements and our needs for additional financing.

In some cases, you can identify forward looking statements by terms such as “anticipates,” “believes,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “will,” “would” and similar expressions intended to identify forward looking statements. Forward looking statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Because of these risks and uncertainties, the forward looking events and circumstances discussed in this prospectus may not transpire. We discuss many of these risks in this prospectus under the heading “Risk factors.”

Given these uncertainties, you should not place undue reliance on these forward looking statements. Also, forward looking statements represent our estimates and assumptions only as of the date of this document. You should read this document with the understanding that our actual future results may be materially different from what we expect. Except as required by law, we do not undertake any obligation to update or revise any forward looking statements contained in this prospectus whether as a result of new information, future events or otherwise.

 

 

 

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Use of proceeds

We estimate that we will receive net proceeds from this offering of approximately $28.6 million, after deducting the underwriting fees and commissions and estimated offering expenses paid or payable by us, based upon the expected initial public offering price of $7.00 per share. If the underwriters’ over-allotment option is exercised in full, we estimate our net proceeds will be approximately $33.2 million.

A $1.00 increase (decrease) in the expected initial public offering price of $7.00 per share, would increase (decrease) the net proceeds to us from this offering by $4.4 million, assuming that the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same and after deducting the underwriting discounts and commissions and estimated offering expenses paid or payable by us. Depending on market conditions at the time of pricing of this offering and other considerations, we may sell fewer or more shares and at a price per share different than that set forth on the cover page of this prospectus. As a result, the net proceeds to us from this offering may be lower or higher than the amount set forth above.

We expect to use the net proceeds we receive from this offering primarily for the following purposes:

 

Ø  

approximately $15.0 million to fund the commercial launch of our lead product, BGM Galectin-3, including establishing a commercial organization and infrastructure, and to fund development, potential regulatory submission and potential commercial launch activities for the second indication of our galectin-3 test to identify patients at elevated risk for heart failure following a heart attack;

 

Ø  

approximately $8.0 million to fund development, potential regulatory submission and potential commercial launch activities for our other cardiovascular diagnostic product candidates, including AMIPredict and LipidDx;

 

Ø  

approximately $3.0 million for biomarker discovery and potential clinical development of additional diagnostic product candidates; and

 

Ø  

the remainder for other general corporate purposes, including capital expenditures, licensing of intellectual property, repayment of debt and working capital.

This expected use of net proceeds from this offering represents our current intentions based upon our present plans and business conditions. The amounts and timing of our actual expenditures depend on numerous factors, including the success of our commercialization efforts for our galectin-3 test; the timing and progress of our development activities for additional indications for our galectin-3 test and our other product candidates, AMIPredict and LipidDx; the results of our discovery activities for our cardiovascular and other projects; and the timing and revenue derived from additional collaborations that we may enter into with third parties for our product candidates. The costs and timing of product discovery and development activities, particularly conducting clinical studies and obtaining regulatory clearance, are highly uncertain, subject to substantial risks and can often change. Depending on the outcome of these activities, our plans and priorities may change, and we may apply the net proceeds from this offering differently than we currently anticipate. For example, in the event we identify other opportunities that we believe are in the best interest of our stockholders, we may use a portion of the net proceeds from this offering for the acquisition of, or investment in, technologies, products or companies that complement our business, although we have no current understandings, commitments or agreements to do so. As a result, our management will retain broad discretion over the allocation of the net proceeds from this offering.

Pending use of the net proceeds of this offering, we intend to invest the net proceeds in accordance with our investment policy guidelines, which currently provide for investment of funds in cash equivalents, government obligations, high grade and corporate notes and commercial paper.

 

 

 

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Dividend policy

We have never declared or paid any dividends on our common stock. In addition, the terms of our loan and security agreement with Silicon Valley Bank currently prohibit us from paying cash dividends on our common stock. We currently intend to retain any future earnings to finance our research and development efforts and the expansion of our business and do not intend to declare or pay cash dividends on our capital stock in the foreseeable future. Any future determination to pay dividends will be at the discretion of our board of directors and will depend upon a number of factors, including our results of operations, financial condition, future prospects, contractual restrictions, restrictions imposed by applicable law and other factors our board of directors deems relevant.

 

 

 

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Capitalization

The table below sets forth our cash, cash equivalents and marketable securities and capitalization as of September 30, 2010:

 

Ø  

on an actual basis;

 

Ø  

on an unaudited pro forma basis, after giving effect upon the completion of this offering to (i) the automatic conversion of all shares of our convertible preferred stock into an aggregate of 9,541,931 shares of our common stock; (ii) the conversion of warrants to purchase 92,305 shares of preferred stock into warrants to purchase 55,381 shares of common stock; (iii) the issuance in November 2010 of the remaining $2.0 million in principal amount of bridge notes and the issuance of warrants to purchase 138,449 shares of our common stock, which resulted in a charge to operations totaling approximately $650,000; and (iv) the issuance of 857,127 shares of our common stock upon the automatic conversion of $6.0 million in principal amount of outstanding bridge notes upon the completion of this offering based upon the expected initial public offering price of $7.00 per share; and

 

Ø  

on an unaudited pro forma as adjusted basis, after giving effect to the pro forma adjustments described above and the receipt by us of $28.6 million from the sale of 4,750,000 shares of our common stock offered by us in this offering based upon the expected initial public offering price of $7.00 per share after deducting underwriting discounts and commissions and estimated offering expenses paid or payable by us.

You should read this table together with our consolidated financial statements and the related notes thereto, as well as the information under “Management’s discussion and analysis of financial condition and results of operations.” The unaudited pro forma and pro forma as adjusted information below is prepared for illustrative purposes only and our capitalization following the completion of this offering will be adjusted based on the actual initial public offering price and other terms of the offering determined at pricing.

 

 

 

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Capitalization

 

 

 

    As of September 30, 2010  
     Actual     Pro forma     Pro forma
as adjusted
 
    (in thousands)  

Cash, cash equivalents and marketable securities

  $ 2,855      $ 4,855      $ 34,948   
                       

Long-term debt, including current portion

  $ 4,509      $ 388      $ 388   
                       

Warrant liability

    509        46        46   
                       

Redeemable convertible preferred stock:

     

Series A redeemable preferred stock; $0.001 par value, 16,017,067 shares authorized; 15,823,566 shares issued and outstanding, actual; no shares authorized, issued or outstanding, pro forma and pro forma as adjusted

    23,735                 

Series A-1 redeemable exchangeable preferred stock; $0.001 par value, 2,475,247 shares authorized, issued and outstanding; actual; no shares authorized, issued or outstanding, pro forma and pro forma as adjusted

    5,000                 

Series C redeemable preferred stock; $0.001 par value, 1,369,863 shares authorized; issued and outstanding; actual; no shares authorized, issued or outstanding, pro forma and pro forma as adjusted

    3,583                 

Series D redeemable preferred stock; $0.001 par value, 6,246,151 shares authorized; 6,153,846 issued and outstanding; actual; no shares authorized, issued or outstanding, pro forma and pro forma as adjusted

    39,510                 
                       

Total redeemable convertible preferred stock

    71,828                 
                       

Stockholders’ (deficit) equity:

     

Series B preferred stock; $0.001 par value, 2,000,000 shares authorized; 1,138,716 shares issued and outstanding; actual; no shares authorized, issued or outstanding, pro forma and pro forma adjusted

    1,708                 

Common stock; $0.001 par value, 60,000,000 shares authorized, actual and pro forma; 100,000,000 shares authorized, pro forma as adjusted; 2,994,549 shares issued and outstanding, actual; 13,393,607 shares issued and outstanding, pro forma; 18,143,607 shares issued and outstanding, pro forma as adjusted

    3        13        18   

Additional paid in capital

    15,837        96,597        125,201   

Accumulated deficit

    (92,415     (93,065     (93,065
                       

Total stockholders’ (deficit) equity

  $ (74,867   $ 3,545      $ 32,154   
                       

Total capitalization

  $ 1,979      $ 3,979      $ 32,588   
                       

Each $1.00 increase (decrease) in the expected initial public offering price of $7.00 per share would increase (decrease) each of our unaudited pro forma as adjusted cash and cash equivalents and marketable securities, additional paid-in capital, total stockholders’ equity (deficit) and total capitalization by approximately $4.4 million, assuming that the number of shares offered by us under this prospectus remains the same, and after deducting underwriting discounts and commissions and estimated offering expenses paid or payable by us.

 

 

 

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Capitalization

 

 

The outstanding share information in the capitalization table above is based on the number of shares outstanding as of September 30, 2010, and excludes:

 

Ø  

2,442,662 shares of common stock issuable upon the exercise of outstanding options as of September 30, 2010, with a weighted-average exercise price of $4.37 per share;

 

Ø  

521,098 shares of common stock reserved for future issuance under our 2001 Stock Option and Incentive Plan, or our 2001 Stock Plan, as of September 30, 2010; provided, however, that immediately upon completion of this offering, our 2001 Stock Plan will terminate so that no further awards may be granted under our 2001 Stock Plan;

 

Ø  

an aggregate of up to 1,199,976 shares of common stock reserved for future issuance under our 2010 Employee, Director and Consultant Stock Plan, or our 2010 Stock Plan, which will become effective upon completion of the offering;

 

Ø  

1,217,197 shares of common stock issuable upon the exercise of outstanding warrants as of September 30, 2010, with a weighted-average exercise price of $0.54 per share, on an actual basis and on a pro forma and pro forma as adjusted basis;

 

Ø  

138,449 shares of common stock issuable upon the exercise of outstanding warrants issued on November 4, 2010, with an exercise price of $0.02 per share; and

 

Ø  

3,304 shares of common stock issuable upon the automatic net exercise of a warrant to purchase 14,018 shares of our common stock upon the completion of this offering at an exercise price of $5.35 per share and based upon the expected initial public offering price of $7.00 per share.

 

 

 

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Dilution

If you invest in our common stock, your interest in our net tangible book value will be diluted to the extent of the difference between the initial public offering price and the net tangible book value per share of our common stock immediately after the completion of this offering. Dilution results from the fact that the initial public offering price is substantially in excess of the book value per share attributable to the existing stockholders for the presently outstanding stock.

As of September 30, 2010, we had a net tangible book value (deficit) of $(75.4 million), or approximately $(25.19) per share of common stock. Net tangible book value (deficit) per share represents the amount of our total tangible assets less total liabilities and redeemable convertible preferred stock, divided by 2,994,549, the number of common shares outstanding. Our pro forma net tangible book value as of September 30, 2010 was $3.0 million, or $0.22 per share of common stock. Pro forma net tangible book value per share represents the amount of our total tangible assets less our total liabilities, divided by the number of shares of our common stock outstanding, as of September 30, 2010, after giving effect to (i) the conversion of all of our outstanding preferred stock into 9,541,931 shares of common stock; (ii) the issuance in November 2010 of the remaining $2.0 million in principal amount of bridge notes; and (iii) the issuance of 857,127 shares of our common stock upon the automatic conversion of $6.0 million in principal amount of outstanding bridge notes upon completion of this offering.

After giving effect to the sale by us of shares of our common stock in this offering at the expected initial public offering price of $7.00 and after deducting underwriting discounts and commissions and estimated offering expenses paid or payable by us, our adjusted pro forma net tangible book value as of September 30, 2010 would have been approximately $31.6 million, or approximately $1.74 per share. This amount represents an immediate increase in pro forma as adjusted net tangible book value of $1.52 per share to our existing stockholders and an immediate dilution in pro forma as adjusted net tangible book value of approximately $5.26 per share to new investors purchasing shares of our common stock in the offering. We determine dilution by subtracting the pro forma as adjusted net tangible book value per share after the offering from the amount of cash that a new investor paid for a share of common stock.

The following table illustrates this dilution on a per share basis:

 

Expected initial public offering price per share

      $ 7.00   

Pro forma net tangible book value as of September 30, 2010

   $ 0.22      

Increase per share attributable to new investors

     1.52      
           

Pro forma as adjusted net tangible book value per share after the offering

        1.74   
           

Dilution in pro forma net tangible book value per share to new investors

      $ 5.26   
           

A $1.00 increase (decrease) in the expected initial public offering price of $7.00 would increase (decrease) our pro forma as adjusted net tangible book value after this offering by $4.4 million and the pro forma as adjusted net tangible book value per share after this offering by $0.24 per share and would increase (decrease) the dilution per share to new investors in this offering by $0.76 per share, assuming the number of shares offered by us under this prospectus remains the same and after deducting underwriting discounts and commissions and estimated expenses paid or payable by us. The information discussed above is illustrative only and will adjust based on the actual initial public offering price and other terms of the offering determined at pricing.

 

 

 

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Dilution

 

 

The following table shows, as of September 30, 2010, the differences between the number of shares purchased from us, the total consideration paid to us and the average price per share that existing stockholders before this offering and investors participating in this offering paid. The table gives effect to the conversion of all of our outstanding preferred stock into common stock and the automatic conversion of the bridge notes, as described above.

 

     Shares purchased     Total consideration    

Average price

per share

 
      Number      Percentage     Amount      Percentage    

Existing stockholders before this offering

     13,393,607         73.8   $ 85,155,000         71.9   $ 6.36   

Investors participating in this offering

     4,750,000         26.2        33,250,000         28.1        7.00   
                                    

Total

     18,143,607         100.0   $ 118,405,000         100.0  
                                    

A $1.00 increase (decrease) in the expected initial public offering price of $7.00 per share would increase (decrease) total consideration paid by investors participating in this offering and total consideration paid by all stockholders each by approximately $4.8 million, assuming the number of shares offered by us, as set forth on the cover page of this prospectus, remains the same.

The discussion and tables above assume no exercise of the underwriters’ over-allotment option. If the underwriters’ over-allotment option is exercised in full, the pro forma as adjusted net tangible book value per share after giving effect to this offering would be $1.92 per share and the dilution in pro forma net tangible book value per share to investors in this offering would be $5.08 per share. Additionally, if the underwriters’ over-allotment option is exercised in full, the number of shares of our common stock held by existing stockholders before this offering will be further reduced to 71.0% of the total number of shares of our common stock to be outstanding after the offering, and the number of shares of our common stock held by investors participating in this offering will be further increased to 29.0% of the total number of shares of our common stock to be outstanding after the offering.

In addition, except as noted, the above discussion and table assume no exercise of stock options or warrants after September 30, 2010. As of September 30, 2010, we had outstanding options to purchase a total of 2,442,662 shares of our common stock at a weighted-average exercise price of $4.37 per share and warrants to purchase a total of 1,231,215 shares of our common stock, with a weighted-average exercise price of $0.60 per share. In November 2010, we issued warrants to purchase 138,449 shares our common stock at an exercise price of $0.02 per share in connection with our bridge note financing. If all such options and warrants had been exercised as of September 30, 2010, pro forma as adjusted net tangible book value per share, would be $1.96 per share and dilution to investors participating in this offering would be $5.04 per share.

 

 

 

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Selected consolidated financial information

The following table summarizes our selected consolidated financial data for the periods and as of the dates indicated. Our selected consolidated statements of operations data for each of the years in the periods ended December 31, 2007, 2008 and 2009 and our selected consolidated balance sheet data as of December 31, 2008 and 2009 have been derived from our audited consolidated financial statements and related notes included elsewhere in this prospectus. Our selected consolidated statements of operations data for each of the years in the periods ended December 31, 2005 and 2006 and our selected consolidated balance sheet data as of December 31, 2005, 2006 and 2007 have been derived from our audited consolidated financial statements that are not included in this prospectus. The consolidated statement of operations data for the nine months ended September 30, 2009 and 2010 and the consolidated balance sheet data as September 30, 2010 have been derived from our unaudited condensed consolidated financial statements included elsewhere in this prospectus. Our unaudited interim financial statements have been prepared on the same basis as the annual financial statements and, in the opinion of our management, reflect all adjustments, which include only normal recurring adjustments necessary to present fairly our financial position at September 30, 2010 and results of operations for the nine months ended September 30, 2009 and 2010. Our results for the periods shown below are not necessarily indicative of the results to be expected for any future periods. Our selected consolidated financial data should be read together with “Management’s discussion and analysis of financial condition and results of operations” and with our consolidated financial statements and related notes included elsewhere in this prospectus. The report from our independent registered public accounting firm on our 2009 consolidated financial statements expresses an unqualified opinion on the consolidated financial statements and includes an explanatory paragraph relating to substantial doubt about our ability to continue as a going concern.

 

    Years ended December 31,     Nine Months Ended
September 30,
 

Consolidated statements of
operations data:

  2005     2006     2007     2008     2009     2009     2010  
    (in thousands, except share and per share data)        

Revenue

  $ 1,532      $ 6,046      $ 8,982      $ 14,580      $ 8,490      $ 8,117      $ 620   
                                                       

Operating expenses:

             

Cost of revenue

           2,457        7,301        13,822        8,431        7,902        650   

Research and development

    7,131        5,331        5,832        6,858        8,527        6,502        5,596   

Selling, general and administrative

    2,412        2,450        3,820        4,475        7,520        5,541        6,224   

Costs related to abandoned stock offering

                  3,154                               

Gain on sale of property and equipment

    (307            (118                            
                                                       

Total operating expenses

    9,236        10,238        19,989        25,155        24,478        19,945        12,470   
                                                       

Loss from operations

    (7,704     (4,192     (11,007     (10,575     (15,988     (11,828     (11,850

Gain on extinguishment of debt

    1,035                                             

Interest income

    22        24        302        422        121        102        4   

Interest expense(1)

    (1,585     (574     (689     (4,921     (244     (203     (1,964

Other income (expense)

                                (26     29        (29
                                                       

Net loss

    (8,232     (4,742     (11,394     (15,074     (16,137     (11,900     (13,839

Accretion of redeemable convertible preferred stock

                  (368     (872     (977     (727     (769
                                                       

Net loss attributable to common stockholders

  $ (8,232   $ (4,742   $ (11,762   $ (15,946   $ (17,114   $ (12,627   $ (14,608
                                                       

Net loss attributable to common stockholders per share —basic and diluted

  $ (2.92   $ (1.68   $ (4.14   $ (5.52   $ (5.84   $ (4.32   $ (4.93
                                                       

 

 

 

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Selected consolidated financial information

 

 

    Years ended December 31,     Nine Months Ended
September 30,
 

Consolidated statements
of operations data:

  2005     2006     2007     2008     2009     2009     2010  
    (in thousands, except share and per share data)        

Weighted-average common shares outstanding used in computing per share amounts — basic and diluted

    2,815,468        2,817,102        2,843,773        2,889,513        2,930,818        2,925,131        2,963,626   

Pro forma net loss attributable to common stockholders per share — basic and diluted(2)

          $ (1.29     $ (1.11
                         

Pro forma weighted-average common shares outstanding used in computing per share amounts — basic and diluted(2)

            12,472,749          12,505,557   

 

(1)   Interest expense in 2008 and in the nine months ended September 30, 2010 includes non-cash charges of $4.0 million and $1.7 million, respectively, related to expense arising from the issuance of warrants issued in connection with convertible debt that were accounted for as debt discount and beneficial conversion features on convertible debt. Such amounts were immediately recognized as interest expense because the debt was due upon demand.

 

(2)   Net loss used in computing pro forma basic and diluted net loss per share and the number of weighted-average common shares used in computing pro forma basic and diluted net loss per share in the table above give effect to the automatic conversion of all of our outstanding convertible preferred stock into 9,541,931 shares of common stock upon the completion of this offering as if such conversion had occurred at the beginning of the period.

 

    As of December 31,     As of September 30,  
Consolidated balance
sheet data:
  2005     2006     2007     2008     2009     2010  
    (in thousands)  

Cash, cash equivalents and marketable securities

  $ 1,148      $ 1,010      $ 1,214      $ 24,302      $ 10,393      $ 2,855   

Deferred offering costs

                                65        1,484   

Total assets

    3,103        6,169        8,780        35,217        12,625        5,969   

Warrant liability

                         445        471        509   

Long-term debt and capital leases, including current portion

    5,088        1,310        4,478        2,465        1,252        4,509   

Total liabilities

    11,486        9,918        16,330        14,299        5,467        9,008   

Redeemable convertible preferred stock

    19,971        28,735        31,035        70,082        71,059        71,828   

Convertible preferred stock

    1,708        1,708        1,708        1,708        1,708        1,708   

Accumulated deficit

    (31,229     (35,971     (47,365     (62,439     (78,576     (92,415

Total stockholders’ (deficit)

    (28,354     (32,484     (38,585     (49,164     (63,901     (74,867

 

 

 

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Management’s discussion and analysis of financial condition and results of operations

You should read the following in conjunction with the “Selected consolidated financial information” and our consolidated financial statements and the related notes thereto that appear elsewhere in this prospectus. In addition to historical information, the following discussion and analysis includes forward looking information that involves risks, uncertainties and assumptions. Our actual results and the timing of events could differ materially from those anticipated by these forward looking statements as a result of many factors, including those discussed under “Risk factors” elsewhere in this prospectus. See also “Special note regarding forward looking statements” included elsewhere in this prospectus.

OVERVIEW

We are a life sciences company focused on the discovery, development and commercialization of novel diagnostic tests based on biomarkers for high-value market opportunities in healthcare that we identify. We believe that our tests will provide clinicians with improved information to better detect and characterize disease states. We are developing multiple product candidates to address significant unmet needs in cardiovascular and other diseases.

Our lead product, the BGM Galectin-3 test for heart failure, is a novel diagnostic test for measuring galectin-3 levels in blood plasma or serum. We are also developing our galectin-3 test for a second indication as a predictor of heart failure development in patients following acute coronary syndrome, a condition which includes heart attack or a serious form of cardiac chest pain called unstable angina.

We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. This test is indicated for use in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. In addition, we obtained CE Mark in the European Union for a manual galectin-3 test in October 2009 and have begun limited sales and marketing activities in certain countries in Europe, but, to date, we have recognized only a limited amount of product revenue. We have entered into worldwide development and commercialization agreements with Abbott Laboratories, Alere, bioMérieux and Siemens for the inclusion of our galectin-3 test on a variety of automated laboratory instruments and point-of-care instruments. Under these agreements, we have the right to enter into one additional agreement with another diagnostic laboratory instrument manufacturer for use on its instruments. We believe that, subject to completion of development of the galectin-3 test on these instruments, one or more of these laboratory instrument manufacturers will be in a position to submit a 510(k) premarket notification to the FDA no later than the fourth quarter of 2011 in order to obtain regulatory clearance to market automated instrument versions of our galectin-3 test in the United States. Subject to clearance from the FDA, we expect an automated instrument version of this test to be available for commercial use through one or more of these instrument manufacturers in the first half of 2012. We believe that it will take considerably less time for laboratory instrument manufacturers to develop and obtain FDA regulatory clearance for an automated version of our galectin-3 test than it took for us to develop and receive FDA regulatory clearance for the manual version of the test, since only the method for performing the test will change. The automated version of the test will be designed in the same way and be indicated for the same use as the manual test, and the manual test will serve as the predicate device under the FDA’s 510(k) clearance requirements. As a result, we expect that the FDA will be able to rely on much of the data and information reviewed, and knowledge gained, during the clearance process for the manual version of our test, thereby reducing the time necessary to receive clearance for the automated version of the test. Notwithstanding these factors, the FDA may not clear the automated version of this test as and when we expect.

 

 

 

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In May 2010, we entered into a license and supply agreement with LabCorp under which LabCorp began offering galectin-3 testing services to clinicians in the United States in January 2011. The galectin-3 testing services offered by LabCorp utilize the manual versions of our diagnostic test. Additionally, LabCorp has agreed to perform certain sales and marketing activities to promote galectin-3 testing, which are expected to commence in the first quarter of 2011.

We were founded in February 2000 as Beyond Genomics, Inc. In October 2004, we changed our name to BG Medicine, Inc. We have incurred substantial losses since our inception, and we expect to continue to incur losses for the next several years. For the years ended December 31, 2007, 2008 and 2009, we incurred net losses of $11.4 million, $15.1 million and $16.1 million, respectively, and for the nine months ended September 30, 2010, we incurred net losses of $13.8 million. Through September 30, 2010, we have an accumulated deficit of $92.4 million. To date, we have funded our operations primarily through private placements of preferred and common stock and debt financing, as well as through revenue generated from collaborative research and development and services agreements with pharmaceutical manufacturers, non-profit organizations and other entities.

In the coming years, we expect to devote substantially all of our resources to the development and commercialization of our diagnostic product candidates, as well as the discovery of new biomarkers. Historically, we have generated revenue from our collaborative research and development agreements and biomarker discovery and analysis services agreements, but we do not expect to continue to receive significant revenue from these sources going forward. As we continue our discovery, development and commercialization of diagnostic product candidates, we expect our research and development, sales and marketing, and general and administrative expenses to increase significantly.

During the nine months ended September 30, 2010, we incurred a net loss totaling $13.8 million and used cash in operating activities totaling $9.4 million. We expect to continue to incur losses and use cash in operating activities during 2011 and beyond. Our projected uses of cash include cash to fund operations, including continued research and product development, sales and marketing related to our launch of our first commercial product, capital expenditures, and existing debt service costs. Our existing cash resources are not sufficient to fund our current business plans beyond the end of March 2011. We will need additional funds to continue operations and the development and commercialization of our galectin-3 test and AMIPredict.

MATERIAL FACTORS AFFECTING OUR RESULTS OF OPERATIONS AND FINANCIAL CONDITION

We believe that the factors described in the following paragraphs have had and are expected to continue to have a material effect on our operational results and financial condition.

Revenue

To date, our revenue has been generated primarily through initiatives, collaborations and biomarker discovery and analysis services agreements. These services included the analysis of preclinical or clinical samples to identify biomarkers related to, for example, disease mechanism, drug response or toxicity. In some cases, we have retained rights to the biomarkers identified in the course of these agreements. Our revenue has tended to be concentrated, with arrangements with a limited number of large customers generating a significant percentage of revenue in any given year. In the future, we do not expect to generate significant revenue from these collaborative research and development and services agreements. We expect to receive the substantial portion of any future revenue from sales of our diagnostic tests, subject to obtaining regulatory clearance or approval in the United States and other jurisdictions.

We initiated and are leading the HRP initiative for atherothrombotic cardiovascular disease such as heart attack and stroke. This initiative, which we began in 2006, is sponsored by Abbott, AstraZeneca, Merck,

 

 

 

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Philips and Takeda. To date, we have recognized $24.2 million in revenue from the contributions we received from the HRP initiative participant companies.

Operating expenses

We classify our operating expenses into three categories: cost of revenue, research and development, and selling, general and administrative. Our operating expenses primarily consist of personnel costs, outside services, laboratory consumables and overhead, license fees, royalties on products, development costs, marketing program costs and legal and accounting fees. Personnel costs for each category of operating expenses include salaries, bonuses, employee benefit costs and stock-based compensation.

Cost of revenue

Our cost of revenue to date consists primarily of research and development expenses incurred to support our initiatives, collaborative research and development agreements and biomarker discovery and analysis services agreements. These expenses include both outside services and internal personnel costs, laboratory consumables, license fees and overhead expenses. Cost of revenue in the future will depend on the timing of regulatory approvals, if any, and the commercial success of our product candidates. For our most advanced diagnostic product candidate, our galectin-3 test for heart failure, our cost of revenue is expected to consist of manufactured kits, royalties and milestone payments under our agreement with our licensor, and freight costs.

Research and development expenses

We incur research and development expenses in connection with our internal biomarker discovery and development efforts. Our research and development expenses consist primarily of direct personnel costs, fees for consultants and outside services, laboratory consumables and overhead expenses. We use consultants and outside services to provide expertise or services which we do not have. We anticipate that research and development expenses will increase significantly, primarily due to our increased biomarker discovery and development efforts related to our product candidates.

Selling, general and administrative expenses

Selling expenses consist primarily of personnel-related expenses for employees engaged in market assessment, market development and pre-launch activities for our product candidates. We expect significant increases in our selling and marketing expenses as we hire additional personnel, establish our sales force, and conduct marketing activities for the commercialization of our product candidates.

General and administrative expenses consist primarily of personnel related expenses, occupancy expenses and professional fees, such as legal, auditing and tax. We expect that our general and administrative expenses will increase significantly as we expand our business operations to accommodate new product offerings and add commercial infrastructure. We expect that general and administrative expenses will also increase due to increased regulatory, legal, insurance, accounting and financial reporting expenses associated with being a public company.

Provision for income taxes

We have historically generated operating losses in all jurisdictions in which we may be subject to income taxes. As such, we have not incurred any income taxes. We have accumulated significant net operating losses and other deferred tax assets. Because of our history of losses and the uncertainty as to the realization of those deferred tax assets, a full valuation allowance has been recorded. We do not expect to report a provision for income taxes until we have a history of earnings, if ever, that would support the realization of our deferred tax assets.

 

 

 

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CRITICAL ACCOUNTING POLICIES AND SIGNIFICANT JUDGMENTS AND ESTIMATES

Our management’s discussion and analysis of financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States. The preparation of our consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenue and expenses and related disclosure of contingent assets and liabilities. On an ongoing basis, we evaluate our estimates based on historical experience and make various assumptions, which we believe to be reasonable under the circumstances, which form the basis for judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.

A summary of our significant accounting policies is contained in the notes to our audited consolidated financial statements, which are included elsewhere in this prospectus. We consider the following accounting policies to be critical to the understanding of the results of our operations:

 

Ø  

revenue recognition;

 

Ø  

stock-based compensation; and

 

Ø  

financial instruments.

Revenue recognition

Historically, our revenue has been generated through initiatives, collaborations and biomarker discovery and analysis agreements. The services which we provide under these agreements typically include the integrated analysis of preclinical or clinical samples to identify biomarkers related to, among other things, disease mechanisms and drug effects and, in some cases, undertaking clinical studies as part of an initiative to collect biological patient samples. In some cases, we have retained rights to the biomarkers identified in the course of these collaborations. The revenue arrangements have a stated term, and we generally have no obligations or ongoing commitments after the specified term of the arrangement.

We recognize revenue when the following criteria have been met: (i) persuasive evidence of an arrangement exists; (ii) delivery has occurred and risk of loss has passed; (iii) the seller’s price to the buyer is fixed or determinable; and (iv) collectability is reasonably assured. Revenue arrangements with multiple deliverables are divided into separate units of accounting when certain criteria are met.

Revenue generated from our collaborations and initiatives includes revenue from research services and technology licensing agreements. Under these arrangements, we are contractually obligated to provide research services and project oversight and administration. The rights to the results of the research, including any intellectual property developed, are licensed to all the members of the collaboration at the inception of the arrangement. We have accounted for all deliverables, which include the research services, oversight and administration and the rights to the intellectual property developed, as a single unit of accounting as there is no standalone value of the individual elements and no evidence of fair value for the undelivered elements. We consider the terms and conditions of each agreement and recognize revenue based upon a proportional performance methodology. This methodology involves recognizing revenue over the term of the agreement, as underlying research costs are incurred, and measured on the basis of input measures such as labor or instrument hours expended. We believe that these input measures approximate the output measures as the costs incurred are directly proportional to the services that are being provided. We make adjustments, if necessary, to the estimates used in these calculations as work progresses and as such changes become known. The principal costs under these agreements are for personnel and instrumentation expenses to conduct research and development but also include costs for materials and other direct and indirect items necessary to complete the research under these agreements. Actual results may vary from our estimates. Payments received on uncompleted long-term contracts may

 

 

 

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be greater than incurred costs and estimated earnings and have been recorded as deferred revenue. Payments received prior to commencement of a contract are recorded as customer deposits.

The proportional performance revenue methodology relies on estimates of total project costs and costs incurred as of each reporting date. Our estimates of revenue and cost are developed in detail for each revenue arrangement. We believe, based on our experience, that our current systems of management and accounting controls allow us to produce materially reliable estimates of total contract revenue and costs during any accounting period. However, many factors can and do change during the performance period of each revenue arrangement, which can result in changes to these estimates from one financial reporting period to another. Some of the factors that can change the estimate of total contract revenue and cost include changes in the scope of our projects by our customers, the performance of major vendors and subcontractors to deliver on time and in accordance with original budgets, and the accuracy of the original project cost estimate. Changes in estimates of total project costs and our estimates of state of completion can have a material impact on our financial statements and are reflected in our results of operations when they become known. To date, the changes in estimates have not been material in any period.

If we are successful in the commercial launch of our product candidates, product revenue will include revenue from our customer agreements and sales of our diagnostic products.

Stock-based compensation

Stock-based compensation expense is recognized based on the grant date fair value. We estimate the fair value of the share-based awards, including stock options, using the Black-Scholes option-pricing model. Determining the fair value of share-based awards requires the use of highly subjective assumptions, including the fair value of our common stock underlying the award, the expected term of the award and expected stock price volatility. The assumptions used in calculating the fair value of share-based awards granted in the three years ended December 31, 2009 and the nine months ended September 30, 2010 are set forth below:

 

    Years ended December 31,     For nine months
ended September 30,
2010
 
     2007     2008     2009    

Risk-free interest rate

    4.47% – 5.06%        3.48%        1.64% – 3.19%        2.37% – 3.09%   

Expected dividend yield

    0%        0%        0%        0%   

Expected life

    5.00 – 6.25 years        5.25 – 6.25 years        5.25 – 6.25 years        4.0 – 6.25 years   

Expected volatility

    63% – 65%        61% – 63%        64% – 67%        68% – 69%   

Weighted-average grant date fair value

  $ 13.80      $ 3.70      $ 4.42      $ 6.08   

The risk-free interest rates are based on the United States Treasury yield curve in effect at the time of grant, with maturities approximating the expected life of the stock options. We have no history of paying dividends nor do we expect to pay dividends over the contractual terms of these options. The expected life of the awards is estimated based on the simplified method, as defined in Staff Accounting Bulletin No. 110, Share-Based Payment, which uses the mid-point between the vesting date and the end of the contractual term. We use the simplified method because we do not have sufficient option exercise data to provide a reasonable basis upon which to estimate the expected term. Because there was no public market for our common stock, we lacked company-specific historical and implied volatility information. Therefore, we estimated our expected stock volatility based on that of publicly-traded peer companies, and we expect to continue to use this methodology until such time as we have adequate historical data regarding the volatility of our publicly-traded stock price.

 

 

 

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We are required to recognize compensation expense for only the portion of options that are expected to vest; however, due to the small size of our employee base and the quarterly vesting provisions of our option awards, forfeitures of awards have been nominal. Therefore, we have applied a 0% forfeiture rate in recognizing stock-based compensation expense. If our actual forfeiture rate varies from our historical rates and estimates, additional adjustments to compensation expense may be required in future periods. If there are any modifications or cancellations of the underlying unvested securities or the terms of the stock option, we may be required to accelerate, increase or cancel any remaining unamortized stock-based compensation expense.

We also account for equity instruments issued to our non-employee directors and consultants at fair value. All transactions in which goods or services are the consideration received for the issuance of equity instruments are accounted for based on the fair value of the consideration received or the fair value of the equity instrument issued, whichever is more reliably measurable. The measurement date of the fair value of the equity instrument issued is the date on which the counterparty’s performance is complete. Awards to nonemployees have been nominal in the three years ended December 31, 2009 and through the nine months ended September 30, 2010.

The following table presents the grant dates and exercise prices of stock options granted during the twenty-one months ended September 30, 2010, along with estimates for the fair value of the underlying common stock and resultant estimated fair value of the stock options:

 

Date of issuance    Number of
shares
subject to
options
granted
     Per share
exercise
price of
options
     Per share
estimated
fair value
of common
stock(1)
    

Per share

estimated

fair value

of options(2)

 

January 23, 2009

     553,949       $ 7.50       $ 7.50       $ 4.35   

April 7, 2009

     410,559         7.50         7.50         4.37   

June 30, 2009

     367,788         7.50         7.50         4.48   

November 25, 2009

     26,695         9.45         9.45         5.68   

January 23, 2010

     63,689         10.67         10.67         6.08   
                 

Total

     1,422,680            
                 

Weighted-average

      $ 7.65       $ 7.65       $ 4.47   

 

(1)   The per share estimated fair value of common stock represents the determination by our board of directors of the fair value of our common stock as of the date of grant, taking into account various objective and subjective factors.

 

(2)   The per share estimated fair value of options was estimated for the date of grant using the Black-Scholes options pricing model.

Based upon the expected initial public offering price set forth on the cover of this prospectus, the aggregate intrinsic value of our outstanding stock options as of September 30, 2010 was $6.4 million.

Our board of directors has historically estimated the fair value of our common stock, with input from management, as of the date of each stock option grant. Because there has been no public market for our common stock, our board of directors determined the fair value of our common stock by considering a number of objective and subjective factors, including:

 

Ø  

the sale price of the most recent preferred stock financing rounds, which was $6.50 per share for the Series D redeemable convertible preferred stock in July 2008;

 

Ø  

the liquidation preferences of our preferred stock, including any additional fundraising activities that may have occurred in the period;

 

 

 

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Ø  

the illiquid nature of our common stock, including the opportunity and timing for any expected liquidity events;

 

Ø  

our size and historical operating and financial performance, including our recent operating and financial projections as of each grant date;

 

Ø  

achievement of enterprise milestones;

 

Ø  

the market value of a peer group comprised of selected publicly-traded companies and guideline transactions identified as being comparable to us; and

 

Ø  

market conditions for early-stage diagnostic companies and other life science companies.

Our board of directors considered and applied these and other factors in determining an estimate of the fair value of our common stock on each stock option grant date. With the information discussed above and information provided by management, and in accordance with the guidance set forth by the American Institute of Certified Public Accountants, or the AICPA, in the AICPA Technical Practice Aid, Valuation of Privately-Held-Company Equity Securities Issued as Compensation, referred to as the AICPA Practice Aid, the board of directors arrived at the grant date fair value of each option award as of each grant date. Specifically, we applied the probability-weighted expected return method, as prescribed by the AICPA Practice Aid. Under the probability-weighted expected return method, the fair value of our common stock is estimated based upon an analysis of future values of our company assuming various future outcomes, the timing of which is based on the plans of our board of directors and management. Share value is based on the probability-weighted present value of expected future investment returns, considering each of the possible outcomes available to us as well as the rights of each share class. The fair value of our common stock was estimated using a probability weighted analysis of the present value of the investment returns. This valuation method took into consideration the following scenarios:

 

Ø  

two different scenarios for the completion of an initial public offering – a short-term view (6 months) and a long-term view (18 months or more);

 

Ø  

a sale to a strategic acquirer at a significant premium to the liquidation preference;

 

Ø  

a sale to a strategic acquirer at a premium to the liquidation preference; and

 

Ø  

a sale to an acquirer below the liquidation preference.

The valuation methodology our board of directors considered to determine the fair value of our common stock was based on the probability-weighted expected return method, liquidation preferences, progress towards a liquidity event and historical market data of liquidity transactions for similar companies.

The fair value through June 30, 2009 was consistent with the fair value at December 31, 2008, which was derived primarily by reference to the completion of the Series D preferred stock financing in July 2008, which was deemed reasonable because our operations and progress towards product development milestones was consistent with the projections that existed at the time of that financing. The fair value of our common stock was determined to be $7.50 per share as of June 30, 2009. The probability of an initial public offering was estimated to be 55% (30% likely in the short-term and 25% likely in 18 months). The fair value of our common stock through June 30, 2009 also reflected the following factors:

 

Ø  

the submission of our 510(k) premarket notification with the FDA for the clearance of our galectin-3 diagnostic test (March 2009);

 

Ø  

additions to our senior management team (January - June 2009);

 

Ø  

significant deterioration in the U.S. economy and the valuations of comparable companies; and

 

Ø  

significant deterioration in the prospects for the funding of early stage companies such as ours.

 

 

 

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The fair value of our common stock was determined to be $9.45 per share as of November 25, 2009. The probability of an initial public offering was estimated to be 60% (40% likely in the short-term and 20% likely in 21 months). The fair value of our common stock as of that date also reflects the following factors:

 

Ø  

the decision by the FDA to deny our 510(k) submission for our galectin-3 test (August 2009);

 

Ø  

the issuance of CE mark permitting sales of our galectin-3 test in the European Union (November 2009);

 

Ø  

the receipt of favorable data from an additional clinical study in support of our galectin-3 test (November 2009), which we submitted to the FDA in December 2009 with our new 510(k) application;

 

Ø  

the first shipment of galectin-3 trial kits to our distributor in Europe (November 2009); and

 

Ø  

our commercial partnership with Abbott (November 2009).

Since December 31, 2009 through the date of this prospectus, we granted options to purchase 63,689 shares of our common stock at an exercise price of $10.67 per share on January 23, 2010. The fair value of our common stock was determined to be $10.67 per share as of January 23, 2010, an increase of $1.22 from the prior fair value on November 25, 2009. The probability of an initial public offering was estimated to be 60% (50% likely in the short-term and 10% likely in the next 18 months). The short-term probability was based, in part, on our belief in the increased likelihood of obtaining regulatory clearance from the FDA for our galectin-3 test and completing an initial public offering of our common stock, in light of prevailing market conditions and our relative financial condition at the time. The increase in the fair value of our common stock from November 25, 2009 was previously determined to reflect the following factors:

 

Ø  

our submission of a new 510(k) premarket notification to the FDA for our galectin-3 test (December 2009);

 

Ø  

the holding of an organizational meeting with the representative of the underwriters for the initial public offering of our common stock contemplated by this prospectus (December 2009);

 

Ø  

ongoing discussions with the FDA relating to the clearance of our 510(k) submission; and

 

Ø  

our liquidity and needs for financing, including our bridge note financing where we issued $6.0 million in principal amount of bridge notes (March 2010 through November 2010).

Total stock-based compensation expense has been recognized in the statement of operations as follows:

 

     Years ended December 31,     

Nine months ended

September 30,
2010

 
      2007      2008      2009     

Research and development expenses

   $ 884       $ 452       $ 565       $ 375   

Selling, general and administrative expenses

     1,026         1,152         1,816       $ 1,363   
                                   

Total

   $ 1,910       $ 1,604       $ 2,381       $ 1,738   
                                   

Stock-based compensation expense of approximately $3.0 million was unrecognized for non-vested awards as of September 30, 2010, and is expected to be recognized over a weighted-average period of 2.3 years.

The assumptions used in determining fair value of share-based awards represent management’s and our board of directors’ best estimates, but these estimates involve inherent uncertainties and the application of judgment. As a result, if factors change, and we use different assumptions, our share-based compensation expense could be materially different in the future. We believe that the valuation methodologies used in the valuations are reasonable and consistent with the AICPA Practice Aid.

 

 

 

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Valuation models require the input of highly subjective assumptions. Because pre-IPO common stock has characteristics significantly different from that of a publicly traded common stock and because changes in the subjective input assumptions can materially affect the fair value estimate, in management’s opinion, the existing models do not necessarily provide a reliable, single measure of the fair value of our common stock.

The foregoing valuation methodologies are not the only valuation methodologies available to value our awards prior to becoming a public company. We cannot make assurances of any particular valuation of our stock. Accordingly, investors are cautioned not to place undue reliance on the foregoing valuation methodologies as an indicator of future stock prices.

Financial instruments

We have issued certain freestanding warrants related to shares that are redeemable or contingently redeemable, as well as common stock warrants that are not considered indexed to our own stock. These warrants are required to be carried as liabilities and are measured at fair value. Changes in the fair value of these warrants are recorded in the statement of operations. We measure the fair value of the warrants using a Black-Scholes option pricing model, using similar assumptions to those described above in the section entitled “—Stock-based compensation.” The expected term of all warrants is the remaining contractual term. Upon the closing of this offering, the warrants that are exercisable into redeemable shares will be converted into warrants to purchase common stock, and there will be no future impact on the statement of operations related to these warrants. However, the warrants for common stock that are not considered indexed to our own stock will remain outstanding.

The assumptions used in determining fair value represent management’s best estimates, but these estimates involve inherent uncertainties and the application of management judgment. As a result, if factors change, including the changes in fair value of the underlying common stock, our fair value estimates could be materially different in the future.

RESULTS OF OPERATIONS

Comparison of the nine months ended September 30, 2010 and 2009

Revenue

Revenue decreased by 92%, or $7.5 million, to $620,000 in the nine months ended September 30, 2010 from $8.1 million in the same period in 2009. This decrease was primarily due to the completion of the HRP Initiative phase I clinical trial activities in July 2009. Revenue during the nine months ended September 30, 2009 from the HRP initiative was $6.5 million, or 80% of total revenue, and from three service agreements, was $1.6 million. During the nine months ended September 30, 2010, we recognized revenue from the HRP initiative phase II clinical trial activities and from four service agreements.

Operating expenses

The following table sets forth certain information concerning our operating expenses for the periods shown:

 

     Nine months ended
September 30,
     Change  
      2009      2010      $     %  
     (in thousands)  

Cost of revenue

   $ 7,902       $ 650       $ (7,252     (92 )% 

Research and development

     6,502         5,596         (906     (14 )% 

Selling, general and administrative

     5,541         6,224         683        12
                                  

Total operating expenses

   $ 19,945       $ 12,470       $ (7,475     (37 )% 
                                  

 

 

 

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Cost of Revenue. Cost of revenue decreased by 92%, or $7.3 million, to $650,000 in the nine months ended September 30, 2010 from the same period in 2009. The reduction in cost of revenue was primarily attributable to the decrease in costs associated with reduced activity from the HRP initiative and other service agreements.

Research and development expenses. Research and development expenses decreased by 14%, or $906,000, to $5.6 million in the nine months ended September 30, 2010 from the nine months ended September 30, 2009. The decrease was primarily due to the decreased activity and personnel-related costs associated with our internal biomarker discovery and development efforts, primarily our galectin-3 program. The galectin-3 program expenses consisted primarily of clinical and regulatory costs associated with the 510(k) submissions.

Selling, general and administrative expenses. Selling, general and administrative expenses increased by 12%, or $683,000, to $6.2 million in the nine months ended September 30, 2010 from the nine months ended September 30, 2009. Marketing expenses increased $170,000, primarily due to increased pre-market activities related to our product candidates, primarily galectin-3. General and administrative expenses increased $513,000 due to increased personnel-related costs.

Interest income and expense. Interest income for the nine months ended September 30, 2010 decreased by $98,000 to $4,000 in the nine months ended September 30, 2009 due to lower average cash balances. Interest expense and other financing costs for the nine months ended September 30, 2010 increased by $1.8 million to $2.0 million in the nine months ended September 30, 2009. Interest expense and other financing costs in the nine months ended September 30, 2010 was comprised of the non-cash expenses arising from the issuance of warrants for the convertible debt and term loans of $1.9 million, as well as cash interest from the term loans of $104,000.

Comparison of the years ended December 31, 2009 and 2008

Revenue

Revenue decreased by 42%, or $6.1 million, to $8.5 million in 2009 from $14.6 million in 2008, primarily due to the completion of phase I of the HRP initiative and the decreased number of projects completed under our other service agreements. During the year ended December 31, 2009, we recognized revenue from only six months of work related to the HRP initiative, as well as from other service agreements, compared to the year ended December 31, 2008, when we recognized revenue from six ongoing studies with the HRP initiative, as well as under various other agreements. Revenue from the HRP initiative in 2009 was $6.5 million, or 76% of total revenue, compared with $12.1 million, or 83% of total revenue, in 2008. As of June 30, 2009, we had recognized all of the revenue committed under the initiative.

Operating expenses

The following table sets forth certain information concerning our operating expenses for the periods shown:

 

     Years ended
December 31,
     Change  
      2008      2009      ($)     (%)  
     (in thousands)  

Cost of revenue

   $ 13,822       $ 8,431       $ (5,391     (39 )% 

Research and development

     6,858         8,527         1,669        24   

Selling, general and administrative

     4,475         7,520         3,045        68   
                                  

Total operating expenses

   $ 25,155       $ 24,478       $ (677     (3 )% 
                                  

 

 

 

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Cost of revenue. Cost of revenue decreased by 39%, or $5.4 million, in the year ended December 31, 2009 from the year ended December 31, 2008. Of the decrease, $3.9 million was attributable to a decrease in third party costs, primarily due to the conclusion of screening, enrollment and baseline evaluation for the BioImage study under the HRP initiative. The reduction was also due to the decrease in personnel-related costs of $1.5 million as employees were redeployed from the HRP initiative to internal research and development efforts.

Research and development expenses. Research and development expenses increased by 24%, or $1.7 million, in the year ended December 31, 2009 from the year ended December 31, 2008. The increase was primarily due to the increased activities and personnel-related costs associated with our internal biomarker discovery and development efforts, primarily our galectin-3 program. The galectin-3 program expenses consisted primarily of clinical and regulatory costs associated with the 510(k) submissions.

Selling, general and administrative expenses. Selling, general and administrative expenses increased by 68%, or $3.0 million, in the year ended December 31, 2009 from the year ended December 31, 2008. Marketing expenses increased $2.7 million, primarily due to increased personnel and pre-market activities related to our product candidates, primarily our galectin-3 test. General and administrative expenses increased $270,000 due to increased personnel-related costs.

Interest income and expense. Interest income for the year ended December 31, 2009 decreased by $301,000 to $121,000 from $422,000 in the year ended December 31, 2008 due to lower average cash balances. Interest expense for the year ended December 31, 2009 decreased $4.7 million to $244,000 from $4.9 million in the year ended December 31, 2008. In the year ended December 31, 2009, interest expense was attributable to our outstanding term loan with Silicon Valley Bank, which matures in 2011 and bears interest at 10.25% as well as the amortization of debt discounts on the Silicon Valley Bank that arose from the issuance of warrants. Interest expense in the year ended December 31, 2008 consisted of the beneficial conversion of the convertible debt of $3.1 million, non-cash expenses arising from the issuance of warrants in connection with the term loans and the convertible debt of $1.1 million, and interest on the term loans and convertible debt of $724,000.

Comparison of the years ended December 31, 2008 and 2007

Revenue

Revenue increased by 62%, or $5.6 million, to $14.6 million in 2008 from $9.0 million in 2007, primarily due to the increased number of projects conducted under our service agreements. During the year ended December 31, 2008, we recognized revenue from the HRP initiative and five other service agreements, compared to the year ended December 31 2007, when we recognized revenue from the HRP initiative and three other service agreements. Revenue from the HRP initiative in 2008 was $12.1 million, or 83% of total revenue, compared with $5.1 million, or 57% of total revenue, in 2007.

 

 

 

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Operating expenses

The following table sets forth certain information concerning our operating expenses for the periods shown:

 

     Years ended
December 31,
     Change  
      2007     2008      ($)     (%)  
     (in thousands)  

Cost of revenue

   $ 7,301      $ 13,822       $ 6,521        89

Research and development

     5,832        6,858         1,026        18   

Selling, general and administrative

     3,820        4,475         655        17   

Costs related to abandoned stock offering

     3,154                (3,154     (100

Gain on sale of property and equipment

     (118             118        (100
                                 

Total operating expenses

   $ 19,989      $ 25,155       $ 5,166        26
                                 

Cost of revenue. Cost of revenue increased by 89%, or $6.5 million, in the year ended December 31, 2008 from the year ended December 31, 2007. The increase in cost of revenue is proportional to the increase in revenue from the HRP initiative. The costs of outside services increased by $6.5 million, primarily due to the third party costs associated with the increased activities from the HRP initiative of $7.0 million, partially offset by a decrease of $390,000 in other services activities.

Research and development expenses. Research and development expenses increased by 18%, or $1.0 million, in the year ended December 31, 2008 from the year ended December 31, 2007. The costs of outside services increased by $1.8 million due to increased research and development activity on our product candidates, primarily our galectin-3 and AMIPredict programs, partially offset by a decrease of $780,000 in personnel- related costs due to a staffing reduction. The galectin-3 expenses consisted primarily of product development, as well as clinical and regulatory development costs. The AMIPredict expenses included costs primarily associated with biomarker discovery and research and development.

Selling, general and administrative expenses. Selling, general and administrative expenses increased by 17%, or $655,000, in the year ended December 31, 2008 from the year ended December 31, 2007. Personnel and personnel related costs increased by $700,000 for employees responsible for assessing the commercial opportunity of and developing market awareness and launch plans for our product candidates.

Costs related to abandoned stock offering. In the year ended December 31, 2007, we incurred $3.2 million in legal, accounting and other costs associated with our abandoned initial public offering of common stock. In the year ended December 31, 2008, we did not incur any such expenses.

Interest/Other income and expense. Interest income for the year ended December 31, 2008 increased by $120,000 to $422,000, from $302,000 in the year ended December 31, 2007 due to higher average cash balances. Interest expense for the year ended December 31, 2008 increased by $4.2 million to $4.9 million from $689,000 in the year ended December 31, 2007. In the year ended December 31, 2008, interest expense consisted of $3.1 million attributable to our convertible debt beneficial conversion, $1.1 million in non-cash expenses arising from the issuance of warrants in connection with the term loan and the convertible debt and $724,000 in interest from our term loans and convertible debt. In the year ended December 31, 2007, interest expense consisted of $434,000 attributable to our convertible debt beneficial conversion, $65,000 in non-cash expenses arising from the amortization of debt discounts that arose from the issuance of warrants in connection with loans and $190,000 in interest expense from the various loans.

 

 

 

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LIQUIDITY AND CAPITAL RESOURCES

As of September 30, 2010, we had $2.9 million of cash, cash equivalents and marketable securities and a working capital deficit of $5.3 million, which includes $4.0 million in outstanding bridge notes as of September 30, 2010 from the March 2010 bridge note financing discussed below. Our primary sources of liquidity have been funds generated from our equity financings, which have included the sale of shares of our common stock and preferred stock, debt financings, and cash payments from our research and development collaborations and service agreements. Through September 30, 2010 we have received gross proceeds of $83.2 million from the sale of our securities as follows:

 

Ø  

$0.7 million through the sale of 2,178,976 shares of common stock;

 

Ø  

$23.7 million through the sale of 15,823,566 shares of Series A redeemable convertible preferred stock;

 

Ø  

$5.0 million through the sale of 2,475,247 shares of Series A-1 redeemable convertible preferred stock;

 

Ø  

$4.8 million through the sale of 1,138,716 shares of Series B convertible preferred stock;

 

Ø  

$5.0 million through the sale of 1,369,863 shares of Series C redeemable convertible preferred stock;

 

Ø  

$6.0 million through the sale of convertible promissory notes, which converted into 949,720 shares of Series D redeemable convertible preferred stock;

 

Ø  

$34.0 million through the sale of 5,204,126 shares of Series D redeemable convertible preferred stock; and

 

Ø  

$4.0 million through the sale of convertible promissory notes, which will convert into 571,418 shares of our common stock upon the completion of this offering at the expected initial public offering price of $7.00 per share.

In November 2007, we entered into a term loan with a financial institution to borrow up to $3.0 million. We have borrowed a total of $3.0 million under the agreement in two separate tranches and as of September 30, 2010, there was $400,000 of principal outstanding with monthly payments due through January 2011.

On March 30, 2010, we entered into an agreement to issue up to an aggregate of $6.0 million principal amount of convertible promissory notes, or bridge notes, to certain of our principal stockholders. We refer to this financing as our bridge note financing. We issued $4.0 million of the bridge notes as of September 30, 2010 and the balance of $2.0 million in November 2010. Interest on the bridge notes accrues at the rate of 12% per year. The unpaid principal amount of the bridge notes, together with any interest accrued but unpaid thereon will automatically convert upon the closing of this offering into a number of shares of our common stock equal to the quotient obtained by dividing the unpaid principal amount of the notes plus interest accrued but unpaid thereon by the initial public offering price. Based upon the expected initial public offering price of $7.00 per share, the $6.0 million in principal amount of the outstanding bridge notes will convert into approximately 857,127 shares of our common stock. In connection with the bridge note financing, we issued warrants to purchase 415,347 shares of our common stock. The warrants will be exercisable at an exercise price of $0.02 per share. The relative fair value of the warrants, aggregating $1,697,000, was recorded as interest expense in the nine months ended September 30, 2010. An additional charge totaling approximately $650,000 will be recognized in November 2010 as a result of the issuance of the $2.0 million remaining principal on the bridge notes.

In July 2010, we applied to the Internal Revenue Service for a one-time tax incentive being offered by the U.S. Government, the Qualifying Therapeutic Discovery Project, or QTDP, program. In letters dated October 29, 2010, we were notified that we were awarded $489,000 under the QTDP program for qualified past expenditures related to our development efforts related to the galectin-3 and AMIPredict diagnostic tests. We received the funds from the QTDP program during the fourth quarter of 2010.

 

 

 

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Net cash used

For the nine months ended September 30, 2010, we used cash in operating activities of $9.4 million, which reflects the net loss incurred totaling $13.8 million, offset by $4.0 million of non-cash charges and $350,000 in changes in working capital balances. Cash flows provided by investing activities of $2.0 million consisted of $2.1 million in net proceeds from the purchase and sale of marketable securities offset by $59,000 in purchases of property, equipment and intangibles. Net cash flows provided by financing activities were $2.0 million, which included proceeds from the issuance of convertible promissory notes of $4.0 million offset by $2.0 million from the repayment of our term loan and payment of the transaction fees related to the proposed initial public offering. As a result, we had negative cash flows for the nine months ended September 30, 2010 of $5.5 million.

For the nine months ended September 30, 2009, we used cash in operating activities of $14.4 million, which reflects the net loss incurred totaling $11.9 million and $4.8 million in use of cash for working capital, offset by $2.3 million of non-cash charges. Cash flows provided by investing activities of $1.6 million consisted of $2.3 million in net proceeds from the purchase and sale of marketable securities and restricted investments offset by $694,000 in purchases of property, equipment and intangibles. Net cash used by financing activities of $936,000 resulted principally from the repayment of our term loan and capital leases. As a result, we had negative cash flows for the nine months ended September 30, 2009 of $6.3 million.

In 2009, we had negative cash flows from operating activities of $18.0 million, which reflects the net loss incurred totaling $16.1 million, offset by $1.8 million of non-cash charges and changes in working capital balances. Cash flows provided by investing activities of $7.5 million consisted of $8.2 million in net proceeds of investments and restricted investments offset by $697,000 in purchases of property, equipment and intangibles. Net cash flows used in financing activities were $1.2 million, including repayment of our term loan and capital leases. As a result, we had negative cash flows for 2009 of $11.7 million.

In 2008, we had negative cash flows from operating activities of $9.6 million, which reflects the net loss incurred totaling $15.1 million, offset by $6.6 million of non-cash charges. Cash flows used in investing activities of $7.5 million consisted of $7.1 million in net purchases of investments and restricted investments and $385,000 in purchases of property and equipment. Net cash flows from financing activities were $36.0 million, including proceeds from the issuance of our Series D redeemable convertible preferred stock, convertible promissory notes and term loan, partially offset by repayment of our term loan, capital leases and equipment notes. As a result, we had positive cash flows in 2008 of $18.8 million.

In 2007, we had negative cash flows from operating activities of $3.9 million, which reflects the net loss incurred totaling $11.4 million, offset by $7.5 million of non-cash charges and changes in working capital balances. Proceeds from the sale of property and equipment and the sale of short-term investments, offset by purchases of restricted investments and purchases of property and equipment, resulted in cash flows used in investing activities of $3.8 million. Net cash flows from financing activities were $8.0 million, including proceeds from the issuance of our Series C redeemable convertible preferred stock, convertible promissory notes, term loan and from the issuance of promissory notes to GE Capital, partially offset by repayment of capital leases and equipment notes. As a result, we had positive cash flows in 2007 of $204,000.

Funding requirements

To date, we have generated revenue primarily through the provision of services to third parties in connection with our initiatives, collaborations and biomarker discovery and analysis services agreements. However, as we transition into a commercial organization, we expect to generate revenue from the sale of our products and do not expect to generate significant service-based revenue of this kind in the future

 

 

 

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under collaborative research and development and services agreements. We have generated only a limited amount of product revenue since our inception and do not expect to generate any significant revenue from the sale of our testing products before the second half of 2011, at the earliest. During the nine months ended September 30, 2010, we incurred a net loss totaling $13.8 million and used cash in operating activities totaling $9.4 million. We expect to continue to incur losses and use cash in operating activities during 2011 and beyond. Our projected uses of cash include cash to fund operations, including continued research and product development, sales and marketing related to our launch of our first commercial product, capital expenditures, and existing debt service costs. Our existing cash resources are not sufficient to fund our current business plans beyond the end of March 2011. This projection is based on our current operations and planned activities at normal levels and does not assume any cash inflows from partnerships, disposition of additional non-core assets or successful completion of any equity or debt financings. We believe that the net proceeds from this offering, together with our existing cash, cash equivalents and marketable securities (including the proceeds from our bridge note financing in November 2010), will be sufficient to meet our anticipated cash requirements through 2012.

If we are not able to generate significant revenues from sales of our galectin-3 tests by the end of 2012, we will need to raise funds, in addition to the net proceeds from this offering, to continue our operations and to develop and potentially commercialize our second product candidate, AMIPredict. We may consider any of the following options:

 

Ø  

partnering opportunities with pharmaceutical or biotechnology companies to pursue the development of our product candidates as companion diagnostic tests to their therapeutic products;

 

Ø  

license, sublicense, or other sources of financing relating to the development programs of our product candidates and other intellectual property; or

 

Ø  

sale of equity or debt securities.

If we are unable to obtain financing or enter into licensing or partnering arrangements on acceptable terms at that time, we will be required to implement aggressive cost reduction strategies. The most significant portion of the research and development expenses, as well as some portion of sales and marketing expenses, are discretionary and are in anticipation of development and commercial launch of our galectin-3 test. These cost reduction strategies could reduce the scope of the activities related to these development and commercialization activities and could harm our long-term financial condition and results of operations.

Our forecast of the period of time through which our financial resources will be adequate to support our operations, the costs to complete development of product candidates and the cost to commercialize our future products are forward looking statements and involve risks and uncertainties, and actual results could vary materially and negatively as a result of a number of factors, including the factors discussed in the “Risk factors” and “Special note regarding forward looking statements” sections of this prospectus. We have based these estimates on assumptions that may prove to be incorrect, and we could utilize our available capital resources sooner than we currently expect. Our future liquidity and capital funding requirements will depend on numerous factors, including:

 

Ø  

the rate of progress and cost of our commercialization activities;

 

Ø  

the success of our research and development efforts;

 

Ø  

the expenses we incur in marketing and selling our products;

 

Ø  

the revenue generated by sales of any future products;

 

Ø  

the emergence of competing or complementary products;

 

 

 

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Ø  

the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; and

 

Ø  

the terms and timing of any collaborative, licensing or other arrangements that we have or may establish.

Contractual obligations and commitments

The following table sets forth our payment obligations as of December 31, 2009 under contracts that provide for fixed and determinable payments over the periods indicated. Other than the bridge note financing described above, no significant changes have occurred since December 31, 2009.

 

     Total      2010      2011      2012      2013      2014 and
beyond
 
     (in thousands)  

Operating leases

   $ 2,002       $ 616       $ 616       $ 616       $ 154           

Term loan, including interest

     1,379         1,278         101                      

Contract services

     1,312         625         487         100         100           
                                                     

Total

   $ 4,693       $ 2,519       $ 1,204       $ 716       $ 254           
                                                     

We lease approximately 22,000 square feet of office and laboratory space with a term expiring in March 2013. We have a term loan which bears a fixed interest rate of 10.25% and requires us to make payments, which commenced in July 2008, in 30 equal monthly installments. Our contract service obligations relate to biomarker discovery, product development, manufacturing and other business activities. In addition, we may be obligated to pay up to $800,000 in milestone payments under a funding agreement with Fujirebio for our galectin-3 test. The payments are contingent upon the achievement of certain development milestones. The table does not include any possible milestone payments, royalties or other fees payable under certain of our license agreements. We are obligated to pay royalties to ACS Biomarker on our galectin-3 test, for which we owe $250,000 as a prepayment because we received FDA clearance of our 510(k) submission. We are obligated to make royalty payments to ACS Biomarker in the future and such royalty payments will be dependent on the amount and nature of the revenues we generate from our galectin-3 test and the other technologies that we have licensed from them. We believe that we are reasonably likely to make additional license payments in the future, although the amounts and timing are not currently determinable.

We believe that our facilities are adequate to meet our current needs, although if additional space is needed in the future, we believe that such space will be available on commercially reasonable terms. In the future, we expect that we will require additional property, plant and equipment to accommodate our anticipated growth. We may choose to lease or directly purchase such property, plant and equipment depending upon the nature of the purchase, the current lease rate and our cash position.

OFF BALANCE SHEET ARRANGEMENTS

Since inception, we have not engaged in any off balance sheet activities as defined in Item 303(a)(4) of Regulation S-K.

RECENT ACCOUNTING PRONOUNCEMENTS

In June 2008, the Financial Accounting Standards Board, or FASB, issued guidance that requires an entity to use a two step approach to evaluate whether an equity-linked financial instrument (or embedded feature) is indexed to its own stock, including evaluating the instrument’s contingent exercise and settlement provisions. We adopted this guidance beginning January 1, 2009, and the impact of adoption was not material to the consolidated financial statements.

 

 

 

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In September 2009, the FASB issued authoritative guidance that modifies the accounting for revenue arrangements with multiple elements. This guidance requires an entity to allocate revenue to each unit of accounting in multiple deliverable arrangements based on the relative selling price of each deliverable. It also changes the level of evidence of stand-alone selling prices required to separate deliverables by allowing an entity to make its best estimate of the stand-alone selling price of the deliverables when more objective evidence of selling price is not available. Implementation of this guidance is required no later than fiscal years beginning after June 15, 2010, and this guidance may be applied prospectively to new or materially modified arrangements after the effective date or retrospectively. Early application is permitted. We have not yet evaluated the impact that this guidance may have on our financial statements.

QUALITATIVE AND QUANTITATIVE DISCLOSURES ABOUT MARKET RISK

Our exposure to market risk is limited to our cash, cash equivalents and marketable securities, all of which have maturities of less than one year. The goals of our investment policy are preservation of capital, fulfillment of liquidity needs and fiduciary control of cash and investments. We also seek to maximize income from our investments without assuming significant risk. To achieve our goals, we maintain a portfolio of cash equivalents and investments in a variety of securities that management believes to be of high credit quality. The securities in our investment portfolio are not leveraged, are classified as available for sale and are, due to their short-term nature, subject to minimal interest rate risk. We currently do not hedge interest rate exposure. Because of the short-term maturities of our investments, we do not believe that an increase in market rates would have a material negative impact on the value of our investment portfolio.

Our debt consists of fixed rate term debt that matures in January 2011 and the bridge notes that will convert to common stock upon the closing of this offering. We do not believe that an increase in interest rates would have a material negative impact on our financial position or results of operations.

We do not have any material foreign currency exposure.

 

 

 

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Business

OVERVIEW

We are a life sciences company focused on the discovery, development and commercialization of novel diagnostic tests based on biomarkers for high-value market opportunities in healthcare that we identify. Our lead product, the BGM Galectin-3 test for heart failure, received FDA clearance in November 2010, and galectin-3 testing services are currently being offered for use by clinicians in the United States through Laboratory Corporation of America, or LabCorp. This manual version of our test obtained CE Mark in the European Union in October 2009 and we have begun limited sales and marketing activities in certain countries in Europe. We are also developing multiple product candidates for cardiovascular and other diseases. We believe that our tests will provide clinicians with improved information to better detect and characterize disease states. We believe that this information may enable physicians to achieve better patient outcomes and contain healthcare costs through, for example, earlier diagnosis, segmentation based on underlying disease processes, more accurate prognosis, more personalized treatment selection or monitoring of disease based on disease activity. We focus on blood-based tests due to the ease and low cost of access to evaluable samples for testing and the opportunity for repeat sampling to monitor changes in a patient’s medical condition. We are developing our initial product candidates to address significant unmet needs in cardiovascular disease. We intend to sell our tests, subject to regulatory clearance or approval, through various channels, including through leading diagnostic instrument manufacturers that will offer our tests as novel assays on their instruments.

Our lead product, the BGM Galectin-3 test for heart failure, is a novel assay for measuring galectin-3 levels in blood plasma or serum. Galectin-3, a member of the galectin family of proteins, is a biomarker that has been shown to play an important role in heart failure. Heart failure is a condition caused by a combination of diseases or factors that damage or overwork the heart muscle, resulting in its inability to pump blood efficiently to meet the requirements of other body organs. This condition often leads to serious medical complications and is a leading cause of death. According to the American Heart Association, heart failure affects an estimated 5.8 million Americans, with an approximate 670,000 new cases occurring each year, and we believe the prevalence and incidence of heart failure are similar in Europe. In the United States alone, heart failure is expected to cost the healthcare system over an estimated $39 billion in 2010. We have measured galectin-3 in eight controlled studies involving over 5,300 patients with chronic or acute heart failure. In these studies, galectin-3 was found to be a strong independent predictor of mortality or hospitalization, the primary endpoints of the studies. We believe that the data from these studies indicate that heart failure patients with high levels of galectin-3 have a more progressive form of the disease, which we refer to as galectin-3-dependent heart failure. We believe that our galectin-3 test will provide physicians with meaningful information that may lead to more clinically- and cost-effective management of heart failure patients.

We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. This test is indicated for use in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. In addition, we obtained CE Mark in the European Union for our manual galectin-3 test in ELISA microtiter format, a form of test kit, in October 2009, and have begun limited sales and marketing activities in certain countries in Europe, but, to date, we have recognized only a limited amount of product revenue.

Although our manual BGM Galectin-3 test is an important element of our commercialization strategy, we believe that automated instrument versions of our test will be required for us to achieve broad customer acceptance and clinical adoption. In furtherance of our strategy to become the leading provider of high-

 

 

 

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value diagnostic tests that can be sold through leading diagnostic instrument manufacturers for use as novel assays on their existing automated diagnostic laboratory instruments, we have entered into worldwide development and commercialization agreements with Abbott Laboratories, or Abbott, Alere Inc., or Alere, bioMérieux SA, or bioMérieux, and Siemens Healthcare Diagnostics Inc., or Siemens, for the inclusion of our galectin-3 test on a variety of automated instruments, including point-of-care instruments. Under these agreements, we have the right to enter into one additional agreement with another diagnostic laboratory instrument manufacturer for use on its instruments. We believe that, subject to completion of development of the galectin-3 test on these instruments, one or more of these laboratory instrument manufacturers will be in a position to submit a 510(k) premarket notification to the FDA no later than the fourth quarter of 2011 in order to obtain regulatory clearance to market automated instrument versions of our galectin-3 test in the United States. Subject to clearance from the FDA, we expect an automated instrument version of this test to be available for commercial use through one or more of these instrument manufacturers in the first half of 2012. We believe that it will take considerably less time for laboratory instrument manufacturers to develop and obtain FDA regulatory clearance for an automated version of our galectin-3 test than it took for us to develop and receive FDA regulatory clearance for the manual version of the test, since only the method for performing the test will change. The automated version of the test will be designed in the same way and be indicated for the same use as the manual test, and the manual test will serve as the predicate device under the FDA’s 510(k) clearance requirements. As a result, we expect that the FDA will be able to rely on much of the data and information reviewed, and knowledge gained, during the clearance process for the manual version of our test, thereby reducing the time necessary to receive clearance for the automated version of the test. Notwithstanding these factors, the FDA may not clear the automated version of this test as and when we expect. We are also developing our galectin-3 test for a second indication as a predictor of heart failure development in patients following acute coronary syndrome, a condition which includes heart attack and a serious form of cardiac chest pain called unstable angina.

In May 2010, we entered into a license and supply agreement with LabCorp under which LabCorp began offering galectin-3 testing services to clinicians in the United States in January 2011. The galectin-3 testing services offered by LabCorp utilize the manual versions of our diagnostic test. Additionally, LabCorp has agreed to perform certain sales and marketing activities to promote galectin-3 testing, which are expected to commence in the first quarter of 2011.

In addition to the two indications for our galectin-3 test, we are also developing a test that we refer to as AMIPredict, a multivariate biomarker blood-based test for atherothrombotic cardiovascular disease, commonly known as vulnerable plaque. This test is designed to identify patients with a high risk of suffering a heart attack or stroke within the following two to four years. Our development work to date suggests that AMIPredict could be an improved diagnostic test compared to conventional risk factor-based approaches for heart attack and stroke risk, such as the Framingham Risk Score in the United States and the Systematic Coronary Risk Evaluation in Europe. We have initiated the development of an automated version of this test using currently approved laboratory instrumentation and reagents that are commercially available. We are currently conducting additional studies using this automated version intended to validate our previous findings. In addition to AMIPredict, we are developing LipidDx, a blood-based protein assay, that we believe may aid in the management of common lipid disorders.

Our discovery efforts are focused on leveraging our proprietary technology platform and our initiatives and collaborations to discover new diagnostic tests for clinically and commercially important diseases. In contrast to the prevailing development approach in diagnostics in which companies identify commercial market opportunities for a product following a serendipitous discovery, our platform allows us to initiate a structured process for discovering biomarkers for high-value market opportunities in healthcare that we identify in conjunction with our partners, such as third-party payors. As part of our product development process for internally discovered and licensed biomarkers, we develop and optimize our own first generation assays, conduct clinical development studies utilizing these tests and then seek

 

 

 

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regulatory clearance or approval if the clinical studies are successful. Initially we expect that most of our products will be manual in vitro diagnostic assays offered in kit form, or for the more complex assays such as multivariate index assays, subject to FDA clearance, offered as a laboratory service. However, if our products are suitable for automated instrument or point-of-care applications, we intend to seek partnerships with leading diagnostic laboratory instrument manufacturers for the development and commercialization of our products on their instruments, such as our agreements with Abbott, Alere, bioMérieux and Siemens. We believe that focusing on the development of diagnostic tests that can be sold through leading diagnostic instrument manufacturers for use as novel assays on their existing automated laboratory instruments will facilitate broader and more rapid adoption of our diagnostic tests.

As part of our strategy, we plan to continue to use the patient samples and data generated from our existing and any new collaborations and initiatives to successfully advance the development and commercialization of our products. For example, in 2006 we initiated and are leading the HRP (“high-risk plaque”) Initiative, for atherothrombotic cardiovascular disease, which consists of a series of pre-competitive, multi-party research and development projects with Abbott, AstraZeneca, Merck, Philips and Takeda. As part of the HRP initiative, we have conducted several studies and related activities involving approximately 7,000 Humana members enrolled in the study who provided biological specimens to which we have certain rights for our discovery and development projects that we conduct independent of this research initiative. In addition to the HRP initiative, in 2009, we entered into a five-year Cooperative Research and Development Agreement with the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, or NHLBI, and Boston University to conduct certain biomarker discovery studies in the area of metabolic syndrome and atherosclerotic cardiovascular disease using samples and data from the Framingham Heart Study. We were selected for this collaboration through a peer-reviewed process by NHLBI and have certain rights to multivariate markers discovered as part of the joint research.

THE CURRENT HEALTHCARE LANDSCAPE AND ITS LIMITATIONS

The increasing cost of healthcare is driving a need for reform. In the United States, for example, healthcare expenditures in 2009 represented approximately 18% of the Gross Domestic Product, or GDP, according to the President’s Council of Economic Advisors. Absent healthcare reform that addresses the cost of healthcare, these expenditures are expected to continue to rise sharply. If the historical growth trend continues, the share of GDP devoted to healthcare in the United States is projected to reach 34% by 2040, according to this same source. Furthermore, with nearly half of current healthcare spending being covered by local, state and federal government, government programs like Medicare and Medicaid will continue to demand an ever increasing share of tax dollars. Current healthcare reform efforts are focused on improving overall financing and purchasing, such as the use of value-based purchasing to drive quality and clinical improvements. Although reform in healthcare financing and administration can offer some opportunity to mitigate increases in healthcare cost, we believe improved medical management is needed to improve patient care outcomes and concurrently reduce the overall cost of care.

Healthcare reform is happening against the backdrop of substantial growth in biomedical information and an increasing complexity of medical care. Scientific experiments and clinical observations have documented the heterogeneity, or differences, in the underlying causes and symptoms among patients, of medical conditions and the variability in patient responses to treatments. Physicians currently have limited information about the underlying cause of disease to enable individualized treatment decisions for patients. Consequently, the current treatment paradigm is commonly based on a one-size-fits-all treatment model and a trial-and-error approach to finding the most suitable treatment for an individual patient. We believe that the combination of disease and patient disparateness and an increasing number of available therapeutic options creates an urgent need and a significant opportunity to more accurately

 

 

 

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match patients with appropriate treatments. We believe that diagnostic tests can play a central role in the solution to this important medical challenge of matching patients with appropriate treatments and can contribute to improved medical outcomes at reduced cost.

In addition, the current medical treatment model for most diseases continues to largely rely on detection and, in most cases, characterization of disease based on signs observed by physicians and symptoms perceived by the patient. Many disease conditions have a subclinical stage during which these signs and symptoms are not present or are insufficient to prompt the patient to seek medical care. Moreover, when a patient seeks medical care in the early stages of disease, these signs and symptoms are often not specific. With the lack of noticeable clinical symptoms, physicians may make incorrect or inconclusive diagnoses. However, many medical conditions are easier to treat in the early stage of the disease, and long-term complications and high-cost medical interventions can often be avoided when the disease is detected and treated early. These considerations apply to many common serious medical conditions, particularly in cardiovascular and metabolic diseases, and some forms of cancer and central nervous system diseases. We believe that novel diagnostic tests can play a pivotal role in the early detection and characterization of diseases, enabling more effective and often lower cost treatments as compared to the current medical model, which relies on the presence and recognition of signs and symptoms.

DIAGNOSTIC INDUSTRY OVERVIEW

The in vitro diagnostics, or IVD, industry focuses on developing products used to evaluate and analyze biological specimens derived from bodily fluids, such as blood, blood plasma and serum, urine, cells and other substances taken from patients. The information generated may be used by physicians to help identify persons at risk of disease, diagnose disease, stratify disease severity among patients, determine prognosis, monitor disease state and progression, guide and monitor therapy, and aid in the clinical management of patients. According to Kalorama Information, an independent market research firm, the global IVD market was approximately $42 billion in 2007 and is projected to reach $56 billion in 2012, growing at a compound annual growth rate, or CAGR, of 6%. Leading IVD manufacturers include Abbott, Siemens, Roche, Ortho Clinical Diagnostics and Beckman Coulter. “Customers” for in vitro diagnostic tests typically include a patient, whose specimen is used to measure the biomarker or analyte, a physician, who orders and interprets the results of the test, a laboratory which purchases the in vitro diagnostic kits and instruments to perform the test and a payor, which may reimburse for some or all expenses associated with conducting the test.

Molecular diagnostics currently represent a significant portion of the IVD market. According to Kalorama Information, the molecular diagnostics market, including a variety of laboratory tests, such as consumer diagnostics (over-the-counter and at-home tests), clinical research, biomarker discovery and testing and novel molecular analyses, was approximately $18 billion in 2006 and could be projected to exceed $92 billion in potential revenue (if every patient who could be tested were tested with molecular diagnostics) in major markets by 2016, representing a CAGR of 18%. The term molecular diagnostics refers to tissue and blood-based laboratory tests that measure DNA, RNA, proteins or metabolites to detect genotypes, mutations or biochemical changes that are markers of these biological characteristics, or biomarkers. Although tissue-based tests, such as certain genomic tests typically used in cancer, provide important new options to clinicians and patients, access to evaluable tissue samples is often difficult and expensive. We believe these factors severely limit the opportunities for tissue-based biomarker tests, in contrast to blood-based tests, which benefit from the ease and low cost of access to evaluable samples.

A biomarker is one or more biological characteristics that can be objectively measured and evaluated as an indicator of normal or pathogenic processes. Since biomarkers correlate with an underlying process within the body, tests to measure these biomarkers can be used effectively to aid physicians in a variety of ways. While genes are typically associated with the presence or absence of a genetic disease

 

 

 

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predisposition, proteins and metabolites often reflect the presence, severity or activity of a disease state. Therefore, the presence or amount of proteins or metabolites in the body can often serve as biomarkers for detecting presence of disease states such as cardiovascular disease and monitoring the progress of these diseases during treatment.

Conventional diagnostic assays are typically used to evaluate the concentration of a particular biomarker or other analyte, with the actual concentration providing information to the physicians ordering the test. This measured value is then compared to a determined normal range, a particular target value, a cut-off value, or the patient’s own baseline or prior values. It has increasingly been recognized that the clinical utility of a biomarker may be significantly greater when analyzed as a composite with one or more other biomarkers, often referred to in test form as a multivariate index assay. In its simplest format, multivariate index assays can produce a ratio between two analyte values, but when larger numbers of analytes are measured, mathematical formulas called algorithms are utilized to calculate either a score or a clinical categorization such as low, intermediate or high risk.

Over the past several decades, leading diagnostic laboratory instrument manufacturers have achieved significant improvements in automated testing methods and systems for hematology, chemistry and immunoassays. An immunoassay is a biochemical test that measures the concentration of a substance in a biological liquid, such as blood serum, or a biochemical test that measures the concentration of an analyte using chemical antibodies. In addition to developing and manufacturing these advanced diagnostic laboratory instruments, these manufacturers have established significant manufacturing and supply chain logistics and sales and marketing infrastructures for the diagnostic reagents used by their systems. The diagnostic instrument systems they offer range in size from small hand-held devices for point-of-care usage to large robotic laboratory systems that can handle more than 1,000 samples per hour and hold reagents for more than 50 assays. These immunoassay systems rely on established antibody methods in which one or more antibodies bind to the analyte, or substance being measured, which is usually a protein. These systems also utilize a method to detect such binding and are able to analyze the absolute concentration of the protein in question. These systems can be used to run various assays and manufacturers typically offer comprehensive menus of immunoassays, with the majority of analytes overlapping between manufacturers. We believe that this installed base of automated instruments offers an exceptional opportunity to make novel biomarker tests available to laboratories globally without the need for investment in development and commercialization of instrumentation specific to the “content” of the tests. We refer to this strategy as “separation of content and instrument,” which contrasts with the traditional model where manufacturers of automated laboratory instruments also discover and develop their own proprietary diagnostic tests for use as content exclusively for their instruments.

The FDA proposed a regulatory framework for in vitro diagnostic multivariate index assays, or IVDMIAs, and issued draft guidance that indicates how it may regulate IVDMIAs. Although the draft guidance has not been finalized and may never be issued, the FDA has cleared several IVDMIAs consistent with the draft guidance. In February 2007, the FDA cleared the first premarket notification 510(k) submission of an IVDMIA, Agendia’s MammaPrint® breast cancer recurrence assay. Subsequently, two additional IVDMIA products were cleared under the FDA’s IVDMIA draft guidance. We believe that with these regulatory clearances, representing a variety of multivariate diagnostic tests, a regulatory framework appears to be forming consistent with the FDA’s guidance, and we plan to develop our diagnostic product candidates and seek regulatory clearance in a similar way.

OUR SOLUTION

We have discovered biomarkers and are developing novel diagnostic tests based on biomarkers using our proprietary technology platform. In order to facilitate market acceptance and broad adoption of our

 

 

 

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biomarker-based diagnostic tests, we plan to make them available to the laboratories that perform these tests on behalf of physicians and their patients in several ways. We are pursuing three distinct paths for commercialization of our diagnostic tests:

 

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Sales of manual versions of our diagnostic tests through laboratory service providers;

 

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Sales by us through certified clinical laboratories; and

 

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Sales of automated versions of our diagnostic tests through leading diagnostic instrument manufacturers for use on their instruments.

Sales through laboratory service providers

We plan to develop and optimize our own first generation assays, conduct clinical development studies utilizing the assays and then seek regulatory clearance or approval if the clinical studies are successful. Initially, we expect that most of our product candidates, if cleared or approved by regulatory authority, will be in vitro diagnostic assays in kit form marketed to a variety of clinical laboratories. These clinical laboratories then offer testing services to physicians and their patients and collect a testing fee from the patient or the patient’s health plan or insurer if the test is eligible for reimbursement. Our agreement with LabCorp to offer galectin-3 testing services to physicians in the United States is an example of a sale of our manual test product to a laboratory service provider which, in turn, makes laboratory testing available to physicians.

Sales by us through certified clinical laboratories

We expect that our more complex assays, such as IVDMIAs, will be marketed as a laboratory service to physicians and patients by one or a few laboratories which would perform and offer these services on our behalf for physicians and patients. In this model, we would contract with established CLIA-certified laboratory service providers suitable for providing these specialized services, but we would be directly or indirectly responsible for collection of fees from patients and their health plans or insurers for these services. We currently have no such laboratory service offering, but, as part of the development program for AMIPredict, we have identified and commenced discussions with several potential providers of these specialized testing services.

Sales through leading diagnostic instrument manufacturers

Although manual forms of our tests are an important element of our commercialization strategy, we believe that automated instrument versions of our test will be required for us to achieve broad customer acceptance and clinical adoption. If our product candidates are suitable for automated instrument or point-of-care applications, we plan to seek collaborations with leading diagnostic laboratory instrument manufacturers for the development and commercialization of our product candidates on their instruments. In this model, we would collaborate with the manufacturer to develop an automated version of our test specifically for their automated instruments. Automated instruments offer marked advantages over our first generation manual test version in terms of speed, throughput and operating efficiency. We expect that under most agreements the instrument manufacturer will be responsible for development and manufacturing of our test for their automated instruments and additionally be responsible for distribution and sale of the test to clinical laboratories that operate their instruments. We have entered into agreements to date with Abbott, Alere, bioMérieux and Siemens. Under these four agreements, the diagnostic laboratory instrument manufacturers will be responsible for the development of our galectin-3 test on their respective automated instruments for use in their clinical laboratories or at the point-of-care. The terms of these agreements permit us to enter into one additional similar non-exclusive collaboration for our galectin-3 test. We intend to retain primary marketing responsibilities to promote automated galectin-3 testing.

 

 

 

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We believe that our solution offers several important benefits over existing approaches in diagnostics by:

 

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Enabling us to structure a discovery process for high-value market opportunities. The prevailing development and commercialization approach among life sciences companies is to identify commercial market opportunities for a product following a serendipitous discovery. In contrast, we believe that our proprietary technology platform offers us an opportunity to initiate a structured process for discovering biomarkers for high-value market opportunities that we identify. Our initial focus is on discovering or in-licensing biomarkers, and then developing novel diagnostic tests based on these biomarkers for significant unmet clinical needs in cardiovascular disease.

 

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Providing novel tests for laboratory instruments. We are focused on discovering, developing and commercializing biomarker-based diagnostic tests that can be sold through leading diagnostic instrument manufacturers for use as novel assays on their extensive installed base of laboratory instruments.

 

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Selecting and developing the best commercialization model for each test. Many factors influence how diagnostic tests are commercialized, including their complexity and ability to be offered as simple first generation products, potential need for rapid turn-around, testing volume and reimbursement level, among others. Our multi-pronged commercialization strategy allows us to consider these factors and tailor our commercialization strategy for each product in a manner that best suits the particular test, whether it be manual or automated, offered as in vitro diagnostic test kits to clinical laboratories or as a testing service directly to physicians or patients.

 

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Improving characterization of disease process. We are developing diagnostic tests to identify disease during the subclinical stage, or before signs and symptoms are present. We believe that early detection and characterization of disease can help physicians better match patients with appropriate treatments, resulting in better clinical outcomes.

 

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Reducing healthcare costs. We are developing novel diagnostic tests for costly disease states that place tremendous demands on healthcare systems. We believe that our tests can help improve medical management and care outcomes, while reducing healthcare costs in our target markets.

 

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Involving stakeholders to plan our discoveries. We involve payors, leading scientists and other stakeholders in the selection and execution of our discovery and development projects so that our diagnostic tests may better address unmet medical needs. We believe our approach, in which we identify a significant unmet medical need then attempt to discover a solution to meet the need, provides us with a competitive advantage relative to the prevailing paradigm of attempting to find or establish a market after making an academic discovery.

OUR STRATEGY

Our objective is to become a leader in discovering, developing and commercializing novel diagnostic tests based on novel biomarkers we discover or in-license from others. We seek to provide physicians with better information for the diagnosis, prognosis, treatment and monitoring of disease, which we believe will result in improved patient outcomes and more efficient use of healthcare resources. We plan to use the patient samples and data generated from our initiatives and collaborations to discover and develop new diagnostic tests, including multivariate index assays, for commercially important diseases using our proprietary technology platform. Key elements of our strategy include to:

 

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Obtain regulatory clearance or approval for and launch our product candidates. We intend to seek FDA clearance under Section 510(k) of the Federal Food, Drug and Cosmetic Act, or FDCA, for all of our novel diagnostic tests, including our IVDMIA tests, prior to their launch for clinical use. We believe that this strategy will significantly simplify the regulatory clearance process for our commercialization partners and pave the way for an expedited launch of each product. We received

 

 

 

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510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. In October 2009, we obtained CE Mark for this test in the European Union and have begun limited sales and marketing activities there.

 

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Use the patient samples and data generated from partnerships with third-party payors and government programs to discover clinically-relevant biomarkers for high-value market opportunities using our proprietary technology platform. We believe that our proprietary discovery platform is disease and drug-class agnostic, allowing us to be market focused. We believe third-party payors have financial incentives to encourage the market acceptance of diagnostic tests in order to control costs and have the ability to facilitate market penetration of our product candidates. Consequently, we focus on high-value opportunities where the interests of third-party payors are aligned with those of other key stakeholders, such as patients, physicians, laboratory providers and hospitals.

 

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Partner with leading laboratory service providers to provide widespread access to our tests upon clearance or approval. We intend to partner with leading U.S. national and regional laboratory service providers for the inclusion of our diagnostic tests, upon regulatory clearance or approval, in their laboratories. This strategy provides clinicians convenient regional or national access to our tests, without the need for the local or facility laboratory to offer our assays. These laboratory service providers offer broad menus of assays and can incorporate our in vitro diagnostic products in their existing work flow. We believe this strategy will provide convenient and national access to our biomarker-based tests and help drive market penetration prior to the availability of an automated version of our tests, which may allow widespread adoption by institutional clinical laboratories. We have entered into a semi-exclusive agreement with LabCorp to include galectin-3 testing as part of the routine laboratory tests available from LabCorp and to provide galectin-3 laboratory testing services to physicians throughout the United States. The availability of galectin-3 testing services through LabCorp commenced in January 2011. LabCorp has also agreed to provide sales and marketing support to promote appropriate galectin-3 testing in heart failure, which is expected to commence in the first quarter of 2011.

 

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Partner with leading diagnostic laboratory instrument manufacturers for the development and commercialization of novel diagnostic tests on their automated or point-of-care instruments. We are positioning ourselves as the leading provider of biomarker-based diagnostic tests that can be sold through leading diagnostic instrument manufacturers for use as novel assays on their existing installed base of laboratory instruments. These systems, developed over the past two decades by the leading diagnostic laboratory instrument manufacturers, are content-agnostic and currently offer comprehensive menus of immunoassay tests. This extensive installed base of high-end automated analyzers offers an exceptional opportunity to make our novel biomarker-based diagnostic tests available to laboratories globally without the need for costly investment in our own instruments. We intend to enter into non-exclusive licenses for our diagnostic tests and product candidates with these companies for the development and commercialization of assays on their instruments. We have entered into non-exclusive development and commercialization agreements with Abbott, Alere, bioMérieux and Siemens, for the inclusion of our galectin-3 test on their automated laboratory and point-of-care instruments, and we have the right to enter into one additional agreement with another diagnostic company for this test. We believe that focusing on diagnostic tests for use as novel assays on existing automated laboratory instruments will facilitate broader and more rapid adoption of our diagnostic tests.

 

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Continue to use the patient samples and data generated from existing and new collaborations to successfully advance the development and commercialization of our product candidates. We intend to continue participating in research collaborations such as those with the Copenhagen Heart Study

 

 

 

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and the NHLBI, for the Framingham Heart Study. Partnering with these leading studies provides us with unique access to biological samples, and the resulting data sets and medical histories that form the foundation of our biomarker discovery and clinical validation. We also intend to continue establishing collaborations with pharmaceutical companies and leverage these relationships to expand our capabilities and develop new product opportunities.

 

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Retain primary commercial responsibility for our biomarker tests to drive market penetration and clinical support for our products. We intend to retain primary responsibility for our biomarker tests through our various commercial activities, including the development of new indications, management of intellectual property rights, marketplace education, market development and reimbursement strategies and plans. We plan to build scientific support to drive physician awareness and utilization of our products through additional studies and publications, key opinion leader engagement and assist in the positioning of our tests in patient management guidelines. As part of this effort, we intend to deploy a limited specialty sales force and leverage the resources of our collaborators to drive demand for our products.

PRODUCT PIPELINE

Our product pipeline consists of our galectin-3 test and a number of other in vitro diagnostic product candidates that target important unmet medical needs. We will need to complete additional development activities for each of these product candidates and submit these product candidates for regulatory clearance or approval prior to commercialization in each of the markets where we plan to introduce them. We currently plan to follow the same 510(k) regulatory pathway for these other product candidates in the United States that we are following for our galectin-3 test.

The following table describes the status of our approved product and our product development projects:

 

Test name / disease area

 

Description

  

Stage

Cardiovascular Disease

BGM Galectin-3

Heart Failure (manual version)

  Galectin-3 as an aid in assessing the prognosis of patients with heart failure    Commercialization (United States, December 2010; and European Union, since October 2009)

BGM Galectin-3

Heart Failure (automated version)

  Galectin-3 as an aid in assessing the prognosis of patients with heart failure    Development

BGM Galectin-3

Heart Failure Risk Following Heart Attack

  Galectin-3 to identify patients at elevated risk for heart failure following a heart attack    Development

AMIPredict

Acute Atherothrombosis

  Multivariate index assay to identify patients at high risk of near-term atherothrombotic event    Development
  (heart attack or stroke)   

LipidDx

Lipid Disorders

  An aid in the management of patients with lipid disorders    Development

 

 

 

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We have initiated or are planning to initiate the following discovery projects:

 

Disease area

 

Description

Cardiovascular Disease and

Metabolic Syndrome

  Multiple discovery projects in collaboration with Framingham Heart Study

Multiple Sclerosis

  Biomarker of disease activity in multiple sclerosis

Anti-TNF Alpha Drug Response

  Biomarker of response to administration of anti-TNF alpha drugs

OUR PRODUCTS AND PRODUCT CANDIDATES

Creating new clinical paradigms in cardiology

We believe our product discovery and development pipeline addresses several important related unmet needs in cardiovascular medicine and enables several promising new clinical paradigms:

 

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Segmenting Heart Failure. Segmenting patients based on the underlying cause of heart failure to enable more clinically- and cost-effective personalized clinical management of the patient.

 

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Finding Subclinical Heart Failure. Identifying patients at elevated risk for heart failure among patients with previous heart attack before the manifestation of heart failure signs and symptoms.

 

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Finding Those at Greater Risk for Heart Attack and Stroke. Testing for biomarkers related to vulnerable plaque disease to identify and treat those at near-term risk for heart attack or stroke.

 

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Enabling Better Management of Lipid Disorders. Using biomarker testing of patients with lipid disorders to enable patients and providers to more quickly achieve treatment targets with fewer office visits.

BGM galectin-3 in heart failure

Overview

Galectins are a family of proteins that play many important roles in inflammation, immunity and cancer. Galectin-3, a member of this family of proteins, has been shown to play an important role in heart failure in animal and human studies. In animal experiments, administration of galectin-3 to the heart resulted in the formation of cardiac fibrosis, or stiffening, in the heart muscle, a process often referred to as adverse remodeling. In these animal studies, adverse remodeling reduced the heart’s ability to pump normally, causing the animals to develop heart failure. This link between galectin-3 and adverse remodeling is significant, as cardiac remodeling is an important determinant of the clinical outcome of heart failure and is linked to disease progression and poor prognosis. We have obtained an exclusive worldwide license to certain galectin-3 rights from a company that was spun out of the University of Maastricht in The Netherlands pertaining to the application of this protein in heart failure, and we have filed several of our own patent applications related to galectin-3.

We have developed and optimized a novel assay, which we call BGM Galectin-3, for measuring galectin-3 levels in blood plasma or serum. We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test, and galectin-3 testing services are currently being offered for use by clinicians in the United States through LabCorp. This test is indicated for use in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. In addition, we obtained CE Mark in the European Union in October 2009 for the test in ELISA microtiter format, enabling commercialization of the assay in the European Union and other countries that recognize the CE Mark. We have begun limited sales and marking activities of the assay in certain countries in Europe.

 

 

 

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Commercialization

As part of our commercialization strategy for our galectin-3 test, we have transferred our assay to a contract manufacturer based in the United States and have produced multiple production-scale batches of the assay in ELISA microtiter format. In May 2010, we entered into a license and supply agreement with LabCorp under which LabCorp began offering galectin-3 testing services to clinicians nationwide in January 2011 so that clinicians now have convenient regional or national access to our tests. Although our manual BGM Galectin-3 test is an important element of our commercialization strategy, we believe that automated instrument versions of our test will be required for us to achieve broad customer acceptance and clinical adoption. In furtherance of our strategy to become the leading provider of high-value diagnostic tests that can be sold through leading diagnostic instrument manufacturers for use as novel assays on their existing automated immunochemistry equipment, we also expect to enter into worldwide, non-exclusive development and commercialization agreements with leading diagnostic laboratory instrument manufacturers. Since November 2009, we have entered into agreements with Abbott, Alere, bioMérieux and Siemens for the inclusion of our galectin-3 test on various automated laboratory instruments, including point-of-care instruments. We have the right to enter into one additional similar agreement with another diagnostic laboratory instrument manufacturer for the inclusion of our galectin-3 test on its automated instruments. We believe that, subject to completion of development of the galectin-3 test on these instruments, one or more of these laboratory instrument manufacturers will be in a position to submit a 510(k) premarket notification to the FDA no later than the fourth quarter of 2011 in order to obtain regulatory clearance to market automated instrument versions of our galectin-3 test in the United States. Subject to clearance from the FDA, we expect an automated instrument version of this test to be available for commercial use through one or more of these instrument manufacturers in the first half of 2012. We believe that it will take considerably less time for laboratory instrument manufacturers to develop and obtain FDA regulatory clearance for an automated version of our galectin-3 test than it took for us to develop and receive FDA regulatory clearance for the manual version of the test, since only the method for performing the test will change. The automated version of the test will be designed in the same way and be indicated for the same use as the manual test, and the manual test will serve as the predicate device under the FDA’s 510(k) clearance requirements. As a result, we expect that the FDA will be able to rely on much of the data and information reviewed, and knowledge gained, during the clearance process for the manual version of our test, thereby reducing the time necessary to receive clearance for the automated version of the test. Notwithstanding these factors, the FDA may not clear the automated version of this test as and when we expect.

Heart failure overview

Heart failure is a condition caused by a combination of diseases or factors that damage or overwork the heart muscle, resulting in its inability to pump blood efficiently to meet the needs of other body organs. Heart failure may lead to serious complications and is a leading cause of death. The most common cause of heart failure is coronary artery disease, including heart attack and unstable angina. The cardiac injury caused by coronary artery disease often results in the development of adverse remodeling. Heart failure can be caused by many other factors, including high blood pressure, diabetes and defects of the heart valves or muscle itself. Patients with heart failure typically exhibit non-specific signs and symptoms such as swollen legs or ankles, shortness of breath or weight gain. Although the condition is usually progressive, the rate of progression varies markedly from no noticeable deterioration over multiple years to rapidly progressive, resulting in death in just weeks or months. Galectin-3 dependent adverse remodeling is a common cause for heart failure progression, and we refer to this as galectin-3 dependent heart failure.

 

 

 

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Natriuretic peptides are hormones released by the heart muscle in response to increased cardiac pressure or volume and have proven clinical utility in the diagnosis and management of heart failure. In late 2001, a blood test for B-type natriuretic peptide, or BNP, became commercially available, followed in 2003 by a blood test for N-terminal prohormone BNP, or NT-proBNP. Since the release of the BNP test by Biosite, which is now part of Alere, on a point-of-care instrument, the U.S. heart failure diagnostics market has experienced significant growth. According to Frost & Sullivan, an independent market research and consulting firm, the BNP and NT-proBNP diagnostics market worldwide was estimated at approximately $570 million in 2009 and is expected to grow to $800 million by 2013, a 9% CAGR.

According to the American Heart Association, an estimated 5.7 million Americans suffer from heart failure, with an approximate 670,000 new cases occurring each year, and we believe the prevalence and incidence of heart failure are similar in Europe. It is estimated that heart failure is responsible for over 277,000 deaths per year in the United States. Once diagnosed, overall mortality for heart failure is high, with one in five dying within a year of diagnosis. Survival is lower in men than in women, with 59% of men and 45% of women dying within five years of diagnosis. The incidence of heart failure increases with age, with approximately 73% of patients discharged from hospitals in the United States with a diagnosis of heart failure aged 65 years or older. Treating these patients is associated with a high rate of hospitalizations and ambulatory care visits, with an estimated 1.1 million hospitalizations in 2006 and an estimated 3.4 million ambulatory care visits in 2007. Re-hospitalization of these patients is a significant factor in the utilization of healthcare resources. A recent review of Medicare claims data for re-hospitalization showed that patients with a discharge diagnosis of heart failure had a 30-day re-hospitalization rate of 27%, the highest among any group of patients. The estimated direct and indirect cost of heart failure in the United States for 2010 is estimated at $39.2 billion, which is likely understated greatly because it is based on data for heart failure as the primary diagnosis or underlying cause of death.

Assessing the prognosis of patients with heart failure to improve patient care and outcomes

Patients with heart failure are commonly classified based on signs and symptoms using the New York Heart Association, or NYHA, functional classification scale based on a patient’s symptoms. The scale ranges from Class I patientsthose with no limitation of physical activity and for whom ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath to Class IV patientsthose who are unable to carry out any physical activity without discomfort and who have symptoms of cardiac insufficiency at rest. However, the NYHA functional classification scale does not specifically correlate with underlying disease process. We believe that stratifying patients with heart failure on the basis of underlying disease process will enable more individualized treatment and clinical management, leading to improved clinical outcomes and reduced healthcare costs. Galectin-3 dependent heart failure represents a common cause of heart failure development and rapid progression.

Natriuretic peptides such as BNP and NT-proBNP do not segment patients with heart failure on the basis of a specific underlying disease process, but the presence of these hormones rather reflects the degree of pressure or volume overload in the heart. In other words, increases in natriuretic peptides reflect the degree of cardiac overload, not the actual underlying cause. Consequently, galectin-3 and natriuretic peptides provide the clinician with information on two independent processes. For this reason, patients with elevated levels of galectin-3 may have normal or elevated levels of natriuretic peptides, and likewise, only a portion of patients with elevated levels of natriuretic peptides may have galectin-3-dependent heart failure. We believe that galectin-3 provides important incremental clinical information to natriuretic peptides in patients with heart failure.

 

 

 

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Clinical development and validation of our galectin-3 assay for patients with heart failure

Galectin-3 has been known to play a role in health and disease. Galectin-3 can be found in low concentrations in blood of healthy individuals. In a study that we conducted, involving over 1,000 healthy volunteers free from cardiovascular disease, we measured galectin-3 levels to determine a reference range in blood plasma. Analyzing this data, we found a near normal distribution, with minimal effect of age, gender, or presence of intercurrent conditions such as diabetes and other variables. The mean blood plasma galectin-3 level was found to be 13.3 ng/mL and the median 12.4 ng/mL. The upper limit of the normal range (90% percentile) was found to be 19.0 ng/mL.

We have also measured galectin-3 in eight controlled studies involving more than 5,300 patients with chronic or acute heart failure. In these studies, galectin-3 was found to be a strong independent predictor of mortality or hospitalization, the primary end-points of these studies, meeting the criteria for statistical significance (p-value <0.05). We believe that the data from these studies supports the premise that galectin-3 may be used to segment and stratify heart failure patients and that patients with galectin-3 dependent heart failure have a more progressive form of the disease associated with increased hospital utilization and premature death. These studies were completed in 2009 and 2010, and we intend to publish the results of these studies in peer reviewed journals under the authorship of the principal investigators who conducted the studies.

The following two studies illustrate the performance of our galectin-3 assay in heart failure and were submitted in support of our 510(k) application:

Study I — Multicenter study conducted in Europe

Galectin-3 levels were measured in 582 plasma samples from an independent, controlled, prospective, multi-center clinical study conducted in Europe enrolling NYHA class II, III and IV subjects. The average age of the patients was 71 years and 38% were female. The median follow-up time was greater than 18 months and the primary endpoint was the composite of all-cause mortality and hospitalization for heart failure. Two cutoff values were derived that in turn defined three ordered galectin-3 categories. The association of these galectin-3 categories with the primary endpoint was assessed by Cox regression survival analysis. High galectin-3 levels measured at baseline were found to be significantly associated with increased risk of all-cause mortality and hospitalization for heart failure and, further, remained significantly associated with increased risk upon adjustment for other baseline risk factors of age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status and smoking status. After accounting for these other baseline risk factors, patients with the highest baseline levels of galectin-3 (>25.9 ng/mL) had an approximately 2.4-fold increased hazard of death or hospitalization for heart failure, relative to patients with low galectin-3 levels (<17.8 ng/mL).

Study II — Multicenter study conducted in the United States and Canada

Galectin-3 levels were measured in 895 plasma samples from an independent, controlled, prospective, multi-center clinical study conducted in the United States and Canada. This study represented a sub-study to a study funded by NHLBI. The study involved heart failure patients with left ventricular dysfunction and with NYHA class II, III or IV symptoms. The average age of the patients was 58 years, 29% were female and 36% were non-white. The median follow-up time was approximately 30 months. Participants were categorized based on the galectin-3 risk categories defined in Study I. Cox regression models and Kaplan-Meier analysis were used to evaluate the association of baseline galectin-3 levels in heart failure patients, with the composite endpoint of all-cause mortality and all-cause hospitalization. The study data demonstrated that an elevated baseline galectin-3 level (>17.8 ng/mL) had an approximate 1.4-fold increased hazard of death or hospitalization for heart failure, relative to patients with low galectin-3 levels, even after accounting for other baseline risk factors of age, gender, NYHA functional classification, left ventricular ejection fraction, diabetes status and smoking status.

 

 

 

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Studies on use of galectin-3 in support of heart failure treatment decisions

We have initiated studies to further investigate the implications of galectin-3 elevation for efficacy or safety of current medications used by patients with heart failure. We initiated these studies because we believe that patients with galectin-3-dependent heart failure may respond differently to medications than patients with other forms of heart failure. One of these studies is a prospective substudy of the CORONA study (Controlled Rosuvastatin in Multinational Trial in Heart Failure) sponsored by AstraZeneca. The study was designed to investigate whether galectin-3 can be used to identify certain segments of patients with advanced heart failure that derive a clinical benefit from rusovastatin (CRESTOR®) treatment. We completed the study and data analysis in December 2010. In this study, the benefit of rusovastatin (CRESTOR®) was limited to those patients with low galectin-3 levels (<19.0 ng/mL), which benefit is statistically significant. In addition to investigating whether galectin-3 plays a role in guiding the selection of drug treatment, we are also investigating the role galectin-3 testing may play in the selection of patients who may be good candidates for medical device treatment, such as advanced pace makers used in heart failure, known as cardiac resynchronization therapy devices, or CRTs.

Clinical utility and benefits of galectin-3 testing for patients with heart failure

Heart failure is a condition caused by a combination of diseases or factors. Only a segment of heart failure patients have elevated levels of galectin-3, suggesting the presence of galectin-3-dependent heart failure. Clinical studies using our galectin-3 assay have demonstrated that patients with elevated galectin-3 levels have worse prognosis in terms of mortality or risk of hospitalization than comparable patients with low or normal levels of galectin-3. Accordingly, we believe that measurement of galectin-3 in patients with heart failure offers clinically useful information and that physicians may use information pertaining to risk of adverse outcomes based on galectin-3 blood plasma or serum levels and other clinical parameters in routine clinical management of patients with heart failure, such as:

 

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Spacing of patient visit intervals. We believe physicians may monitor galectin-3 levels to determine the time interval between patient visits, with greater time between visits for patients exhibiting normal galectin-3 levels and more frequent visits for those patients that have elevated galectin-3 levels.

 

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Assessing the need for referral to a cardiologist or heart failure specialist. The majority of heart failure patients are managed by clinicians other than a heart failure specialist. We believe physicians may use galectin-3 levels as a determinant of which patients are at highest risk for adverse outcomes and therefore should be referred to a cardiologist or possibly a heart failure specialist.

 

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Determining proper timing of hospital discharge and appropriate patient care following discharge. Discharge planning often starts soon after a patient’s admission to the hospital. Improved discharge planning for heart failure patients is considered one of the most important steps in reducing costly readmissions following discharge. We believe that elevated galectin-3 levels upon discharge are associated with a significant increase in risk of hospital readmission.

 

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Selecting patients for disease management. Several forms of disease management programs are currently used by healthcare providers and payors for heart failure patients. These programs aim to reduce the use of inpatient care through patient and caregiver support. Components of these programs may include building self-management skills, such as daily weighing and knowing when to contact a physician in case of sudden weight increase; telephonic nurse support, such as appointment and medication reminders, periodic telephonic assessment; promotion of adherence to established guidelines for treatment. We believe that patients with elevated levels of galectin-3 have poor prognosis and therefore are often appropriate candidates for disease management.

 

 

 

 

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Telemonitoring. Remote monitoring technology solutions are increasingly used by clinicians or as part of disease management programs to monitor physical parameters, such as body weight, blood pressure or cardiac measurements, to identify patients at risk for acute decompensation that often require hospitalization, resulting in high cost. We believe that patients exhibiting elevated levels of galectin-3 are at elevated risk of hospitalization and that galectin-3 measurements in conjunction with other clinical parameters and patient history, may be used in selecting patients for telemonitoring services.

 

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Evaluating advanced therapeutic options. An increasing number of advanced therapeutic options are available, such as left ventricular assist devices, CRTs, cardiac netting, stem-cell therapy and cardiac transplantation. Physicians are using many variables to judge the suitability of patients for such heart failure treatments. We believe that galectin-3 testing may offer additional information to assist clinicians in selecting patients for these advanced and expensive therapeutic options.

In addition to potentially guiding clinical management of patients with heart failure, we believe that biomarkers like galectin-3 may one day form the basis for stratified pharmacotherapy where proper drug treatment is selected, among alternative drugs, based on the patient’s level of galectin-3. We intend to partner with companies developing novel heart failure therapies to study whether galectin-3 can be used as a companion diagnostic to these therapies. We have initiated the first of such partnerships and we have provided our galectin-3 assay to measure samples from a study conducted by a leading pharmaceutical manufacturer. Additionally, we are conducting studies to identify possible differences in treatment outcomes between patients with elevated and low levels of galectin-3. The success of these endeavors and the outcomes of these studies will have a significant impact on the market opportunity for our galectin-3 tests.

BGM galectin-3 to identify patients at risk for heart failure development following a heart attack

Based on the biology of adverse remodeling in post-myocardial, or heart muscle, injury and consistent with our own observations in heart failure, we expect that elevated levels of galectin-3 will occur in a segment of patients who have suffered a myocardial injury, such as during a heart attack. We expect that elevated levels of galectin-3 in these patients is associated with an elevated risk of heart failure development. We are currently investigating this premise in the condition known as acute coronary syndrome, a condition which includes unstable angina and heart attack. Patients surviving a heart attack remain at high risk of death from adverse remodeling. An estimated 20–40% of individuals in the United States who suffer a heart attack develop heart failure within five years. According to the American Heart Association, an estimated 8.5 million Americans alive today have suffered a heart attack, with an approximate 935,000 new or recurring heart attacks occurring each year in the United States, and we believe the prevalence and incidence of heart failure are similar in Europe.

We have concluded the first of our studies for galectin-3 in this supplemental indication in collaboration with the TIMI Study Group in Boston, Massachusetts. This first study was a case-control study using samples of the TIMI-22 or PROVE IT study. The study involved patients who had suffered acute coronary syndrome with a hospitalization for new or worsening heart failure and matched controls. The results of the study are consistent with our expectations that elevated galectin-3 levels are associated with an increased risk for the development of heart failure in patients following acute coronary syndrome. We are conducting additional clinical validation studies and expect to seek FDA input as to the regulatory clearance or approval requirements for such a supplemental indication. If we receive positive clinical data from these additional studies, we expect to seek FDA clearance for this supplemental indication for periodic galectin-3 testing in patients following a heart attack, or in the broader indication following acute coronary syndrome, to identify patients at elevated risk of heart failure development before the onset of signs and symptoms. If our development and regulatory activities are successful for this

 

 

 

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additional indication of galectin-3 measurement in patients following acute coronary syndrome, our goal will be to commercialize a first generation manual test kit in 2011 and any automated versions in 2012 or thereafter.

AMIPredict for acute atherothrombosis (cause of heart attack or stroke)

Overview

We are developing a test that we refer to as AMIPredict, a multivariate biomarker blood-based test for patients at risk for atherothrombotic cardiovascular disease, commonly known as vulnerable plaque. We are designing AMIPredict to identify patients with a high risk of suffering heart attack or stroke within the next two to four years. Our development work to date suggests that AMIPredict could be an improved diagnostic test compared to conventional risk factor-based approaches such as the Framingham Risk Score in the United States and the Systematic Coronary Risk Evaluation, or SCORE, in Europe.

Atherosclerosis overview

Atherosclerosis is a systemic disease that is characterized by the buildup of lipid-rich plaques within the walls of the large arteries. It progresses through three stages: gradual and continuous plaque buildup that occurs over decades, focal plaque degradation resulting in vulnerable plaques, or plaques at risk of rupture, and acute plaque disruption with superimposed thrombosis, or blood clot formation occurring after plaque rupture. Atherosclerosis is by far the most common cause of coronary heart disease and it underlies the clinical conditions of heart attack, chronic stable angina, stroke and peripheral vascular disease. According to the American Heart Association, it is estimated that in the United States alone, over one million people die annually from the complications of these conditions and that the total yearly cost of treating these diseases exceeds $360 billion.

Atherothrombosis, the final step in atherosclerosis, involves the acute disruption of plaque with superimposed thrombosis. The resulting blood clot formation can block the flow of oxygen-rich blood to the heart or brain, causing heart attacks and strokes. Most heart attacks and strokes occur as the consequence of acute atherothrombosis in individuals with low or intermediate risk profiles according to traditional risk factor-based approaches recommended in the United States and Europe. For example, in the Framingham Heart Study, the Physicians’ Health Study, the Women’s Health Study and the Northwick Park Heart Study, more than 75% of all coronary events occurred in individuals at low or intermediate risk that, consequently, were not offered optimal preventive therapy. In women, this figure may surpass 90%. For this reason, we believe that the detection of degrading arterial wall plaques through a blood test or non-invasive imaging is critical to the development of a shift in clinical paradigm to screening for and treatment of vulnerable plaque disease. Based on 2008 U.S. census data, we believe there are an estimated 43.3 million men ages 50 or over and 39.8 million women ages 55 or over, or 80 million Americans, who may be at risk for developing vulnerable plaques.

Discovery and clinical development of AMIPredict

Study I — CATHGEN based study

In 2007, we commenced our first case-control research study to pursue the discovery and development of a new test to detect vulnerable plaque. We analyzed approximately 140 samples from the Duke CATHGEN Research Project belonging to patients who underwent angiography and who developed a heart attack or stroke within two years following the enrollment angiography. The controls in this study were patients who were generally similar to the cases at the time of the enrollment angiography, but who

 

 

 

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did not develop the cardiovascular event. As a result of this study, we discovered a multivariate biomarker using our proprietary platform, which we believe had promising performance and therefore we initiated a follow on study.

Study II — Copenhagen heart study

From 2008 to 2009, we conducted a second case-control study involving samples from approximately 750 participants in either the Copenhagen Heart Study or Copenhagen General Population Study. The sample study comprised samples from approximately 250 individuals who suffered a first heart attack within four years of enrolling in the study and approximately 500 matched controls. The results corroborated earlier findings and allowed us to further refine the multivariate assay. This refined multiplex assay also showed favorable performance and met the study’s clinical endpoints with statistical significance. If confirmed in one or more independent larger case cohort studies, we believe the results of such studies may form the basis for a regulatory submission for a new screening test for individuals over a certain age.

Additional studies planned

We have initiated the development of an automated version of this test using currently approved laboratory instrumentation and reagents that are commercially available. We are currently conducting additional studies intended to validate these previous findings and we expect to complete these studies in the first half of 2011. If our validation studies are successful, we intend to seek FDA input as to the requirements for the filing of a 510(k) submission for this IVDMIA test when offered as an FDA-cleared laboratory service. We expect that if AMIPredict receives regulatory clearance or approval, this test will be indicated in individuals over a certain age, such as 55 for men and 60 for women. If we successfully develop and receive regulatory clearance or approval for this test, we expect to contract with existing specialty, regional or national providers of laboratory services to commercialize our tests. We also expect to pursue key partnerships with leading providers of existing automated immunoassay systems to develop automated versions of this test on their systems. If our development and regulatory activities are successful for AMIPredict, our goal will be to commercialize a first generation manual AMIPredict product in 2012, and we would plan to develop automated product versions thereafter.

LipidDx for management of lipid disorders

Lipid disorders overview

An estimated 36 million adult Americans have elevated levels of cholesterol of greater than 240 mg/dL. The problem of elevated cholesterol is generally well known and well understood among the population, with nearly 75% of adults having been screened for high blood cholesterol in the preceding five years. Reducing plasma cholesterol remains a national priority. According to a study conducted by the Centers for Disease Control, it is estimated that a 10% population-wide decrease in total cholesterol levels would result in an approximate 30% reduction in the incidence of coronary heart disease. Despite the recognition of its importance and the availability of a variety of generally effective pharmacological and non-pharmacological means to reduce levels of plasma cholesterol and triglycerides, overall results remain disappointing. Non-adherence to treatment is an important contributor to this problem. For example, fewer than half of the persons who qualify for any kind of lipid-modifying treatment for coronary heart disease risk reduction are actually receiving such treatment. Of those patients treated, only about one-third are achieving their goal for low-density lipoprotein, or LDL, often referred to as bad cholesterol, while fewer than 20% are at their goal.

Failure to achieve treatment targets in lipid disorders is complex and based on many factors. Some patients are not prescribed standard therapy, while for some patients, standard therapy does not work,

 

 

 

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thus requiring some process of trial and error by the physician to find the right medication or combination therapy. In addition, some patients discontinue treatment because of adverse side effects, lack of subjective benefits, or cost associated with the medication. Finally, there exists a certain set of patients who are unable to achieve treatment goals despite optimal treatment.

Clinical development of LipidDx

In collaboration with Merck, which manufactures and sells lipid-lowering agents and other cardiovascular therapies, we are currently conducting several studies to investigate the clinical utility of LipidDx, a blood-based protein assay, in the management of common lipid disorders and to assess its contribution to cardiovascular risk assessment. If successful, we expect to conduct one or more clinical validation studies and seek FDA input as to the requirements for 510(k) clearance for this indication. If our development and regulatory activities are successful for LipidDx, our goal will be to commercialize a first generation manual LipidDx product in 2012, and we would plan to develop automated versions thereafter.

OUR DISCOVERY PIPELINE

Our biomarker discovery efforts are market and opportunity driven, starting with identifying an unmet clinical need and product opportunity. Obtaining suitable samples for discovery or validation is often an important gating factor for our discovery projects. We continue to evaluate our discovery priorities and as a result, our discovery pipeline will undergo periodic changes due to project completions, new emerging opportunities, issues related to access of samples, and changes in medical care or treatment options.

Cardiovascular disease and metabolic syndrome

In 2009, we entered into a Cooperative Research and Development Agreement, or CRADA, with NHLBI and Boston University to conduct certain biomarker discovery studies in the area of metabolic syndrome and atherosclerotic cardiovascular disease using samples and data from the Framingham Heart Study. A CRADA is an agreement between the federal government and one or more nongovernment parties for conducting specified research or development that could lead to useful, marketable products that benefit public health. The Framingham Heart Study is one of the leading cardiovascular research studies, the results of which have been published in approximately 2,000 scientific articles since its inception in 1948. Research from the Framingham Heart Study has provided the scientific basis for many of the generally established clinical paradigms related to cardiovascular disease, such as management of obesity, hypertension and lipid disorders.

Under this CRADA with NHLBI and Boston University, we have certain rights to multivariate markers discovered as part of the joint research. In 2009, we successfully completed the pilot phase of this project and we are currently conducting the first of three case control studies representing phase one of the collaboration. Three related topics will be investigated in the current phase of the research:

 

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blood-based biomarkers predicting the onset of first major cardiovascular event;

 

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blood-based biomarkers of metabolic syndrome, a condition comprised of a cluster of ailments, such as increased blood pressure, elevated insulin levels, excess body fat around the waist or abnormal cholesterol levels that occur together, which increase a patient’s risk of heart disease, stroke and diabetes; and

 

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blood-based biomarkers corresponding to coronary artery calcium scoring, a widely accepted marker of cardiovascular disease based on a special X-ray exam.

 

 

 

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The CRADA contemplates research to be conducted over a five-year period. We have received specimens from the Framingham Heart Study at our facility and are currently conducting the first of these experiments.

Multiple sclerosis — marker of disease activity

Multiple Sclerosis, or MS, is a serious medical condition that affects approximately 350,000 people in the United States and an estimated 3.0 million individuals worldwide according to Espicom Business Intelligence, a provider of market information. MS is a debilitating disease in which a patient’s immune system degrades the protective sheath that covers the nerves. This disease interferes with the communication between the brain and the rest of the body. Ultimately, the disease may result in deterioration of the nerves themselves, a process that is irreversible. The most common form of MS is characterized by an irregular pattern of remissions and exacerbations of disease symptoms. By allowing doctors to monitor the underlying disease activity, biomarkers have the potential to markedly change and advance care for individuals with MS. We have access to certain samples from patients with MS and are planning to conduct one or more discovery studies in 2011.

TNF alpha blockers — markers of treatment response

TNF alpha blockers represent an important class of drugs used in the treatment of several autoimmune diseases, such as moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis and Crohn’s disease. Enbrel, Remicade and Humira are the most commonly prescribed TNF alpha blockers on the market.

Response to TNF alpha blockers varies among patients and use of these agents has been associated with certain serious adverse side effects. Blood biomarkers that predict treatment response prior to initiation of therapy or blood biomarkers that reflect the biological effects leading to treatment response, will enable improved patient selection and more personalized treatment of patients with these agents.

We have developed a protocol with our partner Humana and intend to commence a discovery study for these biomarkers in 2011.

OUR DISCOVERY AND PRODUCT DEVELOPMENT PROCESS

We rely on internal discovery and in-licensing of technology in our disease fields of interest. We use a multi-phased discovery and development process which is outlined below:

Discovery. Our biomarker discovery phase generally starts with identifying an unmet clinical need and product opportunity. We may involve Humana, a pharmaceutical or device manufacturer, or a patient advocacy organization in the evaluation of the unmet need and planned discovery. We then develop a target product profile for the new test to guide the discovery and development process and support stage-gate decisions. The target product profile may be reviewed and adapted from time to time.

In this phase, we apply our proprietary technology platform on a large scale to discover and validate novel biomarkers that may be used for developing novel diagnostic tests. Our platform integrates molecular measurement technologies based on specialized mass spectrometry, chromatography, nuclear magnetic resonance spectroscopy and multiplexed assay technologies. Through this platform, we are able to detect, quantify and characterize over 1,000 biological molecules, including proteins, protein variants, lipids, fatty acids, amino acids and many other compounds that may be key indicators of health, disease and drug response, from less than a few drops of blood or other bodily fluids. Our biomarker discovery workflow includes three main elements: molecular measurement, statistical analysis and bioinformatics. We believe that our technology platform represents a significant competitive advantage in our ability to discover and develop new biomarkers.

 

 

 

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Development. Following the completion of one or more discovery studies in support of a project, we will review the results to determine if the results are consistent with our target product profile. We will then determine if the results warrant continuation to the next phase. We generally seek to verify our discovery results prior to initiation of a development project for a given test.

The development process is designed to be consistent with industry standards and practices, and when applicable, is guided by FDA or European Union final or draft guidance documents, and standards and guidance documents published by the Clinical Laboratory Standards Institute and other recognized entities. Although our discovery may have been based on our advanced mass spectrometry platform, for commercialization, we intend to seek, when possible, low cost generally accepted and widely available means to measure the same analyte, such as common sandwich ELISA assay formats. Our development process includes the development and optimization of an assay and acquisition of suitable specimens and data from appropriate clinical studies for the endpoints to support the targeted claims. As part of this process, we also seek appropriate institutional review board or ethical committee approval. Finally, we test the clinical samples using the assay and we then analyze the clinical data and prepare the appropriate regulatory submission documents.

Historically, we have incurred research and development expenses in connection with our internal biomarker discovery and development efforts. We anticipate that research and development expenses will increase significantly, primarily due to our increased biomarker discovery and development efforts related to our product candidates. Research and development expenses were $5.8 million, $6.9 million and $8.5 million for the years ended December 31, 2007, 2008 and 2009, respectively, and $5.6 million for the nine months ended September 30, 2010. In addition, we incur research and development expenses to support our initiatives, collaborative research and development agreements and biomarker discovery and analysis services agreements. Customer-sponsored research activities were $7.3 million, $13.8 million and $8.4 million for the years ended December 31, 2007, 2008 and 2009, respectively, and $650,000 for the nine months ended September 30, 2010.

Launch. Prior to the launch of a product, we plan to contract with third-party manufacturers for our in vitro diagnostic kits or laboratory service providers for our regulated laboratory service, and commence the transfer of technology and validation in preparation for commercial product introduction.

Automated Assay Format Development. Following the completion of our validation studies or submission of regulatory filings, we plan to seek development and commercialization partnerships with leading diagnostic laboratory instrument manufacturers for a non-exclusive license for a given assay. Once we have entered into such an agreement, we intend to initiate the collaborative development of the assay for the manufacturer’s automated system, which we believe may take on average between 24 and 36 months.

OUR COLLABORATIONS

Our key research, development and commercialization collaborations are summarized below.

Abbott

In November 2009, we entered into a strategic collaboration with Abbott Laboratories, to develop and commercialize Galectin-3 assay kits and related control kits and calibrators, or Galectin-3 Products, utilizing our Galectin-3 technology and patent rights, for use on Abbott’s Architect® Immunochemistry Diagnostics Platform, or the Abbott Architect, and other Abbott diagnostic instruments. As part of the collaboration, we entered into a non-exclusive license and distribution agreement with Abbott, or the Abbott Agreement, pursuant to which we provided Abbott and its affiliates with a non-exclusive, worldwide license under our patent rights related to galectin-3 to commercialize Galectin-3 Products for

 

 

 

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use on the Abbott Architect and other Abbott diagnostic instruments. We also entered into an umbrella product development agreement, or the Umbrella Agreement, with Abbott and Fujirebio Diagnostics, Inc., or Fujirebio, and a funding agreement with Fujirebio, pursuant to which Fujirebio will develop and seek regulatory approval of the Galectin-3 Products for use on the Abbott Architect and we will fund, based on the achievement of development milestones, the development by Fujirebio of the Galectin-3 Product for use on the Abbott Architect.

Under the Abbott Agreement, Abbott is prohibited from sublicensing its rights to commercialize our Galectin-3 Products and, except for the Galectin-3 Products described above, is prohibited from developing Galectin-3 assays covered by our patent rights. We have the right to enter into up to four additional licenses of our patent rights related to Galectin-3 for the commercialization of Galectin-3 Products during the five year period from the date on which Abbott makes its first commercial sale of Galectin-3 Products, and unlimited additional licenses thereafter, provided that (i) such other licensees’ Galectin-3 assays are commercialized only under the other licensees’ names and brands and only with respect to diagnostic instruments or technologies that are owned or controlled by such licensees and (ii) if another licensee receives financial terms that would reasonably be believed to be more favorable than those granted to Abbott, Abbott will be entitled to the benefit of such favorable terms. Since the execution of the Abbott Agreement, we have entered into three similar agreements with Alere, bioMérieux and Siemens. Under the Abbott Agreement, Abbott will pay us a product access fee and a marketing service fee for each Galectin-3 Product they sell. Under certain circumstances, based primarily on market prices for Galectin-3 assays, Abbott will be entitled to product fee reductions to be determined by negotiation, or if the parties fail to agree, by arbitration. Additionally, if the average sales price of the Galectin-3 Products sold by us, Abbott and other licensees falls below a certain amount, Abbott will be entitled to discontinue its sale of the Galectin-3 Products. If Abbott were to discontinue its sales, Abbott would have no further rights or obligations to us under the agreement.

Abbott is required to use its commercially reasonable efforts to promote, market, sell and distribute the Galectin-3 Products worldwide. We are required to use our commercially reasonable efforts to pursue certain clinical development objectives, perform certain marketing services in the United States and certain foreign countries, and develop and implement a reimbursement strategy for Galectin-3 assays in those countries.

Unless terminated earlier, the agreement will expire on the expiration date of the last-to-expire patent in our patent rights related to Galectin-3. Either party may terminate the agreement upon 60 days written notice of a material breach of the agreement that is not cured within such 60 days, and Abbott may terminate the agreement upon 30-days written notice upon the occurrence of certain events, including if the Galectin-3 Products fail to meet certain product claims, performance requirements or manufacturing requirements, Fujirebio becomes subject to government or regulatory restrictions, Abbott becomes aware of possible third party patent infringement of our patent rights relating to galectin-3, the Galectin-3 Products negatively impact other assay or system performance parameters that cannot be resolved, the predicate device does not receive regulatory approval in the United States or galectin-3 is either not accepted by, or a new marker showing superior clinical utility is adopted by, the physician community. In addition, if Abbott voluntarily discontinues the Galectin-3 development pursuant to the Umbrella Agreement or discontinues the commercialization of Galectin-3 Products, then it may terminate the agreement upon 30-days written notice, but is required to either, in Abbott’s discretion, (i) pay us an amount equal to the amount we paid Fujirebio pursuant to the Umbrella Agreement, or (ii) allow us to sell Galectin-3 Products developed by Fujirebio under the Umbrella Agreement pursuant to the terms and conditions of a distribution arrangement negotiated in good faith between us and Abbott.

In March 2010, we entered into an amendment to the November 2009 agreement that grants Abbott non-exclusive rights to develop and commercialize a galectin-3 assay for use on its iSTAT point-of-care

 

 

 

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instruments. Under the amendment Abbott is responsible for developing the galectin-3 assay for the iSTAT instruments, conducting clinical studies, and preparing and submitting regulatory filings.

ACS Biomarker

We have exclusively licensed from ACS Biomarker B.V., or ACS Biomarker, a portion of the intellectual property rights covering our galectin-3 tests. In May 2007, we entered into a biomarker product license and collaboration agreement with ACS Biomarker, a company that was formed with technology exclusively licensed from the University of Maastricht in The Netherlands, and other parties. ACS Biomarker was founded to develop and commercialize cardiovascular biomarkers discovered at the Cardiovascular Research Institute Maastricht. Pursuant to the agreement, as supplemented by two licensing addenda entered into in May 2007, ACS Biomarker granted to us an exclusive, worldwide sublicense to develop and commercialize two proprietary cardiovascular biomarkers for heart failure, galectin-3 and thrombospondin-2 and a proprietary cardiovascular multivariate biomarker for the early confirmation of a suspected heart attack. Each of these biomarkers is licensed by ACS Biomarker from the University of Maastricht. Our licenses are perpetual in duration and permit us to sublicense the rights to third parties. In addition, we sublicensed from ACS Biomarker the rights to certain peptides for use in diagnosing atherothrombic vascular disease. We also have the right to exclusively negotiate a license to any additional biomarkers for which ACS Biomarker holds rights and determines to offer to any third party, but ACS Biomarker is not obligated to grant us rights to such biomarkers.

Under the terms of the agreement, we have executed certain plans for the development of the licensed biomarkers and are required to establish a scientific advisory board to provide input and guidance on the development plan. As consideration for the licenses, we were required to pay ACS Biomarker an up-front payment and are required to pay milestone payments and royalty prepayments to the extent that we achieve specified development and regulatory milestones. Additionally, we are obligated to pay ACS Biomarker royalties on any net sales, together with a percentage of any sublicense revenue, from our galectin-3 tests and any other products that we develop utilizing the licensed intellectual property. As of September 30, 2010, we have paid $750,000 in up-front and milestone payments and have not paid any royalties on sublicense revenue or net sales.

The agreement has an initial five-year term through 2012 and automatically renews for additional one year periods unless either party gives not less than 30-days written notice of termination to the other party. Either party may terminate the agreement if the other party fails to perform a material obligation under the agreement, or upon the occurrence of certain bankruptcy events involving the other party. The licenses granted by ACS Biomarker to us will survive any such termination, except that if ACS Biomarker terminates the agreement for our failure to perform any material obligation (including our payment obligations or any obligation under any implementation plan), the exclusive licenses granted to us under the agreement will be converted into non-exclusive licenses.

Humana

In May 2007, we entered into a strategic agreement with Humana Inc., one of the largest health benefits companies in the United States, with more than 11 million medical members, and the second largest provider of Medicare benefits in the United States. Under the terms of the agreement, we and Humana intend to collaborate with the goal of accelerating the development of blood-based biomarkers and identifying the role of blood-based biomarkers in improving health outcomes and containing healthcare costs through individualized medicine. In furtherance of this goal, we and Humana may conduct biomarker discovery and validation studies among Humana members, for which we will pay Humana. For example, we have developed a protocol with Humana and intend to commence a discovery study for TNF alpha blocker related biomarkers in 2011. We may also conduct research on the design and testing

 

 

 

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of methods to promote adoption of individualized medicine among covered populations. We believe that this agreement will allow us to conduct biomarker studies faster, at lower cost and in a manner that better reflects the intended use of biomarkers as compared to traditional academic research studies. We expect that the results of these studies may provide the basis for authoritative cost-benefit calculations for our diagnostic product candidates. Pursuant to the agreement, we will offer any blood-based biomarker diagnostic products that we develop from data or services provided by Humana to Humana on preferred terms to the extent sold by Humana to Humana members. In addition, in the event we commercialize blood-based biomarker diagnostic products under this partnership, we will be required to make certain payments to Humana based on such products.

The agreement has an initial three-year term and automatically renews for an additional period of 12 months unless either party gives not less than 120 days written notice of termination to the other party. Either party may terminate the agreement upon 60-days written notice if the other party is in material default of any of its material obligations under the agreement, or upon the occurrence of certain bankruptcy events involving the other party.

Merck

In January 2010, we entered into a research collaboration agreement with Merck for the purpose of development and validation of an immunoassay for a novel biomarker for use in patients with certain lipid disorders, or at elevated risk for cardiovascular disease because of such disorders. Our responsibilities under the agreement include the in-house validation of the assay, investigating the levels of the biomarker in approximately 1,000 samples provided by Merck and delivering the resulting data to Merck, and measuring the biomarker in certain samples under ownership or control by us or with respect to which we have permission to perform such analysis. Merck is required to transfer certain assay technologies to us, provide the samples from selected Merck clinical studies, and to perform certain data analysis upon receipt of our biomarker data. If clinical utility is sufficiently established as a result of work performed under the agreement, we must notify Merck of our intentions with regard to development of an in vitro diagnostic test for the biomarker intended for commercialization, subject to regulatory clearance or approval. We refer to the product candidate based on the biomarker as “LipidDx”.

Under the agreement, Merck granted us a non-exclusive license to certain Merck intellectual property rights and technologies for use and development of an in vitro diagnostic test. We granted to Merck a non-exclusive license to information and inventions resulting from the research and developed solely by us, for research, discovery and development purposes, excluding commercial development of an in vitro diagnostic test by Merck or a third party working on Merck’s behalf. We also granted Merck a non-exclusive option to have us measure the levels of the biomarker in specimens under our control and ownership and to report such results to Merck. We have agreed to perform measurements of the biomarker at no cost to Merck if we deem such study to have regulatory importance or commercial interest to us. All other samples, except those initial approximately 1,000 samples provided by Merck, are subject to a reasonable and customary laboratory service fee for the biomarker determination. Under the agreement, Merck has agreed to make certain payments to us upon our achievement of milestones. Unless terminated earlier, this agreement will expire in July 2011. Either party may terminate the agreement upon 30 days written notice.

Laboratory Corporation of America

In May 2010, we entered into a license and supply agreement with LabCorp pursuant to which LabCorp agreed to use commercially reasonable efforts to make manual galectin-3 tests available to physicians in the United States within 45 days of clearance by the FDA of our galectin-3 test. Under the terms of the

 

 

 

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agreement, we granted LabCorp and its affiliates a semi-exclusive worldwide license under our patent rights related to galectin-3 to market, offer for sale and otherwise commercialize galectin-3 testing services using our manual galectin-3 test. The license is semi-exclusive in the United States through the third year following the commercial launch of the manual test, or the semi-exclusive period, after which the license will be non-exclusive. The license is non-exclusive in Canada and the United Arab Emirates for the entire term of the agreement. During the semi-exclusive period, we are prohibited from licensing any of our patent rights related to galectin-3 to perform manual tests to certain restricted licensees, including competitors of LabCorp.

We are entitled to a payment for each manual test kit, or the kit price, purchased by LabCorp and its affiliates. We have agreed, with limited exceptions, that the kit price to be charged to LabCorp and its affiliates shall be no less favorable than the price charged to any other third party in the United States.

Pursuant to the agreement, we are required to pay certain rebate amounts to LabCorp if the aggregate number of automated tests that are capable of being performed in the United States using automated test kits sold by us or our business partners exceeds a certain amount during a specified period. We have also agreed that, to the extent we enter into agreements with third parties after May 13, 2010 to manufacture, supply or distribute automated test kits, we will require such third parties to supply such automated test kits to LabCorp and its affiliates.

Under the agreement, we will also provide LabCorp with certain clinical market development resources, programs and assistance as reasonably requested by LabCorp and LabCorp has agreed to perform certain sales, marketing and market education activities in support of our manual galectin-3 test.

The agreement will terminate on the earlier of May 13, 2015 or the end of the semi-exclusive period. LabCorp may terminate the agreement at any time and for any reason upon 120-days’ written notice and LabCorp may terminate the agreement immediately if we undergo a change of control to a competitor of LabCorp. Either party may terminate the agreement upon 60-days’ written notice for failure to comply with the terms of the agreement, unless the defaulting party remedies such failure within the 60-day notice period.

OUR INITIATIVES

HRP initiative

In 2006, we initiated and are leading the HRP initiative for atherothrombotic cardiovascular disease. The HRP initiative consists of a series of pre-competitive, multi-party research and development projects, which are administered and coordinated by us pursuant to participation agreements with Abbott, AstraZeneca, Merck, Philips and Takeda. The overall goals of the HRP initiative are to advance the understanding, recognition and management of atherothrombotic cardiovascular disease, to provide a roadmap for the development and registration of screening, diagnostic and therapeutic interventions for high-risk plaque and to promote the use of these interventions by patients, pharmaceutical companies and third-party payors. We believe the HRP initiative is the most extensive coordinated biomarker discovery and validation project ever undertaken.

The specific goals of the initiative include:

 

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Discovering and validating a blood-based biomarker for high-risk plaque suitable for high-volume patient screening;

 

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Developing and validating novel non-invasive imaging methods to characterize and classify patients with high-risk plaque and establishing the relationship between such imaging methods and blood biomarkers;

 

 

 

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Developing a regulatory framework for high-risk plaque-related products; and

 

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Establishing an authoritative third-party source for high-risk plaque-related information.

Pursuant to the participation agreements, each of Abbott, AstraZeneca, Merck, Philips and Takeda has provided the aggregate of $5.0 million to support the HRP initiative, with a portion of the funds provided by Philips in the form of in-kind contributions, as described in the participation agreement. As of September 30, 2010, all of the initial funds provided under the HRP initiative were expended and we were seeking additional funds for the continuation of work in the initiative. As of January 31, 2011, we had received an additional $990,000 and commitments for an additional $990,000 from certain parties to continue this work. As set forth in the participation agreements, the HRP initiative is governed by a joint steering committee, or JSC, which is comprised of designees of participating companies, and is led by a scientific program board consisting of academic experts in the cardiovascular field, which advises the JSC and assists in the design of the research protocols. The JSC is responsible for overseeing the conduct and progress of the HRP initiative, including finalizing and approving program activities, program and activity budgets, external communications, patent filings, third-party licensing and commercialization of data and rights under the HRP initiative. We will own any inventions and data that are conceived in the conduct of the HRP initiative and have agreed to grant each participating company a non-exclusive, perpetual, royalty-free license to all such inventions and data for any and all uses. Each participation agreement expires upon the earlier of the completion of the HRP initiative or the fifth anniversary of such agreement, unless otherwise terminated by the parties.

We have conducted several studies and related activities as part of the HRP initiative, including a clinical study, referred to as the BioImage Study, involving approximately 7,000 Humana members who underwent a comprehensive clinical evaluation in temporary research facilities which we set-up in Illinois and Florida, and who provided plasma, serum, RNA and DNA as well as access to medical and pharmacy claims from a period preceding and following their enrollment in the study. Approximately 6,000 of these individuals also underwent certain non-invasive imaging investigations. We are currently following this cohort for a minimum of three years using their medical claims and other information to determine the occurrence of certain cardiovascular events and other outcomes. We have certain rights to biological specimens and associated data from the BioImage Study for our discovery and development projects that we conduct independent of the HRP initiative.

As part of the HRP initiative we also conducted a plaque biomarker discovery study with the Cardiovascular Research Institute Maastricht, in which we measured over 1,500 proteins and metabolites in atherosclerotic plaque of patients undergoing carotid endarterectomy, a surgical procedure in which a vascular surgeon removes the inner lining of the carotid artery to eliminate plaque buildup, to study the biology of inflamed plaque lesions in comparison with plaque lesions that previously ruptured.

We also provided funding for a diagnostic-economic study conducted by Humana and the Brookings Institute to develop an advanced economic model and software application to model the cost-benefit of the new clinical paradigm of screening for vulnerable plaque using a blood test followed by pharmacotherapy to reduce cardiac events. The model used Humana medical claims and cost data with an objective to approximate the real cost and economic benefit that could be accrued by a typical U.S. payor.

Framingham Heart Study and Boston University

We were selected for this project through a peer reviewed process by NHLBI, part of the National Institutes of Health, to participate in the NHLBI-Framingham Heart Study Biomarkers of Cardiovascular Risk Initiative, also known as the Systems Approach to Biomarker Research in Cardiovascular Disease, or SABRe CVD. The research will be conducted in collaboration with Boston University School of Medicine and School of Public Health, or Boston University.

 

 

 

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In the first quarter of 2009, we executed a five-year CRADA with NHLBI and Boston University to conduct biomarker discovery studies involving blood samples and data from the Framingham Heart Study. This collaboration is the first time that the Framingham Heart Study is partnering with a commercial entity in a CRADA research project. We have certain commercial rights to biomarker inventions resulting from this research.

The Framingham Heart Study is a prospective, community-based, family study that began in 1948 among residents of Framingham, Massachusetts, to study the development of cardiovascular disease over time. The Framingham Heart Study has previously provided insights that have led to new clinical paradigms related to, among others, hypertension, lipid disorders, obesity and smoking. The findings of the Framingham Heart Study have been published in over 2,000 scientific articles. This cooperative research program commenced in the second quarter of 2009 and we have successfully completed the feasibility stage of the research and the first phase of the research plan involving proteomic discovery studies on specimens from the Framingham Heart Study. The CRADA contemplates research to be conducted over a five-year period.

INTELLECTUAL PROPERTY

The focus of our work is the discovery, development and commercialization of novel diagnostic tests based on biomarkers. Through our research and development efforts, we have developed expertise in proprietary methods using experimental design, biological sample preparation, high throughput biomolecular analyses exploiting high-performance chromatography, mass spectrometry, immunological techniques, nuclear magnetic resonance spectrometry, analytical chemistry, data normalization, statistical analyses, integration of diverse instrument-generated data sets, specialized bioinformatics methods to interpret data sets, and quality assurance and control. We seek to protect these methods as trade secrets and, in some cases, by filing patent applications.

We seek to protect the diagnostic tests that we have developed based on our biomarker discoveries primarily through patents. The patentability of test methods and products based on biomarkers is well-established in most countries. Because we use an empirical as well as a hypothesis-driven approach to biomarker discovery, we measure many different molecules in each biological specimen. Thus, we may be able to identify multiple biomarkers and biomarker combinations that are associated with a clinical outcome of interest. We believe that this may enhance our ability to obtain patents for diagnostic tests based on our discoveries. However, due to technological changes that may affect our proposed products or judicial interpretation of the scope of our patents, our proposed products might not, now or in the future, be adequately covered by our patents.

We have a non-exclusive license to practice and commercialize technology covered by two issued U.S. patents and their foreign counterparts that relate to our methods for discovering biomarkers. In addition, as of January 31, 2011, we have 20 pending patent applications filed either with the U.S. Patent and Trademark Office or under the Patent Cooperation Treaty, or PCT, and foreign counterparts of certain of these patent applications. Where we consider it to be strategic to our business, we file patent applications in other countries or regions including Europe, Canada, Australia and Japan, or we file international applications under the PCT reserving our right to file such applications in countries who are party to the treaty. Of our pending U.S. and PCT patent applications, six applications relate to methods for discovering biomarkers, 13 applications relate to diagnostic products that are related to our biomarker discoveries, and one application relates to therapeutic methods that are related to our biomarker discoveries. We intend, where appropriate, to file additional patent applications and to in-license additional technology covered by patents or patent applications relating to new methods, discoveries or products. A subset of the intellectual property that we own or license relates to our

 

 

 

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galectin-3 test for heart failure. This intellectual property includes U.S. Patent Application No. 10/575,745 exclusively licensed from ACS Biomarker B.V. and nine corresponding patent applications pending in the U.S. and abroad. We received an issue notification dated January 26, 2011, which indicates that U.S. Patent Application No. 10/575,745 will issue as a patent on February 15, 2011, and that the term of the patent is adjusted to expire in November 2026. We own a U.S. and PCT application relating to a specific method and kit for detecting galectin-3. Any patent issuing from this U.S. application could expire as early as 2029. In addition, we own two U.S. patent applications related to methods for clinical evaluation of subjects and therapies based on galectin-3 measurements.

In addition to our internal biomarker discovery and diagnostic product development efforts, for which we plan to seek to obtain exclusive ownership rights, we participate in a Cooperative Research and Development Agreement, or CRADA, with NHLBI and Boston University to conduct certain biomarker discovery studies in the area of metabolic syndrome and atherosclerotic cardiovascular disease using samples and data from the Framingham Heart Study, through which we expect to obtain certain rights to patentable subject matter. We also expect to obtain certain ownership rights to intellectual property conceived in the conduct of the HRP initiative, a study of atherothrombotic cardiovascular disease that we initiated, and from our research, development and commercialization collaboration with Humana, as well as from our other initiatives or collaborations that we may undertake.

We maintain a policy of requiring our employees and consultants to execute confidentiality and invention assignment agreements upon commencement of their relationships with us. These agreements are designed both to enable us to protect and maintain the confidentiality of our trade secret information by prohibiting unauthorized disclosure or use of our technology, and to secure title to technology developed by us or on our behalf so that it may be protected through patent filings or other means.

SALES AND MARKETING

We intend to retain worldwide marketing rights to our products and we plan to be primarily responsible for generating demand, increasing market adoption, working with payors to make reimbursement and coverage determinations and ensuring that our biomarker-based tests realize their market potential. We plan to collaborate with our partners on the promotion of our tests, including the development of commercial plans by our partners, which will be governed by our partnership agreements. For promoting the utility of our tests to clinicians, laboratory decision makers, patients and other stakeholders, we intend to leverage the commercial capabilities of our partners, including diagnostic laboratory instrument manufacturers of automated assays for our tests and laboratory service providers. We intend to develop a limited sales force that will focus on promoting the utility of our tests with physicians, which will complement the sales activities by our partners. We have hired a senior executive to build our sales force and expect to have a limited specialty sales team in place for our galectin-3 test in the first quarter of 2011. We have entered into an agreement with Kordia N.V. for the initial sales and distribution of our manual galectin-3 test in selected European countries.

MANUFACTURING

As part of our development and commercialization activities, we and our contract manufacturers will be required to comply with the FDA’s quality system regulation, or QSR, and other regulations which cover, among other things, the methods and documentation for the design, testing, production, control, quality assurance, labeling, packaging, storage and shipping of our products. The FDA monitors compliance with QSR through periodic inspections. In November 2010, the FDA conducted an inspection of our facilities in Waltham, Massachusetts for the first time. Following that inspection, the FDA issued a Form FDA-483 listing three inspectional observations (variances from protocols or other

 

 

 

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deficiencies) with respect to our facilities. The first observation related to how we documented our procedures and findings for an in-use stability study. This study was designed to determine the conditions under which our test components may be stored for reuse once opened. In response to the FDA observations, we have repeated this study using our third-party manufacturer, Corgenix. The results from the Corgenix-run study corroborated the results from our earlier study, which confirmed that our test components are stable (and therefore reliable) under specified storage conditions, and therefore, no further action is required. The second observation related to our documentation and implementation of corrective and preventative action procedures. The third observation related to documentation and implementation of training programs for our staff. We have taken corrective actions and believe we have remediated the noted deficiencies. While it is our intention to outsource the commercial manufacturing of our galectin-3 test and our other products under development, we do intend to continue performing studies as part of our internal product development activities. The Form FDA-483 did not require us to cease manufacturing or any other activities, and we intend to continue our operations in the normal course. For the commercial supply of our products, we intend to use established manufacturers that have experience with manufacturing diagnostic products using similar assay technologies that are also subject to FDA clearance and oversight. In 2009, we entered into a development and manufacturing agreement with Corgenix Medical Corporation. Corgenix develops, manufactures, distributes and markets in vitro diagnostic products based on ELISA technology using the microtiter format. Under this exclusive agreement, Corgenix will manufacture the BGM Galectin-3 test for distribution in the United States, Europe and elsewhere.

COMPETITION

We believe that our technology platform, our ability to discover novel, proprietary diagnostic tests that aim to address unmet medical needs and our ability to provide such tests on a non-exclusive basis through established manufacturers and laboratory service providers represent the principal methods in which we intend to compete in the diagnostic industry.

We intend to compete by involving payors, leading scientists and other stakeholders in the selection and execution of our discovery and development projects so that our diagnostic tests may better address unmet medical needs. Access to patient samples and collaboration with leading scientists through our agreement with Humana and our leading role in the HRP initiative are examples of our engagement of these stakeholders. In addition, we are pursuing three distinct paths for commercialization of our diagnostic tests, including sales of manual versions of our diagnostic tests through laboratory service providers, sales by us through certified clinical laboratories and sales of automated versions of our diagnostic tests through leading diagnostic instrument manufacturers for use on their instruments, which we believe sets us apart from our competitors.

Established diagnostics companies, such as Abbott Diagnostics, Beckman Coulter, Roche Diagnostics, General Electric, Alere, Ortho Clinical Diagnostics, Mitsubishi, Philips and Siemens have expanded into the molecular diagnostics area to complement their legacy routine testing businesses. In addition, commercial laboratories with extensive service networks for diagnostic tests, such as LabCorp and Quest Diagnostics, have expanded their testing capabilities to include molecular diagnostics. Specialized laboratories, such as Genzyme Genetics and Myriad Genetics, also offer molecular diagnostic testing services.

We have identified a number of recent entrants to the field with competing technologies and approaches in molecular diagnostics. Companies that may compete with us in our current areas of focus, namely, cardiovascular disease, immune disorders and central nervous system disorders, include Athena Diagnostics, Atherotech, Celera Group, Dako, diaDexus, Liposcience, QIAGEN, Rules-Based Medicine, and XDx.

 

 

 

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REGULATORY

We intend to seek regulatory clearance, or if required, approval, for all of our diagnostic tests currently under development in the United States, European Union member states and other countries in which we believe that there are commercial opportunities the tests. The FDA recommends that sponsors such as us interact with the agency early and often in the development of these types of diagnostic products. We intend to follow this recommendation in an effort to reduce development risks and facilitate the regulatory process. In light of the importance of the U.S. market for our potential products, and because of the opportunity to seek and receive early FDA input on development programs, we will prioritize U.S. regulatory plans and submissions over other jurisdictions. In addition, we intend to identify opportunities to prepare and submit applications to European Union member states in compliance with EU-Directive 98/79/EC and other applicable standards. We plan to prioritize European Union member states based on market size, regulatory approvals and other considerations.

U.S. Regulations

Food and Drug Administration

In the United States, in vitro diagnostics are regulated by the FDA as medical devices. We plan to seek FDA clearance or approval for all of our diagnostic products currently under development. There are two regulatory pathways to receive authorization to market in vitro diagnostics, a 510(k) premarket notification and a premarket approval application, or PMA. The FDA makes a risk-based determination as to which pathway a particular in vitro diagnostic is eligible. For our first product, the BGM Galectin-3 test for heart failure, we submitted a 510(k) premarket notification to the FDA in March 2009. Upon review of our 510(k) application, the FDA determined that our device was not substantially equivalent to the legally marketed device to which we claimed substantial equivalence and therefore denied clearance. The FDA indicated that additional clinical and other data were required in support of our filing, and we re-submitted a 510(k) application in December 2009 with additional data. In February 2010, we received a letter from the FDA regarding our 510(k) application that requested additional clinical and statistical information to support our application and, after further contact with the FDA, we submitted our formal response to the FDA letter in August 2010. We received 510(k) clearance from the FDA in November 2010 for a manual version of our BGM Galectin-3 test.

The information that must be submitted to the FDA in order to obtain clearance or approval to market a new medical device varies depending on how the medical device is classified by the FDA. Medical devices are classified into one of three classes on the basis of the controls deemed by the FDA to be necessary to reasonably ensure their safety and effectiveness. Class I devices are subject to general controls, including labeling, premarket notification and adherence to FDA’s quality system regulation, which are device-specific good manufacturing practices. Class II devices are subject to general controls and special controls, including performance standards and postmarket surveillance. Class III devices are subject to most of the previously identified requirements as well as to premarket approval. Class I devices are exempt from premarket submissions to the FDA; most Class II devices require the submission of a 510(k) premarket notification to the FDA; and Class III devices require submission of a PMA. Most in vitro diagnostic kits are regulated as Class I or II devices and are either exempt from premarket notification or require a 510(k) submission.

510(k) premarket notification

A 510(k) notification requires the sponsor to demonstrate that a medical device is substantially equivalent to another marketed device, termed a “predicate device”, that is legally marketed in the United States and for which a PMA was not required. A device is substantially equivalent to a predicate

 

 

 

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device if it has the same intended use and technological characteristics as the predicate; or has the same intended use but different technological characteristics, where the information submitted to the FDA does not raise new questions of safety and effectiveness and demonstrates that the device is at least as safe and effective as the legally marketed device. Under current FDA policy, if a predicate device does not exist, the FDA may make a risk-based determination based on the complexity and clinical utility of the device that the device is eligible for de novo 510(k) review instead of a requiring a PMA. The de novo 510(k) review process is similar to clearance of the 510(k) premarket notification, despite the lack of a suitable predicate device.

The FDA’s performance goal review time for a 510(k) application is 90 days from the date of receipt, however, in practice, the review often takes longer. In addition, the FDA may require information regarding clinical data in order to make a decision regarding the claims of substantial equivalence. Clinical studies of in vitro diagnostic products are typically designed with the primary objective of obtaining analytical or clinical performance data. If the FDA believes that the device is not substantially equivalent to a predicate device, it will issue a “Not Substantially Equivalent” letter and designate the device as a Class III device, which will require the submission and approval of a PMA before the new device may be marketed. Under certain circumstances, the sponsor may petition the FDA to make a risk-based determination of the new device and reclassify the new device as a Class I or Class II device.

In August 2010, the FDA issued an assessment of the 510(k) program which contains certain recommendations to strengthen and clarify the 510(k) premarket review process for medical devices that do not need to undergo a full premarket approval review. The report recommends that CDRH develop a guidance document defining a subset of moderate-risk (Class II) devices, called Class IIb, for which clinical or manufacturing data typically would be necessary to support a substantial equivalence determination. In the event that such new Class IIb sub-classification is adopted, we believe that most of the tests that we may pursue would be classified as Class IIb devices. We cannot predict whether the FDA will adopt this sub-classification or, if adopted, what impact this sub-classification might have on the development and approval by the FDA of our galectin-3 tests. Based on the information currently available, however, we believe that the new sub-classification will provide additional clarity as to the requirements for FDA clearance and we believe that requirements for development and FDA clearance for novel products, such as our galectin-3 tests, will not materially change.

Premarket approval

The PMA process is more complex, costly and time consuming than the 510(k) process. A PMA must be supported by more detailed and comprehensive scientific evidence, including clinical data, to demonstrate the safety and efficacy of the medical device for its intended purpose. If the device is determined to present a “significant risk,” the sponsor may not begin a clinical trial until it submits an investigational device exemption, or IDE, to the FDA and obtains approval from the FDA to begin the trial.

After the PMA is submitted, the FDA has 45 days to make a threshold determination that the PMA is sufficiently complete to permit a substantive review. If the PMA is complete, the FDA will file the PMA. The FDA is subject to a performance goal review time for a PMA is 180 days from the date of filing, although in practice this review time is longer. Questions from the FDA, requests for additional data and referrals to advisory committees may delay the process considerably. Indeed, the total process may take several years and there is no guarantee that the PMA will ever be approved. Even if approved, the FDA may limit indication for which the device may be marketed. The FDA may also request additional clinical data as a condition of approval or after the PMA is approved. Any changes to the medical device may require a supplemental PMA to be submitted and approved.

 

 

 

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Laboratory developed tests

Although the FDA has consistently claimed that it has the regulatory authority to regulate laboratory-developed tests that are validated by the developing laboratory and has imposed labeling requirements for the results of tests utilizing analyte-specific reagents, it has generally exercised enforcement discretion and has not otherwise regulated most tests performed by laboratories that are certified under the Clinical Laboratory Improvement Act, or CLIA. In recent years, the FDA indicated that it was reviewing the regulatory requirements that will apply to laboratory-developed tests, and in September 2006, the FDA published a draft guidance document, which it revised in September 2007, or the Draft Guidance, that may be relevant to some of the tests we develop. The Draft Guidance describes the FDA’s position regarding potential regulation of in vitro diagnostic multivariate index assays, or IVDMIAs, and the revision provided additional examples of the types of tests that would be subject to the Draft Guidance. An IVDMIA is a test system that employs data, derived in part from one or more in vitro assays, and an algorithm that usually, but not necessarily, runs on software, to generate a result that diagnoses a disease or condition or is used in the cure, mitigation, treatment, or prevention of disease. The FDA has recently issued numerous letters to corporations marketing genetic tests, which according to the letters, appear to meet the definition of a device as that term is defined in section 201(h) of the Federal Food Drug and Cosmetic Act. We consider the FDA’s recent statements and actions pertaining to other diagnostic tests consistent with our interpretation that the kind of tests we are pursuing are subject to FDA regulation.

In February 2007, the FDA cleared a 510(k) submission for Agendia’s MammaPrint® breast cancer recurrence test as the first IVDMIA cleared since the first version of the Draft Guidance was published. This was a complex test, based on profiling of 70 genes to determine if the patient was likely to develop a metastatic form of the disease in the future. In August 2008 the FDA cleared AlloMap by XDx as an aid in the management of patients following cardiac transplantation, and in September 2009 the FDA cleared OVA1 by Vermillion as an aid in the management of a patient with possible ovarian cancer. With these clearances, a regulatory framework appears to be forming in line with the Draft Guidance. The clearance of these complex tests suggests that the 510(k) process is the likely route for most, if not all, of the diagnostic tests that we are currently developing, and we intend to seek clearance under Section 510(k) for each of our diagnostic tests. Nevertheless, the FDA may require us to submit PMAs for our pipeline product candidates. We intend to conduct early and ongoing dialog with the FDA on each of our pipeline product candidates in order to obtain clarity around the classification and requirements prior to the commencement of larger-scale studies.

CLIA

Laboratories that perform testing on human specimens for the purpose of providing information for diagnosis, prevention or treatment of disease or assessment of health are subject to CLIA. This law imposes quality standards for laboratory testing to ensure the accuracy, reliability and timeliness of patient test results. The FDA is responsible for the categorization of commercially marketed IVD tests under CLIA into one of three categories based upon the potential risk to public health in reporting erroneous results. The categories were devised on the basis of the complexity of the test, and includes waived tests, tests of moderate complexity, and tests of high complexity. Laboratories performing moderate- or high-complexity testing must meet the CLIA requirements for proficiency testing, patient test management, quality control, quality assurance and personnel.

If, in the future, we choose to set up a clinical laboratory to offer a testing service following FDA clearance of our tests, we will be required to hold certain federal, state and local licenses, certifications and permits to conduct our business. Any clinical laboratory with which we might contract or to which we might sell our diagnostic tests would also be subject to these same requirements. Under CLIA, we will be required to hold a certificate applicable to the type of work we perform and to comply with standards

 

 

 

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covering personnel, facilities administration, quality systems and proficiency testing. We believe that some of the tests that we are developing will be high-complexity tests. CLIA certified laboratories are typically subject to survey and inspection every two years to assess compliance with program standards. We currently do not have any plans to set up our own laboratory to offer clinical testing services.

We may also seek accreditation by the College of American Pathologists, or CAP, and licensed by some states. The CAP Laboratory Accreditation Program is an internationally recognized program that utilizes teams of practicing laboratory professionals as inspectors, and accreditation by CAP can often be used to meet CLIA and state certification requirements.

We currently do not intend to offer a testing service for any laboratory-developed tests, or LDTs, as defined under CLIA.

HIPAA and other privacy laws

The Health Insurance Portability and Accountability Act of 1996, or HIPAA, established for the first time comprehensive protection for the privacy and security of health information. The HIPAA standards apply to three types of organizations, or “Covered Entities”: health plans, healthcare clearing houses, and healthcare providers which conduct certain healthcare transactions electronically. Covered Entities and their Business Associates must have in place administrative, physical, and technical standards to guard against the misuse of individually identifiable health information. Additionally, some state laws impose privacy protections more stringent than HIPAA. Most of the institutions and physicians from which we obtain biological specimens that we use in our research and validation work are Covered Entities and must obtain proper authorization from their patients for the subsequent use of those samples and associated clinical information. We are not presently subject to HIPAA; however, we may become subject to the requirements of HIPAA in the future if we provide clinical laboratory testing services or enter into specific kinds of relationships with a Covered Entity or a Business Associate of a Covered Entity.

Our activities must also comply with other applicable privacy laws. For example, there are also international privacy laws that impose restrictions on the access, use, and disclosure of health information. All of these laws may impact our business. Our failure to comply with these privacy laws or significant changes in the laws restricting our ability to obtain tissue samples and associated patient information could significantly impact our business and our future business plans.

European regulations

In the European Union, IVD medical devices are regulated under EU-Directive 98/79/EC, or the IVD Directive, and corresponding national provisions. The IVD Directive requires that medical devices meet the essential requirements set out in an annex of the directive. These requirements include the safety and efficacy of the devices. According to the IVD Directive, the Member States presume compliance with these essential requirements in respect of devices which are in conformity with the relevant national standards transposing the harmonized standards of which the reference numbers have been published in the Official Journal of the European Communities. These harmonized standards include ISO 13485:2003, the quality standard for medical device manufacturers.

IVD medical devices, other than devices for performance evaluation, must bear the CE marking of conformity when they are placed on the market. The CE mark is a declaration by the manufacturer that the product meets all the appropriate provisions of the relevant legislation implementing the relevant European Directive. As a general rule, the manufacturer must follow the procedure of the EC Declaration of conformity to obtain this CE marking. In the fourth quarter of 2009 we obtained CE Mark for the BGM Galectin-3 test for use as an aid in assessing the prognosis of patients with heart failure.

 

 

 

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Each European country must adopt its own laws, regulations and administrative provisions necessary to comply with the IVD Directive. Member States may not create any obstacle to the placing on the market or the putting into service within their territory of devices bearing the CE marking according to the conformity assessment procedures.

Development

Article 152 of the EC-Treaty requires a high level of human health protection to be ensured in the definition and implementation of all Community policies and activities. Community action, which complement national policies, must be directed towards improving public health, preventing human illness and diseases, and obviating sources of danger to human health. On the basis of article 152(4)(a) of the EC-Treaty, the European Legislator is required to contribute to the achievements of these objectives through adopting measures setting high standards of quality and safety of organs and substances of human origin, blood and blood derivatives. These measures, however, may not prevent any Member State, however, from maintaining or introducing more stringent protective measures.

The use of bodily material, which already has been taken from humans, is not regulated by the European Legislator through specific directives. However, in the European Union the protection of individuals with regard to the processing of personal data is regulated under EU-Directive 95/46/EC, or the PD Directive. If specimens, such as blood plasma and urine, taken from patients relate to an identified or identifiable natural person, the use of such specimens fall within the scope of the PD Directive.

Member States prohibit the processing of personal data concerning health, unless processing of the data is required for the purposes of preventive medicine, medical diagnosis, the provision of care or treatment or the management of healthcare services, and where those data are processed by a health professional subject under national law or rules established by national competent bodies to the obligation of professional secrecy or by another person also subject to an equivalent obligation of secrecy. Individual European countries are free to further restrict the collection and the use of such bodily material

REIMBURSEMENT

United States

In the United States, payments for diagnostic tests come from several sources, including third party payors such as insurance companies and health maintenance organizations; government health programs such as Medicare and Medicaid; and patients; and, in certain circumstances, hospitals or referring laboratories (who then bill health third-party payors for testing). If we offer our diagnostic tests as a service through a CLIA certified laboratory contracted by us, we would directly or indirectly be responsible for billing and collection of fees for the tests. Otherwise, billing and collection would be the responsibility of the companies that purchase or license our products.

Code Assignment. In the United States, a third-party payor’s decisions regarding coverage and payment are driven, in large part, by the specific Current Procedural Terminology, or CPT, code used to identify a test. The American Medical Association, or AMA, publishes the CPT Code, which is a listing of descriptive terms and identifying codes for reporting medical services and procedures. The purpose of the CPT Code is to provide a uniform language that accurately describes medical, surgical, and diagnostic services and therefore to ensure reliable nationwide communication among healthcare providers, patients, and third-party payors.

A manufacturer of in vitro diagnostic kits or a provider of laboratory services may request establishment of a Category I CPT code for a new product. Assignment of a specific CPT code ensures routine processing and payment for a diagnostic test by both private and government third-party payors. We have initiated the process to obtain an analyte-specific CPT code for measuring galectin-3 in plasma or

 

 

 

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serum, and based on the AMA’s submission process, we expect to be eligible to obtain an analyte-specific CPT Code for galectin-3 testing beginning with the 2013 Clinical Laboratory Fee Schedule. In the interim and prior to potentially obtaining an analyte-specific CPT code for galectin-3 testing, galectin-3 testing will be eligible, in accordance with coding requirements, for CPT-coding using established CPT method codes.

The AMA has specific procedures for establishing a new CPT code and, if appropriate, for modifying existing nomenclature to incorporate a new test into an existing code. If the AMA concludes that a new code or modification of nomenclature is unnecessary, the AMA will inform the requestor how to use one or more existing codes to report the test.

While the AMA’s decision is pending, billing and collection may be sought under an existing, non-specific CPT code. A manufacturer or provider may decide not to request assignment of a CPT code and instead use an existing, non-specific code for reimbursement purposes. However, use of such codes may result in more frequent denials and/or requests for supporting clinical documentation from the third-party payor and in lower reimbursement rates, which may vary based on geographical location.

Coverage Decisions. When deciding whether to cover a particular diagnostic test, private and government third-party payors generally consider whether the test is a covered benefit and, if so, whether it is reasonable and necessary for the diagnosis or treatment of illness and injury. Most third-party payors do not cover experimental services. Coverage determinations often are influenced by current standards of practice and clinical data, particular at the local level. The Centers for Medicare & Medicaid Services, or CMS, which is the government agency responsible for overseeing the Medicare program, has the authority to make coverage determinations on a national basis, but most Medicare coverage decisions are made at the local level by contractors that administer the Medicare program in specified geographic areas. Private and government third-party payors have separate processes for making coverage determinations, and private third-party payors may or may not follow Medicare’s coverage decisions. If a third-party payor has a coverage determination in place for a particular diagnostic test, billing for that test must comply with the established policy. Otherwise, the third-party payor makes reimbursement decisions on a case-by-case basis.

Payment. Payment for covered diagnostic tests is determined based on various methodologies, including prospective payment systems and fee schedules. In addition, private third-party payors may negotiate contractual rates with participating providers or set rates as a percentage of the billed charge. Diagnostic tests furnished to Medicare inpatients generally are included in the bundled payment made to the hospital under Medicare’s Inpatient Prospective Payment System. Payment for diagnostic tests furnished to Medicare beneficiaries in most other circumstances is made based on the Clinical Laboratory Fee Schedule, under which a payment amount is assigned to each covered CPT code. The law technically requires fee schedule amounts to be adjusted annually by the percentage increase in the consumer price index, or CPI, for the prior year, but Congress has frozen payment rates in certain years. For the 2010 calendar year the Clinical Laboratory Fee Schedule, or CLFS, was reduced across all listed tests by 1.9%. Currently, the ceiling for established tests is set at 74% of the median of all contractor fee schedule amounts for a particular test and 100% of the median for diagnostic tests for which no limitation amount was established prior to 2001. Medicaid programs generally pay for diagnostic tests based on a fee schedule, but reimbursement varies by state.

European Union

In the European Union the reimbursement mechanisms used by private and public health insurers vary by country. For the public systems reimbursement is determined by guidelines established by the legislator or responsible national authority. As elsewhere, inclusion in reimbursement catalogues focuses on the medical usefulness, need, quality and economic benefits to patients and the healthcare system. Acceptance for reimbursement comes with cost, use and often volume restrictions, which again can vary by country.

 

 

 

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LEGAL PROCEEDINGS

We are not currently subject to any material legal proceedings.

FACILITIES

We lease approximately 22,000 square feet of office and laboratory space at 610 Lincoln Street North, Waltham, Massachusetts 02451. The term of our lease expires in March 2013. We believe that our facilities are adequate to meet our current needs, although if additional space is needed in the future, we believe that such space will be available on commercially reasonable terms.

EMPLOYEES

As of December 31, 2010, we employed 40 full-time employees, of whom 20 had advanced degrees, 26 were engaged in research and development, 6 performed sales and marketing functions and 8 performed general and administrative functions. We plan to continue to expand our research and development and commercialization activities. To support this growth, we will need to expand managerial, research and development, operations, finance and other functions. None of our employees is represented by a labor union, and we consider our relationships with our employees to be good.

 

 

 

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Management

EXECUTIVE OFFICERS AND DIRECTORS

Our executive officers and directors and their respective ages and positions as of December 31, 2010 are as follows:

 

Name   Age     Position

Executive Officers

   

Pieter Muntendam, M.D.

    52      President, Chief Executive Officer and Director

Michael W. Rogers

    50      Executive Vice President, Chief Financial Officer and Treasurer

Neal F. Gordon, Ph.D.

    49      Senior Vice President, Biomarker Discovery

Anastasia Rader

    49      Senior Vice President, Executive Operations & Human Resources

Aram Adourian, Ph.D.

    40      Vice President, Scientific Affairs

Wayne K. Shepherd

    39      Vice President, Sales and Marketing

Non-Employee Directors

   

Noubar Afeyan, Ph.D.(2).

    48      Chairman of the Board

Harrison M. Bains(1)(3)

    67      Director

Stéphane Bancel

    38      Director

Timothy Harris, Ph.D, D.Sc.(1)(2)

    60      Director

Stelios Papadopoulos, Ph.D.(1)(3)

    62      Vice Chairman of the Board

Pieter van der Meer, M.Sc.(2)(3)

    40      Director

 

(1)   Current member of our Audit Committee. Mr. Bains is the chairman of the committee.

 

(2)   Current member of our Compensation Committee. Dr. Harris is the chairman of the committee.

 

(3)   Current member of our Nominating and Governance Committee. Dr. Papadopoulos is the chairman of the committee.

The biographies of each of the directors below contain information regarding each person’s service as a director, business experience, director positions held currently or at any time during the last five years, information regarding involvement in certain legal or administrative proceedings, if applicable, and the experiences, qualifications, attributes or skills that caused the Board to conclude that the person should serve as a director for the company as of the date of this prospectus.

Pieter Muntendam, M.D., joined us as President in November 2004 and was appointed as Chief Executive Officer in December 2005. He also has served as a member of our board of directors since November 2004. He is a biopharmaceutical and healthcare executive with over 20 years of business experience ranging from early stage enterprises to multinational corporations. Dr. Muntendam joined us from NetNumina Solutions, Inc., a professional services company, where he served as Director of the Biopharma Healthcare Practice from April 2003 to October 2004. Prior to joining NetNumina, he co-founded Vitivity Inc., a subsidiary of Millennium Pharmaceuticals, Inc., and served as Vice President, Medicine from July 2001 to April 2003. He founded the health management firm ProMedex Inc. in 1996, where he served as President and Chief Executive Officer and chairman of the board until ProMedex was acquired by Landacorp, Inc. in 2001. Prior to that, he served as Vice President of Care Management at Glaxo Wellcome (now GlaxoSmithKline plc), where he was responsible for the development and implementation of its entry strategy within the field of care and disease management. Dr. Muntendam began his career with Organon International Inc. in December of 1982, after which he was appointed Vice President of Research and Development, International at Johnson & Johnson, and appointed as a member of the boards of directors for two Johnson & Johnson operating companies.

 

 

 

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Dr. Muntendam received his M.D. from Leiden University in the Netherlands. The Board concluded that Dr. Muntendam should serve as a director as of the date of this prospectus because he is our Chief Executive Officer and has helped grow and transform us from a research services organization into a discovery-based diagnostic company. The Board values Dr. Muntendam’s extensive medical, scientific and executive leadership expertise.

Michael W. Rogers joined us in June 2009 as our Executive Vice President, Chief Financial Officer and Treasurer. Prior to joining us and since 1999, Mr. Rogers held the position of Executive Vice President, Chief Financial Officer and Treasurer at Indevus Pharmaceuticals, Inc., which was acquired by Endo Pharmaceuticals in 2009. In 1998, Mr. Rogers was Executive Vice President and Chief Financial and Corporate Development Officer at Advanced Health Corporation, a publicly-traded healthcare information technology company. From 1995 to 1997, he was Vice President, Chief Financial Officer and Treasurer of AutoImmune, Inc., a publicly-traded biopharmaceutical company. From 1994 to 1995, Mr. Rogers was Vice President, Investment Banking at Lehman Brothers, Inc. From 1990 to 1994, he was associated with PaineWebber, Inc., serving most recently as Vice President, Investment Banking Division. Mr. Rogers serves as a director of pSivida, Inc., a publicly-traded medical device company. Mr. Rogers received an M.B.A. from the Darden School at the University of Virginia and a B.A. from Union College.

Neal F. Gordon, Ph.D., joined us in January 2009 as Senior Vice President, Biomarker Discovery. Dr. Gordon has 20 years of experience in the biotechnology industry serving both as a senior executive and in product development. From July 2004 to December 2008, Dr. Gordon was President of Epitome Biosystems, where he spearheaded the development and subsequent market introduction of a line of multiplexed protein immunoassay products. From 1998 to 2004, Dr. Gordon was at Antigenics Inc., first as Vice President of Process Development and then as Senior Vice President of Manufacturing Operations. Dr. Gordon joined Antigenics in 1998, following 10 years at PerSeptive Biosystems, which is now part of Life Technologies, Inc. As part of the founding technology team, he led the development, application and market launch of technologies for the purification and analysis of proteins, including the BIOCAD perfusion chromatography workstation, and prior to that he was a product development engineer at Proctor & Gamble. Dr. Gordon obtained a bachelors degree in chemical engineering from McGill University, and a Ph.D. in biochemical engineering from Massachusetts Institute of Technology.

Anastasia Rader joined us in January 2004 as our Vice President, Human Resources and was appointed as our Senior Vice President, Executive Operations & Human Resources in January 2010. Prior to joining us and since 1999, Ms. Rader was a Vice President at Flagship Ventures and Vice President, Human Resources, of NewcoGen. During her tenure with Flagship, Ms. Rader consulted with numerous portfolio companies on human resources operational issues. Prior to joining Flagship, Ms. Rader was Corporate Director of Worldwide Employment and Staffing for Applera Corporation (now Life Technologies) following the merger of Perkin Elmer and PerSeptive Biosystems in 1998. Ms. Rader was responsible for all human resources functions at PerSeptive from 1992 to 1998. During this period, she oversaw the hiring of 600 global employees and the implementation of core human resources processes and programs as well as equity and compensation structures to accommodate the company’s growth. Ms. Rader was also a key member of corporate due diligence teams for a number of PerSeptive acquisitions and was instrumental in the integration and assimilation process for the merger of Perkin Elmer and PerSeptive Biosystems in 1998. Ms. Rader holds a B.S. from Babson College.

Aram Adourian, Ph.D., joined us in August 2000 as Director, Advanced Technologies, and served in such position until June 2002. From June 2002 until October 2003, Dr. Adourian worked as our Senior Director, Technology Assessment. In October 2003, Dr. Adourian was promoted to Vice President, Computational Sciences and served in such position until January 2007, when he was designated a general Vice President and served in such position until January 2009. In January 2009, Dr. Adourian

 

 

 

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was appointed as our Vice President, Scientific Affairs. Prior to joining us, Dr. Adourian worked at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. While at MIT, Dr. Adourian served as Project Manager for Bioinformatics specializing in the development of novel systems and approaches for biomolecular sequencing, analysis and modeling. Dr. Adourian earned his Ph.D. at Harvard University in Statistical Physics, where he was a recipient of the Rudenberg Research Prize, and received his undergraduate degree in Physics from Cornell University.

Wayne K. Shepherd joined us in June 2009 as our Vice President, Market Development. In May 2010, Mr. Shepherd was promoted to Vice President, Sales and Marketing. Mr. Shepherd has over 15 years of experience in the biotechnology and device industry. Prior to joining us, Mr. Shepherd held the position of Regional Sales Director at Biosite, Inc., from November 2007 to June 2009. While at Biosite, he managed a sales team responsible for selling capital cardiac diagnostic equipment and reagent sales. Mr. Shepherd also held the position of Senior BNP Product Manager at Biosite from April 2006 to November 2007, where he managed all global aspects of the Triage BNP Test brands for the Triage meter and Beckman Immunoassay Systems. From September 2003 to April 2006, Mr. Shepherd held field sales positions at Biosite as Regional Trainer and Account Executive. From April 1994 to September 2003, Mr. Shepherd held sales positions at Medtronic, Wesley Jessen and The Dial Corporation. Mr. Shepherd received an M.B.A. from Averett University and a B.S. in Marketing Education at Virginia Polytechnic Institute and State University, or Virginia Tech.

Noubar Afeyan, Ph.D., is a founder and has served on our board of directors since our inception in 2000. He has served as Managing Partner and Chief Executive Officer of Flagship Ventures, an early stage venture capital firm, since he co-founded the firm in 2000. Prior to founding Flagship Ventures in 2000, Dr. Afeyan participated in co-founding and helping launch the following ventures: PerSeptive Biosystems, ChemGenics Pharmaceuticals, EXACT Sciences, Antigenics, Color Kinetics and Celera Genomics. Dr. Afeyan was Chief Executive Officer of PerSeptive Biosystems during its five years as a public company and until its merger with Perkin Elmer Corporation. During the past five years, Dr. Afeyan has served on the board of directors of Antigenics and Color Kinetics and currently serves as a director of Helicos BioSciences. Additionally, he currently serves as a director of the following private companies: Affinnova, Inc., BIND Biosciences, Inc., Eleven Biotherapeutics, Ensemble Therapeutics, Joule Unlimited, Inc. and LS9, Inc. He earned his Ph.D. in biochemical engineering from the Massachusetts Institute of Technology (MIT) following a B.S. in chemical engineering from McGill University. Dr. Afeyan has authored numerous scientific publications and patents and is currently a Senior Lecturer at MIT in the Sloan School of Management. The Board concluded that Dr. Afeyan should serve as a director as of the date of this prospectus because he is a technologist, entrepreneur and venture capitalist who has extensive experience founding, building, leading, investing in and growing life science companies. Dr. Afeyan has extensive experience taking companies public and evaluating and engaging corporate combination transactions. In addition, the Board values his experience serving on many private and public company boards, as well as several advisory boards, and his familiarity with a full range of corporate and governance matters.

Harrison M. Bains has served on our board of directors since June 2007. Since Mr. Bains retired in 2004, he has served on various boards or directors or trustees, as set forth below. Mr. Bains served in multiple roles at Bristol Myers Squibb Company from 1988 until 2004, including Vice President, Treasurer and acting Chief Financial Officer. Mr. Bains’ career also includes serving as Senior Vice President of the Primary Industries Group at Chase Manhattan Bank in 1987 and 1988 and 11 years with RJR Nabisco and two of its predecessor companies as Senior Vice President and Treasurer. He currently serves as the chair of the board of directors and previously served as the chair of the audit committee of MGI Funds, Inc. an investment company registered under the Investment Company Act of 1940, as amended. He has served as a member of the boards of trustees of the University of Redlands since October 1989, the Greater Newark Conservancy since January 2005, the Park Avenue Armory since October 2007, the Civil War Preservation Trust since September 2007 and Summer Search since November 2007. Mr. Bains earned an M.B.A. from

 

 

 

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the University of California, Berkeley and a B.A. in economics from the University of Redlands. He also completed the Advanced Management Program at Harvard Business School. The Board concluded that Mr. Bains should serve as a director as of the date of this prospectus because Mr. Bains has extensive experience in corporate finance, accounting, governance and strategic planning for life science companies, informed most recently by his 16 years with global biopharmaceutical company, Bristol Myers Squibb.

Stéphane Bancel has served on our board of directors since January 2010. Mr. Bancel serves as Chief Executive Officer of bioMérieux, a leader in the field of in vitro diagnostics for clinical and industrial applications, and has done so since January 2007, and prior to that, served as Vice President of Strategy from July 2006 to December 2006. From 2000 to 2006, Mr. Bancel worked for Eli Lilly and Company in the United States, Great Britain and Belgium, where he successively held the positions of Managing Director, Executive Director for Global Manufacturing Strategy, Global Supply Chain and U.S. Distribution, and Supply Chain Manager. From 1995 to 1998, Mr. Bancel worked with bioMérieux in Japan, where he managed the industrial microbiology business for the Asia-Pacific region. During the past five years, Mr. Bancel has served on the board of directors of Targanta Therapeutics Corp. and he currently serves on the board of directors of bioTheranostics, Inc. and Knome, Inc. Mr. Bancel is a graduate of the Ecole Centrale Paris Engineering School. He holds an M.S. in biochemical engineering from the University of Minnesota and an M.B.A. from Harvard Business School. The Board concluded that Mr. Bancel should serve as a director as of the date of this prospectus because of Mr. Bancel’s experience in the diagnostics industry, managing international commercial organizations and in strategic planning. The Board values his experience serving on other private and public company boards.

Timothy Harris, Ph.D, D.Sc., has served on our board of directors since April 2007. Dr. Harris has served as the Director of the Advanced Technology Program at SAIC Frederick since 2007 and Chief Technology Officer for SAIC Frederick since 2008. Prior to holding these positions, he served as the President and Chief Executive Officer of Novasite Pharmaceuticals Inc. from January 2005 to September 2006. Prior to that, he served as Chief Executive Officer for Structural GenomiX, Inc. (now part of Eli Lilly), a drug discovery and development company focused on innovative cancer therapeutics from 2003 to 2004 and as its President and Chief Executive Officer from 1999 to 2003. Dr. Harris started his career in biotechnology in 1981 as a group leader in Molecular Biology at Celltech Group (now UBC Pharma) and from 1989 to 1993 was Director of Biotechnology at Glaxo Group Research in the U.K. From 1993 until 1999, Dr. Harris was Chief Scientific Officer and Vice President of Research and Development at Sequana Therapeutics Inc. in San Diego, which became Axys Pharmaceuticals, Inc. in 1998 and was subsequently acquired by Celera Genomics. During the past five years, Dr. Harris has served on the board of directors of Dendreon Corp. and he currently serves on the boards of directors of Origen Therapeutics, Inc. and Gyrasol Technologies and is Chairman of the Scientific Advisory Board of Bionomics Inc. in Australia. Dr. Harris received his Ph.D. in molecular virology from the University of Birmingham, U.K. The Board concluded that Dr. Harris should serve as a director as of the date of this prospectus because he has extensive experience managing and serving on the boards of directors of life science companies. In addition, he brings valuable management, scientific and technological expertise to us, as well as extensive knowledge of commercial operations.

Stelios Papadopoulos, Ph.D., has served on our board of directors since 2003 and as Vice Chairman of our board of directors since April 2007. Since 2000, he has served as Chairman of Fondation Sante, a private charitable foundation whose mission is to improve the health and education of those in need, whether countries, regions or individuals. Dr. Papadopoulos served as Vice Chairman of Cowen and Company, LLC from 2003 until 2006 and as Managing Director from 2000 until 2003. While at Cowen and Company, LLC, he worked as an investment banker focused on the biotech and pharmaceutical sectors. Prior to joining Cowen and Company, LLC, he worked as an investment banker at PaineWebber, Incorporated, from 1987 to 2000, where he was Chairman of PaineWebber Development Corp., a PaineWebber subsidiary focusing on biotechnology from 1996 to 2000. Dr. Papadopoulos is a co-founder

 

 

 

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and Chairman of the Board of Exelixis, Inc., and he is a co-founder and member of the boards of directors of Anadys Pharmaceuticals, Inc. and Cellzome, Inc. Dr. Papadopoulos currently serves on the board of directors of Biogen Idec, Inc., Regulus Therapeutics, Inc. and Joule Unlimited, Inc. and during the past five years, he also served on the board of directors of GenVec, Inc. and SGX Pharmaceuticals, Inc. He is also a member of the board of visitors of Duke University School of Medicine and the board of directors of the National Marrow Donor Program. Dr. Papadopoulos holds a Ph.D. in biophysics and an M.B.A. in finance, both from New York University. The Board concluded that Dr. Papadopoulos should serve as a director as of the date of this prospectus because of his valuable corporate finance expertise and his deep scientific knowledge and familiarity with public and private life science companies. Having been a member of the compensation, audit and governance committees of public company boards, Dr. Papadopoulos is also familiar with a broad range of corporate and board functions. Dr. Papadopoulos brings a wealth of experience in founding, building and investing in life science companies.

Pieter van der Meer, M.Sc., has served on our board of directors since February 2002. Since January 2005, he has served as a Managing Director of Gilde Healthcare Partners, a venture capital firm, where he focuses on start-up and early stage investments in healthcare companies with novel technologies, platforms and drug discovery approaches. Mr. van der Meer also represents Gilde on the boards of directors of certain of its portfolio companies, including Agendia B.V. and Acacia Pharma Ltd. He is also a member of the project screening committee at Amsterdam & Leiden Universities. Mr. van der Meer joined Gilde in 1998 after working several years with KPMG Management Consulting, where he was closely involved with due diligence and strategic projects in venture capital and the pharmaceutical sector across Europe. Mr. van der Meer earned his M.Sc. in chemistry at Leiden University where he specialized in bio-organic synthesis and molecular modeling. The Board concluded that Mr. van der Meer should serve as a director as of the date of this prospectus because he has extensive experience building, investing in and growing life science companies globally. In addition, the Board values his scientific background, international perspective and experience, as we commence our commercial activities in Europe.

Board composition

Our restated certificate of incorporation and restated bylaws, each of which will become effective completion of this offering, provide that the authorized number of directors may be changed only by resolution of the board of directors. We currently have seven directors. In accordance with our restated certificate of incorporation and restated bylaws, our board of directors will be divided into three classes with staggered three-year terms. At each annual meeting of stockholders commencing with the meeting in 2012, the successors to the directors whose terms then expire will be elected to serve until the third annual meeting following the election. At the closing of this offering, our directors will be divided among the three classes as follows:

 

Ø  

the Class I directors will be Dr. Afeyan, Dr. Papadopoulos and Mr. Bains and their terms will expire at the annual meeting of stockholders to be held in 2012;

 

Ø  

the Class II directors will be Mr. van der Meer and Dr. Harris and their terms will expire at the annual meeting of stockholders to be held in 2013; and

 

Ø  

the Class III directors will be Mr. Bancel and Dr. Muntendam and their terms will expire at the annual meeting of stockholders to be held in 2014.

Any additional directorships resulting from an increase in the number of directors will be distributed among the three classes so that each class will consist of approximately one-third of the directors.

Director independence

Our board of directors has reviewed the materiality of any relationship that each of our directors has with us, either directly or indirectly. Based on this review, our board has determined that the following

 

 

 

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directors are “independent directors” as defined by the applicable rules and regulations of The NASDAQ Stock Market, or NASDAQ: Dr. Afeyan, Mr. Bains, Mr. Bancel, Dr. Harris, Dr. Papadopoulos and Mr. van der Meer.

Committees of the board of directors

Our board of directors has an audit committee, a compensation committee and a nominating and governance committee. The composition and function of each of these committees are described below.

Audit Committee. Our audit committee is comprised of Mr. Bains (chairman), Dr. Harris and Dr. Papadopoulos. Our board of directors has determined that Mr. Bains is an audit committee financial expert, as defined by the rules of the Securities and Exchange Commission. Our audit committee is authorized to:

 

Ø  

approve and retain the independent auditors to conduct the annual audit of our financial statements;

 

Ø  

review the proposed scope and results of the audit;

 

Ø  

review and pre-approve audit and non-audit fees and services;

 

Ø  

review accounting and financial controls with the independent auditors and our financial and accounting staff;

 

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review and approve transactions between us and our directors, officers and affiliates;

 

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recognize and prevent prohibited non-audit services; and

 

Ø  

establish procedures for complaints received by us regarding accounting matters; oversee internal audit functions, if any.

We believe that the composition of our audit committee meets the independence requirements of the applicable rules of the Securities and Exchange Commission and NASDAQ on the date of this prospectus.

Compensation Committee. Our compensation committee is currently comprised of Dr. Harris (chairman), Dr. Afeyan and Mr. van der Meer. Prior to the completion of the offering, we expect that Dr. Afeyan will step down from the compensation committee and Mr. Bains will be his replacement. Upon completion of the offering, all members of the compensation committee will qualify as independent under the current definition promulgated by NASDAQ. Our compensation committee is authorized to:

 

Ø  

review and recommend the compensation arrangements for management;

 

Ø  

establish and review general compensation policies with the objective to attract and retain superior talent, to reward individual performance and to achieve our financial goals;

 

Ø  

administer our stock incentive and purchase plans; and

 

Ø  

oversee the evaluation of the board of directors and management.

Nominating and Governance Committee. Prior to the completion of the offering, we will form a nominating and governance committee, which we anticipate will be comprised of Dr. Afeyan (chairman), Dr. Papadopoulos and Mr. Bancel. Upon completion of the offering, all members of the nominating and governance committee will qualify as independent directors under the current definition promulgated by NASDAQ. Our nominating and governance committee will be authorized to:

 

Ø  

identify and nominate candidates for election to the board of directors; and

 

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develop and recommend to the board of directors a set of corporate governance principles applicable to our company.

 

 

 

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Compensation committee interlocks and insider participation

No member of our compensation committee has at any time been an employee of ours. None of our executive officers serves as a member of our board of directors or compensation committee of any other entity that has one or more executive officers serving as a member of our board of directors or compensation committee.

Code of business conduct and ethics

Prior to the completion of the offering, we will adopt a code of business conduct and ethics that applies to all of our employees, officers and directors, including those officers responsible for financial reporting. The code of business conduct and ethics will be available on our website at www.bg-medicine.com. We expect that any amendments to the code, or any waivers of its requirements, will be disclosed on our website.

Limitation of directors’ and officers’ liability and indemnification

The Delaware General Corporation Law authorizes corporations to limit or eliminate, subject to specified conditions, the personal liability of directors to corporations and their stockholders for monetary damages for breach of their fiduciary duties. Our existing certificate of incorporation and the restated certificate of incorporation to be effective upon the completion of this offering limits the liability of our directors to the fullest extent permitted by Delaware law.

We have obtained director and officer liability insurance to cover liabilities our directors and officers may incur in connection with their services to us. Our restated certificate of incorporation and restated bylaws to be effective upon the completion of this offering also provide that we will indemnify and advance expenses to any of our directors and officers who, by reason of the fact that he or she is one of our officers or directors, is involved in a legal proceeding of any nature. We will repay certain expenses incurred by a director or officer in connection with any civil, criminal, administrative or investigative action or proceeding, including actions by us or in our name. Such indemnifiable expenses include, to the maximum extent permitted by law, attorney’s fees, judgments, fines, settlement amounts and other expenses reasonably incurred in connection with legal proceedings. A director or officer will not receive indemnification if he or she is found not to have acted in good faith and in a manner he or she reasonably believed to be in, or not opposed to, our best interest.

We have entered into agreements to indemnify our directors and officers. These agreements provide that we will, among other things, indemnify and advance expenses to our directors and officers for certain expenses, including attorneys’ fees, judgments, fines and settlement amounts incurred by any such person in any action or proceeding, including any action by us arising out of such person’s services as our director or officer, or any other company or enterprise to which the person provides services at our request. We believe that these provisions and agreements are necessary to attract and retain qualified persons as directors and officers.

Such limitation of liability and indemnification does not affect the availability of equitable remedies. In addition, we have been advised that in the opinion of the Securities and Exchange Commission, indemnification for liabilities arising under the Securities Act is against public policy as expressed in the Securities Act and is therefore unenforceable.

There is no pending litigation or proceeding involving any of our directors, officers, employees or agents in which indemnification will be required or permitted. We are not aware of any threatened litigation or proceeding that may result in a claim for such indemnification.

 

 

 

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Compensation

COMPENSATION DISCUSSION AND ANALYSIS

The primary objectives of the compensation committee of our board of directors with respect to executive compensation are to attract and retain the best possible executive talent, to motivate our executive officers to enhance our growth and profitability and increase stockholder value and to reward superior performance and contributions to the achievement of corporate objectives. The focus is to tie short- and long-term cash and equity incentives to the achievement of measurable corporate and individual performance goals and to align executives’ incentives with stockholder value creation. To achieve these objectives, the compensation committee has developed and maintains a compensation plan that ties a substantial portion of our executives’ overall compensation to our research, clinical, regulatory and financial and operational performance. Because we believe that the performance of every employee is important to our success, we are mindful of the effect our executive compensation and incentive program has on all of our employees.

Determining and setting executive compensation

The compensation committee of our board of directors, pursuant to its charter, has the responsibility of formulating, evaluating and approving the compensation of our directors and named executive officers, and assisting the full board of directors in establishing and administering appropriate incentive compensation and equity-based plans. The compensation committee, with the input of management, develops our compensation plans by utilizing publicly available compensation data and subscription compensation survey data for national and regional companies in the biotechnology industry. Specifically, we use composite survey data obtained from the Radford Global Life Sciences Executive Pre-IPO Report, or the Radford Report, prepared by AON Consulting, Inc., and occasionally other reports to benchmark base salaries. We believe that these composite data provide us with appropriate compensation benchmarks because the companies included in the composite data are in our industry and have similar organizational structures and stages of development, and accordingly, tend to compete with us for executives and other employees. For benchmarking executive compensation, we typically review the composite compensation data in the Radford Report, as well as various subsets of these data, in particular, the data for companies with an outside (non-employee) investment level of over $80.0 million.

In addition, our compensation committee periodically engages third-party compensation consultants to analyze our existing compensation policies and recommend changes to those policies based on current market data and compensation trends in our industry. The compensation committee did not engage a compensation consultant in 2010. Using the Radford Report and any information provided by compensation consultants, the compensation committee evaluates the competitive nature of our various forms of compensation, including salary and benefits as well as equity-based compensation, relative to other biotechnology and pharmaceutical companies.

The compensation committee has approved a pay-for-performance compensation philosophy, which is intended to bring base salaries and total executive compensation in line with approximately the 50th percentile of the companies in our industry of similar size to us represented in the compensation data we review.

 

In deciding to perform the benchmarking at this stage in our development, our compensation committee acknowledged that benchmarking is not an ideal measure in isolation for setting executive compensation. However, it believes that benchmarking can be an important tool in the decision-making process, in light of the executive compensation program’s primary objective to attract, retain and motivate executive talent in a competitive marketplace.

 

 

 

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We have worked within the framework of this pay-for-performance philosophy to determine each component of an executive’s initial compensation package based on numerous factors, including:

 

Ø  

the individual’s particular background and circumstances, including training and prior relevant work experience;

 

Ø  

the individual’s role with us and the compensation paid to similar persons in the companies represented in the compensation data that we review;

 

Ø  

the demand for people with the individual’s specific expertise and experience at the time of hire;

 

Ø  

performance goals and other expectations for the position;

 

Ø  

comparison to other executives within our company having similar levels of expertise and experience; and

 

Ø  

uniqueness of industry skills.

The terms of the compensation for our President and Chief Executive Officer, Dr. Pieter Muntendam, and our other named executive officers are derived from our employment arrangements with them and from annual performance reviews conducted by the compensation committee in the case of our President and Chief Executive Officer, and by our President and Chief Executive Officer and the compensation committee in the case of our other named executive officers. The employment arrangements provide, among other things, the named executive officer’s initial annual base salary, annual bonus target and initial stock option grant. Following the execution of these employment arrangements, the compensation paid to each executive is subject to adjustment based on our annual performance evaluation process. Annual base salary increases and annual bonus awards, if any, for our President and Chief Executive Officer are determined by the compensation committee. Our President and Chief Executive Officer recommends annual base salary increases and the amount of annual bonus awards, if any, for the other named executive officers, which are reviewed and approved by the compensation committee.

Our annual performance evaluation process is described below. The details of our employment arrangements with our named executive officers are described in the section titled “Compensation — Employment arrangements with our named executive officers.”

Compensation components

The compensation program for our named executive officers consists principally of base salary, annual cash incentive compensation, long-term compensation in the form of stock options and severance and change of control benefits.

Base salary

Base salaries for our named executive officers are established based on the scope of their responsibilities and their prior relevant background, training and experience, taking into account competitive market compensation paid by the companies represented in the compensation data we review for similar positions and the overall market demand for similar executives at the time of hire. We believe that executive base salaries should generally target the 50th percentile of the range of salaries for executives in similar positions and with similar responsibilities in the biotechnology companies of similar size to us represented in the compensation data we review. A named executive officer’s base salary is also evaluated together with other components of the executive’s compensation to ensure that the executive’s total compensation is in line with our overall compensation philosophy.

Base salaries are reviewed annually as part of our performance management evaluation process and may be increased for merit reasons, based on the named executive officer’s success in meeting or exceeding

 

 

 

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individual performance goals and an assessment of whether corporate goals were achieved. We also assess whether there are any significant differences in how a person is compensated compared to industry benchmarks by utilizing data from the Radford Report to benchmark the biotechnology industry. If through this assessment we determine that an employee’s compensation is below a certain benchmark level, we may recommend a market adjustment. Additionally, we review base salaries and make adjustments as warranted for changes in the scope of a named executive officer’s role or responsibilities and any internal inequities we identify.

Annual bonus

The compensation committee designs the annual incentive component of our compensation program. We provide this opportunity as a way to attract and retain highly skilled and experienced executives and to motivate them to achieve annual corporate and individual goals. Our practice has been to provide all employees with the opportunity to earn an annual bonus up to a certain percentage of their annual base salaries, which may be composed of cash, stock options or a combination of cash and stock options. A significant element of the cash compensation of our named executive officers is an annual performance-based bonus. An executive’s target bonus is generally set as a percentage of base salary to reward strong performance and retain employees in a competitive labor market. As described in more detail below under “— Establishment of company and individual goals and annual performance evaluations,” bonuses are based on the achievement of corporate goals, including research, development, financial and operational milestones, as well as the achievement of individual goals.

Our named executive officers have bonus targets ranging from 30% to 35% of their base salaries, with the exception of our President and Chief Executive Officer who has a target bonus percentage of 50% of his base salary. The compensation committee has set the target bonus percentage for our President and Chief Executive Officer at a higher level than those of our other named executive officers in order to bring the overall compensation paid to our President and Chief Executive Officer in line with the 50th percentile of the companies in our industry of similar size to us represented in the Radford Report. In determining bonus awards for each of our named executive officers, the compensation committee weighs the achievement of corporate goals and the achievement of individual goals. The amount of a named executive officer’s bonus compensation typically increases in relation to such named executive officer’s responsibilities and ability to meet individual goals and our achievement of the corporate goals. The compensation committee believes that making a significant portion of a named executive officer’s bonus contingent on corporate performance more closely aligns the named executive officer’s interests with those of our stockholders.

The target bonus percentages are based on competitive practices for each comparable position in the survey data reviewed. This practice is designed to enable us to attract senior level employees and add an additional compensation opportunity in the form of variable pay. Annual bonuses granted to our named executive officers, including our President and Chief Executive Officer, are primarily tied to the achievement of the corporate goals and, to a lesser extent, by individual goals. For each executive, we refer to the composite of heavily-weighted corporate goals and lesser-weighted individual goals generally as his or her performance goals. After determining the percentage achievement by the company of its corporate goals, the compensation committee considers each executive’s progress toward the company’s achievement of its goals. Decisions regarding our Chief Executive Officer’s annual bonus awards are based predominantly on the company’s level of achievement of its goals. Decisions regarding annual bonus awards for each of our other executive officers are based on his or her contributions toward the achievement of the corporate goals for the given year as well as the level of achievement of individual goals developed at the beginning of the year in support of these corporate goals, as adjusted to reflect changes in key assumptions or external factors impacting the business. No specific numerical weightings or ratings are applied to achievement of the individual goals; rather the performance of the officer is evaluated as a whole.

 

 

 

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Long-term incentives

We believe that long-term performance will be enhanced through stock and equity awards that reward our executives for maximizing stockholder value over time and that align the interests of our executives and management with those of our stockholders. The compensation committee believes that the use of stock and equity awards offers the best approach to achieving our compensation goals because equity ownership ties a significant portion of an executive’s compensation to the performance of our company’s stock. We have historically elected to use stock options as the primary long-term equity incentive vehicle.

Stock Options. Stock options are awarded based on various factors, including the responsibilities of the individual named executive officer, his or her past performance, anticipated future contributions, prior option grants (including the vesting schedule of such prior grants) and the executive’s total cash compensation. We have used and expect to continue to use stock options as a long-term incentive vehicle because we believe that:

 

Ø  

stock options and the vesting period of stock options attract and retain executives;

 

Ø  

stock options are inherently performance-based because stock options enhance the executives’ incentive to increase our stock price and maximize stockholder value; and

 

Ø  

stock options help to provide a balance to the overall executive compensation program as base salary and our annual performance bonus program focus on short-term compensation, while stock options reward executives for increases in stockholder value over the longer term, as we generally grant stock options vesting over a four-year period.

For a description of the terms and conditions of our stock option plan, see “Compensation — Equity incentive plans.”

Generally, the compensation committee awards stock options to our named executive officers and other employees on an annual basis. Stock options typically vest over four years and have an exercise price equal to the fair market value of our common stock on the date of grant, as determined by our board of directors.

Initial Stock Option Awards. We typically make an initial award of stock options to new executive officers in connection with the commencement of their employment. These grants generally have an exercise price equal to the fair market value of our common stock on the grant date and a vesting schedule of 25% on the first anniversary of the date of hire and the remainder at 6.25% per quarter thereafter. The initial stock option awards are intended to provide the executive with incentive to build value in the organization over an extended period of time and to maintain competitive levels of total compensation. The size of the initial stock option award is determined based on numerous factors, including the executive’s skills and experience, the executive’s responsibilities with us, internal equity and an analysis of the practices of national and regional companies in the biotechnology industry similar in size to us, as set forth above.

Stock Option Grants as Component of Annual Bonus. We have also used stock option awards as a component of our annual bonus program. The compensation committee believes that stock options provide management with a strong link to long-term corporate performance and the creation of stockholder value. Our bonus awards earned in 2008 and 2009 were comprised of a combination of cash and stock options and the bonus awards for the 2010 performance of our named executive officers have yet to be determined.

Other compensation

We maintain benefits that are provided to all employees, including medical, dental and life insurance coverage and a 401(k) plan. In addition, we may assist with certain expenses associated with an executive joining our company. We believe that these forms of compensation create additional incentives for an executive to join our company in a position where there is high market demand.

 

 

 

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Termination-based change of control compensation

Upon termination of employment under certain circumstances, our named executive officers are entitled to receive varying types of compensation. Elements of this compensation may include payments based upon a number of months of base salary, acceleration of vesting of equity, and continued health insurance coverage and other similar benefits. We believe that our termination-based compensation and acceleration of vesting of equity awards, including the severance package for our President and Chief Executive Officer, are comparable to those offered to executives of other similar companies based upon the market information we have reviewed. We also have granted severance and acceleration of vesting of equity benefits to our executives in the event of a change of control if the executive is terminated within a certain period of time of the change of control. Although, a limited amount of stock options held by our named executive officers accelerates solely upon a change of control, we believe this “double trigger” requirement maximizes stockholder value because it prevents an unintended windfall to management in the event of a friendly or non-hostile change of control. Under this structure, unvested equity awards would continue to incentivize our executives to remain with us after a change of control, and therefore, the “double trigger” approach is more appropriate than a “single trigger” acceleration mechanism contingent only upon a change of control. The specifics of each named executive officer’s arrangements are described in further detail below under “Compensation — Potential payments upon termination or change of control.”

Relationship of elements of compensation

Our compensation structure is primarily comprised of base salary, annual performance bonus and stock options. In setting executive compensation, the compensation committee considers the aggregate compensation payable to a named executive officer and the form of the compensation. The compensation committee seeks to achieve an appropriate balance between immediate cash rewards and long-term financial incentives for the achievement of both annual and long-term financial and non-financial objectives.

The compensation committee manages the expected impact of salary increases and performance bonuses by requiring that the size of any salary increases and bonuses be tied to the attainment of corporate and individual goals. For example, the size of each employee’s bonus is determined not only by individual performance, but also by whether we have met our corporate goals.

The compensation committee views the award of stock options as a primary long-term retention benefit. The compensation committee has made the award of stock options a significant component of total compensation and also ties the earning of these awards to long-term vesting schedules, generally four years. If an employee leaves our employ before the completion of the vesting period, then that employee would not receive any benefit from the non-vested portion of his award. We believe that this feature makes it more attractive to remain with us and these arrangements do not require substantial cash payments by us.

The compensation committee reviews from time to time the mix of the compensation elements for named executive officers against comparable companies in our industry. The size and mix of each element in a compensation package is based on the impact of the position on the company, market practice and overall corporate and individual performance relative to stated corporate goals. The level of incentive compensation typically increases in relation to a named executive officer’s responsibilities and ability to meet individual and corporate goals. The compensation committee believes that making a significant portion of a named executive officer’s compensation contingent on corporate performance more closely aligns the named executive officer’s interests with those of our stockholders.

The compensation committee may decide, as appropriate, to modify the mix of base salary, annual and long-term incentives to best fit a named executive officer’s specific circumstances or if required by

 

 

 

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competitive market conditions for attracting and retaining skilled personnel. For example, the compensation committee may make the decision to award more cash and not award stock options. The compensation committee may also decide to award additional stock options to a named executive officer if the total number of stock option grants received during an individual’s employment with us does not adequately reflect the executive’s current position. We believe that this discretion and flexibility allows the compensation committee to better achieve our compensation objectives.

Establishment of company and individual goals and annual performance evaluations

Corporate goals

Our compensation committee establishes our corporate goals at the beginning of each year and these goals are used to assess corporate performance for the year. The key strategic, corporate, financial and operational goals that may be identified by our compensation committee include:

 

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clinical diagnostic development;

 

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targeted biomarker development;

 

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commercialization of our diagnostic product candidates; and

 

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implementation of appropriate financing or business development strategies.

Our corporate goals for 2010 were as follows:

 

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obtain 510(k) clearance of our galectin-3 test for heart failure from the FDA;

 

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execute a partner agreement with a national laboratory service provider;

 

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initiate development of the galectin-3 assay for two or more automated platforms;

 

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execute an additional galectin-3 development and commercialization agreement;

 

Ø  

initiate U.S. sales and marketing operations in accordance with commercial plans;

 

Ø  

complete validation studies for AMIPredict;

 

Ø  

ascertain clinical utility of LipidDx against the target product profile and pursue FDA pre-IDE; and

 

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ensure the company has sufficient capital to fund operations for the next twelve months.

Individual goals

At the beginning of each year, individual goals for our named executive officers are established by our President and Chief Executive Officer and individual goals for our President and Chief Executive Officer are established by the compensation committee. These goals represent significant milestones that must be met by each executive. Factors are identified and specified that will be used to measure success in reaching each goal. Objectives are established based on the executive’s principal areas of responsibility. For example, our scientific executives will have measurable objectives established for areas such as key research or scientific milestones.

The performance of our named executive officers in 2010 will be evaluated against the 2010 individual goals listed below:

Pieter Muntendam, M.D., President and Chief Executive Officer — add key members to the executive team; lead the executive team in all aspects of devising, planning and executing corporate, financial and strategic business plans and objectives, research and development initiatives and commercialization activities; interface with the board of directors and existing and potential stockholders; and further our corporate growth.

 

 

 

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Michael W. Rogers, Executive Vice President, Chief Financial Officer and Treasurer — prepare the company for the initial public offering process; be strategically involved in all financial transactions of the company; lead the five-year strategic planning process; and plan for year-end audit activities.

Anastasia Rader, Senior Vice President, Executive Operations and Human Resources — lead business teams in support of initial public offering and commercialization activities, lead company strategic recruitment plan, direct the administration of certain programs, including benefits, compensation and compliance.

Neal F. Gordon, Ph.D., Senior Vice President, Biomarker Discovery — enhance our internal in vitro diagnostics product development group; continue to leverage our systems biology-based discovery platform; and expand our technology platform capabilities by developing new targeted measurement strategies for both proteins and lipid metabolites.

Aram Adourian, Ph.D., Vice President, Scientific Affairs — lead scientific assessment, experimental design and data evaluation aspects of our molecular diagnostics programs; continue to be strategically involved in our systems biology-based study planning and execution; contribute to scientific interface with external partners and regulatory entities; and coordinate intellectual property strategy.

Evaluations

After the completion of each fiscal year, we evaluate individual and corporate performance against stated goals for the year. Consistent with our overall compensation philosophy, each executive undergoes an annual performance evaluation. This evaluation leads to a recommendation for annual salary increases, bonuses and equity awards, if any, which are then reviewed and approved by our compensation committee. The performance of our named executive officers is generally assessed by our President and Chief Executive Officer. In the case of our President and Chief Executive Officer, his performance is assessed primarily by the compensation committee. Our compensation committee evaluates the named executive officers’ and our overall corporate performance relative to the approved goals and determines the percentage of corporate goals achieved. For 2009, the compensation committee determined to reward the achievement of such goals through the payment of cash bonuses and stock option awards, as described in more detail below, and for 2010, the compensation committee has yet to make such determinations. Annual bonuses, as well as base salary increases and annual stock option awards, are granted within the discretion of the compensation committee and, to the extent granted, are implemented during the first calendar quarter of the year.

2010 Compensation of named executive officers

Base salaries paid in 2010

In January 2010, the compensation committee used composite compensation data from the Radford Report to evaluate the compensation of our President and Chief Executive Officer. The data from this report indicated that, for an incumbent Chief Executive Officer, a base salary of $290,000 was approximately at the 25th percentile and, therefore, the compensation committee decided to maintain his salary at $290,000 for 2010. Also, in January 2010, the annual base salaries for our other named executive officers were set by the compensation committee at $275,000 for Mr. Rogers, $225,000 for Dr. Gordon, $210,000 for Dr. Adourian and $210,000 for Ms. Rader based on the following data from the Radford Report. For the Chief Financial Officer position, a base salary of $234,336 was at the 25th percentile, a base salary of $265,000 was at the 50th percentile and a base salary of $288,462 was at the 75th percentile. For positions comparable to the Senior Vice President, Biomarker Discovery, the data from the Radford Report indicated that a base salary of $225,000 was at the 25th percentile, a base salary of $240,061 was at the 50th percentile and a base salary of $250,000 was at the 75th percentile.

 

 

 

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For positions comparable to the Vice President, Scientific Affairs, the data from the Radford Report indicated that a base salary of $190,000 was at the 25th percentile, a base salary of $213,107 was at the 50th percentile and a base salary of $282,771 was at the 75th percentile. For positions comparable to the Senior Vice President, Executive Operations & Human Resources, the data from the Radford Report indicated that a base salary of $210,000 was at the 25th percentile, a base salary of $236,355 was at the 50th percentile and a base salary of $259,400 was at the 75th percentile.

Annual bonus awards earned in 2009 and 2010

The annual bonus awards, if any, to be earned by our named executive officers for their performance during 2010 have not yet been determined by the compensation committee. The amounts of annual bonus awards earned by each of our named executive officers for performance during 2009 were determined in January 2010 by the compensation committee. The compensation committee examined our operating and financial results and evaluated the performance of each named executive officer against the corporate goals and each named executive officer’s individual goals. Based on the subjective assessment of the company’s 2009 qualitative goals described above, the compensation committee determined that we achieved 70% of our corporate goals. We did not have any quantitative goals for 2009. The bonuses earned by our named executive officers in 2009 were paid in a combination of cash and fully-vested stock options as set forth in the table below.

 

Name    Cash bonus     

Stock option

award (shares)(1)

 

Pieter Muntendam, M.D.

   $50,750        10,149   

President and Chief Executive Officer

       

Michael W. Rogers

   $12,000        2,399   

Executive Vice President, Chief Financial
Officer and Treasurer

       

Anastasia Rader

   $22,500        4,499   

Senior Vice President, Executive
Operations & Human Resources

       

Neal F. Gordon, Ph.D.

   $19,688        3,937   

Senior Vice President, Biomarker Discovery

       

Aram Adourian, Ph.D.

   $24,375        4,874   

Vice President, Scientific Affairs

       

 

(1)   The options to purchase shares of our common stock were fully vested, with exercise prices of $10.67 per share, the fair market value of our common stock on the date of grant, January 23, 2010.

In setting the bonus award for performance in 2009 for our President and Chief Executive Officer, the compensation committee determined that Dr. Muntendam achieved 70% of his performance goals. His target bonus level for 2009 was 50% of his base salary in effect in 2009. Dr. Muntendam was paid $50,750 in cash and received a fully-vested option to purchase 10,149 shares of our common stock.

Our Chief Financial Officer’s employment agreement provided for a cash bonus in the minimum amount of $24,000 for 2009. Mr. Rogers elected to receive 50% of his bonus award in cash and 50% as a fully-vested stock option, and therefore, his bonus for 2009 consisted of $12,000 and an option to purchase 2,399 of our common stock.

 

 

 

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Table of Contents

Compensation

 

 

In setting the bonus award for performance in 2009 for our Senior Vice President, Executive Operations & Human Resources, the compensation committee determined that Ms. Rader achieved 100% of her performance goals. Her target bonus level for 2009 was 25% of her base salary in effect in 2009. Ms. Rader was paid $22,500 in cash and received a fully-vested option to purchase 4,499 shares of our common stock.

In setting the bonus award for performance in 2009 for our Senior Vice President, Biomarker Discovery, the compensation committee determined that Dr. Gordon achieved 70% of his performance goals. His target bonus level for 2009 was 25% of his base salary in effect in 2009. Dr. Gordon was paid $19,688 in cash and received a fully-vested option to purchase 3,937 shares of our common stock.

In setting the bonus award for performance in 2009 for our Vice President, Scientific Affairs, the compensation committee determined that Dr. Adourian achieved 100% of his performance goals. His target bonus level for 2009 was 25% of his base salary in effect in 2009. Dr. Adourian was paid $24,375 in cash and received a fully-vested option to purchase 4,874 shares of our common stock.

SUMMARY COMPENSATION TABLE

The following table sets forth the compensation paid or accrued during the fiscal years ended December 31, 2010 and 2009 to (1) our chief executive officer, (2) our chief financial officer, and (3) our three other highest paid executive officers during 2010. We refer to these officers as our named executive officers.

 

Name and principal position    Year      Salary      Bonus(1)     Option
awards(2)
     Total  

Pieter Muntendam, M.D.

     2010 &