-----BEGIN PRIVACY-ENHANCED MESSAGE----- Proc-Type: 2001,MIC-CLEAR Originator-Name: webmaster@www.sec.gov Originator-Key-Asymmetric: MFgwCgYEVQgBAQICAf8DSgAwRwJAW2sNKK9AVtBzYZmr6aGjlWyK3XmZv3dTINen TWSM7vrzLADbmYQaionwg5sDW3P6oaM5D3tdezXMm7z1T+B+twIDAQAB MIC-Info: RSA-MD5,RSA, Wv174fql0hPPxY/13oXko98wGAcj317GeCxg1fwjn0S5Ok30XN9n1aqA+8kx7oj+ GXTu9YmWAFLtwx9YqEy2Kg== 0000872947-08-000021.txt : 20080522 0000872947-08-000021.hdr.sgml : 20080522 20080522140123 ACCESSION NUMBER: 0000872947-08-000021 CONFORMED SUBMISSION TYPE: 424B3 PUBLIC DOCUMENT COUNT: 1 FILED AS OF DATE: 20080522 DATE AS OF CHANGE: 20080522 FILER: COMPANY DATA: COMPANY CONFORMED NAME: APPLIED NEUROSOLUTIONS INC CENTRAL INDEX KEY: 0000872947 STANDARD INDUSTRIAL CLASSIFICATION: BIOLOGICAL PRODUCTS (NO DIAGNOSTIC SUBSTANCES) [2836] IRS NUMBER: 391661164 STATE OF INCORPORATION: DE FISCAL YEAR END: 1231 FILING VALUES: FORM TYPE: 424B3 SEC ACT: 1933 Act SEC FILE NUMBER: 333-113821 FILM NUMBER: 08854208 BUSINESS ADDRESS: STREET 1: 50 LAKEVIEW PARKWAY S STREET 2: STE 111 CITY: VERNON HILLS STATE: IL ZIP: 60061 BUSINESS PHONE: 847 573 8000 MAIL ADDRESS: STREET 1: 50 LAKEVIEW PARKWAY STREET 2: STE 111 CITY: VERNON HILLS STATE: IL ZIP: 60061 FORMER COMPANY: FORMER CONFORMED NAME: HEMOXYMED INC DATE OF NAME CHANGE: 20020820 FORMER COMPANY: FORMER CONFORMED NAME: OPHIDIAN PHARMACEUTICALS INC DATE OF NAME CHANGE: 19970714 424B3 1 prosp424b3amend6may2008.htm 424B3 AMEND. #6 MAY 2008 prosp424b3amend6may2008.htm



Pursuant to Rule 424(b)(3)
File Number: 333-113821

                                                                                 

APPLIED NEUROSOLUTIONS, INC.
                                                                                 


42,940,714 shares of common stock
48,084,795 shares issuable upon exercise of warrants


This prospectus relates to the disposition by the selling security holders listed on page 18 or their transferees, of up to 42,940,714 shares of our common stock already issued and outstanding and 48,084,795 shares of our common stock issuable upon the exercise of warrants held by the selling security holders.  We will receive no proceeds from the disposition of already outstanding shares of our common stock by the selling security holders.  We will receive proceeds of $0.30 per share from the exercise of any of the remaining, unexercised 34,690,824 warrants.

For a description of the plan of distribution of the shares, please see page 22 of this prospectus.

Our common stock is included for quotation on the over-the-counter bulletin board under the symbol "APNS."  The closing price for the common stock on May 5, 2008 was $0.085 per share.

The securities offered hereby involve a high degree of risk.  Please read the "Risk factors" beginning on page 3.

                                                                          

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of the prospectus.  Any representation to the contrary is a criminal offense.

Our principal executive offices are located at 50 Lakeview Parkway, Suite 111, Vernon Hills, Illinois 60061.  Our telephone number is (847) 573-8000.





















The date of the prospectus is May 22, 2008.



 
 

 


TABLE OF CONTENTS

Prospectus Summary
1
Special Note Regarding Forward Looking Statement
3
Risk Factors
3
Use of Proceeds
14
Selling Security Holders
14
Plan of Distribution
22
Description of Securities
24
Interest of Named Experts and Counsel
28
Description of Business
 28
Description of Property
 38
Legal Proceedings
 38
Market for Common Equity and Related Stockholder Matters
 38
Financial Statements
 41
Management’s Discussion and Analysis of Financial Condition and Results of Operations
 67
Changes In and Disagreements with Accountants on Accounting and Financial Disclosure
 75
Directors, Executive Officers, Promoters and Control Persons
75
Executive Compensation
 77
Security Ownership of Certain Beneficial Owners and Management
80
Certain Relationships and Related Transactions
81
Disclosure of Commission Position of Indemnification for Securities Act Liabilities
81


You should rely only on the information contained in this prospectus.  We have not, and the selling security holders have not, authorized anyone to provide you with different information.  If anyone provides you with different information, you should not rely on it.  We are not, and the selling security holders 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 contained 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. In this prospectus, "Applied NeuroSolutions", “APNS”, “the Company”, "we", "us" and "our" refer to Applied NeuroSolutions, Inc., a Delaware company, unless the context otherwise requires.

 
 

 


 
PROSPECTUS SUMMARY
 
The following summary is qualified in its entirety by the more detailed information and financial statements including the notes thereto, appearing elsewhere in this prospectus.  Because it is a summary, it does not contain all of the information you should consider before making an investment decision.

 
Company Summary
 
We are Applied NeuroSolutions, Inc. (“APNS”), a development stage biopharmaceutical company primarily engaged in the research and development of novel therapeutic targets for the treatment of Alzheimer's disease (“AD”) and diagnostics to detect AD.
 
Alzheimer’s disease is the most common cause of dementia among people age 65 and older.  Dementia is the loss of memory, reason, judgment and language to such an extent that it interferes with a person’s daily life and activities.  Currently it is estimated that over five million people in the U.S. have Alzheimer’s disease and the national cost of caring for people with Alzheimer’s is estimated to exceed $148 billion annually.  The market for AD therapy is estimated to grow to 21 million patients by 2010 in the seven major pharmaceutical markets (USA, France, Germany, Italy, Spain, U.K. and Japan), according to BioPortfolio, Ltd.

Our core technology in the AD field is based on exclusive licenses with Albert Einstein College of Medicine (“AECOM”) covering all diagnostic and therapeutic applications in the field of neurodegenerative disease discovered in Dr. Peter Davies’ laboratories at AECOM.  Dr. Davies’ research has focused on AD and the roll of certain proteins; primarily hyperphosphorylated tau, which are involved in the formation of neurofibrillary tangles within neurons (nerve cells).  Excessive phosphorylation of tau (the addition of one or more phosphate groups, which are comprised of phosphorous and oxygen, to a molecule) prevents it from stabilizing microtubules, thereby causing the breakdown of the transit system of the nerve cell.  This internal neuronal damage leads to the development of the paired helical filaments and neurofibrillary tangles which are contributing factors to the eventual death of the neurons related to Alzheimer’s disease.  Tau in this abnormally phosphorylated form is the building block for the paired helical filaments and the neurofibrillary tangles (“NFTs”); one of the hallmark pathologies associated with AD.  There is a high correlation among the presence of hyperphosphorylated tau, NFTs and AD.  Thus, it is believed that the hyperphosphorylated tau represents an early abnormality in the progression of Alzheimer’s disease.

In November 2006, we entered into an agreement with Eli Lilly and Company to develop therapeutics to treat AD.  Pursuant to the terms of the agreement, we received $2 million in cash, including an equity investment of $500,000, from Lilly, plus we will receive annual research and development support for the duration of the collaboration agreement.  In addition, Lilly will, based on the achievement of certain defined milestones, providing us over time with up to $20 million in milestone payments for advancing our proprietary target to a therapeutic compound.  The collaboration has also made progress on other targets that are part of the collaboration that could provide milestone payments to us over time of up to $10 million for advancing each of these other targets to a therapeutic compound.  There is no limit to the number of targets that we could receive milestone payments from Lilly.  Royalties are to be paid to us for AD drug compounds brought to market that result from the collaboration.  There is no limit on the number of drug compounds for which royalty payments may be due to us.  Lilly received the exclusive worldwide rights to the intellectual property related to our expertise in understanding the molecular neuropathology of AD as it pertains to the formation of neurofibrillary tangles in the development of AD therapeutics.  Lilly will fund the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from our collaboration.

Since the start of our collaboration with Lilly, the collaboration management structure, working teams and external resources have become fully operational.  The key assets and proprietary tools have been appropriately transferred to support work being undertaken by each of Dr. Davies, Lilly and APNS.  The first internal milestone on the proprietary tau-related APNS target was reached in the second quarter of 2007 and the next internal milestone is scheduled to be achieved by the end of the first quarter of 2008.  Key in-vivo models have been established with the goal to validate our tau-based target.  Our collaboration with Lilly has made good progress on the milestones established by the program management for the proprietary tau-related APNS target.  Our first paid milestone is targeted for achievement in late 2008 to early 2009.  Our collaboration with Lilly continues to make good progress toward additional tau-based targets with an additional target being screened and validation studies underway for other targets.

 
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We have also been working on both a cerebrospinal fluid (“CSF”) based test and serum based tests to detect AD at an early stage.  In a research setting, our CSF-based test has demonstrated an ability to differentiate AD patients from those with other diseases that have similar symptoms.  There is currently no FDA approved diagnostic test to detect Alzheimer's disease.

We are utilizing the knowledge gained during the development of our CSF-based diagnostic test to aid in the development of serum-based diagnostic tests to detect Alzheimer’s disease, specifically a screening test to rule out AD as well as the detection of our ptau biomarker to support the diagnosis of AD.  In January 2006, we entered into a research agreement with Nanosphere, Inc., a nanotechnology-based molecular diagnostics company, to assist us in the development of a serum-based diagnostic test for AD.  Work performed during the research agreement resulted in Nanosphere and APNS scientists achieving a better understanding (in January 2007) of the tools necessary to advance the development of a serum-based AD diagnostic test with our scientifically accepted biomarkers.  APNS established a project plan and began developing these key tools in early 2007.  The first of these tools to meet our criteria for potential use in serum diagnostic development were identified as appropriate in the first quarter of 2008.

We sought additional expertise and resources by conducting a scientific advisory board meeting that brought together APNS scientists, Dr. Davies and three outside diagnostic experts to assist us in assessing the most effective approaches and resources to advance our diagnostic development programs.  Through 2007, we followed our work plans to develop antibody tools and we achieved a key milestone in the first quarter of 2008 by identifying several high affinity antibodies that meet our requirements.  These tools will support advancing development of a “rule out” serum based test for AD.  Additional back up tool options to support a “rule out” test are also in development.  In addition, tools directed toward the development of a ptau biomarker based test in serum that could support the early identification of AD are targeted for completion in the second quarter 2008.  Throughout the tool development process we have been identifying specialized technologies that may enable us to advance our diagnostic development programs.  Technology assessments have been initiated.  In order to maximize the value, and minimize the time to market, of our diagnostic programs, we may seek some form of partnering, such as collaborations, strategic alliances and/or licensing arrangements.  Currently there is no FDA-approved diagnostic test to detect AD.

On September 28, 2007, we entered into a Purchase Agreement with SF Capital Partners Ltd. pursuant to which SF Capital agreed to purchase from us (i) 20,714,286 shares of our common stock at $0.14 per share and (ii) 6,214,286 warrants exercisable to purchase shares of common stock at an exercise price of $0.19 per share for an aggregate purchase price of $2.9 million.  We did not incur any banking fees associated with the transaction, which closed on September 28, 2007.  The transaction with SF Capital was an exemption from registration under Section 4(2) of the Securities Act as a transaction by the issuer not involving a public offering.  We granted registration rights to SF Capital with respect to the shares of common stock acquired in the transaction and the common stock underlying the warrants.

We have had net losses for each of the years ended December 31, 2007 and 2006, and we have an accumulated deficit of approximately $48.0 million as of December 31, 2007.  Since the financial statements for each of these periods were prepared assuming that we would continue as a going concern, in the view of our independent registered public accountants, these conditions raise substantial doubt about our ability to continue as a going concern.  We anticipate that our cash balances at December 31, 2007, coupled with our annual R & D support from Eli Lilly and Company, should be sufficient to fund operations through the first quarter of 2009.  We will need additional funding prior to the end of the first quarter of 2009 in order to continue our research, product development and our operations.

At May 8, 2008, we had 130,217,808 shares of common stock outstanding and 44,418,453 warrants outstanding.

We are subject to risks and uncertainties common to small cap biotech companies, including competition from larger, well capitalized entities, patent protection issues, availability of funding and government regulations.  We have experienced significant operating losses since our inception.  As of March 31, 2008, we had an accumulated deficit of approximately $48.6 million.  Notwithstanding payments that we may receive under our collaboration agreement with Eli Lilly and Company, we expect to incur operating losses over the next several years as our research and development efforts continue.

We currently have no approved products on the market and have not received any commercial revenues from the sale or license of any products.


 
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Key Facts of the Offering

Shares of common stock being registered
    42,940,714
Total shares of common stock outstanding as of the date of this prospectus
  130,217,808
Number of shares of common stock issuable upon the exercise of warrants
    34,690,824
 
Total proceeds raised by us from the disposition of the common stock by the selling security holders or their transferees
We will receive no proceeds from the disposition of already outstanding shares of our common stock by the selling security holders or their transferees.
 
We will receive proceeds of up to $10,407,247 from the exercise of the remaining 34,690,824 unexercised warrants covered by this registration statement.

Recent Developments

On April 7, 2008, we announced the attainment of a program milestone in our collaboration with Eli Lilly and Company (Lilly) to develop therapeutics to treat Alzheimer’s disease (AD).  Attainment of this milestone supports the continuation of our collaboration with Lilly.  Pursuant to our collaboration agreement with Lilly to develop therapeutics to treat AD, Lilly has been funding the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from this collaboration.  Our proprietary tau-related target has now achieved two significant unpaid program milestones.  The next milestone, if achieved, represents a paid milestone for APNS.  The next milestone is currently targeted for achievement in late 2008 to early 2009.  The collaboration with Lilly continues to make good progress toward additional tau-based targets with an additional target being screened and validation studies underway for other targets.


SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
 
This Form S-1 contains forward-looking statements.  For this purpose, any statements contained in this Form S-1 that are not statements of historical fact may be deemed to be forward-looking statements.  You can identify forward-looking statements by those that are not historical in nature, particularly those that use terminology such as "may," "will," "should," "expects," "anticipates," "contemplates," "estimates,"  "believes," "plans," "projected," "predicts," "potential," or "continue" or the negative of these similar terms.  In evaluating these forward-looking statements, you should consider various factors, including those listed below under the heading "Risk Factors".  The Company's actual results may differ significantly from the results projected in the forward-looking statements.  The Company assumes no obligation to update forward-looking statements.


RISK FACTORS

Investing in us entails substantial risks.  Factors that could cause or contribute to differences in our actual results include those discussed in the following section.  You should consider carefully the following risk factors, together with all of the other information included in this prospectus.  Each of these risk factors could adversely affect our business, operating results and financial condition, as well as adversely affect the value of our common stock.

Our cash balances, coupled with our annual R & D support from Eli Lilly and Company, should be sufficient to fund our current planned development activities through the first quarter of 2009.  We will need to raise funds prior to the end of the first quarter of 2009 in order to continue operations and we may have to amend our charter to increase our authorized shares of common stock in order to raise adequate capital which would be costly for us to do and may not be successful in which event we may have difficulty raising capital.

 
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As of December 31, 2007, we had cash of $2,960,141.  We anticipate that our cash balances at December 31, 2007, coupled with our annual R & D support from Eli Lilly and Company, should be sufficient to fund operations through the first quarter of 2009.  We will need additional funding prior to January 2008 in order to continue our research, product development and our operations.  The cash on hand will be used for ongoing research and development, working capital, general corporate purposes and possibly to secure appropriate partnerships and expertise.  Since we do not expect to generate significant revenues from operations in 2008 and 2009, we will be required to raise additional capital in financing transactions or through some form of collaborative partnership in order to satisfy our expected cash expenditures after the first quarter of 2009. We expect to raise such additional capital by selling shares of our capital stock, proceeds from exercises of existing warrants and/or stock options and/or by borrowing money.  However, such additional capital may not be available to us at acceptable terms or at all.  As of February 29, 2008, we have 6,121,392 authorized shares of common stock available for issuance.  In order to raise funds through the sale of capital stock, we will most likely need to increase our authorized common stock, which will require the time and expense of obtaining stockholder approval.  Because most of our stockholders hold their shares in street name and a charter amendment is not a discretionary item for which brokers can cast a vote without instruction from their clients, we would have to hire a solicitation firm to assist us in getting sufficient stockholder votes to increase our authorized common stock.  If we are unable to increase the number of authorized shares of common stock, we will have significant difficulty in raising sufficient additional capital to support operations.  Further, if we sell additional shares of our capital stock, current ownership positions in our Company will be subject to dilution. In the event that we are unable to obtain additional capital, we may be forced to reduce our operating expenditures or to cease operations altogether.

The financial statements are prepared assuming that we would continue as a going concern.  We have had recurring net losses and we have an accumulated deficit of approximately $48.0 million as of December 31, 2007.  These conditions raise substantial doubt about our ability to continue as a going concern.  We anticipate that our cash balances at December 31, 2007, coupled with our annual R & D support from Eli Lilly and Company, should be sufficient to fund operations through the first quarter of 2009.  We will need additional funding prior to the end of the first quarter of 2009 in order to continue our research, product development and our operations.  Since we do not expect to generate any material revenues for the foreseeable future, our ability to continue as a going concern depends, in large part, on our ability to raise additional capital prior to the end of the first quarter 2009, either through some form of partnership or debt or equity financing, including exercise of outstanding stock options and/or warrants.   If we are unable to raise additional capital, we may be forced to discontinue our business.

We are a development stage company without any products currently in clinical trials
 
    We are a development stage company.  Our product furthest along is a diagnostic test which detects Alzheimer’s disease utilizing cerebrospinal fluid (CSF).  Our other potential diagnostic and therapeutic products and technologies are early in the research and development phase, and product revenues may not be realized from the sale of any such products for at least the next several years, if at all.  Our proposed products will require significant additional research and development efforts prior to any commercial use, including extensive preclinical and clinical testing as well as lengthy regulatory approval.  There can be no assurances that our research and development efforts will be successful, that our potential products will prove to be safe and effective in clinical trials or that we will develop any commercially successful products.  We currently have no approved products on the market and have not received any commercial revenues from the sale or license of any diagnostic or therapeutic products.

We have a history of operating losses and expect to sustain losses in the future

We have experienced significant operating losses since our inception.  As of December 31, 2007, we had an accumulated deficit of approximately $48.0 million.  We expect to incur operating losses over the next several years as our research and development efforts continue.  Our ability to achieve profitability depends in part upon our ability, alone or with or through others, to raise additional capital to execute our business plan, to advance development of our proposed products, to obtain required regulatory approvals, to manufacture and market our products, and to successfully commercialize our approved products.

We need to raise additional capital by the end of the first quarter of 2009, however, we may not be able to raise such capital, or we may only be able to raise capital on unfavorable terms

Our operations to date have consumed substantial amounts of cash.  Our development of our technologies and potential products will require substantial funds to conduct the costly and time-consuming activities necessary to research, develop and optimize our technologies, and ultimately, to establish manufacturing and marketing capabilities.  Our future capital requirements will depend on many factors, including:

 
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·  
continued scientific progress in the research and development of our technologies;
·  
our ability to establish and maintain collaborative arrangements with others for product development;
·  
progress with validation testing, pre-clinical and clinical trials;
·  
the time and costs involved in obtaining regulatory approvals;
·  
the costs involved in preparing, filing, prosecuting, maintaining and enforcing patent claims;
·  
competing technological and market developments;
·  
changes in our existing research relationships; and
·  
effective product commercialization activities and arrangements.

We anticipate that our cash balances at December 31, 2007, coupled with our annual R & D support from Eli Lilly and Company should be sufficient to fund operations through the first quarter of 2009.  We will need additional funding prior to the end of the first quarter of 2009 in order to continue our research, product development and our operations.  The cash on hand will be used for ongoing research and development, working capital, general corporate purposes and possibly to secure appropriate partnerships and expertise.  If additional funding is not obtained, we will not be able to continue funding the costs of any programs, and we may have to significantly minimize or eliminate our programs, and possibly discontinue all our product development and/or our operations.  We are currently evaluating our options to maximize the value of our diagnostic technology, including seeking partnerships and licensing arrangements.

We face extensive governmental regulation and any failure to comply could prevent or delay product approval or cause the disallowance of our products after approval

The U.S. Food and Drug Administration, and comparable agencies in foreign countries, impose many requirements on the introduction of new therapeutics through lengthy and detailed clinical testing procedures, and other costly and time consuming compliance procedures relating to the manufacture, distribution, advertising, pricing and marketing of pharmaceutical products.  These requirements make it difficult to estimate when any of our products in development will be available commercially, if at all.

The regulatory process takes many years and requires the expenditure of substantial resources.  Clinical trials for diagnostic products, including the FDA submission and approval process, generally take less time than for therapeutic products.  Data obtained from pre-clinical and clinical activities are subject to varying interpretations that could delay, limit or prevent regulatory agency approval. We may also encounter delays or rejections based on changes in regulatory agency policies during the period in which we develop our products and/or the period required for review of any application for regulatory agency approval of a particular product. Delays in obtaining regulatory agency approvals will make the projects more costly and adversely affect our business.

Diagnostic products have a different path to regulatory approval than the path for pharmaceutical products.  In vitro diagnostic products have a different path to regulatory approval, i.e., the Premarket Approval Application (PMA) process regulated by the Office of In Vitro Diagnostic Device and Safety (OIVD) of the FDA.  The regulatory process leading to a submission of an in vitro diagnostic device PMA for FDA approval to market involves a multistage process including: (1) a Pre-Investigational Device Exemption (Pre-IDE) program in which preliminary information is submitted to the FDA for review and guidance on, and acceptance of, the test protocol and proposed clinical trial to evaluate the safety and effectiveness of an in vitro diagnostic product followed by, (2) an Investigational Device Exemption (IDE) submission for approval to allow the investigational diagnostic device to be used in a clinical study in order to (3) collect safety and effectiveness data required to support a PMA to receive FDA approval to market a device.

Even if we successfully enroll patients in clinical trials for our diagnostic or therapeutic products, setbacks are a common occurrence in clinical trials.  These setbacks often include:

·  
Failure to comply with the regulations applicable to such testing may delay, suspend or cancel our clinical trials,
·  
The FDA might not accept the test results,
·  
The FDA, or any comparable regulatory agency in another country, may suspend clinical trials at any time if it concludes that the trials expose subjects participating in such trials to unacceptable health risks
·  
Human clinical testing may not show any current or future product candidate to be safe and effective to the satisfaction of the FDA or comparable regulatory agencies
·  
The data derived from clinical trials may be unsuitable for submission to the FDA or other regulatory agencies.

 
5

 
In 2005 we filed with the FDA a Pre-Investigational Device Exemption (“Pre-IDE”) application with respect to our CSF-based diagnostic test and we had our Pre-IDE meeting with the FDA in November 2005.    Subsequent to our meeting with the FDA, we worked with our clinical consultants to refine our clinical protocol.  At that time, work was suspended until such time that we, along with our consultants, could identify a cost effective protocol that would be acceptable to the FDA and offer the opportunity to obtain desired claims and indications.   It is uncertain when we will file a Pre-IDE for any of our diagnostic programs in development. We have not filed any Investigation New Drug (“IND”) with respect to our AD therapeutic, and the timing of such filing in the future is uncertain, and subject to the progress of our collaboration with Eli Lilly and Company.  We cannot predict with certainty when we might submit any of our proposed products currently under development for regulatory review.  Once we submit a proposed product for review, the FDA or other regulatory agencies may not issue their approvals on a timely basis, if at all.  If we are delayed or fail to obtain such approvals, our business may be adversely affected.   If the FDA grants approval for a drug or device, such approval may limit the indicated uses for which we may market the drug or device and this could limit the potential market for such drug or device. Furthermore, if we obtain approval for any of our products, the marketing and manufacture of such products remain subject to extensive regulatory requirements. Even if the FDA grants approval, such approval would be subject to continual review, and later discovery of unknown problems could restrict the products future use or cause their withdrawal from the market. If we fail to comply with regulatory requirements, either prior to approval or in marketing our products after approval, we could be subject to regulatory or judicial enforcement actions.  Failure to comply with regulatory requirements could, among other things, result in:

·  
product recalls or seizures;
·  
fines and penalties;
·  
injunctions;
·  
criminal prosecution;
·  
refusals to approve new products and withdrawal of existing approvals; and/or
·  
enhanced exposure to product liabilities.
 
In order to market our products outside of the United States, we must comply with numerous and varying regulatory requirements of other countries regarding safety and quality. The approval procedures vary among countries and can involve additional product testing and administrative review periods. The time required to obtain approval in other countries might differ from that required to obtain FDA approval. The regulatory approval process in other countries includes all of the risks associated with obtaining FDA approval detailed above. Approval by the FDA does not ensure approval by the regulatory authorities of other countries.

In addition, many countries require regulatory agency approval of pricing and may also require approval for the marketing in such countries of any drugs or devices we develop. We cannot be certain that we will obtain any regulatory approvals in other countries and the failure to obtain such approvals may materially adversely affect our business.

Under our agreement with Eli Lilly and Company, however, all aspects of our therapeutic collaboration will be largely funded by Lilly.

We may not identify a cost effective protocol for obtaining FDA approval that could yield desired claims for any of our proposed products

Prior to beginning the clinical testing process required to obtain FDA approval for any of our proposed products, we must determine if there is a cost effective protocol that would be acceptable to the FDA and offer the opportunity to obtain desired claims and indications.  If a cost effective clinical testing protocol cannot be structured in a time appropriate duration for a specific proposed product, we will not attempt to obtain FDA approval for that proposed product.  This may reduce or eliminate any potential revenues we would receive from the proposed product.

Our technologies are subject to licenses and termination of any of those licenses would seriously harm our business

We have exclusive licenses with Albert Einstein College of Medicine ("AECOM") covering virtually all of our Alzheimer's disease technology, including all our AD related diagnostic and therapeutic products currently in development.  We depend on these licensing arrangements to maintain rights to our products under development.  These agreements require us to make payments in order to maintain our rights.  The agreements also generally require us to pay royalties on the sale of products developed from the licensed technologies, fees on revenues from sublicensees, where applicable, and the costs of filing and prosecuting patent applications.  We are currently in compliance with our license agreements, however, we will need to raise additional capital prior to the end of the first quarter of 2009 in order to meet our ongoing obligations to AECOM.  If we fail to raise sufficient funds, and consequently default on our obligations to AECOM, our licenses could terminate, and we could lose the rights to our proprietary technologies. Such a loss would have a material adverse effect on our operations and prospects.

 
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Our collaboration agreement with Eli Lilly and Company may not provide the future payments we anticipate over the course of the agreement or may not provide the future payments in a time frame consistent with our expectations, which could result in the termination of our operations

In November 2006, we entered into an agreement with Eli Lilly and Company to develop therapeutics to treat AD.  Lilly received the exclusive worldwide rights to the intellectual property related to our expertise in understanding the molecular neuropathology of AD as it pertains to the formation of neurofibrillary tangles.  Lilly may not advance any of the technology under the agreement as fast, or as far, as we would anticipate, if at all, to provide us with the milestone and royalty payments we expected when we signed the agreement.  In addition, Lilly may decide to allocate internal resources to other projects and slow down, or stop the work, under our collaboration agreement for a period of time, which could cause our technology under the agreement not to be advanced at the rate we expected, or not be advanced at all.  Such a situation could have a material adverse effect on our operations and prospects and we may have to shut down, or scale back, our operations unless we could enter into a new partnership arrangement or raise capital.

The demand for diagnostic products for Alzheimer’s disease may be limited because there is currently no cure or effective therapeutic products to treat the disease

Since there is currently no cure or therapy that can stop the progression of Alzheimer’s disease, the market acceptance and financial success of a diagnostic technology capable of detecting Alzheimer’s disease may be limited.  As a result, even if we successfully develop a safe and effective diagnostic technology for identifying this disease, its commercial value might be limited.

The value of our research could diminish if we cannot protect, enforce and maintain our intellectual property rights adequately

The pharmaceutical and diagnostic industries place considerable importance on obtaining patent and trade secret protection for new technologies, products and processes, and where possible, we actively pursue both domestic and foreign patent protection for our proprietary products and technologies. Our success will depend in part on our ability to obtain and maintain patent protection for our technologies and to preserve our trade secrets. When patent protection is available, it is our policy to file patent applications in the United States and selected foreign jurisdictions.  During our review of our patent portfolio in 2007, we stopped maintaining some older method patents that we determined did not have the potential for any future benefit.  We currently hold and maintain 8 issued United States patents and various related foreign patents.  Two of the issued United States patents are for our Alzheimer's diagnostic technology, three of the issued United States patents are for our Alzheimer's therapeutic technology and one of the issued United States patents relates to transgenic animals. One of the patents, issued in October 2007, relates to a gene that is nested within the tau gene that in turn creates the tau protein.  One of the issued AD patents is assigned to AECOM and is licensed to us, and four of the issued AD patents are assigned to us.  We currently have three patent applications filed, one has Alzheimer's diagnostic applications, one has Alzheimer's therapeutic applications, and one has both Alzheimer's diagnostic and therapeutic applications.    The issued United States Alzheimer's technology patents expire between 2014 and 2023.  No assurance can be given that our issued patents will provide competitive advantages for our technologies or will not be challenged or circumvented by competitors. With respect to already issued patents, there can be no assurance that any patents issued to us will not be challenged, invalidated, circumvented or that the patents will provide us proprietary protection or a commercial advantage. We also rely on trade secrets and proprietary know-how, which we seek to protect, in part, through confidentiality agreements with employees, consultants, collaborative partners and others. There can be no assurance that these agreements will not be breached.

The ability to develop our technologies and to commercialize products will depend on avoiding the infringement of patents of others.  While we are aware of patents issued to competitors, we are not aware of any claim of patent infringement against us, except as described in the following two paragraphs.  Any potential patent infringement may require us to acquire licensing rights to allow us to continue the development and commercialization of our products.  Any such future claims concerning us infringing patents and proprietary technologies could have a material adverse effect on our business. In addition, litigation may also be necessary to enforce any of our patents or to determine the scope and validity of third-party proprietary rights. There can be no assurance that our patents would be held valid by a court of competent jurisdiction.  We may have to file suit to protect our patents or to defend use of our patents against infringement claims brought by others.  Because we have limited cash resources, we may not be able to afford to pursue or defend against litigation in order to protect our patent rights.

 
7

 
In March 2004 we were notified by email from Innogenetics, a Belgian biopharmaceutical company involved in specialty diagnostics and therapeutic vaccines, that it believes the CSF diagnostic test we have been developing uses technology that is encompassed by the claims of its’ U.S. patents.  Innogenetics also informed us that it could be amenable to entering into a licensing arrangement or other business deal with APNS regarding its patents.  We had some discussions with Innogenetics concerning a potential business relationship, however no further discussions have been held since the second quarter of 2006.

We have reviewed these patents with our patent counsel on several occasions prior to receipt of the email from Innogenetics and subsequent to receipt of the email.  Based on these reviews, we believe that our CSF diagnostic test does not infringe the claims of these Innogenetics patents.  If we were unable to reach a mutually agreeable arrangement with Innogenetics, we may be forced to litigate the issue.  Expenses involved with litigation may be significant, regardless of the ultimate outcome of any litigation.  An adverse decision could prevent us from possibly marketing a future diagnostic product and could have a material adverse impact on our business.

We also rely on trade secrets to protect our proprietary technologies, especially where we do not believe patent protection is appropriate or obtainable.  However, trade secrets can be difficult to protect.  We rely in part on confidentiality agreements with our employees, consultants, outside scientific collaborators, sponsored researchers and others to protect our trade secrets and other proprietary information.  These agreements may not effectively prevent disclosure of confidential information and may not provide an adequate remedy if unauthorized disclosure of confidential information occurs.  In addition, others may independently discover our trade secrets and proprietary information.  Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive position.  None of our employees, consultants, scientific researchers or collaborators has any rights to publish scientific data and information generated in the development or commercialization of our products without our approval, with the exception of Eli Lilly and Company’s rights under our collaboration agreement.  Under the license agreements with us, AECOM has a right to publish scientific results relating to the diagnosis of AD and precursor or related conditions in scientific journals, provided, that AECOM must give us pre-submission review of any such manuscript to determine if it contains any of our confidential information or patentable materials.

We face large competitors and our limited financial and research resources may limit our ability to develop and market new products

The biotechnology, diagnostic and pharmaceutical markets generally involve rapidly changing technologies and evolving industry standards.  Many companies, both public and private, are developing products to diagnose and to treat Alzheimer’s disease.  Most of these companies have substantially greater financial, research and development, manufacturing and marketing experience and resources than we do.  As a result, our competitors may more rapidly develop effective diagnostic products as well as therapeutic products that are more effective or less costly than any product that we may develop.  Under our agreement with Eli Lilly and Company, however, all aspects of our therapeutic collaboration will be largely funded by Lilly.

We also face competition from colleges, universities, governmental agencies and other public and private research institutions.  These competitors are becoming more active in seeking patent protection and licensing arrangements to collect royalties for use of technology that they have developed.  Some of these technologies may compete directly with the technologies being developed by us.  Also, these institutions may also compete with us in recruiting highly qualified scientific personnel.

We do not have manufacturing capability and we must rely on third party manufacturers to produce our products, giving us limited control over the quality of our products and the volume of products produced

While we have internally manufactured some of the reagents and materials necessary to conduct our activities related to research and development of our diagnostic products, we do not currently have any large scale manufacturing capability, expertise or personnel and expect to rely on outside manufacturers to produce material that will meet applicable standards for clinical testing of our products and for larger scale production if marketing approval is obtained.

We will either find our own manufacturing facilities, rely upon third-party manufacturers to manufacture our proposed products in accordance with appropriate regulations, or we will most likely utilize the capabilities of our partners and/or collaborators.  Under our agreement with Eli Lilly and Company, Lilly has an exclusive world-wide license to manufacture, market and sell any AD therapeutic that comes to market from our collaboration agreement. We do not have any outside manufacturing agreements for our proposed diagnostic products.  If we, or Lilly, choose to utilize an outside manufacturer, we cannot assure that any outside manufacturer that we, or Lilly, select will perform suitably or will remain in the contract manufacturing business, in which instances we (or Lilly) would need to find a replacement manufacturer or we would have to develop our own manufacturing capabilities.  If we are unable to do so, our ability to obtain regulatory approval for our products could be delayed or impaired.  Our ability, and Lilly’s ability, to market our products could also be affected by the failure of our third party manufacturers or suppliers to comply with the good manufacturing practices required by the FDA and foreign regulatory authorities.

 
8

 
We do not have marketing and sales staff to sell our products and we must rely on third parties to sell and market our products, the cost of which may make our products less profitable for us

We do not have marketing and sales experience or personnel.  As we currently do not intend to develop a marketing and sales force, we will depend on arrangements with partners or other entities for the marketing and sale of our proposed products.  Under our agreement with Eli Lilly and Company, Lilly has an exclusive world-wide license to market and sell any AD therapeutic that comes to market from our collaboration agreement.  We do not currently have any agreements with corporate partners or other entities to provide sales and marketing services for our proposed diagnostic products.  We may not succeed in entering into any satisfactory third-party arrangements for the marketing and sale of our proposed products, or we may not be able to obtain the resources to develop our own marketing and sales capabilities.  We may never have an AD therapeutic come to market under the Lilly agreement, or we may never have a diagnostic product come to market.  The failure to develop those capabilities, either externally or internally, may adversely affect future sales of our proposed products.

We must rely on third party relationships to develop, manufacture and market our products without which we may fail

We do not possess all the resources necessary to complete the development, clinical testing, regulatory process, manufacturing, marketing and commercialization of our diagnostic and therapeutic products and we will need to obtain such resources from third parties.  In order to obtain such resources, we will need to enter into collaborations with corporate partners, licensors, licensees and possibly relationships with third parties from whom we will outsource the necessary expertise and resources.  Our success may depend on securing such relationships.  This business strategy would utilize the expertise and resources of third parties in a number of areas including:

·  
performing various activities associated with pre-clinical studies and clinical trials;
·  
preparing submissions seeking regulatory approvals;
·  
manufacture of kits and solutions; and
·  
sales and marketing of our products.
 
This strategy of reliance on third party relationships creates risks to us by placing critical aspects of our business in the hands of third parties, whom we may not be able to control as effectively as our own personnel.  For example, under our agreement with Eli Lilly and Company, Lilly has an exclusive world-wide license to manufacture, market and sell any AD therapeutics that comes to market from our collaboration agreement.  We cannot be sure that the Lilly agreement or any future collaborative agreements will be successful.   If these third parties, such as Eli Lilly and Company, do not perform in a timely and satisfactory manner, we may incur additional costs and lose time in our development and clinical programs as well as the commercialization our products.  To the extent we choose not to, or are not able to, establish such arrangements, we could experience increased risk and capital requirements.

We do not have the ability to conduct clinical trials independently. We intend to rely on our partners, clinical investigators and third-party clinical research organizations to perform a significant portion of these functions. There can be problems with using third party clinical research organizations such as:

·  
we are not able to locate acceptable contractors to run this portion of our clinical trials;
·  
we can not enter into favorable agreements with them;
·  
third parties may not successfully carry out their contractual duties; and/or
·  
third parties may not meet expected deadlines.
 
If any of these problems occur, we will be unable to obtain required regulatory approvals and will be unable to commercialize our products on a timely basis, if at all.
 
 
9

 
We are dependent on our key employees and consultants, who may not readily be replaced

We are highly dependent upon the principal members of our management team, especially Ellen R. Hoffing, Chairman, President and Chief Executive Officer, and Peter Davies, Ph.D., our founding scientist, as well as our other officers and directors.  Ms. Hoffing’s employment agreement is effective through August 29, 2009.  Our consulting agreements with Dr. Davies are effective through November 2008.  We do not have employment agreements with John DeBernardis, Ph.D., Chief Scientific Officer, and David Ellison, Chief Financial Officer and Corporate Secretary.  We do not currently maintain key-man life insurance and the loss of any of these persons' services, and the resulting difficulty in finding sufficiently qualified replacements, could adversely affect our ability to develop and market our products and obtain necessary regulatory approvals.

Our success also will depend in part on the continued service of other key scientific personnel, and our ability to identify, hire and retain additional staff, if necessary.  We face intense competition for qualified employees and consultants.  Large pharmaceutical companies and other competitors, which have greater resources and experience than we have, can, and do, offer superior compensation packages to attract and retain skilled personnel.  As a result, we may have difficulty retaining such employees and consultants because we may not be able to match the packages offered by such competitors and large pharmaceutical companies, and we may have difficulty attracting suitable replacements.

We expect that our potential expansion into areas and activities requiring additional expertise, such as clinical trials, governmental approvals, contract and manufacturing and sales and marketing, will be done by working with outside contractors who have the appropriate expertise or by utilizing collaborators / partners.  The management of these processes may require an increase in management and scientific personnel and the development of additional expertise by existing management personnel.  The failure to attract and retain such personnel or to develop such expertise could materially adversely affect prospects for our success.

If our current research collaborators, scientific advisors, and specifically our founding scientist, Dr. Peter Davies, terminate their agreements with us, or develop relationships with competitors, our ability to advance existing programs and add new tools and technologies could be adversely impacted.

We derive significant support and benefit from research collaborators and other expertise that we utilize.  These collaborators are not our employees and operate under consulting agreements that are subject to termination provisions.  Our core technology in the AD field is based on exclusive licenses with AECOM covering all of our diagnostic and therapeutic applications in the field of neurodegenerative diseases.  We therefore cannot control the explicit amount of time or output that is derived from our collaborators through our agreements.  Dr. Davies is currently actively deploying the time and resources at his lab at AECOM that is necessary to advance our collaboration agreement with Eli Lilly and Company.  We may not derive any new or additional tools or technologies from our relationship with Dr. Davies at AECOM, that would be appropriate for us to develop, or that fall outside of the rights of the Lilly collaboration.

We use hazardous materials in our research and that may subject us to liabilities in excess of our resources

Our research and development involves the controlled use of hazardous materials such as acids, caustic agents, flammable solvents and carcinogens.  Although we believe that our safety procedures for handling and disposing of hazardous materials comply in all material respects with the standards prescribed by government regulations, the risk of accidental contamination or injury from these materials cannot be completely eliminated.  In the event of an accident, we could be held liable for any damages that result.  Although we have insurance coverage for third-party liabilities of this nature, such liability beyond this insurance coverage could exceed our resources.  Our insurance for hazardous materials liabilities has a deductible of $5,000 and a cap on coverage for damages of $250,000.  There can be no assurance that current or future environmental or transportation laws, rules, regulations or policies will not have a material adverse effect on us.

If we have any products used in clinical trials or products sold commercially, potential product liability claims against us could result in reduced demand for our products or extensive damages in excess of insurance coverage

The use of our products in clinical trials or from commercial sales will expose us to potential liability claims if such use, or even their misuse, results in injury, disease or adverse effects.  We intend to obtain product liability insurance coverage before we initiate clinical trials for any of our products.   This insurance is expensive and insurance companies may not issue this type of insurance when needed.  Any product liability claim resulting from the use of our diagnostic test in a clinical study, even one that was not in excess of our insurance coverage or one that is meritless, could adversely affect our ability to complete our clinical trials or obtain FDA approval of our product, which could have a material adverse effect on our business.

 
10

 
The healthcare reimbursement environment is uncertain and our customers may not get significant insurance reimbursement for our products, which could have a materially adverse affect on our sales and our ability to sell our products

Recent efforts by governmental and third-party payors, including private insurance plans, to contain or reduce the costs of health care could affect the levels of revenues and profitability of pharmaceutical, diagnostic and biotechnology products and companies.  For example, in some foreign markets, pricing or profitability of prescription pharmaceuticals is subject to government control.  In the United States, there have been a number of federal and state proposals to implement similar government control.  Pricing constraints on our potential products could negatively impact revenues and profitability.

In the United States and elsewhere, successful commercialization of our products will depend in part on the availability of reimbursement to the consumer using our products from third-party health care payors.  Insufficient reimbursement levels could affect demand for our products, and therefore, our ability to realize an appropriate return on our investment in product development.  Third-party health care payors are increasingly challenging the price and examining the cost-effectiveness of medical products and services.  If we succeed in bringing one or more products to market, and the government or third-party payors fail to provide adequate coverage or reimbursement rates for those products, it could reduce our product revenues and profitability.

Current proposed regulations for reference laboratory developed diagnostic tests may impact our ability to sell our proposed diagnostic tests under the Clinical Laboratory Improvement Amendment (“CLIA”) exemption

Governmental agencies are currently reviewing additional regulations to be imposed on reference laboratory developed diagnostic tests, so called “homebrew” tests, including evidence of analytic and clinical validity and enhanced labeling requirements.  In addition, there have been discussions concerning lower Medicare reimbursement for non-FDA approved tests.  Increased FDA regulation of reference laboratory developed diagnostic tests could significantly increase the costs and significantly reduce the demand for such tests.

We must enroll a sufficient number of participants in our clinical trials and generate clinical data that shows our products are safe and effective in order to obtain the necessary regulatory approval to market our products

In order to sell our products, we must receive regulatory approval to market our products.  Before obtaining regulatory approvals for the commercial sale of any of our products under development, we must demonstrate through all necessary regulatory studies, including pre-clinical and clinical trials, that the product is safe and effective for use in each target indication. If our products fail in research, development and/or clinical trials, this may have a significant negative impact on us.

In addition, the results from pre-clinical testing and early clinical trials may not be predictive of results obtained in late stage clinical trials. There can be no assurance that our clinical trials will demonstrate sufficient safety and efficacy to obtain regulatory approvals. The completion rate of our clinical trials is dependent on, among other factors, the patient enrollment rate. Patient enrollment is a function of many factors including:

·  
patient population size;
·  
access to patients;
·  
competitive trials;
·  
the nature of the protocol to be used in the trial;
·  
patient proximity to clinical sites; and
·  
eligibility criteria for the study
 
Delays in patient enrollment would increase costs and delay ultimate sales, if any, of our products.

Our stock price may fluctuate significantly due to reasons unrelated to our operations, our products or our financial results.  Our stock price may decrease if we have to issue a large number of shares of common stock in order to raise the additional funds needed in the first quarter of 2009.

Stock prices for many technology companies fluctuate widely for reasons which may be unrelated to operating performance or new product or service announcements.  Broad market fluctuations, earnings and other announcements of other companies, general economic conditions or other matters unrelated to us or our operations and outside our control also could affect the market price of the Common Stock.  During the 2006 and 2007 fiscal years, the highest interday price of our stock was $0.50 and the lowest interday price of our stock during the same period was $0.08.  We have sufficient cash to last through the first quarter of 2009, and we will need to raise additional funds prior to the end of the first quarter of 2009.  In order to raise additional funds, we may have to sell a significant number of shares of our common stock and/or issue warrants exercisable to purchase shares of our common stock.  While the inflow of additional funds may cause our stock price to increase, the prospect of issuing, or the actual issuance of, a substantial number of additional shares of common stock may cause our stock price to decrease.

 
11

 
We will need to increase the number of our authorized shares of common stock in order to raise a meaningful amount of capital through the sale of equity securities.  Such increase will require approval of our stockholders.  If our stockholders do not approve the increase in authorized common stock, we will be limited in our ability to raise a significant amount of capital through the sale of equity securities.

We have 200,000,000 authorized shares of common stock.  As of December 31, 2007, we had 130,217,808 shares of common stock issued and outstanding, and we have reserved (i) 44,418,453 shares of common stock for issuance upon the exercise of outstanding warrants and (ii) 19,242,347 shares of common stock for issuance upon the exercise of outstanding options.  We currently have 6,121,392 shares of common stock available for issuance in any capital raising transaction.  Because we may to have to issue warrants in any equity deal to raise capital, we could have significantly less than 6.1 million shares to sell, which reduces the amount of capital we could raise.  In order to be able to raise a significant amount of capital for future operations, we will need to increase our authorized common stock to at least 300 million shares, or more.  To increase our authorized common stock, we will need to secure stockholder approval.  Because of the large number of shares held in street name, we expect to incur significant expenses in order to obtain such approval. Most of our stockholders hold their shares in street name and a charter amendment is not a discretionary item for which brokers can cast a vote without instruction from their clients.  We would have to hire a solicitation firm to assist us in getting sufficient stockholder votes to increase our authorized common stock.

Our share price may decline due to a large number of shares of our common stock eligible for sale in the public markets and a large number of shares of our common stock that could be issued upon the exercise of warrants and options should our stock price increase to a level above the exercise price of the warrants and options

As of December 31, 2007, we had outstanding 130,217,808 shares of Common Stock, without giving effect to shares of Common Stock issuable upon exercise of (i) warrants issued to SF Capital, exercisable for 6,214,286 shares of or common stock, (ii) warrants issued in the February 2004 Offering, exercisable for 31,547,489 shares of our common stock (at an exercise price of $0.30 per share), (iii) the Placement Agent's warrants, exercisable for 3,143,335 shares of our common stock (at an exercise price of $0.30 per share), (iv) 10,575,680 options granted under our stock option plan, (v) 8,666,667 options granted outside of our stock option plan, and (vi) 3,513,343 other warrants previously issued.  Of such outstanding shares of common stock, all are freely tradable, except for any shares not yet registered, shares underlying stock options that are not yet vested, and any shares held by our "affiliates" within the meaning of the Securities Act (officers, directors and 10% security holders), which shares will be subject to the resale limitations of Rule 144 promulgated under the Securities Act.  We will need to raise capital prior to the end of the first quarter of 2009 and this may cause us to issue additional shares of our common stock in 2009.

The holders of our outstanding warrants and stock options may not exercise them, or they may expire before we are able to receive any proceeds from the exercise of these warrants and stock options

As of December 31, 2007, we had 44,418,453 outstanding warrants and 19,242,347 outstanding stock options.  34,690,824 of these warrants, with an exercise price of $0.30, expire on February 6, 2009.  The remaining 9,727,629 outstanding warrants have an average exercise price of $0.16 and have expiration dates between 2008 and 2012.  The outstanding stock options have exercise prices ranging from $0.15 to $0.285 and have expiration dates between 2008 and 2017.  We may not receive any significant proceeds from the exercise of these outstanding warrants and stock options due to market conditions and/or the expiration of the warrants and stock options prior to exercise.  This could impact our future fund raising options.

We have not paid any dividends and do not anticipate paying dividends in the foreseeable future

A predecessor of Applied NeuroSolutions liquidated most of its assets and paid a dividend to its shareholders in August 2001.  We have not paid cash dividends on our common stock, and we do not anticipate paying cash dividends on our common stock in the foreseeable future.  Investors who require dividend income should not rely on an investment in our common stock to provide such dividend income.  Potential income to investors in our common stock would only come from any rise in the market price of our common stock, which is uncertain and unpredictable.

 
12

 
A limited market for our common stock and “Penny Stock” rules may make buying or selling our common stock difficult

Our common stock presently trades in the over-the-counter market on the OTC Bulletin Board. As a result, an investor may find it difficult to sell, or to obtain accurate quotations as to the price of, our securities.  In addition, our common stock is subject to the penny stock rules that impose additional sales practice requirements on broker-dealers who sell such securities to persons other than established customers and accredited investors.  The SEC regulations generally define a penny stock to be an equity that has a market price of less than $5.00 per share, subject to certain exceptions.  Unless an exception is available, those regulations require the delivery, prior to any transaction involving a penny stock, of a disclosure schedule explaining the penny stock market and the risks associated therewith and impose various sales practice requirements on broker-dealers who sell penny stocks to persons other than established customers and accredited investors (generally institutions and high net worth individuals).  In addition, the broker-dealer must provide the customer with current bid and offer quotations for the penny stock, the compensation of the broker-dealer and its salesperson in the transaction and monthly account statements showing the market value of each penny stock held in the customer's account.  Moreover, broker-dealers who recommend such securities to persons other than established customers and accredited investors must make a special written suitability determination for the purchaser and receive the purchaser's written agreement to transactions prior to sale.  Regulations on penny stocks could limit the ability of broker-dealers to sell our common stock and thus the ability of purchasers of our common stock to sell their shares in the secondary market.

Our disclosure controls and procedures and our internal controls over financial reporting are not adequate and may result in our failure to disclose items that we may be required to disclose under the Securities Act or the Securities Exchange Act or may result in financial statements that are incomplete or subject to restatement

Section 404 of the Sarbanes Oxley Act of 2002 (“Section 404”) requires significant additional procedures and review processes of our system of internal controls.  Section 404 requires that we evaluate and report on our system of internal controls over financial reporting beginning with our Annual Report on Form 10-KSB for the year ended December 31, 2007.  In addition, our independent auditors must report on management’s evaluation of those controls for the year ending December 31, 2008.  The additional costs associated with this process may be significant.  Our internal controls under Section 404 may not be adequate.  After documenting and testing our system, we have identified the following material weaknesses:

·  
We lack segregation of duties in the period-end financial reporting process, and
·  
Our accounting software has inherent control deficiencies.

Additionally, our chief executive officer and chief financial officer concluded that as of December 31, 2007, our disclosure controls and procedures were not effective to ensure that information required to be disclosed by us in reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in SEC rules and forms.  Consequently, we may fail to disclose items that we are required to report in our SEC filings, including registration statements, proxy statements and periodic reports.  If we are required to amend prior reports as a result of failing to disclose required information, investors may react adversely to such amendments and our stock price may decrease.

Our Independent Registered Public Accountants have substantial doubt about our ability to continue as a going concern

We have had net losses for each of the years ended December 31, 2007 and 2006, and we have an accumulated deficit as of December 31, 2007.  Since the financial statements for each of these periods were prepared assuming that we would continue as a going concern, in the view of our independent registered public accountants, these conditions raise substantial doubt about our ability to continue as a going concern.  We anticipate that our cash balances at December 31, 2007, coupled with our annual R & D support from Eli Lilly and Company, should be sufficient to fund operations through the first quarter of 2009.  We will need additional funding prior to the end of the first quarter of 2009 in order to continue our research, product development and our operations.  Since we do not expect to generate any material revenues for the foreseeable future, our ability to continue as a going concern depends, in large part, on our ability to raise additional capital prior to the end of the first quarter 2009, either through some form of collaboration or joint venture or debt or equity financing, which may include the exercise of outstanding stock options and/or warrants.  If we are unable to raise additional capital, we may be forced to discontinue our business.



 
13

 

USE OF PROCEEDS

We will not receive any proceeds from the disposition of the shares of common stock by the selling security holders or their transferees.  On April 27, 2007, several large selling security holders exercised their warrants to purchase 9,782,805 shares of common stock at a reduced exercise price of $0.17 per share.  We received an aggregate of $1,663,077 in gross proceeds from this exercise of warrants.  We may receive proceeds up to an additional $10,407,247 upon the exercise of all the remaining warrants.  As we cannot predict when or if we will receive such proceeds, we expect to use these proceeds, if received, for working capital purposes, which shall be allocated to projects or needs of the Company at such time.  The proceeds received from the securities sold in the Offering were intended to be used to advance our various programs.  The additional proceeds we could receive from the exercise of the warrants have not yet been earmarked for any specific use beyond working capital needs because there is no certainty that we will ever receive proceeds from the exercise of the warrants.


SELLING SECURITY HOLDERS

We are registering shares of our common stock purchased by investors in our 2004 private placement offering, the shares of our common stock issuable upon the exercise of warrants purchased by those investors in the same offering, the shares of our common stock purchased by bridge loan holders upon conversion of outstanding convertible promissory loans, including accrued interest, the shares of our common stock issuable upon the exercise of warrants purchased by the bridge loan holders, the shares of our common stock issuable upon the warrants issued to the placement agent and sub-agents engaged in our 2004 private placement, and the shares of common stock issuable upon the exercise of certain warrants previously issued by us to investors and consultants.

Beneficial ownership is determined in accordance with Rule 13d-3(d) promulgated by the Commission under the Securities Exchange Act of 1934. Unless otherwise noted, each person or group identified possesses sole voting and investment power with respect to the shares, subject to community property laws where applicable.

Each of the selling security holders (i) purchased the securities covered by this prospectus in the ordinary course of business, and (ii) at the time of purchase of such securities, the selling security holder had no agreement or understanding, directly or indirectly, with any person to distribute such securities.

Other than the costs of preparing this prospectus and a registration fee to the SEC, we are not paying any costs relating to the sales by the selling security holders.

 
 
Selling Stockholder
 
Common Stock Beneficially Owned Before Offering (1)
Shares of Common Stock Being Offered in the Offering (1)
Common Stock Beneficially Owned After Offering (1)
 
Percent After Offering
Charles Abramovitz (2)
400,000
400,000
0
*
Eric Berger (2)
200,000
200,000
0
*
Douglas G. Liu
6801 Wolf Creek Court
Columbia, Maryland
300,000
300,000
0
*
Roy D. Mittman (2)
200,000
200,000
0
*
James R. Porter (2)
200,000
200,000
0
*
Mohammad S. Rahman
One SW Columbia, Suite 850
Portland, Oregon
165,000
130,000
35,000
*
Larry Roher and Deborah Hessel-Roher
One Gracewood Drive
Manhasset, New York
380,000
380,000
0
*
Steven M. Sack
135 East 57th Street
12th Floor
New York, New York
655,000
500,000
155,000
*
Jay Solan and Sandra Solan
15 Mohawk Drive
Westbury, New York
1,030,000
1,030,000
0
*
Scott Ziegler
570 Lexington Avenue
44th Floor
New York, New York
200,000
200,000
0
*
High Peak Ltd. (3)
57 Dartmouth Park Road
London NW5 1SL UK
100,000
100,000
0
*
Arbuthnot SIPP A/C SE Sanbar (4)
57 Dartmouth Park Road
London NW5 1SL UK
200,000
200,000
0
*
Edward J. Sisk (2)
160,000
160,000
0
*
Alpha Capital AG (5)
Pradatant 7
Furstentums 9490
Vaduz, Liechtenstein
Germany
1,000,000
1,000,000
0
*
Nathan Sugerman (2)
100,000
100,000
0
*
Bruce and Janet Allen Joint Revocable Trust dated July 31, 2003 (6)
83 Idlewood Road
San Francisco, California
665,000
665,000
0
*
G. Richard Hicks (2)
200,000
200,000
0
*
The O'Hara Family Trust (7)
1621 Ocean Front Street
San Diego, California
200,000
200,000
0
*
Guerrilla Partners, L.P.(8)
247 Park Avenue
New York, New York 10017
395,000
395,000
0
*
Guerrilla IRA Partners, L.P. (9)
247 Park Avenue
New York, New York
395,000
395,000
0
*
Odin Partners (10)
237 Park Avenue
New York, New York
740,000
740,000
0
*
Erik Franklin
534 Penaki Road
Denville, New Jersey
500,000
500,000
0
*
Q Capital Investment Partners, L.P. (11)
2 Executive Drive
Fort Lee, New Jersey
500,000
500,000
0
*
Mark Lenowitz
11 Fred Street
Old Tappan, New Jersey
1,000,000
1,000,000
0
*
Castle Creek Healthcare Partners, LLC (12)
111 West Jackson Blvd.
Suite 2020
Chicago, Illinois
1,000,000
1,000,000
0
*
Steven Epstein (2)
360,000
360,000
0
*
Wells Family Revocable Living Trust (13)
22 Battery Street
Suite 800
San Francisco, California
180,000
180,000
0
*
American Health Care Fund, L.P. (14)
2748 Adeline
Berkeley, California
380,000
380,000
0
*
Vincent Smith
c/o Quest Software
800 Irvine Center Drive
Irvine, California
1,400,000
1,400,000
0
*
Marshall Senk
P.O. Box 824
Corona Del Mar, California
320,000
300,000
20,000
*
J. Leroy Thompson, Jr.
126 Via Monte
Walnut Creek, California
320,000
320,000
0
*
MicroCapital Fund, L.P.(15)
201 Post Street
San Francisco, California
2,000,000
2,000,000
0
*
MicroCapital Fund, Ltd. (16)
201 Post Street
San Francisco, California
1,000,000
1,000,000
0
*
Samuel Gerald Birin
46 Barrington Drive
Bedford, New Hampshire
600,000
600,000
0
*
The Timken Living Trust (17)
7 Mercury Avenue
Tiburon, California
800,000
800,000
0
*
My Dang
7135 South Durango Drive
Las Vegas, Nevada
400,000
400,000
0
*
Robert T. Lempert (2)
100,000
100,000
0
*
Ronald Leong
75 27th Avenue
San Francisco, California
200,000
200,000
0
*
Kenneth G. Cala
425 Sheffield Road
Alameda, California
331,000
331,000
0
*
Adam Hershey (2)
800,000
800,000
0
*
Hutchinson Family Trust (18)
1059 Bryant Way
Sunnyvale, California
50,000
50,000
0
*
The Bolloten Family Trust (19)
3039 Ryan Avenue
Santa Clara, California
50,000
50,000
0
*
Gregory Bolloten
3811 Anza Street
San Francisco, California
2,258,417
2,258,417
0
*
John Coulthurst
1990 Marin Avenue
Berkeley, California
80,000
80,000
0
*
Joan M. Hammond (2)
100,000
100,000
0
*
J. Paul Irvin (2)
60,000
60,000
0
*
William C. Irvin Revocable Trust (20)
1641 Wild Azalea Lane
Athens, Georgia
200,000
200,000
0
*
David M. Spada, IRA (2)
100,000
100,000
0
*
Clarion Capital Corporation (21)
1801 East 9th Street, Suite 1120
Cleveland, Ohio
1,000,000
1,000,000
0
*
Samuel and Jennifer Skinner 2000 Trust (22)
505 Sansome Street
San Francisco, California
100,000
100,000
0
*
Samuel D. Skinner IRA (23)
505 Sansome Street
San Francisco, California
232,000
200,000
32,000
*
Omicron Master Trust (24)
810 Seventh Avenue, 39th Floor
New York, New York
683,233
683,233
0
*
Rockmore Investment Master Fund Ltd. (24A)
150 East 58th Street, 28th Floor
New York, New York
316,767
316,767
0
*
Jam Capital Assoc. LLC (25)
c/o Leonard D. Pearlman
112 West 56th Street
Suite 20S
New York, New York
100,000
100,000
0
*
John Peter Christensen (2)
400,000
400,000
0
*
Jonathan Heller Money Purchase Plan (26)
775 Bryant Street
Woodmere, New York
100,000
100,000
0
*
Jerome Heller (2)
100,000
100,000
0
*
Benjamin Family Trusts (27)
8,307,780
5,189,572
3,118,208
2.4%
Central Yeshiva (28)
418 Avenue I
Brooklyn, New York
288,382
288,382
0
*
David Baker (2)
751,637
203,277
548,360
*
George Rohr (2)
1,412,657
1,412,657
0
*
Harry J. Blumenthal, Jr. (2)
546,984
453,277
93,707
*
Howard P. Milstein (2)
3,759,955
2,271,852
1,488,103
1.5%
Joshua Schein (2)
2,264,840
745,120
1,519,720
1.5%
Judson Cooper (2)
1,769,084
124,550
1,644,534
1.7%
Ashton Partners LLC (2)
100,000
100,000
0
*
Kevin Eilian
2025 Broadway, #30H
New York, New York
214,209
214,209
0
*
Ravinia Capital Opportunity Fund, LP (28A)
115 East 57th Street, Suite 1003
New York, New York
428,686
428,686
0
*
Lee Schlesinger (2)
472,394
435,402
36,992
*
Leon Khoury, Jr. (2)
172,478
172,478
0
*
Louis Zauderer (2)
524,993
324,993
200,000
*
Richard Lipsey (2)
242,569
214,410
28,159
*
Richard Stone (29)***
c/oBluegrass Growth Fund, L.P.
122 E. 42nd St, Suite 2606
New York, New York
3,107,056
1,042,299
2,064,757
2.1%
Clubhouse Partners, L.L.C. (30)
228 St. Charles Ave.
New Orleans, LA 70130
419,632
419,632
0
*
Everett Place Partners, L.L.C. (31)
228 St. Charles Ave.
New Orleans, LA 70130
53,841
53,841
0
*
Redwood Capital Partners (32)
228 St. Charles Ave.
New Orleans, LA 70130
1,078,668
1,078,668
0
*
Theofania Merkos (2)
10,000
10,000
0
*
Marcia Kucher (2)
5,160
5,000
160
*
Jeffrey Steingarten (2)
100,000
50,000
50,000
*
Smithfield Fiduciary LLC (33)
9 West 57th Street, 27th Floor
New York, New York
1,158,507
1,158,507
0
*
Sunrise Securities** (34)
135 East 57th St., 11th Floor
New York, NY
400,000
400,000
0
*
Michael Marrale***
43 Kensington Circle
North Hills, New York
400,000
400,000
0
*
David Roffe (2)
100,000
100,000
0
*
Christopher Basta***
18 Peppermill Lane
Dix Hills, New York
200,000
200,000
0
*
Harry Gruszecki
269-27D Grand Central Parkway
Floral Park, New York
255,499
255,499
0
*
John Mon
16903 Harbour Town Drive
Silver Spring, Maryland
50,000
50,000
0
*
Michael Palin and Dean Palin
235 Park Avenue South
New York, New York 10003
800,000
800,000
0
*
Brosig 2000 Family Revocable Trust (35)
160,000
160,000
0
*
Sachs Investing Company (36)
155 East 55th Street
New York, New York
300,000
300,000
0
*
Thomas Lackovic (2)
80,000
80,000
0
*
Special Situations Private Equity Fund LP (37)
527 Madison Avenue, Suite 2600
New York, New York
               6,250,000
              6,250,000
0
*
Moors & Cabot, Inc.**  (38)
505 Sansome Street
San Francisco, California
151,840
151,840
0
*
John Dakin*** (2), (39)
766,660
766,660
0
*
Alexandra Dakin*** (2), (39)
466,660
466,660
0
*
Sam Skinner*** (39)
81,480
81,480
0
*
William Payne*** (39)
162,960
162,960
0
*
MCC Securities** (40)
575 Madison Avenue
New York, New York
388,800
388,800
0
*
Eric Gier*** (41)
216,000
216,000
0
*
Karl Kirwan*** (41)
189,335
189,335
0
*
Daniel S. Gulick*** (41)
43,200
43,200
0
*
Guy G. Clemente***
c/o Andrew Garrett, Inc.
380 Lexington Avenue
Suite 2135
New York, New York
258,800
258,800
0
*
Gregg Lerman***
c/o SW Bach & Co.
Two Expressway Plaza
Suite 200
Roslyn Heights, New York
129,400
129,400
0
*
Scott Shapiro***
c/o SW Bach & Co.
Two Expressway Plaza
Suite 200
Roslyn Heights, New York
129,400
129,400
0
*
CK Cooper & Co.** (42)
18300 Von Karman Avenue
Suite 440
Irvine, California
160,000
160,000
0
*
Westcap Securities** (43)
8201 Von Karman Avenue
Irvine, California
8,800
8,800
0
*
Ezra Fabiarz*** (44)
20,000
20,000
0
*
 
*     Indicates ownership of less than 1.0%
 
**  Registered broker-dealer
 
***Affiliate of a registered broker-dealer

(1)    Includes shares of common stock issuable upon the exercise of warrants, and is adjusted to reflect the sale of shares pursuant to this offering.  Shares have been adjusted to reflect sales of common stock made prior to the date of this prospectus.

(2)    Address is c/o Applied NeuroSolutions, Inc., 50 Lakeview Parkway, Suite 111, Vernon Hills, IL  60061.

(3)    S E Sanbar, director of High Peak Limited (“High Peak”), has voting, investment and dispositive power over the shares of common stock held by High Peak and the shares of common stock issuable upon the exercise of the warrants held by High Peak
 
(4)    S E Sanbar, trustee of Arbuthnot SIPP a/c S E Sanbar (“Arbuthnot”), has voting, investment and dispositive power over the shares of common stock held by Arbuthnot and the shares of common stock issuable upon the exercise of the warrants held by Arbuthnot.
 
(5)    Konrad Ackerman, director of Alpha Capital AG, has voting, investment and dispositive power over the shares of common stock held by Alpha Capital and the shares of common stock issuable upon the exercise of the warrants held by Alpha Capital.
 
(6)         Bruce B. Allen, trustee of the Bruce and Janet Allen Joint Revocable Trust dated July 31, 2003 (“Allen Trust”), has voting, investment and dispositive power over the shares of common stock held by the Allen Trust and the shares of common stock issuable upon the exercise of the warrants held by the Allen Trust.
 
(7)         Tim O’Hara, trustee of The O’Hara Family Trust (“O’Hara Trust”), has voting, investment and dispositive power over the shares of common stock held by the O’Hara Trust and the shares of common stock issuable upon the exercise of the warrants held by the O’Hara Trust.
 
(8)         The general partner of Guerrilla Partners, L.P. (“Guerrilla”) is Guerrilla Advisors.  Each of Leigh S. Curry and Peter J. Siris, each a managing director of Guerrilla Advisors, has voting, investment and dispositive power over the shares of common stock held by Guerrilla and the shares of common stock issuable upon the exercise of the warrants held by Guerrilla IRA.
 
 
19

 
(9)         The general partners of Guerrilla IRA Partners, L.P. (“Guerrilla IRA”) is Guerrilla Advisors.  Leigh S. Curry and Peter J. Siris, each a managing director of Guerrilla Advisors, each has voting, investment and dispositive power over the shares of common stock held by Guerrilla and the shares of common stock issuable upon the exercise of the warrants held by Guerrilla.
 
(10)           John A. Gibbons, Jr., the managing partner of Odin Partners L.P. (“Odin”), has voting, investment and dispositive power over the shares of common stock held by Odin and the shares of common stock issuable upon the exercise of the warrants held by Odin.
 
(11)    Erik Franklin, the general partner of Q Capital Investment Partners, L.P. (“Q Capital”), has voting, investment and dispositive power over the shares of common stock held by Q Capital and the shares of common stock issuable upon the exercise of the warrants held by Q Capital.
 
(12)    Daniel Asher and Nathan Fischel each has voting, investment and dispositive power over the shares of common stock held by Castle Creek Healthcare Partners, LLC and the shares of common stock issuable upon the exercise of the warrants held by Castle Creek Healthcare Partners, LLC.
 
(13)    Benjamin G. Wells, trustee of The Wells Family Revocable Living Trust (“Wells Trust”), has voting, investment and dispositive power over the shares of common stock held by the Wells Trust and the shares of common stock issuable upon the exercise of the warrants held by the Wells Trust.
 
(14)           James D. McCamant, the general partner of American Health Care Fund, L.P. (“AHCF”) has voting, investment and dispositive power over the shares of common stock held by AHCF and the shares of common stock issuable upon the exercise of the warrants held by AHCF.

(15)    The General Partner of MicroCapital Fund L.P. is MicroCapital LLC.  Ian P. Ellis, the President of MicroCapital LLC, has voting, investment and dispositive power over the shares of common stock held by MicroCapital L.P. and the shares of common stock issuable upon the exercise of the warrants held by MicroCapital L.P.

(16)           The investment adviser to MicroCapital Fund Ltd. is MicroCapital LLC.  Ian P. Ellis, the President of MicroCapital LLC, has voting, investment and dispositive power over the shares of common stock held by MicroCapital Ltd. and the shares of common stock issuable upon the exercise of the warrants held by MicroCapital Ltd.

(17)    William R. Timken and Judith P. Timken, trustees of The Timken Living Trust U/A/D 9/14/99, each has voting, investment and dispositive power over the shares of common stock held by The Timken Living Trust and the shares of common stock issuable upon the exercise of the warrants held by The Timken Living Trust.
 
(18)    C.H. Hutchinson, trustee of the Hutchinson Family Trust A/CHH (“Hutchinson Trust”), has voting, investment and dispositive power over the shares of common stock held by the Hutchinson Trust and the shares of common stock issuable upon the exercise of the warrants held by the Hutchinson Trust.
 
(19)    Betty F. Bolloten, trustee of the Bolloten Family Trust, has voting, investment and dispositive power over the shares of common stock held by the Bolloten Family Trust and the shares of common stock issuable upon the exercise of the warrants held by the Bolloten Family Trust.
 
(20)    William C. Irvin, trustee of the William C. Irvin Revocable Trust (“Irvin Trust”), has voting, investment and dispositive power over the shares of common stock held by the Irvin Trust and the shares of common stock issuable upon the exercise of the warrants held by the Irvin Trust.
 
(21)           Morton A. Cohen, the Chairman of Clarion Capital Corporation (“Clarion”), has voting, investment and dispositive power over the shares of common stock held by Clarion and the shares of common stock issuable upon the exercise of the warrants held by Clarion.

(22)           Samuel D. Skinner, trustee of the Samuel and Jennifer Skinner 2000 Trust  (“Skinner Trust”), has voting, investment and dispositive power over the shares of common stock held by the Skinner Trust and the shares of common stock issuable upon the exercise of the warrants held by the Skinner Trust.

(23)           Includes 22,000 shares of common stock held by Gerado Trust.

(24)           Omicron Capital, L.P., a Delaware limited partnership (“Omicron Capital”), serves as investment manager to Omicron Master Trust, a trust formed under the laws of Bermuda (“Omicron”), Omicron Capital, Inc., a Delaware corporation (“OCI”), serves as general partner of Omicron Capital, and Winchester Global Trust Company Limited (“Winchester”) serves as the trustee of Omicron.  By reason of such relationships, Omicron Capital and OCI may be deemed to share dispositive power over the shares of our common stock owned by Omicron, and Winchester may be deemed to share voting and dispositive power over the shares of our common stock owned by Omicron.  Omicron Capital, OCI and Winchester disclaim beneficial ownership of such shares of our common stock.  As of the date of this prospectus, Mr. Olivier H. Morali, an officer of OCI, and Mr. Bruce T. Bernstein, a consultant to OCI, have delegated authority from the board of directors of OCI regarding the portfolio management decisions with respect to the shares of our common stock owned by Omicron.  By reason of such delegated authority, Messrs. Morali and Bernstein may be deemed to share dispositive power over the shares of our common stock owned by Omicron.  Messrs.  Morali and Bernstein disclaim beneficial ownership of such shares of our common stock and neither of such persons has any legal right to maintain such delegated authority.  No other person has sole or shared voting or dispositive power with respect to the shares of our common stock being offered by Omicron, as those terms are used for purposes under Regulation 13D-G of the Securities Exchange Act of 1934, as amended.  Omicron and Winchester are not “affiliates” of one another, as that term is used for purposes of the Exchange Act or of any other person named in this prospectus as a selling stockholder.  No person or “group” (as that term is used in Section 13(d) of the Exchange Act or the SEC’s Regulation 13d-G) controls Omicron and Winchester.

 
20

 
(24A)    Rockmore Capital, LLC (“Rockmore Capital”) and Rockmore Partners, LLC (“Rockmore Partners”), each a limited liability company formed under the laws of the state of Delaware, serve as investment manager and general partner, respectively, to Rockmore Investments (US) LP, a Delaware limited partnership, which invests all of its assets through Rockmore Investment Master Fund Ltd., an exempted company formed under the laws of Bermuda (“Rockmore Master Fund”).  By reason of such relationships, Rockmore Capital and Rockmore Partners may be deemed to share dispositive power over the shares of our common stock owned by Rockmore Master Fund.  Rockmore Capital and Rockmore Partners disclaim beneficial ownership of such shares of our common stock.  Rockmore Partners has delegated authority to Rockmore Capital regarding the portfolio management decisions with respect to the shares of common stock owned by Rockmore Master Fund and, as of the date of this prospectus, Mr. Bruce T. Bernstein and Mr. Brian Daily, as officers of Rockmore Capital, are responsible for the portfolio management decisions of the shares of common stock owned by Rockmore Master Fund.  By reason of such authority, Messrs. Bernstein and Daly may be deemed to share dispositive power over the shares of our common stock owned by Rockmore Master Fund.  Messrs. Bernstein and Daly disclaim beneficial ownership of such shares of our common stock and neither of such persons has any legal right to maintain such authority.  No other person has sole or shared voting or dispositive power with respect to the shares of our common stock as those terms are used for purposes under Regulation 13D-G of the Securities Exchange Act of 1934, as amended. No person or “group” (as that term is used in Section 13(d) of the Securities Exchange Act of 1934, as amended, or the SEC’s Regulation 13D-G) controls Rockmore Master Fund.

(25)           Leonard D. Pearlman, Manager of Jam Capital Assoc. LLC (“Jam”), has voting, investment and dispositive power over the shares of common stock held by Jam and the shares of common stock issuable upon the exercise of the warrants held by Jam.
 
(26)           Jonathan Heller, trustee of the Jonathan Heller Money Purchase Plan (the “Heller Plan”), has voting, investment and dispositive power over the shares of common stock held by the Heller Plan and the shares of common stock issuable upon the exercise of the warrants held by the Heller Plan.
 
(27)           Consists of 8,207,780 shares of common stock held by various family trusts and 100,000 shares of common stock held by a family member.  The trustee of these various family trusts is Bank of America Corporation, 100 North Tryon Street, Floor 25, Bank of America Corporate Center, Charlotte, NC 28255.
 
(28)           Rabbi Joffen has voting, investment and dispositive power over the shares of common stock held by Central Yeshiva and the shares of common stock issuable upon the exercise of the warrants held by Central Yeshiva.
 
(28A)  Kevin Eilian, the general partner of Ravinia Capital Opportunity Fund, LP (“Ravinia”), has voting, investment and dispositive power over the shares of common stock held by Ravinia and the shares of common stock issuable upon the exercise of the warrants held by Ravinia.
 
(29)           Richard Stone served as one of our directors from 1994 until October 2005.  Includes shares of common stock issuable upon the exercise of warrants and stock options previously issued to Mr. Stone.
 
(30)           Michael A. Stone has voting, investment and dispositive power over the shares of common stock held by Clubhouse Partners, L.L.C. and the shares of common stock issuable upon the exercise of the warrants held by Clubhouse Partners, L.L.C.
 
(31)           Michael A. Stone has voting, investment and dispositive power over the shares of common stock held by Everett Place Partners, L.L.C. and the shares of common stock issuable upon the exercise of the warrants held by Everett Place Partners, L.L.C.
 
 
21

 
(32)           Harvey M. Stone has voting, investment and dispositive power over the shares of common stock held by Redwood Capital Partners and the shares of common stock issuable upon the exercise of the warrants held by Redwood Capital Partners.
 
(33)           Adam Chill has voting, investment and dispositive power over the shares of common stock held by Smithfield Fiduciary LLC and the shares of common stock issuable upon the exercise of the warrants held by Smithfield Fiduciary LLC.

(34)            Sunrise Securities, which is a registered broker-dealer, is  an underwriter with respect to the shares of common stock held by Sunrise Securities and the shares of common stock issuable upon the exercise of the warrants held by Sunrise Securities, which are being offered for resale under this prospectus.
 
(35)           Margaret J. Hook, trustee of the Brosig 2000 Family Revocable Trust (“Brosig Trust”) has voting, investment and dispositive power over the shares of common stock held by the Brosig Trust and the shares of common stock issuable upon the exercise of the warrants held by the Brosig Trust.

(36)           Marvin Sachs and David Sachs, partners of Sachs Investing Co (“Sachs”), each has voting, investment and dispositive power over the shares of common stock held by Sachs and the shares of common stock issuable upon the exercise of the warrants held by Sachs.

(37)           MG Advisors, L.L.C. (“MG”) is the general partner of and investment adviser to the Special Situations Private Equity Fund, L.P. (the “Private Equity Fund”).  Austin W. Marxe and David M. Greenhouse are the principal owners of MG and are principally responsible for the selection, acquisition and disposition of the portfolio securities by MG on behalf of the Private Equity Fund.

(38)           William Payne, a director of Moors & Cabot, Inc., may be deemed to have voting, investment and dispositive power over the shares of common stock held by Moors & Cabot and the shares of common stock issuable upon the exercise of the warrants held by Moors & Cabot.

(39)           During 2006, Moors & Cabot transferred shares of our common stock and warrants covered by this prospectus to John Dakin, a former employee of Moors & Cabot, Samuel Skinner, a former director of Moors & Cabot, and William Payne, a director of Moors & Cabot.  Mr. Payne is an affiliate of Moors & Cabot, a registered broker dealer.  Mr. Dakin transferred shares of common stock and warrants covered by this prospectus to Alexandra Dakin, his ex-wife pursuant to a court-approved settlement agreement.

(40)    Daniel S. Gulick, a registered principal and managing director of MCC Securities, Inc. (“MCC”), and Ken Denos, General Counsel for MCC, each has voting, investment and dispositive power over the shares of common stock held by MCC and the shares of common stock issuable upon the exercise of the warrants held by MCC.

(41)    During 2006, MCC transferred shares of our common stock and warrants covered by this prospectus to Eric Gier, a former director of MCC, Karl Kirwan, a former director of MCC and Daniel S. Gulick, a registered principal and managing director of MCC.  Mr. Gulick is an affiliate of MCC, a registered broker dealer.

(42)           Mikael Van Loon, a director of C.K. Cooper & Co., may be deemed to have voting, investment and dispositive power over the shares of common stock held by C.K. Cooper & Co. and the shares of common stock issuable upon the exercise of the warrants held by C.K. Cooper & Co.

(43)           Thomas S. Rubin, Chief Executive Officer and majority owner of Westcap Securities, Inc. (“Westcap”) has voting, investment and dispositive power over the shares of common stock issuable upon the exercise of the warrants held by Westcap.

(44)           During 2006, Westcap transferred shares of our common stock and warrants covered by this prospectus to Ezra Fabiarz, a director of Westcap.  Mr. Fabiarz is an affiliate of Westcap, a registered broker dealer.


PLAN OF DISTRIBUTION

The selling security holders, which as used herein includes donees, pledgees, transferees or other successors-in-interest selling shares of common stock or interests in shares of common stock received after the date of this prospectus from a selling security holder as a gift, pledge, partnership distribution or other transfer, may, from time to time, sell, transfer or otherwise dispose of any or all of their shares of common stock or interests in shares of common stock on any stock exchange, market or trading facility on which the shares are traded or in private transactions.  These dispositions may be at fixed prices, at prevailing market prices at the time of sale, at prices related to the prevailing market price, at varying prices determined at the time of sale, or at negotiated prices.

 
22

 
Sunrise Securities, as a registered broker-dealer, is an “underwriter” within the meaning of Section 2(11) of the Securities Act of 1933 in connection with the resale of our securities under this prospectus.  Any commissions received by Sunrise Securities and any profit on the resale of the shares of our common stock  (including the shares of common stock issuable upon the exercise of the warrants) sold by Sunrise Securities while acting as principals will be deemed to be underwriting discounts or commissions.  Because it is deemed to be an underwriter within the meaning of Section 2(11) of the Securities Act of 1933, Sunrise Securities will be subject to prospectus delivery requirements.

The selling security holders may use any one or more of the following methods when disposing of shares or interests therein:

 
- ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers;

 
- block trades in which the broker-dealer will attempt to sell the shares as agent, but may position and resell
 
  a portion of the block as principal to facilitate the transaction;

 
- purchases by a broker-dealer as principal and resale by the broker-dealer for its account;

 
- an exchange distribution in accordance with the rules of the applicable exchange;

 
- privately negotiated transactions;

 
- short sales;

 
- through the writing or settlement of options or other hedging transactions, whether through an options
 
  exchange or otherwise;

 
- broker-dealers may agree with the selling security holders to sell a specified number of such shares at a
 
  stipulated price per share;

 
- a combination of any such methods of sale; and

 
- any other method permitted pursuant to applicable law.

The selling security holders may, from time to time, pledge or grant a security interest in some or all of the shares of common stock owned by them and, if they default in the performance of their secured obligations, the pledgees or secured parties may offer and sell the shares of common stock, from time to time, under this prospectus, or under an amendment to this prospectus under Rule 424(b)(3) or other applicable provision of the Securities Act amending the list of selling security holders to include the pledgee, transferee or other successors in interest as selling security holders under this prospectus.  The selling security holders also may transfer the shares of common stock in other circumstances, in which case the transferees, pledgees or other successors in interest will be the selling beneficial owners for purposes of this prospectus.

In connection with the sale of the common stock or interests therein, the selling security holders may enter into hedging transactions with broker-dealers or other financial institutions, which may in turn engage in short sales of the common stock in the course of hedging the positions they assume.  The selling security holders may also sell shares of the common stock short and deliver these securities to close out their short positions, or loan or pledge the common stock to broker-dealers that in turn may sell these securities.  The selling security holders may also enter into option or other transactions with broker-dealers or other financial institutions or the creation of one or more derivative securities which require the delivery to such broker-dealer or other financial institution of shares offered by this prospectus, which shares such broker-dealer or other financial institution may resell pursuant to this prospectus (as supplemented or amended to reflect such transaction).

The aggregate proceeds to the selling security holders from the sale of the common stock offered by them will be the purchase price of the common stock less discounts or commissions, if any.  Each of the selling security holders reserves the right to accept and, together with their agents from time to time, to reject, in whole or in part, any proposed purchase of common stock to be made directly or through agents.  We will not receive any of the proceeds from this offering. Upon any exercise of the warrants by payment of cash, however, we will receive the exercise price of the warrants.

 
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The selling security holders also may resell all or a portion of the shares in open market transactions in reliance upon Rule 144 under the Securities Act of 1933, provided that they meet the criteria and conform to the requirements of that rule.

The selling security holders and any underwriters, broker-dealers or agents that participate in the sale of the common stock or interests therein may be "underwriters" within the meaning of Section 2(11) of the Securities Act.  Any discounts, commissions, concessions or profit they earn on any resale of the shares may be underwriting discounts and commissions under the Securities Act.  Selling security holders who are "underwriters" within the meaning of Section 2(11) of the Securities Act will be subject to the prospectus delivery requirements of the Securities Act.

To the extent required, the shares of the common stock to be sold, the names of the selling security holders, the respective purchase prices and public offering prices, the names of any agents, dealer or underwriter, any applicable commissions or discounts with respect to a particular offer will be set forth in an accompanying prospectus supplement or, if appropriate, a post-effective amendment to the registration statement that includes this prospectus.

In order to comply with the securities laws of some states, if applicable, the common stock may be sold in these jurisdictions only through registered or licensed brokers or dealers.  In addition, in some states the common stock may not be sold unless it has been registered or qualified for sale or an exemption from registration or qualification requirements is available and is complied with.

We have advised the selling security holders that the anti-manipulation rules of Regulation M under the Exchange Act may apply to sales of shares in the market and to the activities of the selling security holders and their affiliates.  In addition, we will make copies of this prospectus (as it may be supplemented or amended from time to time) available to the selling security holders for the purpose of satisfying the prospectus delivery requirements of the Securities Act.  The selling security holders may indemnify any broker-dealer that participates in transactions involving the sale of the shares against certain liabilities, including liabilities arising under the Securities Act.

We have agreed to indemnify the selling security holders against liabilities, including liabilities under the Securities Act and state securities laws, relating to the registration of the shares offered by this prospectus.

We have agreed with the selling security holders to keep the registration statement of which this prospectus constitutes a part effective until the earlier of (1) such time as all of the shares covered by this prospectus have been disposed of pursuant to and in accordance with the registration statement or (2) the date on which the shares may be sold pursuant to Rule 144(k) of the Securities Act (which was replaced in February 2008 by Rule 144(b)(1)).


DESCRIPTION OF SECURITIES

Under our Certificate of Incorporation, as amended, we are authorized to issue up to 200,000,000 shares of Common Stock, and 5,000,000 shares of Preferred Stock.  As of May 5, 2008 there were 130,217,808 shares of common stock outstanding and no shares of preferred stock outstanding.

Common Stock

The holders of Common Stock are entitled to one vote for each share of such stock held of record by them, and may cumulate their votes for the election of directors.  Subject to the preferences of any then-outstanding Preferred Stock, the holders of Common Stock are entitled to receive dividends when, as and if declared by the Board of Directors out of funds legally available therefore, subject to the prior rights of the holders of outstanding shares of Preferred Stock.  Upon our liquidation or dissolution, holders of Common Stock are entitled to receive all assets available for distribution to security holders, after payment of creditors and preferential liquidation distributions to preferred security holders, if any exist at the time of such liquidation.  The Common Stock has no preemptive or other subscription rights or redemption or sinking fund provisions with respect to such shares.  All outstanding shares of Common Stock are fully paid and non-assessable.

Warrants

Set forth below is information concerning the various warrants issued by us to our investors, placement agents and consultants and warrants issued to consultants and former employees by our predecessor, Hemoxymed, Inc.
 
 
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Warrants issued to SF Capital.  On September 28, 2007, we issued warrants exercisable to purchase 6,214,286 shares of our common stock to SF Capital in a private placement transaction (the “SF Capital warrants”).   The SF Capital warrants are described below.
 
Exercise Price and Terms. The SF Capital warrants are immediately exercisable, commencing September 28, 2007, for a five-year period at an exercise price of $0.19 per share.
 
Cashless Exercise.  The SF Capital warrants may be exercised using a cashless exercise procedure.
 
Transferability. The SF Capital warrants are not listed for trading on any exchange or for quotation on any Nasdaq Market, the OTC Bulletin Board or the Pink Sheets, but are transferable pursuant to a registration statement filed under the Securities Act of 1933 or an exemption from such registration.
 
Adjustments.  The exercise price and the number of shares of our common stock issuable upon the exercise of the warrants are subject to adjustment from time to time as set forth hereinafter.

(a)           Stock dividends, Stock Splits, Reclassification.  If we pay a dividend or make a distribution on our common stock in shares of common stock, subdivide our outstanding shares of common stock into a greater number of shares or combine our outstanding shares of common stock into a smaller number of shares or issue by reclassification of our outstanding shares of common stock any shares of our capital stock (including any such reclassification in connection with a consolidation or merger in which we are the continuing corporation), then the number of shares of common stock issuable upon the exercise of the warrants and the exercise price then in effect shall be adjusted by us so that the holder of the warrant thereafter exercising his, her or its warrants shall be entitled to receive the number of shares of our common stock or other capital stock which the holder of the warrant would have received if the warrant had been exercised immediately prior to such event upon payment of the exercise price that has been adjusted to reflect a fair allocation of the economics of such event to the holder of the warrant.

(b)           Reorganization, reclassification, consolidation, merger or sale of all or substantially all of our assets.  If any capital reorganization, reclassification of our capital stock, our consolidation or merger with another corporation in which we are not the survivor, or sale, transfer or other disposition of all or substantially all of our assets to another corporation shall be effected, then, as a condition of such reorganization, reclassification, consolidation, merger, sale, transfer or other disposition, lawful and adequate provision shall be made whereby each holder of SF Capital warrants shall thereafter have the right to purchase and receive in lieu of shares of our common stock, securities or assets as would have been issuable or payable with respect to or in exchange for a number of shares of our common stock for which the holder’s SF Capital warrants were exercisable immediately prior to such reorganization, reclassification, consolidation, merger, sale, transfer or other disposition. 

(c)           Distribution of indebtedness or assets other than cash or shares of our common stock.  In case we fix a payment date for the making of a distribution to all holders of common stock (including any such distribution made in connection with a consolidation or merger in which the Company is the continuing corporation) of evidences of indebtedness or assets (other than cash dividends or cash distributions payable out of consolidated earnings or earned surplus or dividends or distributions for stock splits and stock dividends), or subscription rights or warrants, the exercise price then in effect will be adjusted by multiplying the exercise price in effect immediately prior to such payment date by a fraction, (x) the numerator of which shall be the total number of shares of our common stock outstanding multiplied by the market price per share of our common stock immediately prior to such payment date, less the fair market value (as determined by our Board of Directors in good faith) of the assets or evidences of indebtedness so distributed, or of related subscription rights or warrants, and (y) the denominator of which shall be the total number of shares of our common stock outstanding multiplied by such market price per share of Common Stock immediately prior to such payment date.

Fractional Shares.  We will not be required to issue fractions of shares of our common stock upon the exercise of the warrant.  If any fractional share of our common stock would be deliverable upon exercise of a warrant, we, in lieu of delivering such fractional share, will pay to the exercising warrantholder an amount in cash equal to the market price of such fractional share of our common stock on the date of exercise.
 
Holder of any warrants Not a Stockholder.  The SF Capital warrants do not confer upon holders thereof any voting, dividends or other rights as our shareholders.
 
 
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Warrants issued to investors, placement agents and certain consultants.  From September 2003 to July 2006, we issued warrants to various investors and consultants.  These warrants were issued as follows:  (A) In September 2003, we issued warrants exercisable for a total of 2.1 million shares of our common stock to: Equity Communications, LLC; Richard Stone, a director of the Company at the time; David Stone, a consultant and the brother of Richard Stone; and MCC Securities (the “September 2003 warrants”); (B) In January 2004, we issued warrants exercisable for 200,000 shares of our common stock to Equity Communications, LLC (the “ECC warrant”); (C) In February 2004, we issued warrants exercisable for a total of 32 million shares of our common stock to investors; warrants exercisable for approximately 11.5 million shares of our common stock upon the conversion of bridge loans by the holders thereof; warrants exercisable for a total of 3.2 million shares of our common stock to Moors & Cabot, Inc., the placement agent in our February 2004 private placement, and its selected dealers (collectively, the “February 2004 warrants”); (D) In February 2004 we issued warrants exercisable for 400,000 shares of our common stock to Sunrise Securities (the “Sunrise warrant”); (E) In November 2004 we issued warrants exercisable for 500,000 shares of our common stock to Equity Communications, LLC (the “November I warrant”); and (F)  In November 2004 we issued warrants exercisable for 200,000 shares of our common stock to David Stone (the “November II warrant”); (G) In November 2004 we issued warrants exercisable for 200,000 shares of our common stock to Edward Benjamin (the “November III warrant”): (H) In July 2006, we issued warrants exercisable for 922,500 shares of our common stock to private investors (the “July 2006 warrant”) and (I) In May 2007, we issued warrants exercisable for 300,000 shares of our common stock to a consultant (the “May 2007 warrant”).
 
The September 2003 warrants, the ECC warrant, the February 2004 warrants, the Sunrise warrant, the November I warrant, the November II warrant, the November III warrant, the July 2006 and the May 2007 warrant have substantially the same terms except for the exercise price, number of shares and the exercise period.  In addition, the February 2004 warrants have a call provision.  These warrants are described below, with any variation in terms specifically described.
 
Exercise Price and Terms. The September 2003 warrants are immediately exercisable, commencing September 2003, for a five year period at exercise prices ranging from $0.15 per share to $0.20 per share.  The ECC warrant is immediately exercisable, commencing January 2004, for a five-year period at an exercise price of $0.20 per share.  The February 2004 warrants issued to Moors & Cabot and its selected dealers are exercisable for a four-year period, commencing February 6, 2005, at an exercise price of $0.30 per share.  The other February 2004 warrants are immediately exercisable for a five-year period, commencing February 6, 2004, at an exercise price of  $0.30 per share.  The Sunrise warrant is immediately exercisable, commencing February 6, 2004, for a five-year period at an exercise price of $0.30 per share.  The November I warrant is immediately exercisable, commencing November 4, 2004, for a five-year period at an exercise price of $0.30 per share.  The November II warrant and November III warrant are immediately exercisable, commencing November 4, 2004, for a five-year period at an exercise price of $0.25 per share.  The July 2006 warrant is immediately exercisable, commencing July 10, 2006, for a five-year period at an exercise price of $0.0025 per share.  The May 2007 warrant is immediately exercisable, commencing May 2, 2007, for a five-year period at an exercise price of $0.305 per share.
 
Transferability. The warrants are not listed for trading on any exchange or for quotation on any Nasdaq Market, the OTC Bulletin Board or the Pink Sheets, but are transferable pursuant to a registration statement filed under the Securities Act of 1933 or an exemption from such registration.  The July 2006 warrants are non-transferable for one year from the date of issuance.
 
Adjustments.  The exercise price and the number of shares of our common stock issuable upon the exercise of the warrants are subject to adjustment from time to time as set forth hereinafter.

(a)           Stock dividends, Stock Splits, Reclassification.  If we pay a dividend or make a distribution on our common stock in shares of common stock, subdivide our outstanding shares of common stock into a greater number of shares or combine our outstanding shares of common stock into a smaller number of shares or issue by reclassification of our outstanding shares of common stock any shares of our capital stock (including any such reclassification in connection with a consolidation or merger in which we are the continuing corporation), then the number of shares of common stock issuable upon the exercise of the warrants and the exercise price then in effect shall be adjusted by us so that the holder of the warrant thereafter exercising his, her or its warrants shall be entitled to receive the number of shares of our common stock or other capital stock which the holder of the warrant would have received if the warrant had been exercised immediately prior to such event upon payment of the exercise price that has been adjusted to reflect a fair allocation of the economics of such event to the holder of the warrant.

(b)           Reorganization, reclassification, consolidation, merger or sale of all or substantially all of our assets.  If any capital reorganization, reclassification of our capital stock, our consolidation or merger with another corporation in which we are not the survivor, or sale, transfer or other disposition of all or substantially all of our assets to another corporation shall be effected, then, as a condition of such reorganization, reclassification, consolidation, merger, sale, transfer or other disposition, lawful and adequate provision shall be made whereby each holder of warrants shall thereafter have the right to purchase and receive in lieu of shares of our common stock, securities or assets as would have been issuable or payable with respect to or in exchange for a number of shares of our common stock for which the holder’s warrants were exercisable immediately prior to such reorganization, reclassification, consolidation, merger, sale, transfer or other disposition.

 
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(c)           Distribution of indebtedness or assets other than cash or shares of our common stock.  In case we fix a payment date for the making of a distribution to all holders of common stock (including any such distribution made in connection with a consolidation or merger in which the Company is the continuing corporation) of evidences of indebtedness or assets (other than cash dividends or cash distributions payable out of consolidated earnings or earned surplus or dividends or distributions for stock splits and stock dividends), or subscription rights or warrants, the exercise price then in effect will be adjusted by multiplying the exercise price in effect immediately prior to such payment date by a fraction, (x) the numerator of which shall be the total number of shares of our common stock outstanding multiplied by the market price per share of our common stock immediately prior to such payment date, less the fair market value (as determined by our Board of Directors in good faith) of the assets or evidences of indebtedness so distributed, or of related subscription rights or warrants, and (y) the denominator of which shall be the total number of shares of our common stock outstanding multiplied by such market price per share of Common Stock immediately prior to such payment date.

Call Provision.  The call provision applies only to the February 2004 warrants.  In the event that the closing bid price of a share of our common stock as reported on the exchange or stock market on which our common stock may then be listed or quoted equals or exceeds $1.00 (appropriately adjusted for any stock split, reverse stock split, stock dividend or other reclassification or combination of the Common Stock occurring after the date hereof) for twenty (20) consecutive trading days commencing after the date of this prospectus, we, upon thirty (30) days prior written notice (the “Notice Period”) given to the holder of the warrants within one business day immediately following the end of such twenty (20) trading day period, may call the warrant, in whole but not in part, at a redemption price equal to $0.05 per share of common stock then purchasable pursuant to the warrant; provided that (i) the Company simultaneously calls all warrants that have been issued on the same terms, (ii) all of the shares of common stock issuable under the warrants either (A) are registered pursuant to an effective registration statement  which has not been suspended and for which no stop order is in effect, and pursuant to which the holder of the warrants is able to sell such shares of common stock at all times during the Notice Period or (B) no longer constitute “registerable securities” (as defined in the applicable registration rights agreement), and (iii) in the case of the February 2004 warrants issued to Moors & Cabot and its selected dealers, the one year lock up period has expired.  Notwithstanding any such notice by us, the holder of the warrants shall have the right to exercise this Warrant prior to the end of the Notice Period.
 
Fractional Shares.  We will not be required to issue fractions of shares of our common stock upon the exercise of the warrant.  If any fractional share of our common stock would be deliverable upon exercise of a warrant, we, in lieu of delivering such fractional share, will pay to the exercising warrantholder an amount in cash equal to the market price of such fractional share of our common stock on the date of exercise.
 
Holder of any warrants Not a Stockholder.  The September 2003 warrants, the ECC warrant, the February 2004 warrants, the Sunrise warrant, the November I warrant, the November II warrant, the November III warrant, the July 2006 warrant and the May 2007 warrant do not confer upon holders thereof any voting, dividends or other rights as our shareholders.
 
Warrants issued to consultants and former employees by our predecessor, Hemoxymed, Inc.  In September 2002, prior to our merger with Molecular Geriatrics, we issued warrants exercisable for (i) approximately 1.6 million shares of our common stock to certain of our shareholders in exchange for past services (the “Hemoxymed warrants”) and (ii) 800,000 shares to Prism Ventures as part of a consulting agreement for financial consulting services (the “PV warrants”).  The terms of the Hemoxymed warrants and the PV warrants are as follows:
 
Exercise Price, Vesting and Term.  The Hemoxymed warrants are exercisable, without any vesting, for a period of seven years, commencing September 2002, at an exercise price of $0.0001 per share.  The PV warrants are exercisable, without any vesting, for a period of ten years, commencing September 10, 2002, at an exercise price of $0.20 per share.
 
Transferability. The Hemoxymed warrants and the PV warrants are transferable only with our prior written consent.
 
 
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Adjustments.  The number of ordinary shares issuable upon the exercise of the Hemoxymed warrants and the PV warrants and the exercise price of the Hemoxymed warrants and the PV warrants will be proportionately adjusted for any increase or decrease in the number of issued shares of common stock as a result of any stock split, reverse stock split, stock dividend combination or reclassification of our common stock or any other increase or decrease in the number of issued and outstanding shares of our common stock effected without the receipt of consideration (excluding any conversion of a convertible security).
 
Merger or Asset Sale.   In the event of a merger of the Company with or into another corporation, or the sale of substantially all of the assets of the Company, the warrant will be assumed or an equivalent warrant or right substituted by the successor corporation or a parent or subsidiary of the successor corporation.
 
Registration.  We have agreed to register the shares of our common stock underlying the Hemoxymed warrants on a Form S-8 within 120 days after the effective date of our prospectus dated July 28, 2004.  We also agreed to register the shares of our common stock underlying the PV warrants.
 
Conversion Right.  In lieu of payment of the exercise price, at any time the exercise price is less than the market price of our common stock (such difference being the “Per Share Value of the PV warrant”), the holder of the PV warrants shall have the right to require us to convert the PV warrants, in whole or part, into shares of our common stock as follows (the “Conversion Right”):  Upon exercise of the Conversion Right, we shall deliver to the holder of the PV warrants (without payment by the holder of any of the exercise price) up to that number of the shares of our common stock equal to the quotient obtained by dividing (x) the product of (i) the Per Share Value of the PV warrant at the time the Conversion Right is exercised and (ii) the number of shares of our common stock issuable upon exercise of the PV warrants immediately prior to the exercise of the Conversion Right by (y) the market price of one share of our common stock immediately prior to the exercise of the Conversion Right.


INTEREST OF NAMED EXPERTS AND COUNSEL

No expert or counsel named in this prospectus as having prepared or certified any part of this prospectus or having given an opinion upon the validity of the securities being registered or upon other legal matters in connection with the registration or offering of the common stock was employed on a contingency basis, or had, or is to receive, in connection with the offering, a substantial interest, direct or indirect, in the registrant or any of its parents or subsidiaries. Nor was any such person connected with the registrant or any of its parents or subsidiaries as a promoter, managing or principal underwriter, voting trustee, director, officer, or employee.

The consolidated financial statements of Applied NeuroSolutions, Inc. and subsidiaries (a company in the development stage) as of December 31, 2007 and 2006 and for each of the years then ended has been included herein and in the Registration Statement in reliance upon the report of Virchow Krause & Company, LLP, an independent registered public accounting firm, appearing elsewhere herein, and upon the authority of said firm as experts in accounting and auditing.

Certain legal matters in connection with this offering and Registration Statement are being passed upon by the law firm Eilenberg, Krause & Paul LLP, New York, New York.


DESCRIPTION OF BUSINESS

Applied NeuroSolutions, Inc. (“APNS” or the “Company”), is a development stage biopharmaceutical company primarily engaged in the research and development of novel therapeutic targets for the treatment of Alzheimer’s disease (“AD”) and diagnostics to detect AD.
 

Alzheimer’s disease is the most common cause of dementia among people age 65 and older.  Dementia is the loss of memory, reason, judgment and language to such an extent that it interferes with a person’s daily life and activities.  Currently it is estimated that over five million people in the U.S. have Alzheimer’s disease and the national cost of caring for people with Alzheimer’s is estimated to exceed $148 billion annually.    The market for AD therapy is expected to grow to 21 million patients by 2010 in the seven major pharmaceutical markets (USA, France, Germany, Italy, Spain, U.K. and Japan), according to BioPortfolio, Ltd.

 Our core technology in the AD field is based on exclusive licenses with AECOM covering all diagnostic and therapeutic applications in the field of neurodegenerative disease discovered in Dr. Peter Davies’ laboratories at Albert Einstein College of Medicine (“AECOM”).  Dr. Davies’ research has focused on AD and the roll of certain proteins; primarily hyperphosphorylated tau, which are involved in the formation of neurofibrillary tangles within neurons (nerve cells).  Excessive phosphorylation of tau (the addition of one or more phosphate groups, which are comprised of phosphorous and oxygen, to a molecule) prevents it from stabilizing microtubules, thereby causing the breakdown of the transit system of the nerve cell.  This internal neuronal damage leads to the development of the paired helical filaments and neurofibrillary tangles which are contributing factors to the eventual death of the neurons related to Alzheimer’s disease.  Tau in this abnormally phosphorylated form is the building block for the paired helical filaments and the neurofibrillary tangles (“NFTs”); one of the hallmark pathologies associated with AD.  There is a high correlation among the presence of hyperphosphorylated tau, NFTs and AD.  Thus, it is believed that the hyperphosphorylated tau represents an early abnormality in the progression of Alzheimer’s disease.

 
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Articles published in the scientific journals Nature (co-authored by Dr. Peter Davies) and Proceedings of the National Academy of Sciences have described research showing that a mutation in the gene that codes for tau is associated with dementia.  The research described in the articles demonstrates that abnormal tau represents an appropriate target for research on neurodegenerative diseases, such as Alzheimer’s disease.  Dr. Davies has been applying his expertise in research directed towards abnormal tau for many years and, together with Applied NeuroSolutions scientists, has developed a large number of proprietary antibodies which are being used in the development of our diagnostic pipeline to detect AD, and targets directed at AD therapeutic solutions.

In a collaboration with Eli Lilly and Company (“Lilly”), we are involved in the discovery and development of novel therapeutics for the development of treatments for Alzheimer’s disease based upon a concept developed by Peter Davies, Ph.D., the Company’s founding scientist and the Burton P. and Judith Resnick Professor of Alzheimer’s Disease Research at AECOM.  As a result of Dr. Davies’ research, we and Lilly are focused on discovery of unique therapeutics that may be involved in a common intracellular phosphorylation pathway leading to the development of the abnormal, destructive brain structures, amyloid plaques and neurofibrillary tangles, that are characteristic of Alzheimer’s disease. We have identified various biomarkers that we believe will aid in the development of diagnostics and drug specific markers that could also play a role in the development of new AD treatments.

In November 2006, we entered into an agreement with Eli Lilly and Company (Lilly”) to develop therapeutics to treat AD. Pursuant to the terms of the agreement, we received $2 million in cash, including an equity investment of $500,000, from Lilly, plus we will receive annual research and development support for the duration of the collaboration agreement. In addition, Lilly will, based on the achievement of certain defined milestones, provide us with up to $20 million in milestone payments for advancing our proprietary target to a therapeutic compound.  The collaboration has also made progress on other targets that are part of the collaboration that could provide milestone payments to us over time of up to $10 million for advancing each of these other targets to a therapeutic compound.  There is no limit to the number of targets that we could receive milestone payments from Lilly.  Royalties are to be paid to us for AD drug compounds brought to market that result from the collaboration.  There is no limit on the number of drug compounds for which royalty payments may be due to us.  Lilly received the exclusive worldwide rights to the intellectual property related to our expertise in understanding the molecular neuropathology of AD as it pertains to the formation of neurofibrillary tangles in the development of AD therapeutics.  Lilly will fund the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from our collaboration.

Since the start of our collaboration with Lilly, the collaboration management structure, working teams and external resources have become fully operational.  The key assets and proprietary tools have been appropriately transferred to support work being undertaken by each of Dr. Davies, Lilly and APNS.  The first internal milestone on the proprietary tau-related APNS target was reached in the second quarter of 2007 and the next internal milestone was achieved in the first quarter of 2008.  Key in-vivo models have been established with the goal to validate our tau-based target.  Our collaboration with Lilly has made good progress on the milestones established by the program management for the proprietary tau-related APNS target.  Our first paid milestone is targeted for achievement in late 2008 to early 2009.  Our collaboration with Lilly continues to make good progress toward additional tau-based targets with an additional target being screened and validation studies underway for other targets.

We have also been working on both a cerebrospinal fluid (“CSF”) based test and serum based tests to detect AD at an early stage.  In a research setting, our CSF-based test has demonstrated an ability to differentiate AD patients from those with other diseases that have similar symptoms.

We are utilizing the knowledge gained during the development of our CSF-based diagnostic test to aid in the development of serum-based diagnostic tests to detect Alzheimer’s disease, specifically a screening test to rule out AD as well as the detection of our ptau biomarker to support the diagnosis of AD.  In January 2006, we entered into a research agreement with Nanosphere, Inc., a nanotechnology-based molecular diagnostics company, to assist us in the development of a serum-based diagnostic test for AD.  Work performed during the research agreement resulted in Nanosphere and APNS scientists achieving a better understanding (in January 2007) of the tools necessary to advance the development of a serum-based AD diagnostic test with our scientifically accepted biomarkers.  We established a project plan and began developing these key tools in early 2007.  The first of these tools to meet our criteria for potential use in serum diagnostic development were identified as appropriate in the first quarter of 2008.

 
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We sought additional expertise and resources by conducting a scientific advisory board meeting that brought together APNS scientists, Dr. Davies and three outside diagnostic experts to assist us in assessing the most effective approaches and resources to advance our diagnostic development programs.  Through 2007, we followed our work plans to develop antibody tools and we achieved a key milestone in the first quarter of 2008 by identifying several high affinity antibodies that meet our requirements.  These tools will support advancing development of a “rule out” serum based test for AD.  Additional back up tool options to support a “rule out” test are also in development.  In addition, tools directed toward the development of a ptau biomarker based test in serum that could support the early identification of AD are targeted for completion in the second quarter 2008.  Throughout the tool development process we have been identifying specialized technologies that may enable us to advance our diagnostic development programs.  Technology assessments have been initiated.

In order to maximize the value, and minimize the time to market, of our diagnostic programs, we may seek some form of partnering, such as collaborations, strategic alliances and/or licensing arrangements.  Currently there is no FDA-approved diagnostic test to detect AD.

Our product farthest along in development is a CSF-based diagnostic test to detect whether a person has AD.  This diagnostic test, based upon the detection of a certain AD associated protein found in the CSF of AD patients, has achieved, based on published research validation studies, overall sensitivity and specificity in the range of 85% to 95%.  This is based on extensive testing in our lab, utilizing in excess of 2,000 CSF samples to differentiate patients diagnosed with AD from patients diagnosed with other forms of dementia and relevant neurological diseases, including major depression, as well as healthy controls.  We are also developing antibodies that may allow for a reduction in the tests incubation time.  Our most recent research has sought to further substantiate the utility of the test in the mild cognitive impairment (“MCI”) population, as evidenced by reports published in Neurobiology of Aging in September 2007 and Neurology in December 2007.

In order to maximize the value, and minimize the time to commercialization, of our diagnostic programs, we are exploring additional partnerships, including collaborations, strategic and technical alliances and/or licensing arrangements.  We are having discussions with experts and companies regarding various approaches, technologies and opportunities for collaboration and to assist us in advancing the development of our diagnostic tests towards commercialization.

History

On September 10, 2002, Hemoxymed, Inc. and Molecular Geriatrics Corporation (“MGC”) established a strategic alliance through the closing of a merger (the “Merger”).  The Merger Agreement provided that the management team and Board of Directors of MGC took over control of the merged company.  The transaction was tax-free to the shareholders of both companies.  In October 2003, we changed our name to Applied NeuroSolutions, Inc.  The Merger transaction has been accounted for as a reverse merger.  For financial reporting purposes, MGC is continuing as the primary operating entity under the Company’s name, and its historical financial statements have replaced those of the Company.  Thus, all financial information prior to the Merger date is the financial information of MGC only.

After the Merger, we had two wholly-owned operating subsidiaries, which we dissolved during 2004.  The assets of these dissolved subsidiaries were transferred to us.

One of the wholly-owned operating subsidiaries we dissolved was MGC, a development stage biopharmaceutical company incorporated in November 1991, with operations commencing in March 1992, to develop diagnostics to detect AD, and therapeutic targets directed at AD solutions.

The other wholly-owned operating subsidiary we dissolved was Hemoxymed Europe, SAS, a development stage biopharmaceutical company incorporated in February 1995 to develop therapies aimed at improving tissue oxygenation by increasing oxygen release from hemoglobin to provide therapeutic value to patients with serious, medical needs.  We are not currently funding the development of this technology.

We are subject to risks and uncertainties common to small-cap and micro-cap biotech companies, including competition from larger, well capitalized entities, patent protection issues, availability of funding and government regulations.  We have experienced significant operating losses since our inception.  As of December 31, 2007, we had an accumulated deficit of approximately $48.0 million.  Notwithstanding payments that we may receive under our collaboration agreement with Eli Lilly and Company, we expect to incur operating losses over the next several years as our research and development efforts continue.  We need to raise additional capital prior to the end of the first quarter 2009 to continue our operations.

 
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We currently have no regulatory approved therapeutic or diagnostic products on the market and have not received any commercial revenues from the sale or license of any such products.

Alzheimer's Disease Background

Alzheimer’s disease is the most common cause of dementia among people age 65 and older.  Dementia is the loss of memory, reason, judgment and language to such an extent that it interferes with a person’s daily life and activities.  Currently it is estimated that over five million people in the U.S., and 30 million people worldwide, have Alzheimer’s disease and the national cost of caring for people with Alzheimer’s is estimated to exceed $148 billion annually.  The market for AD therapy is expected to grow, based on the aging demographic of the seven major pharmaceutical markets (USA, France, Germany, Italy, Spain, U.K. and Japan).  Currently there are only five drugs approved in the U.S. to treat AD.  All of these drugs are primarily acetylcholinesterase inhibitors and are only beneficial in treating symptoms associated with AD in a minority of AD patients for a very limited time period.

Alzheimer’s disease is an intractable, chronic and progressively incapacitating disease characterized by the degeneration and death of several types of neurons in certain regions of the brain.  Patients affected by the disease initially suffer loss of memory, then a decline of intellectual abilities severe enough to interfere with work and activities of daily living, followed by severe dementia and, finally, death.  This illness, currently estimated to affect over five million people in the United States, and as many as twenty-four million people worldwide, is a leading cause of death behind cardiovascular disease and cancer.  While the disease is most common in the elderly, affecting nearly 10% of people age 65 and older and up to 50% of people age 85 and older, it has been diagnosed in patients in their 40’s and 50’s.  Alzheimer’s disease, at present, can be conclusively diagnosed only by histological examination of the brain by biopsy or autopsy.  The diagnosis of patients suspected of having AD is therefore typically made through a process of elimination, by conducting neurological and psychiatric examinations, extensive laboratory tests and brain imaging to rule out other conditions (such as stroke, brain tumor, or depression) that may exhibit similar symptoms.

Alzheimer’s disease was first described in 1907 by Dr. Alois Alzheimer, a German psychiatrist who discovered large numbers of unusual microscopic deposits in the brain of a demented patient upon autopsy.  These deposits, called amyloid plaques and neurofibrillary tangles, are highly insoluble protein aggregates that form in the brains of AD patients in particular regions, including those involved with memory and cognition.  Generally, amyloid plaques are deposited on the surface of neurons, whereas neurofibrillary tangles are formed within neurons.  The plaques and tangles are associated with degeneration and loss of neurons.  The actual loss of neurons, as well as the impaired function of surviving neurons, is generally believed to be the key neuropathological contributors to the memory loss and dementia that characterizes Alzheimer’s disease.

Therapeutic Program

We are working to discover and develop novel therapeutic targets for the development of treatments for AD.  The basis for this work is Dr. Davies discovery of a novel initiation point that we believe is common to the ultimate development of both the neurofibrillary tangles and amyloid plaques.  A patent application was filed in 2005 covering Dr. Davies work relative to this area.  In November 2006, we entered into an agreement with Eli Lilly and Company to develop therapeutics to treat AD.  In conjunction with Lilly, we are developing novel therapeutics for the treatment of Alzheimer’s disease based upon a concept developed by Dr. Davies.  The agreement forms a collaboration that will combine the expertise, research tools and tau-based approach advanced by Dr. Davies and our team at APNS with the scientists, therapeutic development expertise and financial resources at Eli Lilly and Company.   Lilly has an exclusive world-wide license to manufacture, market and sell any AD therapeutic that comes to market from our collaboration agreement.

The market potential for a drug to effectively treat Alzheimer’s disease is extremely large.  Currently there are only five drugs approved in the U.S. to treat AD.  All of these drugs are primarily acetylcholinesterase inhibitors and are only beneficial in treating symptoms associated with AD in a minority of AD patients.  Despite the problems with the currently approved therapeutics, market research data indicate that these drugs sold nearly $4.5 billion in the U.S. during 2007.  The therapeutic market has been estimated to be in excess of $6 billion for effective therapeutics by 2010 in the U.S.



 
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Diagnostic Program

Alzheimer’s disease, at present, can be conclusively diagnosed only by histological examination of the brain by biopsy or autopsy.  The diagnosis of patients suspected of having AD is therefore typically made through a process of elimination, by conducting neurological and psychiatric examinations, extensive laboratory tests and brain imaging to rule out other conditions (such as stroke, brain tumor, or depression) with similar symptoms.  The AD predictive accuracy of such exams is generally in the range of 80%-90% in some of the larger AD centers, but is usually closer to 60%, on average, when diagnosed outside of the larger AD centers.  Costs to patients for such testing can range from $1,000 - $4,000, including imaging procedures.  A simple, predictive, accurate and cost effective diagnostic test would therefore address a large unmet medical need.  If the test was a serum based test, it could potentially be utilized as a routine screening test.

Our approach to meeting this need for a diagnostic test is based on Dr. Davies’ research of the tau pathology, and revolves around developing a pipeline of diagnostic tests that could include: (i) the detection of hyperphosphorylated tau in CSF, (ii) a screening test to rule out AD in serum, and (iii) the detection of hyperphosphorylated tau in serum.  Competitive diagnostics in development, as well as some that are marketed through reference laboratories, include approaches which attempt to identify AD patients by measuring: (i) total tau or phosphorylated tau in CSF, either individually, or as part of a panel, (ii) beta amyloid, (iii) neural thread protein in CSF and/or urine, (iv) amyloid derived diffusible ligands (ADDL’s) in CSF, (v) imaging plaques in the brain, or (vi) employing proteomic or genetic markers for AD.

We have developed a prototype diagnostic test utilizing cerebrospinal fluid (“CSF”).  To date, with our diagnostic test, we have conducted numerous validation studies utilizing in excess of 2,000 CSF samples.  These studies were performed in our laboratory and were designed using human CSF, in blinded samples, to determine our test’s ability to differentiate patients diagnosed with AD from patients diagnosed with other forms of dementia and relevant neurological diseases, including major depression, as well as healthy controls.  Published studies have shown the ability of our test to correctly identify the patients diagnosed with AD with an overall sensitivity and specificity in the 85% to 95% range.  The studies have been published in peer reviewed scientific journals such as Neuroscience Letters, Archives of Neurology, and American Journal of Psychiatry.  We currently have 20 peer-reviewed publications that report the performance of our CSF-based test in various patient populations, including AD, mild cognitive impairment (“MCI”), depression, other neurological disorders and normal controls.  We have shown with our test that phosphotau concentrations in CSF correlate well with the degree of cognitive impairment.   A study published in 2001 in Annals of Neurology addressed the relationship between phosphotau levels in CSF and natural AD progression.  In addition, a report published in the November 2006 edition of Brain describes a study utilizing our CSF-based test that importantly shows statistically significant correlations of phosphotau 231 levels from 26 living patients with the neurofibrillary pathology subsequently observed in those 26 patients upon autopsy.

A study published in the January 2004 edition of Archives of General Psychiatry has shown that detecting phosphorylated tau (“ptau”) proteins in CSF comes closest to fulfilling the criteria of a biological marker for AD.  This publication reported that our CSF-based test exceeded standards for an AD diagnostic test established by the National Institute of Aging and the Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association in a 1998 published “Consensus Report”.  It was determined by that group that a successful biological marker would be one that had a sensitivity level and specificity level of at least 80%.   A Position Paper, “Research Criteria for the Diagnosis of Alzheimer’s Disease: Revising the NINCDS-ADRDA Criteria”, was published in the August 2007 edition of Lancet Neurology that describes suggested revisions to the criteria for the diagnosis of Alzheimer’s disease, including the use of CSF biomarkers, specifically referencing our CSF-based p-tau 231 test.

Studies published in the December 2005 edition of Neuroscience Letters and in the March 2006 journal Neurobiology of Aging support the use of our CSF-based diagnostic test in identifying individuals with mild cognitive impairment (“MCI”) who, over time, are most likely to develop AD.

Two studies published in 2007 show the ability of our CSF-based test to be a strong predictor of the decline from MCI to AD.  The September 2007 online edition of Neurobiology of Aging presented a study comparing five of the best-known CSF biomarkers for AD.  Our ptau biomarker was the strongest predictor of the decline from MCI to AD.  The December 2007 issue of Neurology published an internationally based multi-center study that demonstrated our ptau biomarker was a significant predictor of the decline from MCI to AD in a clinically useful time period 1.5 years.

 
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We are utilizing the knowledge gained during the development of our CSF-based diagnostic test to aid in the development of serum-based diagnostic tests to detect Alzheimer’s disease, specifically a screening test to rule out AD as well as the detection of our ptau biomarker to support the diagnosis of AD.   In January 2006, we entered into a research agreement with Nanosphere, Inc., a nanotechnology-based molecular diagnostics company, to assist us in the development of a serum-based diagnostic tests for AD.   Work performed during the research agreement resulted in Nanosphere and APNS scientists achieving a better understanding (in January 2007) of the tools necessary to advance the development of a serum-based AD diagnostic test with our scientifically accepted biomarkers.  APNS established a project plan and began developing these key tools in early 2007. The first of these tools to meet our criteria for potential use in serum diagnostic development were identified as appropriate in the first quarter of 2008.

We sought additional expertise and resources by conducting a scientific advisory board meeting that brought together APNS scientists, Dr. Davies and three outside diagnostic experts to assist us in assessing the most effective approaches and resources to advance our diagnostic development programs.  Through 2007, we followed our work plans to develop antibody tools and we achieved a key milestone in the first quarter of 2008 by identifying several high affinity antibodies that meet our requirements.  These tools will support advancing development of a “rule out” serum based test for AD.  Additional back up tool options to support a “rule out” test are also in development.  In addition, tools directed toward the development of a ptau biomarker based test in serum that could support the early identification of AD are targeted for completion in the second quarter 2008.  Throughout the tool development process we have been identifying specialized technologies that may enable us to best utilize Nanosphere’s proprietary technology, or other appropriate technologies, to further evaluate and develop serum-based diagnostic testsadvance our diagnostic development programs.  Technology assessments have been initiated.  In order to maximize the value, and minimize the time to market, of our diagnostic programs, we may seek some form of partnering, such as collaborations, strategic alliances and/or licensing arrangements.  Currently there is no FDA-approved diagnostic test to detect AD.

Before approval by the FDA for general sale, under certain conditions, companies can supply either “investigational use only” or “research use only” assay kits under the Clinical Laboratory Improvement Amendment (“CLIA”) of 1988.  As part of our plan to seek commercialization opportunities for our proposed diagnostic products, we may pursue some form of agreement with a reference lab.

Transgenic Mice Model

To date, no widely accepted animal model that exhibits both AD pathologies has been developed.  Dr. Peter Davies, through collaboration with a researcher at Nathan Klein Institute (“NKI”), has developed a transgenic mouse containing the human tau (“htau”) gene that develops human paired helical filaments, the building blocks of the neurofibrillary tangles, which are known to be involved in the pathology of Alzheimer’s disease. The pathology in these mice is Alzheimer-like, with hyperphosphorylated tau accumulating in cell bodies and dendrites as neurofibrillary tangles.  In addition, these transgenic mice have exhibited extensive neuronal death which accompanies the tau pathology.  These transgenic mice could be used for testing the efficacy of therapeutic compounds.  AECOM and the New York State Office of Mental Health, the agency that oversees NKI, each have an interest in these transgenic mice.  Through our license agreements with AECOM, we have the license rights to AECOM’s interest in these transgenic mice.  In 2006, we entered into additional license agreements that provide us with the exclusive rights to sell these mice.  The mice are currently available through Jackson Laboratories.  In December 2006, we entered into an agreement to sell a breeding pair of these mice.

Research and Product Development

During the next twenty-four (24) months, we expect to spend a significant amount of our financial resources on research and development activities.  We incurred costs of approximately $1,659,000 in 2007 and $2,119,000 in 2006 on research and development activities.  Since we are not yet engaged in the commercial distribution of any diagnostic or therapeutic products and we have no revenues from the sale of any such products, these research and development costs must be funded through equity or debt financing or payments received from collaborators.  Throughout our collaboration with Eli Lilly and Company, Lilly will provide annual research and development support that partially offsets these expenses.  We estimate that we will incur costs of approximately $150,000 to $180,000 per month on research and development activities over the next twenty-four months.  This excludes the non-cash charges resulting from accounting for equity instruments included in such monthly expenditures.  These expenditures, however, may fluctuate from quarter-to-quarter and year-to-year depending upon the resources available and our development schedule.  Lilly will fund the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from our collaboration.  If we were to conduct diagnostic validation and proof of concept work, and/or diagnostic clinical trials, our research and development expenditures would most likely increase significantly.  In addition, regulatory decisions and competitive developments may significantly influence the amount of our research and development expenditures.

 
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Sales and Marketing

We do not have marketing and sales expertise or personnel.  As we currently do not intend to develop a marketing and sales force, we will depend on arrangements with corporate partners or other entities for the marketing and sale of our proposed products.  Under our agreement with Eli Lilly and Company, Lilly has an exclusive world-wide license to market and sell any AD therapeutic that comes to market from our collaboration agreement.  We do not currently have any agreements with partners or other entities to provide sales and marketing services for our proposed diagnostic products, but would seek those arrangements at the appropriate time.

Manufacturing

We currently do not have any facilities suitable for manufacturing on a commercial scale basis any of our proposed products nor do we have any experience in volume manufacturing.  We will either find our own manufacturing facilities, rely upon third-party manufacturers to manufacture our proposed products in accordance with these regulations, or we will most likely utilize the capabilities of our partners and/or collaborators.  Under our agreement with Eli Lilly and Company, Lilly has an exclusive world-wide license to manufacture any therapeutic for AD that comes to market from our collaboration agreement.

Competition

Companies in the pharmaceutical, diagnostic and biotechnology fields are subject to intense competition.  We compete with numerous larger companies that have substantially greater financial and other resources and more experience.  The principal factors affecting our competitive markets include scientific and technological factors, the availability of patent and other protection for technology and products, the ability, length of time and cost required to obtain governmental approval for testing, manufacturing and marketing and physician acceptance.  Companies that complete clinical trials, obtain regulatory approvals and commence commercial sales of their products before us may achieve a significant competitive advantage.  In addition, such companies may succeed in developing products that are more effective and less costly than products that may be developed by us.  There can be no assurance that developments by other companies will not render our products or technologies obsolete or noncompetitive or that we will be able to keep pace with the technological developments of our competitors.

We believe that some of our competitors are in the process of developing technologies that are, or in the future may be, the basis for competitive products.  Some of these products may have an entirely different approach or means of accomplishing the desired therapeutic or diagnostic effect than products being developed by us.  These competing products may be more effective and less costly than the products developed by us.

Significant levels of research within our fields of interest occur at universities, non-profit institutions, and for-profit organizations.  These entities compete with us in recruiting skilled scientific talent.

We believe that our ability to compete successfully will depend upon our ability to create and maintain scientifically advanced technology, obtain adequate funding, develop proprietary products, attract and retain scientific personnel, obtain patent or other protection for our products, develop strategic alliances to enhance the likelihood of success, obtain required regulatory approvals and manufacture and successfully market our products either directly by us or through our collaboration with Eli Lilly and Company and other collaborations or partnerships we may enter into.

Diagnostics

There is currently no FDA-approved diagnostic to detect Alzheimer’s disease (“AD”), although there are tests available under the CLIA exemption through reference labs.  If any of our current diagnostic programs are ultimately successfully marketed, they would compete against, or augment, the most widely used current practice of detecting AD through a battery of tests, namely neurological and psychiatric examinations, extensive laboratory tests and brain imaging to rule out other conditions (such as stroke, brain tumor, or depression) with similar symptoms.    The AD predictive accuracy of such a battery of exams is generally in the range of 80%-90% in some of the larger AD centers, but is usually closer to 60% when diagnosed outside of the AD centers.  Costs to patients for such testing can range from $1,000 - $4,000, including imaging procedures.  A simple, predictive, accurate and cost effective diagnostic test could, therefore, be an attractive alternative for medical practitioners and insurers to the current practice to detect AD.  If the test was a serum-based test, it could potentially be utilized as a routine screening test.

 
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We are aware of other companies and academic institutions pursuing the development of biochemical markers to be utilized in the diagnosis of AD.  Potential competitors include Nymox Pharmaceutical Corp. and Innogenetics, who have developed diagnostic tests for AD.  Athena Diagnostics has “research use only” type CSF-based tests available, and others (Satoris, Power 3 Medical, Proteosome Science, Acumen and Bio-Rad/Cyphergen) have programs directed toward identifying proteomic or genetic markers for AD.  Competitive diagnostics in development, as well as some that are marketed through reference laboratories, include approaches which attempt to identify AD patients by measuring: (i) normal tau, total tau or phosphorylated tau in CSF, either individually, or as part of a panel, (ii) beta amyloid, (iii) neural thread protein in CSF and/or urine, (iv) amyloid derived diffusible ligands (ADDL’s) in CSF, (v) imaging plaques in the brain, or (vi) employing proteomic or genetic markers for AD.  Much of our knowledge of potential competitors and their diagnostic tests comes from our review of published articles in scientific journals.  Publications and other information publicly available indicate that tests being developed by these companies and others are unable to adequately distinguish AD from other brain disorders or are in too early a development stage to be evaluated.  At this time, we believe our CSF-based diagnostic test exhibits a unique ability to recognize early stage AD and to differentiate patients diagnosed with AD from patients diagnosed with other forms of dementia and relevant neurological diseases, including major depression, as well as healthy controls.  In addition, our CSF-based diagnostic test has shown to be a strong predictor of the decline from MCI to AD.

Therapeutics

The only products with FDA approved label claims for pharmaceutical management of AD in the U.S. provide symptomatic treatment through the use of acetylcholinesterase (“AchE”) inhibitors, of which there are five currently marketed by some of the largest pharmaceutical companies, including Aricept (Pfizer), Exelon (Novartis), Reminyl (Johnson & Johnson), Tacrine (Pfizer) and Memantine (Forest Labs).  Despite limited clinical effectiveness and a poor safety and side effect profile, sales of these drugs in 2007 were nearly $4.5 billion, according to CNN.com.

The market for AD therapy is expected to grow, based on the aging demographics of the seven major pharmaceutical markets (USA, France, Germany, Italy, Spain, U.K. and Japan).  AchE inhibitors remain the largest class of drugs within the late stage development pipeline.  However, their apparent limited efficacy would seem to provide an opportunity for other promising compounds.  It is estimated that over 100 potential compounds are currently being developed by both major pharmaceutical companies as well as small biotech companies.  The lack of current effective pharmacological therapy for an increasing AD population provides an attractive opportunity for therapeutics we may discover utilizing our novel therapeutic approach in our collaboration with Eli Lilly and Company.

Patents, licenses, trade secrets and proprietary rights

Our success depends and will continue to depend, in part, upon our ability to retain our exclusive licenses, to maintain patent protection for our products and processes, to preserve our trade secrets and proprietary information and to operate without infringing the proprietary rights of third parties.  We believe in securing and supporting a strong competitive position through the filing and prosecution of patents where available, and through trade secrets, when patenting is precluded.

We have filed patent applications in the U.S. for composition of matter and use of compounds to treat AD, method of use, as well as aspects of our diagnostic test technologies for use in MCI and methods for developing novel therapeutic screens for the discovery of compounds useful in the treatment of AD, novel approaches to therapeutic intervention, transgenic mouse production and a novel gene.  Patent Cooperation Treaty (P.C.T.) applications have been filed abroad, when applicable.

In March 2004 we were notified by email from Innogenetics, a Belgian biopharmaceutical company involved in specialty diagnostics and therapeutic vaccines, that it believes the CSF diagnostic test we have been developing uses a technology that is encompassed by the claims of their U.S. patents.  Innogenetics also informed us that it could be amenable to entering into a licensing arrangement or other business deal with APNS regarding its patents.  We had some discussions with Innogenetics concerning a potential business relationship, however no further discussions have been held since the second quarter of 2006.

We have reviewed these patents with our patent counsel on several occasions prior to receipt of the email from Innogenetics and subsequent to receipt of the email.  Based on these reviews, we believe that our CSF diagnostic test does not infringe the claims of these Innogenetics patents.  If we were unable to reach a mutually agreeable arrangement with Innogenetics, we may be forced to litigate the issue.  Expenses involved with litigation may be significant, regardless of the ultimate outcome of any litigation.  An adverse decision could prevent us from possibly marketing a future diagnostic product and could have a material adverse impact on our business.
 
 
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Alzheimer's disease technology license
 
We have various License and Collaborative Research Agreements (the "Agreements") with Albert Einstein College of Medicine ("AECOM").  These Agreements grant us the exclusive rights to neurodegenerative disease technology, primarily Alzheimer's disease technology for diagnostic and therapeutic applications from Dr. Peter Davies’ lab at AECOM.  These Agreements were amended in March 2002, in September 2002, and again in October 2006 and remain effective on an evergreen basis.  The minimum annual payments to be made to AECOM, which consist of payments due for support of research conducted in Dr. Davies' lab and for annual license maintenance, are as follows:
 
Year
 
Amount
2008 and each subsequent year
 
$500,000
 
We are obligated to continue to pay AECOM $500,000 for each year after 2007 in which the Agreements are still in effect.  In addition, we are obligated to pay AECOM a percentage of all revenues we receive from selling and/or licensing aspects of the AD technology licensed under the Agreements that exceeds the minimum obligations reflected in the annual license maintenance payments.
 
Confidentiality and assignment of inventions agreements

We require our employees, consultants and advisors having access to our confidential information to execute confidentiality agreements upon commencement of their employment or consulting relationships with us.  These agreements generally provide that all confidential information we develop or make known to the individual during the course of the individual's employment or consulting relationship with us must be kept confidential by the individual and not disclosed to any third parties.  We also require all of our employees and consultants who perform research and development for us to execute agreements that generally provide that all inventions conceived by these individuals will be our property.

Government regulation

The research, development, manufacture, and marketing of our potential products are subject to substantial regulation by the U.S. Food and Drug Administration (”FDA”) in the United States and by comparable authorities in other countries.  These national agencies and other federal, state, and local entities regulate, among other things, research and development activities and the testing, manufacture, safety, effectiveness, labeling, storage, record keeping, approval, advertising, and promotion of our potential products.

Therapeutics

As an initial step in the FDA regulatory approval process for a prospective therapeutic product, preclinical studies are typically conducted in animals to identify potential safety problems.  For certain diseases, animal models may exist which are believed to be predictive of human efficacy.  For these diseases, a drug candidate is tested in an animal model.  The results of the studies are submitted to the FDA as a part of an Investigational New Drug Application (“IND”), which is filed to comply with FDA regulations prior to beginning human clinical testing.

Clinical trials for new therapeutics are typically conducted in three sequential phases, although the phases may overlap.  In Phase I, the compound is tested in healthy human subjects for safety (adverse effects), dosage tolerance, absorption, biodistribution, metabolism, excretion, clinical pharmacology and, if possible, to gain early information on effectiveness.  Phase II typically involves studies in a small sample of the intended patient population to assess the efficacy of the drug for a specific indication, to determine dose tolerance and the optimal dose range, and to gather additional information relating to safety and potential adverse effects.  Phase III trials are comparative clinical studies undertaken to further evaluate clinical safety and efficacy in an expanded patient population at geographically dispersed study sites in order to determine the overall risk-benefit ratio of the drug and to provide an adequate basis for physician labeling.  Each trial is conducted in accordance with certain standards under protocols that detail the objectives of the study, the parameters to be used to monitor safety and efficacy criteria to be evaluated.  Each protocol must be submitted to the FDA as part of the IND.  Further, each clinical study must be evaluated by an independent Institutional Review Board (IRB) at the institution at which the study will be conducted.  The IRB will consider, among other things, ethical factors, the safety of human subjects and the possible liability of the institution.

 
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Data from preclinical testing and clinical trials are submitted to the FDA in a New Drug Application (“NDA”) for marketing approval.  Preparing an NDA involves considerable data collection, verification, analysis and expense, and there can be no assurance that any approval will be granted on a timely basis, if at all.  The approval process is affected by a number of factors, including the severity of the disease, the availability of alternative treatments and the risks and benefits demonstrated in clinical trials.  The FDA may deny an NDA if applicable regulatory criteria are not satisfied or require additional testing or information.  Among the conditions for marketing approval is the requirement that the prospective manufacturer's quality control and manufacturing procedures conform to the FDA's good manufacturing practices (“GMP”) regulations, which must be followed at all times.  In complying with standards set forth in these regulations, manufacturers must continue to expend time, monies and effort in the area of production and quality control to ensure full technical compliance.  Manufacturing establishments serving the U.S. markets, both foreign and domestic, are subject to inspections by, or under the authority of, the FDA and by other federal, state or local agencies.

The process of completing clinical testing and obtaining FDA approval for a new drug is likely to take a number of years from the commencement of the clinical trial and require the expenditure of substantial resources.  Wewould require significant additional funds in the future to finance the clinical testing process if we developed any therapeutic products on our own.  Under our agreement with Eli Lilly and Company, however, Lilly will finance the clinical testing process of any AD therapeutic developed from our collaboration.

Diagnostic

In vitro diagnostic products have a different path to regulatory approval, i.e., the Premarket Approval Application (“PMA”) process regulated by the Office of In Vitro Diagnostic Device and Safety (“OIVD”) of the FDA.  The regulatory process leading to a submission of an in vitro diagnostic device PMA for FDA approval to market involves a multistage process including: (1) a Pre-Investigational Device Exemption (“Pre-IDE”) program in which preliminary information is submitted to the FDA for review and guidance on, and acceptance of, the test protocol and proposed clinical trial to evaluate the safety and effectiveness of an in vitro diagnostic product followed by, (2) an Investigational Device Exemption (“IDE”) submission for approval to allow the investigational diagnostic device to be used in a clinical study in order to (3) collect safety and effectiveness data required to support a PMA to receive FDA approval to market a device.  Data from a clinical trial is used to evaluate the clinical performance of the diagnostic test.  Before FDA approval for general sale, under certain conditions, companies can supply either “investigational use only” or “research use only” assay kits under the Clinical Laboratory Improvement Amendment (“CLIA”) of 1988.  Whether we will be able to market kits under these regulatory categories, or obtain final approval for a kit for specific claims, is uncertain given changing regulatory environments in most major markets.

Whether or not FDA approval has been obtained, regulatory authorities in foreign countries must grant approval prior to the commencement of commercial sales of the product in such countries.  The requirements governing the conduct of clinical trials and market entry vary widely from country to country, and the time required for clearance may be longer or shorter than that required by the FDA.  Although there are some procedures for unified filings for certain European countries, in general, each country at this time has its own procedures and requirements.   We would require significant additional funds in the future to finance the clinical testing process if we developed any diagnostic products on our own.  As funds permit, we will continue advancing the development of our diagnostic program, while pursuing appropriate partnering and/or out-licensing opportunities.

Environmental regulation

In connection with our research and development activities, our business is, and will in the future continue to be, subject to regulation under various state and federal environmental laws. These laws and regulations govern our use, handling and disposal of various biological and chemical substances used in our operations.  Although we believe that we have complied with these laws and regulations in all material respects and we have not been  required to take any action to correct any noncompliance, there can be no assurance that we will not be required to incur significant costs to comply with health and safety regulations in the future.

 
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Employees

As of May 5, 2008 we had six full-time employees, two of whom have advanced scientific degrees.  None of our employees are covered by a collective bargaining agreement and we believe all relations with our employees are satisfactory.  In addition, to complement our internal expertise, we have license agreements with AECOM that provide access to Dr. Peter Davies and the academic researchers in his lab and we may contract with other academic research laboratories, outside organizations with specific expertise and scientific consultants that provide pertinent expertise with therapeutic and diagnostic development.  In the future, we may hire additional research, development and other personnel in addition to utilizing outside organizations and consultants.


DESCRIPTION OF PROPERTY

We lease approximately 7,500 square feet of office and laboratory space in Vernon Hills, Illinois at an annual rental of approximately $125,000.  Our current lease agreement expired in May 2007 and was renewed for a three-year period ending May 2010 at a slightly reduced base rate.  We believe that we can acquire additional space, if needed, on acceptable terms.


LEGAL PROCEEDINGS

We are not currently a party in any legal proceedings.


MARKET FOR COMMON EQUITY AND RELATED STOCKHOLDER MATTERS

Our common stock is quoted on the OTC (Over-the-Counter) Bulletin Board and traded under the symbol, "APNS".  Prior to November 25, 2003, our common stock was traded on the OTC Bulletin Board under the symbol “HMYD”. Our common stock was previously traded on the OTC Bulletin Board under the symbol “OPHD” until February 5, 2002.

The following table sets forth the range of high and low closing bid prices for our common stock from January 1, 2006 through March 31, 2008, and for each of the quarterly periods indicated as reported by the OTC Bulletin Board.  The bid prices represent prices between broker-dealers and don’t include retail mark-ups and mark-downs or any commissions to the dealer.  These bid prices may not reflect actual transactions.


   
High
   
Low
 
2006:
           
First quarter                      
  $ 0.33     $ 0.17  
Second quarter                                                        
    0.24       0.11  
Third quarter                                                        
    0.32       0.16  
Fourth quarter                                                        
    0.42       0.26  
                 
2007:
               
First quarter                      
  $ 0.31     $ 0.23  
Second quarter                                                        
    0.32       0.20  
Third quarter                                                        
    0.24       0.15  
Fourth quarter                                                        
    0.22       0.11  
                 
2008:
               
First quarter                      
  $ 0.13     $ 0.09  
                 

As of May 5, 2008, we had approximately 3,000 record holders of our common stock.  We estimate that as of such date there were more than 2,500 beneficial holders of our common stock.

 
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No dividends were paid in 2005, 2006 and 2007. There are no restrictions on the payment of dividends.  We do not intend to pay dividends for the foreseeable future.
 
All of our securities that were issued or sold by us since March 15, 2001, have been registered with the SEC, except 8,666,667 stock options issued outside our Stock Option Plan in 2006 and 926,316 shares of restricted common stock.  All of these issuances were made in reliance upon the exemption set forth in Section 4(2) of the Securities Act of 1933.  We filed an SB-2 registration statement in July 2004, an S-8 registration statement in December 2004, and an SB-2 registration statement in November 2007. An S-8 registration statement is expected to be filed in the second quarter of 2008 to register the stock options and restricted stock noted above.
 
Securities authorized for issuance under equity compensation plans
 
In October 2002, the Board of Directors approved a Stock Option Plan (the “Plan”) under which officers, employees, directors and consultants may be granted incentive or non-qualified stock option to acquire common stock.  The incentive stock options granted under the Plan are intended to meet the requirements of Section 422 of the Internal Revenue Code of 1986.  The exercise price of each option is no less than the market price of our stock on the date of the grant, and an option’s maximum term is ten years.  Options typically vest over a four-year period.  The Plan calls for a maximum of 12,000,000 options to purchase shares of common stock.  The Plan was approved by shareholders in 2003.  A registration statement, Form S-8, was filed in December 2004, registering the stock option plan.
 
In 2006, our Compensation Committee approved 900,000 stock options to directors under the Plan and 6,000,000 stock options to our President and CEO and 4,000,000 stock options to our Chairman that were granted outside of the Plan and part of their respective individual compensation arrangements.  Additionally, in 2006 stockholders failed to approve proposal three in our proxy statement for our 2006 annual meeting of stockholders, which proposal included ratification of the grant of previously granted options to executive officers and independent directors to purchase approximately 3.6 million shares of common stock (the “Excess Options”).  As a result of the stockholder vote, we cancelled the Excess Options and the approximately 3.6 million shares of our common stock underlying such Excess Options became available for future grants under the Plan.

In 2007, our Compensation Committee approved 300,000 stock options to a director under the Plan.  Additionally, in 2007, our former Chairman returned 1,333,333 unvested stock options that were granted to him in 2006.  These options were cancelled and the underlying shares are available for future issuance.
 
Our only equity compensation plan is the Applied NeuroSolutions, Inc. (formerly Hemoxymed, Inc.) 2003 Stock Option Plan.
 
The following table summarizes outstanding options under our Stock Option Plan as of December 31, 2007.  Options granted in the future under the Plan and outside of the Plan are within the discretion of our Compensation Committee and therefore cannot be ascertained at this time.
 

 
 
 
 
 
 
Plan Category
(a)
 
 
 
Number of Securities to
be Issued Upon Exercise
of Outstanding Options
(b)
 
 
 
Weighted-Average
Exercise Price of
Outstanding Options
(c)
Number of Securities
Remaining Available for
Future Issuance Under
Equity Compensation
Plans (excluding securities
Reflected in column (a)
Equity compensation plans
approved by security holders
 
10,575,680
 
              $0.171
 
914,114
Equity compensation plans
not approved by security
holders
 
       8,666,667(1)
 
$0.221
 
-
                           Total
19,242,347
$0.193
914,114

 
39

 
(1)  Consists of an option exercisable to purchase 6,000,000 shares of our common stock that was granted to Ellen R. Hoffing in connection with her employment as our President and Chief Executive Officer and an option to purchase 4,000,000 shares of common stock that was granted to Robert S. Vaters in connection with his appointment as Chairman of our Board of Directors. In December 2007, Mr. Vaters stepped down as Chairman, while continuing as a Director of the Company, and returned to the Company 1,333,333 unvested options from this grant.  A description of the material terms of the option granted to Ms. Hoffing is set forth in Part III, Item 10 of our Annual Report.  The option granted to Mr. Vaters is now exercisable for a ten-year period to purchase 2,666,667 shares of common stock at an exercise price of $0.20 per share (which was the closing price of our common stock on the OTC Bulletin Board on June 23, 2006).  Mr. Vaters remaining 2,666,667 options are exercisable as of December 31, 2007.

 
40 

 
 
FINANCIAL STATEMENTS



APPLIED NEUROSOLUTIONS, INC.
(a development stage company)
FINANCIAL STATEMENTS
 


Contents


 
Page
For The Years Ended December 31, 2007 and 2006                                                                                                                
 
 
Report of Independent Registered Public Accounting Firm                                                                                                                
42
 
Consolidated Balance Sheets as of December 31, 2007 and 2006                                                                                                                
43
 
Consolidated Statements of Operations for the Years Ended December 31, 2007 and 2006 and for the Cumulative Period From March 14, 1992 (inception) to December 31, 2007
44
 
Consolidated Statements of Stockholders’ Equity/(Deficit) for the Years Ended December 31, 2007 and 2005 and for the Cumulative Period From March 14, 1992 (inception) to December 31, 2007
45
 
Consolidated Statements of Cash Flows for the Years Ended December 31, 2007 and 2006 and for the Cumulative Period From March 14, 1992 (inception) to December 31, 2007
48
 
Notes to Consolidated Financial Statements for the Years Ended December 31, 2007 and 2006 and for the Cumulative Period From March 14, 1992 (inception) to December 31, 2007
50



 
41 

 

REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM


To the Stockholders, Audit Committee and Board of Directors
Applied NeuroSolutions, Inc.
Vernon Hills, Illinois


We have audited the accompanying consolidated balance sheets of Applied NeuroSolutions, Inc. (a development stage company) as of December 31, 2007 and 2006, and the related consolidated statements of operations, shareholders' equity/(deficit) and cash flows for the years then ended.  These consolidated financial statements are the responsibility of the company's management.  Our responsibility is to express an opinion on these consolidated financial statements based on our audits.

We conducted our audits in accordance with the standards of the Public Company Accounting Oversight Board (United States).  Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement.  The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting.  Our audit included consideration of its internal control over financial reporting as a basis for designing audit procedures that are appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting.  Accordingly, we express no such opinion.  An audit includes examining, on a test basis, evidence supporting the amounts and disclosures in the consolidated financial statements.  An audit also includes assessing the accounting principles used and significant estimates made by management as well as evaluating the overall consolidated financial statement presentation.  We believe that our audits provide a reasonable basis for our opinion.

In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of Applied NeuroSolutions, Inc. (a development stage company) as of December 31, 2007 and 2006 and the results of their operations and their cash flows for the years then ended, in conformity with U.S. generally accepted accounting principles.

As discussed in Note 1 to the consolidated financial statements, effective January 1, 2006, the Company adopted Financial Accounting Standards Board Statement No. 123(R), "Share-Based Payment."

The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1(c) to the consolidated financial statements, the Company has suffered recurring losses from operations, has an accumulated deficit and requires additional capital to support the Company's continued development efforts, which raises substantial doubt about its ability to continue as a going concern.  Management’s plans in regard to these matters are also described in Note 1(c).  The consolidated financial statements do not include any adjustments that might result from the outcome of this uncertainty.


/s/ Virchow, Krause & Company, LLP

Chicago, Illinois
February 21, 2008







 
42 

 

APPLIED NEUROSOLUTIONS, INC.
(a development stage company)
 
CONSOLIDATED BALANCE SHEETS
   
December 31,
   
December 31,
 
   
2007
   
2006
 
Assets
Current assets:
           
Cash
  $ 2,960,141     $ 1,433,250  
Accounts receivable2
    -       250,000  
Prepaids and other current assets
    73,615       94,649  
Total current assets
    3,033,756       1,777,899  
                 
Property and equipment:
               
Equipment and leaseholds
    2,167,515       2,162,727  
Accumulated depreciation and amortization
    (2,140,321 )     (2,124,464 )
Net property and equipment
    27,194       38,263  
                 
Other assets:
               
Prepaids
    20,124       42,889  
Deposits
    8,641       15,072  
Total other assets
    28,765       57,961  
Total assets
  $ 3,089,715     $ 1,874,123  
Liabilities and Stockholders’ Equity / (Deficit)
               
Current liabilities:
               
Accounts payable
  $ 74,170     $ 270,698  
Bridge loan
    -       500,000  
Bridge loan, discount on debt
    -       (11,159 )
Deferred revenues, current portion
    333,333       583,333  
Accrued collaborator fees
    -       70,000  
Accrued consultant fees
    4,800       37,000  
Accrued wages
    120,000       56,756  
Accrued vacation wages
    39,060       92,671  
Accrued 401k match
    53,672       30,506  
Accrued interest
    -       29,000  
Other accrued expenses
    28,797       51,616  
Total current liabilities
    653,832       1,710,421  
Long term liabilities:
               
Deferred revenues, net of current portion
    301,399       634,733  
Stockholders' equity / (deficit):
               
Preferred stock, par value $0.0025: 5,000,000 shares authorized; none issued and outstanding
    -       -  
Common stock, par value $0.0025; 200,000,000 shares authorized;
   130,217,808 shares issued and outstanding
    325,547       246,025  
Treasury stock, 23,294 shares, at cost
    (10,614 )     (10,614 )
Additional paid in capital
    49,850,566       44,796,210  
Deficit accumulated during the development stage
    (48,031,015 )     (45,502,652 )
Total stockholders' equity / (deficit)
    2,134,484       (471,031 )
Total liabilities and stockholders' equity / (deficit)
  $ 3,089,715     $ 1,874,123  
 
See accompanying notes to consolidated financial statements.
               


 
43 

 



APPLIED NEUROSOLUTIONS, INC.
(a development stage company)
CONSOLIDATED STATEMENTS OF OPERATIONS

   
Year Ended December 31,
   
Period from March 14, 1992 (inception) to December 31,
 
   
2007
   
2006
   
2007
 
               
(unaudited)
 
Research agreement revenues
  $ 250,000     $ 219,700     $ 1,702,700  
Collaboration revenues
    833,333       31,934       865,267  
Grant revenues
    -       -       669,022  
Total revenues
    1,083,333       251,634       3,236,989  
                         
Operating expenses:
                       
Research and development
    1,659,258       2,119,431       31,040,668  
General and administrative
    2,000,439       2,224,939       16,454,340  
Loss on impairment of intangible assets
    -       -       411,016  
Loss on writedown of leasehold improvements
    -       -       1,406,057  
Total operating expenses
    3,659,697       4,344,370       49,312,081  
                         
Operating loss
    (2,576,364 )     (4,092,736 )     (46,075,092 )
                         
Other (income) expense:
                       
Interest expense
    12,159       218,740       716,344  
Interest income
    (60,160 )     (22,149 )     (878,515 )
Amortization of debt discount
    -       -       272,837  
Beneficial conversion of debt to equity
    -       -       274,072  
Inducement to convert debt to equity
    -       -       1,631,107  
Cost of fund raising activities
    -       -       62,582  
Loss on extinguishments of debt
    -       -       4,707,939  
Gain on derivative instruments, net
    -       -       (4,894,163 )
Net other (income) expense
    -       -       63,720  
Total other (income) expense
    (48,001 )     196,591       1,955,923  
                         
Net loss
    (2,528,363 )     (4,289,327 )     (48,031,015 )
                         
Less: Deemed dividend to common
   Stockholders
    (391,312 )     -       (391,312 )
                         
Less: Fair value of induced preferred stock conversion…………………….
    -       -       (1,866,620 )
Net loss attributable to common stockholders…………………………
  $ (2,919,675 )   $ (4,289,327 )   $ (50,288,947 )
                         
Basic and diluted loss per common share:
                       
Net loss attributable to common stockholders per share – basic
  $ (0.03 )   $ (0.04 )   $ (1.51 )
Weighted average shares outstanding
    113,325,596       95,371,726       33,287,402  
 
See accompanying notes to consolidated financial statements.
         



 
44 

 

APPLIED NEUROSOLUTIONS, INC.
(a development stage company)
CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY / (DEFICIT)
FOR THE PERIOD FROM MARCH 14, 1992 (INCEPTION) TO DECEMBER 31, 2007

   
Shares
   
Common
Stock
   
Treasury
Stock
   
Additional
Paid in
Capital
   
Deficit Accumulated During the Development Stage
   
Total
Stockholders’
Equity
(Deficit)
 
                                     
Issuance of Common Stock
    372,682     $ 932     $ -     $ (332 )   $ -     $ 600  
Net loss
    -       -       -       -       (922,746 )     (922,746 )
Balance at December 31, 1992
    372,682       932       -       (332 )     (922,746 )     (922,146 )
Issuance of Common Stock
    434,793       1,087       -       (387 )     -       700  
Issuance of Preferred Stock, subsequently converted to Common Stock
    165,936       415       -       1,201,750       -       1,202,165  
Issuance of Preferred Stock, subsequently converted to Common Stock
    762,066       1,905       -       5,640,172       -       5,642,077  
Issuance of Common Stock upon conversion of note and accrued interest
    368,322       921       -       2,964,005       -       2,964,926  
Net loss
    -       -       -       -       (4,875,845 )     (4,875,845 )
Balance at December 31, 1993
    2,103,799       5,260       -       9,805,208       (5,798,591 )     4,011,877  
Issuance of Preferred Stock, subsequently converted to Common Stock
    533,020       1,333       -       4,006,404       -       4,007,737  
Retirement of Common Stock
    (1,887 )     (5 )     -       (13,663 )     -       (13,668 )
Net loss
    -       -       -       -       (6,154,275 )     (6,154,275 )
Balance at December 31, 1994
    2,634,932       6,588       -       13,797,949       (11,952,866 )     1,851,671  
Issuance of Preferred Stock, subsequently converted to Common Stock
    493,801       1,235       -       748,765       -       750,000  
Issuance of Preferred Stock upon conversion of bridge loan and accrued interest, subsequently converted to Common Stock
        689,179           1,723           -           1,005,840           -           1,007,563  
Net loss
    -       -       -       -       (2,191,159 )     (2,191,159 )
Balance at December 31, 1995
    3,817,912       9,546       -       15,552,554       (14,144,025 )     1,418,075  
Issuance of Preferred Stock, subsequently converted to Common Stock
    4,957,145       12,393       -       6,864,881       -       6,877,274  
Issuance of Common Stock
    31,802       80       -       96,524       -       96,604  
Net loss
    -       -       -       -       (2,591,939 )     (2,591,939 )
Balance at December 31, 1996
    8,806,859       22,019       -       22,513,959       (16,735,964 )     5,800,014  
Issuance of Common Stock in connection with acquisition of intangible assets
    131,682       329       -       399,671       -       400,000  
Net loss
    -       -       -       -       (2,040,092 )     (2,040,092 )
Balance at December 31, 1997
    8,938,541       22,348       -       22,913,630       (18,776,056 )     4,159,922  
Net loss
    -       -       -       -       (2,549,920 )     (2,549,920 )
Balance at December 31, 1998
    8,938,541       22,348       -       22,913,630       (21,325,976 )     1,610,002  
Net loss
    -       -       -       -       (1,692,356 )     (1,692,356 )
Balance at December 31, 1999
    8,938,541       22,348       -       22,913,630       (23,018,332 )     (82,354 )
Issuance of Preferred Stock, subsequently converted to Common Stock
    1,466,495       3,666       -       983,614       -       987,280  
Issuance of warrants to purchase shares of Common Stock
    -       -       -       83,406       -       83,406  




 
45 

 




   
Shares
   
Common
Stock
   
Treasury
Stock
   
Additional
Paid in
Capital
   
Deficit Accumulated During the Development Stage
   
Total
Stockholders’
Equity
(Deficit)
 
 
Extension of warrants to purchase shares of Common Stock
    -       -       -       154,685       -       154,685  
Stock options granted to non-employees
    -       -       -       315,976       -       315,976  
Net loss
    -       -       -       -       (2,395,538 )     (2,395,538 )
Balance at December 31, 2000
    10,405,036       26,014       -       24,451,311       (25,413,870 )     (936,545 )
Issuance of Common Stock upon conversion of bridge loans/accrd. int
    4,474,649       11,185       -       2,027,696       -       2,038,881  
Issuance of Common Stock
    580,726       1,452       -       211,048       -       212,500  
Stock options granted to non-employees
    -       -       -       77,344       -       77,344  
Issuance of warrants to purchase shares of Common Stock
    -       -       -       27,367       -       27,367  
Options reissued to adjust exercise term
    -       -       -       64,033       -       64,033  
Beneficial conversion feature of convertible debt
    -       -       -       229,799       -       229,799  
Induced conversion of convertible debt
    -       -       -       1,631,107       -       1,631,107  
Net loss
    -       -       -       -       (4,146,913 )     (4,146,913 )
Balance at December 31, 2001
    15,460,411       38,651       -       28,719,705       (29,560,783 )     (802,427 )
Issuance of Common Stock upon conversion of bridge loans, accrued interest, other payables and as payment for services
        7,201,971           18,005           -           1,792,878           -           1,810,883  
Issuance of Common Stock upon conversion of warrants
    156,859       392       -       35,536       -       35,928  
Stock options granted to non-employees
    -       -       -       6,136       -       6,136  
Repurchase of Common Stock
    (23,294 )     (58 )     (10,614 )     58       -       (10,614 )
Merger between the Company and Molecular Geriatrics Corporation
    24,905,151       62,263       -       (62,263 )     -       -  
Issuance of warrants to purchase shares of Common Stock
    -       -       -       159,934       -       159,934  
Net loss
    -       -       -       -       (2,929,955 )     (2,929,955 )
Balance at December 31, 2002
    47,701,098       119,253       (10,614 )     30,651,984       (32,490,738 )     (1,730,115 )
Variable accounting for stock options
    -       -       -       604,100       -       604,100  
Stock options granted to non-employees
    -       -       -       80,975       -       80,975  
Issuance of warrants to purchase shares of common stock
    -       -       -       193,130       -       193,130  
Net loss
    -       -       -       -       (3,301,420 )     (3,301,420 )
Balance at December 31, 2003
    47,701,098       119,253       (10,614 )     31,530,189       (35,792,158 )     (4,153,330 )
Issuance of units in private placement
    32,000,000       80,000       -       1,483,066       -       1,563,066  
Issuance of placement agent warrants
    -       -       -       875,407       -       875,407  
Issuance of units upon conversion of bridge loans
    10,440,714       26,102       -       7,292,016       -       7,318,118  
Issuance of common stock for services
    200,000       500       -       64,500       -       65,000  
Issuance of units for services
    400,000       1,000       -       268,426       -       269,426  
Issuance of warrants to purchase shares of common stock
    -       -       -       124,775       -       124,775  
Variable accounting for stock options
    -       -       -       1,535       -       1,535  
Net loss
    -       -       -       -       (2,800,526 )     (2,800,526 )
Balance at December 31, 2004
    90,741,812       226,855       (10,614 )     41,639,914       (38,592,684 )     3,263,471  
Issuance of stock upon exercise of warrants
    3,755,772       9,389       -       667,745       -       677,134  

 
46 

 


   
Shares
   
Common
Stock
   
Treasury
Stock
   
Additional
Paid in
Capital
   
Deficit Accumulated During the Development Stage
   
Total
Stockholders’
Equity
(Deficit)
 
Issuance of stock options to purchase shares of common stock
    -       -       -       77,057       -       77,057  
Variable accounting for stock options
    -       -       -       219,952       -       219,952  
Net loss
    -       -       -       -       (2,620,641 )     (2,620,641 )
Balance at December 31, 2005
    94,497,584       236,244       (10,614 )     42,604,668       (41,213,325 )     1,616,973  
Issuance of stock upon conversion of warrants
    2,014,195       5,036       -       438,419       -       443,455  
Issuance of stock upon conversion of stock options
    510,206       1,275       -       75,256       -       76,531  
Issuance of stock
    1,387,916       3,470       -       559,054       -       562,524  
Non cash compensation for options FAS123R
    -       -       -       720,322       -       720,322  
Issuance of warrants to purchase shares of common stock
    -       -       -       200,866       -       200,866  
Non cash unrecognized compensation for options granted and cancelled
    -       -       -       197,625       -       197,625  
Net loss
    -       -       -       -       (4,289,327 )     (4,289,327 )
Balance at December 31, 2006
    98,409,901       246,025       (10,614 )     44,796,210       (45,502,652 )     (471,031 )
Issuance of stock upon conversion of warrants
    10,167,305       25,420       -       1,672,119       -       1,697,539  
Issuance of stock
    21,640,602       54,102       -       2,845,898       -       2,900,000  
Non cash compensation for options FAS123R
    -       -       -       496,848       -       496,848  
Issuance of warrants to purchase shares of common stock
    -       -       -       39,491       -       39,491  
Net loss
    -       -       -       -       (2,528,363 )     (2,528,363 )
Balance at December 31, 2007
    130,217,808     $ 325,547     $ (10,614 )   $ 49,850,566     $ (48,031,015 )   $ 2,134,484  
                                                 
                                                 


See accompanying notes to consolidated financial statements.


 
47 

 

APPLIED NEUROSOLUTIONS, INC.
(a development stage company)
CONSOLIDATED STATEMENTS OF CASH FLOWS

   
 
 
Year Ended December 31,
   
Period from March 14, 1992 (inception) to December 31,
 
   
2007
   
2006
   
2007
 
               
(unaudited)
 
Cash flows from operating activities:
                 
Net loss
  $ (2,528,363 )   $ (4,289,327 )   $ (48,031,015 )
Adjustments to reconcile net loss to net cash
used in operating activities:
                       
Depreciation and amortization
    15,857       24,933       2,625,414  
Non-cash expense for equity compensation
    -       -       2,379,241  
Non-cash expense for equity compensation
to employees and directors
    536,340       917,947       2,583,668  
Non-cash interest expense
    11,159       218,707       334,912  
Amortization of deferred financing costscosts
    -       -       111,000  
Non-cash expense for beneficial conversion
of debt
    -       -       274,072  
Non cash expense for induced conversion
of debt
    -       -       1,631,107  
Non-cash expense for loss on
extinguishments of debt
    -       -       4,707,939  
Non-cash income for gain on derivative
instrument, net
    -       -       (4,894,163 )
Amortization of intangible assets
    -       -       328,812  
Loss on writedown of leasehold
Improvements
    -       -       1,406,057  
Loss on impairment of intangible assets
    -       -       411,016  
Gain on sale of equipment
    -       -       (250 )
Fund raising expense
    -       -       62,582  
Changes in assets and liabilities:
                       
Accounts receivable
    250,000       (203,420 )     203,290  
Prepaids and other assets
    50,230       13,731       (87,662 )
Accounts payable
    (196,528 )     167,251       170,774  
Deferred research agreement revenues
    (583,334 )     1,123,866       634,732  
Accrued wages
    63,244       56,756       120,000  
Accrued collaborator payments
    (70,000 )     70,000       -  
Accrued consultant fees
    (32,200 )     18,100       29,800  
Accrued vacation wages
    (53,611 )     27,360       39,060  
Other accrued expenses
    (28,654 )     44,293       205,618  
Net cash used in operating activities 
    (2,565,860 )     (1,809,803 )     (34,753,996 )
                         
Cash flows from investing activities:
                       
Acquisition of investment securities
    -       -       (9,138,407 )
Redemption of investment securities
    -       -       9,138,407  
Acquisition of intangible assets
    -       -       (339,829 )
Acquisition of equipment and
leasehold improvements
    (4,788 )     (1,986 )     (4,044,528 )
Net cash used in investing activitiesActivities
    (4,788 )     (1,986 )     (4,384,357 )
                         
                         


 
48 

 


   
 
 
Year Ended December 31,
   
Period from March 14, 1992 (inception) to December 31,
 
   
2007
   
2006
   
2007
 
 
Cash flows from financing activities:
             
(unaudited)
 
Proceeds from issuance of Preferred Stock 
    -       -       12,193,559  
Proceeds from issuance of units, net of issuance costs
    2,900,000       562,524       22,433,555  
Proceeds from exercise of warrants
    1,697,539       443,455       2,818,128  
Proceeds from exercise of stock options
    -       76,531       76,531  
Proceeds from issuance of (repayments of) debt
    (500,000 )     500,000       -  
Deferred financing costs incurred
    -       -       (111,000 )
Advances from (repayments to) director and shareholders
    -       -       120,000  
Principal payments under capital lease
    -       (1,211 )     (11,766 )
Proceeds from issuance of promissory loans payable
    -       -       4,438,491  
Payments to shareholders for registration statement penalties
    -       -       (84,000 )
Payments to repurchase Common Stock
    -       -       (10,614 )
Payments received on employee stock purchase notes receivable
    -       -       235,610  
Net cash provided by financing activities
    4,097,539       1,581,299       42,098,494  
                         
Net increase (decrease) in cash
    1,526,891       (230,490 )     2,960,141  
                         
Cash beginning of period
    1,433,250       1,663,740       -  
                         
Cash end of period
  $ 2,960,141     $ 1,433,250     $ 2,960,141  
                         
Supplemental cash flow information:
                       
Cash paid for interest 
  $ 30,000     $ 33     $ 72,090  
                         
Supplemental disclosure of non-cash investing and financing activities:
                       
                         
Issuance of stock for prior services
  $ -     $ -     $ 4,149,521  
Intangible assets acquired in exchange for stock
  $ -     $ -     $ 400,000  
Equipment acquired for account payable
  $ -     $ -     $ 31,649  
Equipment acquired under capital lease
  $ -     $ -     $ 11,766  
Issuance of stock for promissory loans payable
  $ -     $ -     $ 2,473,991  
Issuance of stock for accrued interest on promissory loans payable
  $ -     $ -     $ 136,188  
 
See accompanying notes to consolidated financial statements.
         


 
49 

 


APPLIED NEUROSOLUTIONS, INC.
 (a development stage company)

NOTES TO CONSOLIDATED FINANCIAL STATEMENTS


Note 1 – Organization and Summary of Significant Accounting Policies

(a)    Organization and Basis of Presentation

Applied NeuroSolutions, Inc. (“APNS” or the “Company”), is a development stage biopharmaceutical company primarily engaged in the research and development of novel therapeutic targets for the treatment of Alzheimer's disease (“AD”) and diagnostics to detect AD.

Prior to 2004, the Company had two wholly-owned operating subsidiaries.  One of the wholly-owned operating subsidiaries was Molecular Geriatrics Corporation (“MGC”), a development stage biopharmaceutical company incorporated in November 1991, with operations commencing in March 1992, to develop diagnostics to detect, and therapeutics to treat, Alzheimer’s disease (“AD”).

The other wholly-owned operating subsidiary was Hemoxymed Europe, SAS, a development stage biopharmaceutical company incorporated in February 1995 to develop therapies aimed at improving tissue oxygenation by increasing oxygen release from hemoglobin to provide therapeutic value to patients with serious, unmet, medical needs.  We are not currently funding the development of this technology.  The Company dissolved these two subsidiaries, and transferred all of their assets to APNS in 2004.

On September 10, 2002, Hemoxymed, Inc. and Molecular Geriatrics Corporation (“MGC”) established a strategic alliance through the closing of a merger (the “Merger”).  The Merger Agreement provided that the management team and Board of Directors of MGC took over control of the merged company.  The transaction was tax-free to the shareholders of both companies.  In October 2003, the Company changed its’ name to Applied NeuroSolutions, Inc.

This transaction has been accounted for as a reverse merger.  For financial reporting purposes, MGC is continuing as the primary operating entity under the Company’s name, and its historical financial statements have replaced those of the Company.  Thus, all financial information prior to the Merger date is the financial information of MGC only.

The consolidated financial statements have been prepared in accordance with the provisions of Statement of Financial Accounting Standards (“SFAS”) No. 7, "Accounting and Reporting by Development Stage Enterprises," which requires development stage companies to employ the same accounting principles as operating companies.

The Company is subject to risks and uncertainties common to small cap biotech companies, including competition from larger, well capitalized entities, patent protection issues, availability of funding and government regulations.

(b)    Principles of Consolidation

Prior to 2004, the consolidated financial statements include the accounts of the Company and its subsidiaries, MGC and Hemoxymed Europe, SAS.  All significant intercompany balances and transactions have been eliminated.

(c)    Going Concern

The Company has experienced losses since inception in addition to incurring cash outflows from operating activities for the last two years as well as since inception.  The Company expects to incur substantial additional research and development costs and future losses prior to reaching profitability.  These matters have raised substantial doubt about the Company's ability to continue as a going concern for a reasonable period of time.  The Company's ability to continue as a going concern is dependent on obtaining adequate funding and ultimately achieving profitable operations.  In the opinion of management, the Company anticipates cash balances as of December 31, 2007, coupled with annual R & D support from Eli Lilly and Company, will be sufficient to fund operations through the first quarter 2009.  The Company will need additional funding prior to the end of the first quarter 2009 in order to continue its research, product development and operations.  If additional funding is not obtained, the Company will not be able to fund any of its programs, and the Company will possibly discontinue all its product development and/or operations.  Management is currently evaluating its options to maximize the value of the Company’s diagnostic technology, including evaluating partnering and licensing opportunities.  The Company intends to seek such additional funding through private and/or public financing, through exercise of currently outstanding stock options and warrants or through collaborative or other arrangements with partners, however, there is no assurance that additional funding will be available for the Company to finance its operations on acceptable terms, or at all.  This would have a material adverse effect on the Company’s operations and prospects.

 
50

 
(d)    Cash

The Company maintains cash at financial institutions from time to time in excess of the Federal Depository Insurance Corporation (FDIC) insured limit.

(e)    Revenue Recognition

The Company generates revenues from research agreements, collaborations and grants and recognizes these revenues when earned.  Grant revenues represent funds received from certain government agencies for costs expended to further research on the subject of the grant.  In accordance with Emerging Issues Task Force (EITF) 00-21 “Revenue Arrangements with Multiple Deliverables”, for arrangements that contain multiple deliverables, the Company separates the deliverables into separate accounting units if they meet all of the following:  a) the delivered items have stand-alone value to the customer; b) the fair value of any undelivered items can be reliably determined; and c) if the arrangement includes a general right of return, delivery of the undelivered items is probable and substantially controlled by the seller.  Deliverables that do not meet these criteria are combined with one or more other deliverables into one accounting unit.  Revenue from each accounting unit is recognized based on the applicable accounting literature, primarily Staff Accounting Bulletin No. 104 (SAB 104), “Revenue Recognition”.

(f)    Equipment and Leasehold Improvements

Equipment and leasehold improvements are recorded at cost.  Depreciation of equipment is calculated using accelerated methods over their useful lives, approximating five to seven years.  Amortization of leasehold improvements is provided on the straight-line method over the lesser of the asset’s useful life or the lease term.

(g)    Research and Development

All research and development costs are expensed as incurred and include salaries of, and expenses related to, employees and consultants who conduct research and development.  The Company has entered into arrangements whereby the Company will obtain research reimbursements in the form of funds received to partially reimburse the Company for costs expended.  For the years ended December 31, 2007 and 2006, the Company has recorded reimbursements of  $-0- and $32,875 against research and development expenses, respectively.

(h)    Income Taxes

Under the asset and liability method of Statement of Financial Accounting Standards (“SFAS”) No. 109, Accounting for Income Taxes, the Company’s deferred tax assets and liabilities are recognized for the future tax consequences attributable to differences between financial statement carrying amounts of existing assets and liabilities and their respective tax bases, and operating loss and tax credit carryforwards.  In assessing the realizability of the deferred tax assets, management considers whether it is more likely than not that some portion or all of the deferred tax assets will not be realized.  A valuation allowance is recorded for the portion of the deferred tax assets that are not expected to be realized based on the levels of historical taxable income and projections for future taxable income over the periods in which the deferred tax assets are deductible.

In July 2006, the FASB issued Interpretation No. 48, “Accounting for Uncertainty in Income Taxes” (“FIN 48”). FIN 48 prescribes a recognition threshold and measurement attribute for the financial statement recognition and measurement of a tax position taken or expected to be taken in its tax return. FIN 48 also provides guidance on derecognition, classification, interest and penalties, accounting in interim periods, disclosure and transition. FIN 48 is effective in fiscal years beginning after December 15, 2006. The provisions of FIN 48 are to be applied to all tax positions upon initial adoption, with the cumulative effect adjustment reported as an adjustment to the opening balance of retained earnings. Upon adoption, there were no unrecognized income tax benefits and the adoption of FIN 48 had no effect on shareholders’ equity

(i)    Stock Option Plan

Effective January 1, 2006, the Company adopted SFAS No. 123R, Share-Based Payment (SFAS 123R), which requires companies to measure and recognize compensation expense for all stock-based payments at fair value. SFAS 123R is being applied on the modified prospective basis.  Prior to the adoption of SFAS 123R, the Company accounted for its stock-based compensation plans under the recognition and measurement principles of Accounting Principles Board (APB) Opinion No. 25, Accounting for Stock Issued to Employees, and related interpretations, and accordingly, recognized no compensation expense related to the stock-based plans.

 
51

 
Under the modified prospective approach, SFAS 123R applies to new awards and to awards that were outstanding on January 1, 2006, that are subsequently modified, repurchased, cancelled or vest.  Under the modified prospective approach, compensation cost recognized for 2006 includes compensation cost for all share-based payments granted prior to, but not yet vested on, January 1, 2006, based on the grant-date fair value estimated in accordance with the provisions of SFAS 123R, and compensation cost for all shared-based payments granted subsequent to January 1, 2006, based on the grant-date fair value estimated in accordance with the provisions of SFAS 123R.  Prior periods were not restated to reflect the impact of adopting the new standard.

The weighted average estimated fair value of the options granted in 2007 and 2006 was $0.08 and $0.11, respectively, based on the Black-Scholes valuation model using the following assumptions:

 
2007
2006
     
Risk-free interest rate, average
  4.81%
  4.99%
Dividend
  0.00%
  0.00%
Expected volatility
75.00%
75.00%
Expected life in years, average
3
3

From time to time, the Company has issued equity awards to non-employees.  In these instances, the Company applies the provisions of SFAS No. 123 and EITF No. 96-18 Accounting for Equity Instruments That Are Issued to Other Than Employees for Acquiring, or in Conjunction with Selling, Goods or Services which results in the recognition of expense related to these awards over the vesting or service period of an amount equal to the estimated fair value of these awards at their respective measurement dates (see Note 6).

(j)    Restricted Shares

The holder of a restricted share award is generally entitled at all times on and after the date of issuance of the restricted shares to exercise the rights of a shareholder of the Company, including the right to vote the shares and the right to receive dividends on the shares. During 2007 and 2006 the Company granted 526,316 and 400,000 restricted shares, respectively, to its CEO based on the terms of her employment. The restricted shares are valued based on the closing price on the date of grant and vest over a three-year period based on the continuation of employment.

(k)    Use of Estimates

Management of the Company has made a number of estimates and assumptions relating to the reporting of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, and the reported amounts of revenues and expenses during the reporting period, to prepare these financial statements in conformity with accounting principles generally accepted in the United States of America.  Actual results could differ from those estimates.

(l)    Computation of Net Loss Attributable to Common Stockholder per Share

Net loss attributable to common stockholder per share is computed based upon the weighted average number of common shares of outstanding during the period as if the exchange of common shares in the merger between the Company and MGC was in effect at the beginning of all periods presented.

For each period, net loss attributable to common stockholder per share is computed based on the weighted average number of common shares outstanding with potential equivalent shares from all stock options, warrants and convertible investor bridge loans excluded from the computation because their effect is anti-dilutive.  The Company had 19,242,347 stock options and 44,418,453 warrants outstanding to issue common stock at December 31, 2007.  The Company had 20,452,531 stock options and 48,071,472 warrants outstanding to issue common stock at December 31, 2006.

(m)    Fair Value of Financial Instruments

The Company’s financial instruments include cash, accounts receivable, accounts payable, loans payable, and other accrued expenses.  The carrying value of these financial instruments approximates their fair values due to the nature and short-term maturity of these instruments.

 
52

 
(n)    Recent Accounting Pronouncements

In February 2007, the FASB Board issued SFAS No. 159, “The Fair Value Option for Financial Assets and Financial Liabilities” (“SFAS 159”). This statement permits entities to choose to measure many financial instruments and certain other items at fair value. SFAS 159 is effective for fiscal years beginning after November 15, 2007.  We are currently assessing the effect that SFAS 159 will have on our results of operations and financial position.

In December 2007, the FASB issued SFAS No. 160, “Noncontrolling Interests in Consolidated Financial Statements an amendment of ARB No. 51” (“SFAS 160”).  This statement establishes accounting and reporting standards for noncontrolling interests in subsidiaries and for the deconsolidation of subsidiaries and clarifies that a noncontrolling interest in a subsidiary is an ownership interest in the consolidated entity that should be reported as equity in the consolidated financial statements.  This Statement also requires expanded disclosures that clearly identify and distinguish between the interests of the parent owners and the interests of the noncontrolling owners of a subsidiary.  SFAS 160 is effective for fiscal years beginning on or after December 15, 2008.  We do not believe that the adoption of SFAS 160 will have a material effect on our results of operations or financial position.

In December 2007, the FASB issued SFAS No. 141 (Revised 2007), “Business Combinations” (“SFAS 141 (Revised 2007)”).  While this statement retains the fundamental requirement of SFAS 141 that the acquisition method of accounting (which SFAS 141 called the purchase method) be used for all business combinations, SFAS 141 (Revised 2007) now establishes the principles and requirements for how an acquirer in a business combination:  1) recognizes and measures in its financial statements the identifiable assets acquired, the liabilities assumed, and any noncontrolling interests in the acquiree; 2) recognizes and measures the goodwill acquired in the business combination or the gain from a bargain purchase; and 3) determines what information should be disclosed in the financial statements to enable the users of the financial statements to evaluate the nature and financial effects of the business combination.   SFAS 141 (Revised 2007) is effective for fiscal years beginning on or after December 15, 2008.  We do not believe that the adoption of SFAS 141 (Revised 2007) will have a material effect on our results of operations or financial position.

Note 2 – Collaboration Agreement with Eli Lilly and Company

In November 2006, the Company entered into an agreement with Eli Lilly and Company (“Lilly”) to develop therapeutics to treat AD.  Pursuant to the terms of the agreement, the Company received $2 million in cash, including an equity investment of $500,000, from Lilly, plus it will receive annual research and development support for the duration of the collaboration agreement.  In addition, Lilly will, based on the achievement of certain defined milestones, provide the Company over time with up to $20 million in milestone payments for advancing the Company’s proprietary target to a therapeutic compound.  The collaboration has also made progress on other targets that are part of the collaboration that could provide milestone payments to the Company over time of up to $10 million for advancing each of these other targets to a therapeutic compound.  There is no limit to the number of targets that the Company could receive milestone payments from Lilly.  There are no assurances that any milestones will be met.  Royalties are to be paid to the Company for AD drug compounds brought to market that result from the collaboration.  There is no limit on the number of drug compounds for which royalty payments may be due to the Company.  Lilly received the exclusive worldwide rights to the intellectual property related to the Company’s expertise in understanding the molecular neuropathology of AD as it pertains to the formation of neurofibrillary tangles.  Lilly will fund the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from the collaboration.  The Company recorded $1 million received in 2006 as deferred revenues and is amortizing the deferral over 36 months.  Included in collaboration revenues for 2007 and 2006 is an amortization of these deferred revenues of $333,333 and $31,934, respectively.  Also included in collaboration revenues in 2007 is $500,000 received as research and development support.  In addition, $66,173 of legal fees directly associated with the agreement are included in prepaid assets and are being amortized over 36 months.




 
53

 






Note 3  -  Property and Equipment

Property and equipment consist of the following:

   
December 31,
2007
   
December 31, 2006
 
             
Equipment
  $ 2,071,136     $ 2,066,348  
Equipment held under capital lease
    11,766       11,766  
Leasehold improvements
    84,613       84,613  
      2,167,515       2,162,727  
Less accumulated depreciation and
Amortization
    (2,140,321 )     (2,124,464 )
                 
    $ 27,194     $ 38,263  

Depreciation and amortization expense amounted to $15,857 and $24,933 for the years ended December 31, 2007 and 2006, respectively.

Note 4  -  Warrants

The Company issued warrants to investors in conjunction with funds raised in December 1995.  These warrants had an original expiration date of December 2000.  During 2000, these warrants were extended until December 2001.  Compensation expense related to this extension was $154,685 in 2000.  These warrants expired, unexercised, in December 2001.

The Company issued warrants to investors in conjunction with funds raised in August through November 2000.  Compensation expense related to the issuance of these warrants was $83,406 in 2000.  These warrants were converted to shares of Common Stock in the 2001 Recapitalization (see Note 5).

The Company issued warrants to investors in conjunction with funds raised in February through December 2001.  Compensation expense related to the issuance of these warrants was $27,367 in 2001.  The majority of these warrants were converted to shares of Common Stock in the 2001 Recapitalization (see Note 5).  Total compensation expense of $351,811 was recognized upon the conversion of all the warrants in 2002.

The Company, in September 2002 prior to the Merger date, issued 1,562,258 warrants to previous investors in the Company.  These warrants have an exercise price of $0.0001 per share, and expire in September 2009.

The Company issued 800,000 warrants, in September 2002, to an entity controlled by the two largest shareholders of Hemoxymed (prior to the Merger), in lieu of compensation.  Compensation expense related to the issuance of these warrants was $159,934 in 2002.  These warrants have an exercise price of $0.20 per share, and expire in September 2007.

The Company issued 850,000 warrants to consultants in September 2003, in lieu of compensation.  Compensation expense related to the issuance of these warrants was $74,077 in 2003.  These warrants have an exercise price of $0.20 per share, and expire in September 2008.

The Company issued 1,250,000 warrants to a board member and a non-employee in September 2003, in lieu of compensation, for fundraising.  Compensation expense related to the issuance of these warrants was $119,053 in 2003.  These warrants have an exercise price of $0.15 per share, and expire in September 2008.

The Company issued 200,000 warrants to consultants in January 2004, in lieu of compensation, for investor relations and business consulting services and included the value of such warrants, $42,705, in general and administrative expenses for the year ended December 31, 2004.  These warrants have an exercise price of $0.20 per share, and expire in September 2008.

The Company issued 400,000 warrants to consultants in February 2004, in lieu of compensation, for financial advisory and business consulting services and included the value of such warrants, $109,426, in general and administrative expenses for the year ended December 31, 2004.  These warrants have an exercise price of $0.30 per share, and expire in February 2009.

 
54

 
The Company issued 43,564,795 warrants to investors in the February 2004 offering and to bridge loan investors upon conversion of their bridge loans upon closing the February 2004 offering.  These warrants have an exercise price of $0.30 per share, and expire in February 2009.

The Company issued 3,200,000 warrants to the placement agents for the February 2004 offering.  These warrants have an exercise price of $0.30 per share, and expire in February 2009.  These warrants were not eligible to be exercised for a one-year period from the date of grant.

The Company issued 500,000 warrants to consultants in November 2004, in lieu of compensation, for investor relations and business consulting services and included the value of such warrants, $44,160, in general and administrative expenses for the year ended December 31, 2004.  These warrants have an exercise price of $0.30 per share, and expire in November 2009.

The Company issued 400,000 warrants to consultants in November 2004, in lieu of compensation, for financial advisory and business consulting services and included the value of such warrants, $37,910, in general and administrative expenses for the year ended December 31, 2004.  These warrants have an exercise price of $0.25 per share, and expire in November 2009.

In 2005, 3,755,772 warrants were exercised and 27,584 warrants were forfeited by warrant holders.  Net proceeds of $677,134 were received by the Company (at an average exercise price of $0.18 per warrant).

The Company issued 922,500 warrants to bridge loan holders in July 2006.  These warrants have an exercise price of $0.0025 per share, and expire in July 2011.

In 2006, 2,014,195 warrants were exercised and 1,475 warrants were forfeited by warrant holders.  Net proceeds of $443,455 were received by the Company (at an average exercise price of $0.22 per warrant).

The Company issued 300,000 warrants to a consultant in May 2007, as part of compensation paid to the consultant, for investor relations and business consulting services and included the value of such warrants, $39,491, in general and administrative expenses for the year ended December 31, 2007.  These warrants have an exercise price of $0.305 per share, and expire in May 2012.

The Company issued 6,214,286 warrants to the investor in the September 2007 offering.  These warrants have an exercise price of $0.19 per share, and expire in September 2012.

In 2007, 10,167,305 warrants were exercised.  Net proceeds of $1,697,539 were received by the Company (at an average exercise price of $0.17 per warrant).

As of December 31, 2007, the Company has reserved 44,418,453 shares of Common Stock for the exercise and conversion of the warrants described above.

A summary of the status of, and changes in, the Company’s warrants as of and for the years ended December 31, 2007 and 2006, is presented below for all warrants issued:

   
2007
   
2006
 
   
 
Warrants
   
Weighted-
Average-Exercise
Price
   
 
Warrants
   
Weighted-
Average-Exercise
Price
 
 
Outstanding at beginning
of year
      48,071,472     $ 0.29         49,164,642     $ 0.29  
 
Granted
    6,514,286       0.20       922,500       0.0025  
 
Exercised
    10,167,305       0.17       2,014,195       0.22  
 
Forfeited
    -       -       1,475       0.15  
Outstanding at end
of year
    44,418,453     $ 0.27       48,071,472     $ 0.29  

The weighted-average remaining contractual life of the warrants outstanding as of December 31, 2007 is 1.7 years.

 
55

 
Note 5  -  Stockholders' Equity

The stockholders' equity information presented in these financial statements reflects the retroactive recognition of the effects of the Merger (see Note 1), and of the two recapitalizations of the Company's capital structure, the "1996 Recapitalization", which became effective in March, 1996 and the "2001 Recapitalization", which became effective in November, 2001.  The 1996 Recapitalization consisted of (i) the conversion of each share of outstanding Series A Convertible Preferred Stock and Series B Convertible Preferred Stock of the Company into one share of Common Stock, (ii) a 1.0-for-10.6 reverse split of the outstanding shares of Common Stock, and (iii) a reduction in the number of authorized shares of Common Stock and Preferred Stock from 50,000,000 to 20,000,000 and 35,000,000 to 15,000,000, respectively.  The 2001 Recapitalization consisted of (i) the conversion of each share of outstanding Series C Convertible Preferred Stock of the Company into two shares of Common Stock, (ii) the conversion of each share of outstanding Series D Convertible Preferred Stock of the Company into three and one-third shares of Common Stock, (iii) the conversion of convertible debt plus accrued interest into five shares of Common Stock for each $1.50 of convertible debt, and (iv) an increase in the number of authorized shares of Common Stock from 20,000,000 to 50,000,000 (See Note 13).

Pursuant to the terms of the General Corporation Law of the State of Delaware, the Company's Restated Certificate of Incorporation and the Certificates of Designation of the Series C and Series D Convertible Preferred Stock, the increase in authorized shares in the 2001 Recapitalization was approved by the consent of a majority of the aggregate voting power of the holders of the outstanding Common Stock and the Series C and Series D Convertible Preferred Stock.  The conversion of the Series C and Series D Convertible Preferred Stock was approved by a majority of the respective holders of such shares voting separately as a class.  The conversion of the convertible debt was approved by the individual debt holder.

In conjunction with the Merger, each outstanding share of MGC Common Stock was exchanged for .658394 shares of APNS Common Stock and each outstanding MGC warrant and stock option was exchanged for .658394 APNS warrant and stock option.

In December 2002, the Board of Directors approved an increase in the number of authorized shares from 50,000,000 to 205,000,000, consisting of 200,000,000 Common Shares and 5,000,000 Preferred Shares.  Shareholder approval for this increase was obtained in 2003.  See note 13 for an explanation of the Company’s authorized shares.

In the Consolidated Statements of Stockholders’ Equity / (Deficit), the Company has elected to present each issuance of Preferred Stock, which was subsequently converted to Common Stock, as Common Stock as of the date of each issuance of Preferred Stock.

Original Issuances of Preferred Stock

In July 1993, the Company issued 2,671,478 shares of Series A Convertible Preferred Stock (“Series A”).  These shares were subsequently converted to 165,936 shares of Common Stock.

In September through December 1993, the Company issued 12,269,000 shares of Series B Convertible Preferred Stock (“Series B”).  These shares were subsequently converted to 762,066 shares of Common Stock.

In March through May 1994, the Company issued 8,581,400 shares of Series B.  These shares were subsequently converted to 533,020 shares of Common Stock.

In December 1995, the Company issued 375,000 shares of Series C Convertible Preferred Stock (“Series C”).  These shares were subsequently converted to 493,801 shares of Common Stock.

In December 1995, the Company issued 523,371 shares of Series C.  These shares were subsequently converted to 689,179 shares of Common Stock.

In March through July 1996, the Company issued 3,764,550 shares of Series C.  These shares were subsequently converted to 4,957,145 shares of Common Stock.

In January through May 2000, the Company issued 668,202 shares of Series D Convertible Preferred Stock (“Series D”).  These shares were subsequently converted to 1,466,495 shares of Common Stock.

Current Issuances of Common Stock

 
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In November 2001, as part of the 2001 Recapitalization, $2,038,881 of convertible debt, including accrued interest, was converted to 4,474,649 shares of Common Stock.

In January through June 2002, the Company issued 3,846,692 shares of common stock through a private placement, and upon conversion of bridge loans, plus accrued interest.

In June 2002, the Company issued 3,355,279 shares of Common Stock to Company officers, consultants and vendors in exchange for a reduction of $750,000 of amounts due.

In June 2002, the Company issued 156,859 shares of Common Stock to certain warrant holders in exchange for the conversion of 650,139 warrants.

In September 2002, the Company repurchased 23,294 shares of Common Stock.

In September 2002, certain shareholders of a predecessor of the Company were issued, in exchange for past services, 1,562,258 seven-year warrants exercisable at $0.0001 to purchase shares of Common Stock.

In September 2002, an entity controlled by the two largest shareholders of the Company prior to the merger were issued, in lieu of compensation, 800,000 five year warrants exercisable at $0.20 to purchase shares of Common Stock.  Expense of $159,934 was included in general and administrative expense for the issuance of these warrants.

In September 2003, a director of the Company and an advisor were issued, in lieu of compensation for fund raising activities, 1,250,000 five-year warrants exercisable at $0.15 to purchase shares of Common Stock.  Expense of $119,053 was included in general and administrative expenses for the issuance of these warrants.

In September 2003, two entities were issued, in lieu of compensation, 850,000 five-year warrants exercisable at $0.20 to purchase shares of Common Stock.  Expense of $74,077 was included in general and administrative expenses for the issuance of these warrants.

In February 2004, the Company completed an $8,000,000 private placement (net proceeds of $7,354,054) in February.  The private placement included accredited institutional investors and accredited individuals.  In conjunction with this financing, the Company issued an aggregate of 32 million units priced at $0.25 per unit to investors.  Each unit consisted of one share of common stock of the Company and a five-year warrant exercisable to purchase one share of common stock of the Company at an exercise price of $0.30.  The warrants issued to investors were immediately exercisable.

Pursuant to the terms of the Registration Rights Agreement entered into in connection with the transaction, within seven calendar days following the date that the Company filed its Annual Report on Form 10-KSB, the Company was required to file, and did file, with the Securities and Exchange Commission (the “SEC”) a registration statement under the Securities Act of 1933, as amended, covering the resale of all of the common stock purchased and the common stock underlying the warrants, including the common stock underlying the placement agents’ warrants.

The Registration Rights Agreement further provided that if a registration statement was not filed, or did not become effective, within 150 days from the closing date of the private placement, then in addition to any other rights the holders may have, the Company would be required to pay each holder an amount in cash, as liquidated damages, equal to 1.5% per month of the aggregate purchase price paid by such holder in the private placement for the common stock and warrants then held, prorated daily.  The registration statement was filed within the allowed time, however it was declared effective July 28, 2004 under SEC File Number 333-113821, resulting in the Company incurring certain liquidated damages in accordance with the terms of the private placement.  Liquidating damages of $84,000 were paid to the unit holders in the private placement in the third quarter 2004.

In accordance with Emerging Issues Task Force (EITF) Issue No. 00-19, “Accounting for Derivative Financial Instruments Indexed To, and Potentially Settled In a Company’s Own Stock,” the terms of the warrants and the transaction documents, the fair value of the warrants was accounted for as a liability, with an offsetting reduction to additional paid-in capital at the closing date (February 6, 2004).  The warrant liability, net of the liquidated damages, was reclassified to equity on July 28, 2004, when the registration statement became effective.

The fair value of the warrants was estimated using the Black-Scholes option-pricing model with the following assumptions:  no dividends; risk-free interest rate of 3.20%; the contractual life of five years and volatility of 75%.  The fair value of the warrants was estimated to be $8,754,068 on the closing date of the transaction.  The difference between the fair value of the warrants of $8,754,068 and the gross proceeds from the offering was classified as a non-operating expense in the Company’s statement of operations, and included in “Gain on derivative instrument, net”.  The fair value of the warrants was then re-measured at March 31, 2004, June 30, 2004 and July 28, 2004 (the date the registration statement became effective) and estimated to be $3,105,837 at July 28, 2004, with the decrease in fair value since February 6, 2004 due to the decrease in the market value of the Company’s common stock.  The decrease in fair value of the warrants of $5,648,231 from the transaction date to July 28, 2004 was recorded as non-operating income in the Company’s statement of operations, and included in “Gain on derivative instrument, net”.  The fair value of the warrants at July 28, 2004 was reclassified to additional paid in capital as of July 28, 2004.

 
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The Company used $315,783 of the proceeds from the private placement to reimburse officers of the Company for expenses, including compensation that was incurred but unpaid, as of January 31, 2004.

The Company paid the placement agent and its sub-agents $560,000 in cash as fees for services performed in conjunction with the private placement.  The Company also incurred $85,946 in other legal and accounting fees.  The Company also issued a five-year warrant to purchase 3.2 million shares of common stock of the Company at an exercise price of $0.30 per share to the placement agent and its sub-agents in the private placement.  The warrants issued to the placement agent are exercisable commencing on February 6, 2005.  The fair value of the warrants was computed as $875,407 based on the Black-Scholes option-pricing model with the following assumptions:  no dividends; risk-free interest rate of 3.20%; the contractual life of five years and volatility of 75%.  The Company allocated $1,521,353 between issuance costs offsetting the liability for common stock warrants and equity based on a relative fair value allocation of the stock issued and warrants issued to the unit holders.  As a result, the Company initially recorded $621,171 of issuance costs as an offset to the liability for common stock warrants related to these fund raising activities in the Company’s consolidated balance sheet.  The Company further recorded $62,582 of amortization expenses from these issue costs as “Costs of fund raising activities” in the statement of operations for the year ended December 31, 2004.

The adjustments required by EITF Issue No. 00-19 were triggered by the terms of the Company’s agreements for the private placement it completed in February 2004, specifically related to the potential penalties if the Company did not timely register the common stock underlying the warrants issued in the transaction.  The adjustments for EITF Issue No. 00-19 had no impact on the Company’s working capital, liquidity, or business operations.

All of the warrants issued in the transaction provide a call right in favor of the Company to the extent that the price per share of the Company’s common stock exceeds $1.00 per share for 20 consecutive trading days, subject to certain circumstances.

Concurrent with the closing of the private placement, bridge investors, who had made loans to the Company over the past 18 months, agreed to convert the $2,610,179 of loans and unpaid interest into units on substantially the same terms as the investors in the private placement.  The conversion terms accepted by the bridge investors were substantially different than the initial conversion terms of the bridge loans.  As a result, the Company accounted for the change in conversion terms as a substantial modification of terms in accordance with EITF Issue No. 96-19, “Debtor’s Accounting for a Modification or Exchange of Debt Instruments”.  As a result, the Company recorded a $4,707,939 loss on debt extinguishment in the three month period ended March 31, 2004 for the difference between the carrying value of the bridge loans on the date the conversion terms were modified ($2,610,179) and the fair value of the equity issued under the new conversion terms ($7,318,118).  Upon conversion, the Company issued the bridge investors 10,440,714 shares of common stock and 11,484,788 warrants to purchase shares of common stock on the same terms as the unit holders.  The fair value of the common stock was computed as $4,176,286 based on the closing price of the Company’s stock on February 6, 2004.  The fair value of the warrants was determined to be $3,141,832 using the Black-Scholes option-pricing model with the following assumptions:  no dividends; risk-free interest rate of 3.20%; the contractual life of five years and volatility of 75%.  Upon conversion, the $7,318,118 adjusted value of the bridge loans was reclassified as $26,102 of common stock and $7,292,016 of additional paid-in-capital.

In February 2004, the Company issued 400,000 shares of common stock and 400,000 warrants to consultants, in lieu of compensation, for financial advisory and business consulting services valued at $269,426.  Consulting expense related to the issuance of the shares of common stock was $160,000 in 2004 based on the closing price of the Company’s stock on the date of issuance.  Expense related to the issuance of the warrants of $109,426 was included in general and administrative expenses.  These warrants have an exercise price of $0.30 per share, and expire in February 2009.

In February 2004, the Company issued 100,000 shares of common stock to a consultant, in lieu of compensation, for financial advisory and business consulting services.  Expense of $40,000 was included in general and administrative expenses.

 
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In November 2004, the Company issued 100,000 shares of common stock to a consultant, in lieu of compensation, for scientific consulting services.  Expense of $25,000 was included in research and development expenses.

During 2005, The Company issued 3,755,772 shares of common stock to warrant holders upon exercise of warrants.
In August 2006, the Company issued 400,000 shares of restricted common stock to the Company’s President and CEO under terms of her employment.  These restricted shares vest over a three-year period.  Expense of $45,804 and $19,100 was included in general and administrative expense in 2007 and 2006, respectively.

In October 2006, the Company issued 271,845 shares of common stock to a consultant, as part of the compensation to the consultant, for executive search services.  Expense of $62,524 was included in general and administrative expenses.

In November 2006, the Company sold 1,116,071 shares of common stock to Eli Lilly and Company for $500,000 (see Note 2).

During 2006, the Company issued 2,014,195 shares of common stock to warrant holders upon exercise of warrants.

During 2006, the Company issued 510,206 shares of common stock to option holders upon exercise of options.

In September 2007, the Company sold 20,714,286 shares of common stock, along with 6,214,286 warrants to purchase shares of common stock) to an investor in the September 2007 Placement for $2,900,000.

During 2007, the Company issued 10,167,305 shares of common stock to warrant holders upon exercise of warrants.

In December 2007, the Company issued 526,316 shares of restricted common stock to the Company’s President and CEO under terms of her employment.  These restricted shares vest over a three-year period.  Expense of $20,761 was included in general and administrative expense in 2007.

In the event of any liquidation, dissolution or winding up of the affairs of the Company, either voluntary or involuntary, the holders of Preferred Stock are entitled to receive a liquidation preference, adjusted for combinations, consolidations, stock splits or certain issuances of Common Stock.  After payment has been made to the holders of Preferred Stock of the full amounts to which they shall be entitled, the holders of the Common Stock shall be entitled to receive ratably, on a per share basis, the remaining assets.  As of December 31, 2007, no Preferred Stock is outstanding.  The Company has reserved 44,418,453 shares of Common Stock for the exercise and conversion warrants, and 19,242,347 shares of Common Stock for the exercise and conversion of stock options.

Note 6  -  Stock Option Plan

As of December 31, 2002, the Board of Directors approved the Hemoxymed, Inc. (now called Applied NeuroSolutions, Inc.) Stock Option Plan.  This plan is identical to the MGC pre-merger plan (discussed below), with an increase in the number of options in the plan to 12,000,000.  Shareholder approval was obtained in 2003.

In conjunction with the Merger in September 2002, each outstanding MGC stock option was exchanged for .658394 APNS stock options.

In April 2001, management issued non-qualifying stock options to two former employees to replace the incentive stock options previously granted.  All terms of these options remained the same.  Compensation expense of $64,033 was recorded to reflect the fair value of these options.

In April 2001, the Board of Directors granted 13,168 options to a non-employee exercisable at $1.50 per share, which vest monthly over a twenty-four month period.  Compensation expense of $24,170 was recorded to reflect the fair value of these options.

In July 2001, the Board of Directors granted 6,584 options to an employee exercisable at $1.50 per share, which vest one-fourth per year beginning July 2002.  These options were forfeited during 2002.

In November 2001, the Board of Directors granted 2,050,904 options exercisable at $0.30 per share which vest one-fourth immediately and one-fourth per year beginning November 2002.  Non-employees were granted 144,847 of these options, which were vested immediately.  Compensation expense of $53,174 was recorded to reflect the fair value of options issued to non-employees.

 
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In June 2002, the Board of Directors granted 434,172 options exercisable at $0.15 per share which vest one-fourth immediately and one-fourth per year beginning in June 2003.  Non-employees were granted 33,430 of these options.  Compensation expense of $6,136 was recorded to reflect the fair value of options issued to non-employees.

In June 2002, the Board of Directors approved adjusting the exercise price of 4,399,052 options to $0.15 per share.  This changed the accounting treatment for these stock options to variable accounting until they are exercised.  For the year ended December 31, 2003, the Company recorded compensation expense under variable accounting equal to $604,100 related to these modified options.  For the year ended December 31, 2002, no compensation expense had been recorded related to these modified options as the Company’s stock price was below $0.15 as of December 31, 2002.

In September 2003, the Board of Directors granted 5,337,000 options exercisable at $0.15 per share which vest one-fourth immediately and one-fourth per year beginning in September 2004.  Non-employees were granted 752,000 of these options.  Compensation expense of $80,975 was recorded to reflect the fair value of options issued to non-employees.

In November 2004, the Board of Directors granted 120,000 options exercisable at $0.17 per share which vest one-fourth immediately and one-fourth per year beginning in November 2005.

In April 2005, the Company granted 4,045,136 stock options to employees, officers, independent directors and a consultant, of which 3,302,565 options were granted to executive officers and directors, 542,571 options were granted to employees, and 200,000 options were granted to a consultant.  Compensation expense of $31,870 was recorded to reflect the fair value of options issued to the consultant.  In addition, the Company granted 300,000 stock options to independent directors in the second half of 2005.  The 3,602,565 stock options granted to executive officers and independent directors in 2005 were not approved by the Company’s stockholders at the Company’s Annual Stockholder Meeting on June 20, 2006 and were cancelled and not reissued.  Included in general and administrative expense and research and development expense in the quarter ended June 30, 2006 was a non-cash expense of $80,165 and $117,460, respectively, to record unrecognized compensation costs on these options.

In January 2006, 94,041 options were exercised at an average exercise price of $0.l5 and 676,674 options with exercise prices ranging from $0.15 to $5.30 expired, unexercised.  In May 2006, 42,796 options with an exercise price of $0.15 expired, unexercised.

On June 20, 2006, at the Company’s Annual Stockholder Meeting, the stockholders voted against increasing the maximum allowable shares of common stock issuable under the Company’s 2003 stock option plan from 12,000,000 shares to 20,000,000 shares and voted against ratification of the 3,602,565 options granted to executive officers and independent directors in 2005.  Thus, these 2005 stock options were cancelled and not reissued, and consequently, became available for future grants under the Company’s 2003 stock option plan.

On June 27, 2006, the Board of Directors approved a grant of 600,000 stock options to independent directors or the Company.

On June 27, 2006, the Board of Directors also approved a grant of 4,000,000 stock options to the Company’s new Chairman.  This option grant was not made under the Company’s 2003 stock option plan, but was made in consideration of the engagement of the new Chairman.

On August 29, 2006, The Board of Directors approved a grant of 6,000,000 stock options to the Company’s newly appointed President and CEO.  This option grant was made pursuant to the terms of the new CEO’s employment and was not made under the Company’s 2003 stock option plan.  The Board of Directors also approved a grant to the Company’s new CEO of 400,000 restricted shares of common stock, which grant was made (i) on the same day as the new CEO’s option grants and (ii) pursuant to the terms of the new CEO’s employment.  In addition, the Board of Directors approved a grant to the Company’s new CEO of $100,000 of restricted shares of common stock on both the first and second anniversaries of her employment (August 29, 2007 and 2008).

On September 7, 2006, the Board of Directors approved a grant of 300,000 stock options to an outside director of the Company.

On October 23, 2007, the Board of Directors approved a grant of 300,000 stock options to a new outside director of the Company.

During 2007, 176,851 stock options expired, unexercised.

 
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On December 7, 2007, the Company’s Chairman stepped down, remaining as a Director, and offered to return to the Company 1,333,333 unvested stock options.  These options were cancelled and the underlying shares are available for future issuance by the Company.

The Company calculates expected volatility for stock options using historical volatility.  The starting point for the historical period used is September 2002, the timing of the Merger (see Note 1).  The Company currently estimates the forfeiture rate for stock options to be minimal.

The risk-free rates for the expected terms of the stock options and awards and the employee stock purchase plan is based on the U.S. Treasury yield curve in effect at the time of the grant.

As of December 31, 2007, the Company had 10,575,680 outstanding stock options granted under its 2003 stock option plan and had 8,666,667 outstanding stock options granted outside the 2003 stock option plan.  As of December 31, 2007 there was approximately $340,320 of total unrecognized non-cash compensation costs related to the outstanding stock options, which is expected to be recognized over a weighted-average period of 1.89 years.

As of December 31, 2007, 19,242,347 options were outstanding (15,528,374 were fully vested and exercisable) at prices ranging from $0.15 to $2.00 per share.

A summary of the status of, and changes in, the Company’s stock options as of and for the years ended December 31, 2007 and 2006, is presented below for all stock options issued to employees, directors and non-employees:

   
2007
   
2006
 
   
 
Options
   
Weighted-
Average-Exercise
Price
   
 
Options
   
Weighted-
Average-Exercise
Price
 
Outstanding at beginning
of year
    20,452,531     $ 0.20       14,384,772     $ 0.22  
 
Granted
    300,000       0.19       10,900,000       0.22  
 
Voted against at annual
stockholders meeting
      -         -         3,602,565         0.29  
 
Exercised
    -       -       510,206       0.15  
 
Forfeited
    1,510,184       0.21       719,470       0.55  
Outstanding at end
of year
    19,242,347     $ 0.19       20,452,531     $ 0.20  
Options exercisable at
end of year
    15,528,374     $ 0.18       11,746,246     $ 0.17  

The intrinsic value of options outstanding and options exercisable at December 31, 2007 was $0 and $0, respectively.  No options were exercised during 2007.  The intrinsic value at December 31, 2007 of options expected to vest was $0.

Stock Options as of December 31, 2007
 
Exercise
Price
Number
Outstanding at
December 31, 2007
Weighted-Average
Remaining
Contractual Life
Number
Exercisable at
December 31, 2007
$0.15
              8,650,127
4.3 years
              8,650,127
  0.17
                   75,000
6.8 years
                   75,000
 0.19
                 300,000
9.8 years
                 200,000
 0.20
              3,166,667
8.5 years
              3,166,667
 0.23
              6,000,000
8.7 years
              2,666,670
   0.275
                 300,000
8.7 years
             250,000
   0.285
                 722,571
7.3 years
             541,928
 1.50
               14,814
3.1 years
                   14,814
 2.00
                   13,168
0.3 years
                   13,168
 
            19,242,347
 
            15,528,374


 
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Note 7  -  Employee Savings Plan

The Company sponsors a defined contribution benefit plan (the “Savings Plan”) which qualifies under Section 401(k) of the Internal Revenue Code.  The Savings Plan covers all eligible employees who are at least eighteen years of age and have completed six months of service with the Company.  Employee contributions to the Savings Plan are based on percentages of employee compensation plus a discretionary matching contribution by the Company.  Vesting in the Company’s contributions is based on length of service over a five-year period.  The Company amended the Savings Plan, effective January 1, 2001, to increase the Company match from 50% to 100% of the first 5% of an employee’s deferral, subject to certain limitations.  Contributions by the Company for the years ended December 31, 2007 and 2006 were $53,672 and $42,506, respectively.


Note 8  -  Income Taxes

No Federal or state income taxes have been provided for in the accompanying consolidated financial statements because of net operating losses incurred to date and the establishment of a valuation allowance equal to the amount of the Company's deferred tax assets.  At December 31, 2007, the Company has net operating loss and research and development credit carry-forwards for Federal income tax purposes of approximately $39,800,000 and $1,025,000, respectively.  These carry-forwards expire between 2008 and 2027.  In 2007, net operating loss carry-forwards of $892,112 expired and research and development credit carry-forwards of $23,863 expired.  Changes in the Company's ownership may cause annual limitations on the amount of loss and credit carry-forwards that can be utilized to offset income in the future.  Net operating loss and research and development credit carry-forwards, as of December 31, 2007, expiring over the next five years are as follows:

Year Expiring
 
Net Operating Loss
   
Research and Development Credit
 
2008
  $ 4,655,901     $ 121,653  
2009
    6,039,518       208,148  
2010
    2,100,609       31,522  
2011
    2,003,368       21,454  
2012
    2,398,264       51,237  
Total
  $ 17,197,660     $ 434,014  

The net deferred tax assets as of December 31, 2007 and 2006 are summarized as follows:

   
December 31, 2007
   
December 31, 2006
 
             
Deferred tax assets:
           
             
Depreciation
  $ 170,000     $ 190,000  
Net operating loss carry-forwards
    15,900,000       15,500,000  
Tax credit carry-forwards
    1,025,000       970,000  
      17,095,000       16,660,000  
 
Valuation allowance
    (17,095,000 )     (16,660,000 )
 
Net deferred income taxes
  $ -     $ -  

The net change in the valuation allowance during 2007, after taking into account expiring net operating loss and research and development credit carry-forwards, was an increase of $435,000.  The net change in the valuation allowance during 2006 was an increase of $1,360,000.


Note 9  -  Commitments and Contingencies

Operating Lease
The Company operates out of a laboratory and office facility in Vernon Hills, Illinois.  The original lease term was for sixty-three months through May 14, 2002 and included a renewal option for two additional five-year periods.  In May 2002, the lease was extended for a five-year period, through May 14, 2007.  In April 2007, the lease was extended for a three-year period, through May 14, 2010.

 
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Future minimum lease payments as of December 31, 2007, under the terms of the operating lease for the facility in Vernon Hills, Illinois are as follows:
 
Year ending December 31,
 
Amount
 
       
2008
  $ 99,375  
2009
    99,375  
2010
    37,266  

Rental expense, including allocated operating costs and taxes, was $120,038 and $125,995 for the years ended December 31, 2007 and 2006, respectively.

Capital Lease
The Company purchased a telephone system under the terms of a capital lease in March 2003.  The lease called for thirty-six monthly payments of $414 through March 2006, and was fully paid in 2006.

Collaboration, Consulting and Licensing Agreements
Under the terms of various license and collaborative research agreements with Albert Einstein College of Medicine (“AECOM”) the Company is obligated to make semi annual maintenance payments and quarterly funding payments.  In addition, the agreements call for royalty and revenue sharing agreements upon the sale and/or license of products or technology licensed under the agreements.  In March 2002, September 2002 and October 2006 the Company renegotiated various terms of the AECOM agreements.

Total expense for these outside research, collaboration and license agreements, included in research and development expenses, was $505,000 and $450,000 for the years ended December 31, 2007 and 2006, respectively.

The Company has a consulting agreement with Dr. Peter Davies, its founding scientist, which has been renewed through November 2008, but in some instances, may be terminated at an earlier date by the Company and the consultant.  Expense for the consulting agreement, included in research and development expenses, was $108,000 and $108,000 for the years ended December 31, 2007 and 2006, respectively.

Future minimum payments, as of December 31, 2007, under the above agreements are as follows:

Year ending December 31,
 
Collaborations
   
Consulting
 
             
2008
  $ 500,000     $ 99,000  
2009
    500,000       -  
2010
    500,000       -  
2011
    500,000       -  
2012
    500,000       -  
Total
  $ 2,500,000     $ 99,000  

The Company is obligated to pay AECOM $500,000 each year subsequent to 2007 that the Agreements are still in effect.  In addition, the Company is obligated to pay AECOM a percentage of all revenues received from selling and/or licensing aspects of the AD technology licensed from AECOM that exceeds the minimum obligations reflected in the annual license maintenance payments.  The Company can terminate the Agreements at any time with sixty days written notice, but would be required to return all rights granted under the Agreements to AECOM and reimburse AECOM for any salary obligations undertaken by AECOM for the research projects covered by the Agreements for up to one year from the termination date.

Employment Agreement
Under the terms of her employment agreement, Ellen R. Hoffing, the President and CEO, receives a minimum base salary of $300,000 per year, plus a bonus of up to 40% of Ms. Hoffing’s base salary upon attainment of performance objectives established by the Company’s Board of Directors and acceptable to Ms. Hoffing.  On August 29, 2006, the Company granted Ms. Hoffing a stock option to purchase 6,000,000 shares of the Company’s common stock at an exercise price of $0.23 (which was the closing price of the common stock on the over-the-counter market on the date of grant).  The option vests as to 1,000,000 shares of common stock on the sixth month anniversary of the grant, and then will vest as to an additional 166,667 shares for each month thereafter until the option is vested in full (which will be on the third anniversary of the date of grant).  On August 29, 2006, the Company also granted
 
 
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Ms. Hoffing 400,000 shares of restricted stock ($100,000 at $0.25 per share, which was the high price of the common stock on the over-the-counter market on the date of the grant), which vests as to 133,334 shares on the first anniversary of the date of grant and 133,333 shares on the second and third anniversaries of the date of grant.  On October 23, 2007, the Company granted Ms. Hoffing 526,316 shares of restricted stock ($100,000 at $0.19, which was the closing price of the common stock on the over-the-counter market on  the date of the grant), which vests as to 175,439 shares on August 29, 2008 and 2009 and 175,438 shares on August 29, 2010.  In addition, Ms. Hoffing will receive $100,000 worth of shares of restricted stock on her two-year anniversary with the Company (August 29, 2008).  If Ms. Hoffing’s employment is terminated by the Company without cause, she is entitled to her base salary and benefits for a period of 12 months after such termination, and the portion of her options and restricted stock that would have vested during the 12 months following such termination will immediately vest.  If Ms. Hoffing’s employment is terminated upon or in connection with a change of control of the Company, then Ms. Hoffing will be paid the equivalent of one year’s base salary and benefits and any unvested shares of restricted stock and stock options will immediately vest in full upon such change in control.

Prior Employment Agreements
David Ellison, the Chief Financial Officer and Corporate Secretary, was employed pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $174,000 per year, with an annual cost of living increase.  Mr. Ellison had not received an increase in his base salary since April 2005.  Included in general and administrative expense is $8,672 and $4,529 for 2007 and 2006, respectively, representing his earned cost of living increase from April 2006 to October 2007.  Mr. Ellison’s agreement also provided a minimum monthly non-accountable allowance of $300 for automobile and cell phone expenses.  This allowance was increased to $400 per month in April 2005.  In July 2007, the Company gave Mr. Ellison timely notice that his employment agreement was not being renewed.  On October 31, 2007, the Company paid Mr. Ellison $13,201, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Since November 1, 2007, Mr. Ellison has continued in his current position with the Company as an at-will employee with an annual base salary of $205,000.

John F. DeBernardis, Ph.D., the Chief Scientific Officer, was employed pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $282,000 per year, with an annual cost of living increase.  Dr. DeBernardis had not received an increase in his base salary since April 2005.  Included in research and development expense is $14,026 and $7,326 for 2007 and 2006, respectively, representing his earned cost of living increase from April 2006 to October 2007.  Dr. DeBernardis’s agreement also provided a minimum monthly non-accountable allowance of $1,000 for automobile and cell phone expenses.  This allowance was increased to $1,150 per month in April 2005.  In addition, the Company also provided Dr. DeBernardis, at the Company’s expense, a term life insurance policy in the amount of $600,000.  This term life insurance policy was cancelled in April 2007.  In July 2007, the Company gave Dr. DeBernardis timely notice that his employment agreement was not being renewed.  On October 31, 2007, the Company paid Dr. DeBernardis $21,352, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Since November 1, 2007, Dr. DeBernardis has continued in his current position with the Company as an at-will employee with an annual base salary of $185,000.

Daniel J. Kerkman, Ph.D., the Company’s former Vice President of Research and Development, was employed pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $189,000 per year, with an annual cost of living increase.  Dr. Kerkman had not received an increase in his base salary since April 2005.  Included in research and development expense is $9,382 and $4,901 for 2007 and 2006, respectively, representing his earned cost of living increase from April 2006 to October 2007.  Dr. Kerkman’s agreement also provided a minimum monthly non-accountable allowance of $300 for automobile and cell phone expenses.  This allowance was increased to $400 per month in April 2005.  In July 2007, the Company gave Dr. Kerkman timely notice that his employment agreement was not being renewed.  On October 31, 2007, the Company paid Dr. Kerkman $14,283, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Dr. Kerkman’s position was eliminated and his employment ended on October 31, 2007.  Dr. Kerkman received $8,803 in severance in December 2007.  The resources that had been deployed for Dr. Kerkman’s compensation are now being allocated to direct R & D projects and working with outside companies and consultants to access specific expertise and technologies to assist us in advancing our programs.

Contingencies
The Company does not maintain any product liability insurance for products in development.  The Company believes that even if product liability insurance were obtained, there is no assurance that such insurance would be sufficient to cover any claims.  The Company is unaware of any product liability claims.

 
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The ability to develop the Company’s technologies and to commercialize products will depend on avoiding patents of others.  While the Company is aware of patents issued to competitors, as of December 31, 2007, the Company was not aware of any claim of patent infringement against it.

In March 2004, the Company was notified by email from Innogenetics, a Belgian biopharmaceutical company involved in specialty diagnostics and therapeutic vaccines, that it believes the CSF diagnostic test the Company has been developing uses technology that is encompassed by the claims of its’ U.S. patents.  Innogenetics also informed the Company that it could be amenable to entering into a licensing arrangement or other business deal with the Company regarding its patents.  The Company had some discussions with Innogenetics concerning a potential business relationship, however no further discussions have been held since the second quarter of 2006.

The Company has reviewed these patents with its patent counsel on several occasions prior to receipt of the email from Innogenetics and subsequent to receipt of the email.  Based on these reviews, the Company believes that its CSF diagnostic test does not infringe the claims of these Innogenetics patents.  If the Company is unable to reach a mutually agreeable arrangement with Innogenetics, it may be forced to litigate the issue.  Expenses involved with litigation may be significant, regardless of the ultimate outcome of any litigation.  An adverse decision could prevent the Company from possibly marketing a future diagnostic product and could have a material adverse impact on its business.


Note 10 – Bridge Funding

On July 10, 2006, the Company entered into a Note and Warrant Purchase Agreement with private investors pursuant to which the Company sold to the investors 12% senior unsecured notes due January 10, 2007 in the aggregate principal amount of $500,000 (“Bridge Funding”), and five year warrants (the “Warrants”) exercisable to purchase an aggregate of 922,500 shares of the Company’s common stock at an exercise price of $.0025 per share.  The Notes, plus accrued interest, were paid in full as of January 10, 2007.  The Notes were not guaranteed by any third party, and not secured by the Company, and were senior to all of the Company’s indebtedness and were non-transferable.  The Warrants are immediately exercisable, however, the shares of common stock to be issued upon exercise of the warrants have not yet been registered.

Pursuant to FSP EITF 00-19-2, “Accounting for Registration Payment Arrangements” (“FSP”), which addresses an issuer’s accounting for registration payment arrangements, the Company concluded that no obligation should be recorded related to the registration rights for the warrants issued."

The Company accounted for the warrants issued based on guidance from SFAS No. 133, Accounting for Derivative Instruments and Hedging Activities and Emerging Issues Task Force (“EITF”) No. 00-19. Accounting for Derivative Financial Instruments Indexed to and Potentially Settled in a Company’s Own stock.  Accordingly, the warrants are classified as equity.

The Company allocated the proceeds from the Bridge Funding of $500,000 between the debt and the warrants based upon the fair value of the debt and warrants at the transaction date.  The warrants were valued using the Black-Scholes pricing model.  This resulted in an increase in additional paid-in capital at the transaction date related to the warrants in the amount of $200,866.  The carrying value of the debt was reduced by the $200,866 and the discount was amortized over the life of the loan (6 months).  During 2007 and 2006, $11,159 and $189,707 of the discount was recognized as interest expense, respectively.  Included in current liabilities as of December 31, 2006, was a bridge loan balance of $488,841, comprised of the $500,000 Bridge Funding proceeds received, net of the unamortized debt discount of $11,159.

The fair value of the warrants issued was determined using the Black-Scholes option pricing model based on the following assumptions: volatility of 75%, expected life of two years, risk free interest rate of 5.14% and no dividends.


Note 11 – Accounts Receivable

Included in accounts receivable at December 31, 2006 is one signed contract for $250,000.  The revenues from this agreement were not recognized in 2006, and are included in deferred revenues at December 31, 2006, as performance of the agreement had not been completed by either party.  The revenues were recognized in the 2nd quarter of 2007.

 
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Note 12 – Research Agreement with Nanosphere, Inc.

In January 2006, the Company entered into a research agreement with Nanosphere, Inc., a nanotechnology-based molecular diagnostics company, to assist the Company in the development of serum-based diagnostic tests for AD.  The research agreement resulted in Nanosphere and APNS scientists achieving a better understanding of the tools necessary to advance the development of a serum-based AD diagnostic test based on the Company’s scientifically accepted biomarkers.  The Company is currently working on developing additional tools that may enable it to best utilize Nanosphere’s proprietary technology, or other appropriate technologies, to continue to advance its serum diagnostic development work.


Note 13 – Authorized Shares

The Company discovered in the first quarter of 2006 that three prior amendments to its certificate of incorporation were approved by written consent of the stockholders.  The first amendment, approved in October 2001 and filed in November 2001, increased the Company's authorized common stock from 22.4 million shares to 50 million shares, and the second amendment, approved in June 2003 and filed in September 2003, increased the authorized common stock to 200 million shares.  The third amendment to the Company's certificate of incorporation was approved and filed in October 2003 to change the name of the Company to “Applied NeuroSolutions, Inc.”  For each of these amendments, the Company filed an information statement and duly mailed it to stockholders 20 days prior to effective date of the stockholders' written consents becoming effective, all in accordance with the Exchange Act and its applicable rules.

In January 2006, in preparation of the proxy statement for the Company’s annual meeting, the Company discovered that the certificate of incorporation of its predecessor entity, Ophidian Pharmaceuticals, Inc., limited stockholders from taking action by written consent.  That provision is still in effect.  Consequently, the 2001 and 2003 amendments to the certificate of incorporation, while approved by the Board of Directors and approved by a majority of the then-outstanding shares of common stock in the manner described above, were technically not adopted properly under Delaware law.  Such shares may be deemed issued in excess of the Company's 22,400,000 authorized and outstanding shares of common stock.

To remedy this technical error, the Company corrected its certificate of incorporation by means of a subsidiary-parent merger approved by the stockholders, with a new “corrected” certificate of incorporation resulting from such merger.

To assure that this correction would be made, thereby preserving the status quo for the Company's existing common stockholders, the Company created a new class of “super voting” Series A preferred stock, which is permitted by the “blank check” provisions of the current certificate of incorporation that was approved by the stockholders of the Company's predecessor at an annual meeting held in 1999.  The shares of this Series A preferred stock were issued solely to the members of the Company's Audit Committee, in trust for the benefit of the Company's common stockholders.  The members of the Audit Committee agreed to vote the shares in favor of the curative merger transaction.  Following the merger transaction and the correction of the certificate of incorporation to affirm the previous actions of the Company's stockholders, the Company redeemed and canceled the shares of the Series A preferred stock at a nominal cost of $250.

The Board of Directors unanimously approved the Merger Agreement and the approach outlined above.
The Company’s annual meeting was held on June 20, 2006 and the parent-subsidiary merger, as described above, was approved and the Company immediately filed a certificate of merger to effect the technical correction to its certificate of incorporation.  The Company’s authorized common stock under Article IV of the amended and restated certificate of incorporation is now 200 million shares.

Because the holders of the Series A preferred stock had informed the Company of their agreement with each other to vote the Series A preferred shares in favor of the Merger Agreement, the Company continued to treat the over-issued shares of common stock in the same manner as the remaining outstanding shares of the Company’s common stock.








 
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MANAGEMENT’S DISCUSSION AND ANALYSIS
OF FINANCIAL CONDITION AND RESULTS OF OPERATION

General

Our business strategy is to build on our strong scientific research, and commitment to develop a range of solutions to meet the unmet needs of the growing number of Alzheimer patients. Through our tau based approach we continue to develop proprietary technology, know-how and tools. We are seeking to offer options for early diagnosis and high impact therapeutic solutions that will enhance the physicians’ ability to effectively manage their patient’s treatment.

Our unique science, stemming from the work of our founding scientist, Dr. Peter Davies, is focused on developing a range of diagnostic tests.  In addition, through our collaboration with a top tier Pharmaceutical company, Eli Lilly and Company, our tau-based science is the foundation of the development and commercialization of novel therapeutics to modify the course of AD.  Our principal development programs, and plan of operation for each, are as follows:

·  
AD Therapeutic Program – We are involved in the discovery and development of novel therapeutic targets for the development of treatments for Alzheimer’s disease basedupon a concept developed by Peter Davies, Ph.D., the Company’s founding scientist and the Burton P. and Judith Resnick Professor of Alzheimer’s Disease Research at AECOM.  As a result of Dr. Davies’ research, and the Company’s expertise, we are focused on discovery of unique therapeutics that may be involved in a common intracellular phosphorylation pathway leading to the development of the abnormal, destructive brain structures, amyloid plaques and neurofibrillary tangles, that are characteristic of Alzheimer’s disease.  A patent application was filed in 2005 covering Dr. Davies work relative to the therapeutic work.  In November 2006, we entered into an agreement with Eli Lilly and Company to develop therapeutics to treat AD.  The agreement forms a collaboration that combines the expertise, research tools and tau-based approach advanced by Dr. Davies and our team at APNS, with the scientists, therapeutic development expertise and financial resources at Eli Lilly and Company.  The agreement calls for Lilly to receive the exclusive worldwide rights to the intellectual property related to our expertise in understanding the molecular neuropathology of AD as it pertains to the formation of neurofibrillary tangles.  Lilly will fund the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from our collaboration.  Since the start of the collaboration, the collaboration management structure, working teams and external resources have become fully operational.  The key assets and proprietary tools have been appropriately transferred to support work being undertaken by each of Dr. Davies, Lilly and APNS.  The first internal milestone on the proprietary tau-related APNS target was reached in the second quarter of 2007 and the next internal milestone is scheduled for the first quarter of 2008.  Key in-vivo models have been established with the goal to validate our tau-based target.  The collaboration has made good progress on the milestones established by the program management for the proprietary tau-related APNS target.  APNS’s first paid milestone is targeted for achievement in late 2008 to early 2009.  The collaboration continues to make good progress toward additional tau-based targets with an additional target being screened and validation studies underway for other targets.

·  
AD Diagnostic Program – Our diagnostic program is based on Dr. Davies’ research of the tau pathology, and revolves around developing a pipeline of diagnostic tests that could include: (i) the detection of hyperphosphorylated tau in CSF, (ii) a screening test to rule out AD in serum, and (iii) the detection of hyperphosphorylated tau in serum.  Our product farthest along in development is a CSF-based diagnostic test to detect whether a person has AD.  This diagnostic, based upon the detection of a certain AD associated protein found in the CSF of AD patients, has achieved, based on published research validation studies, an overall sensitivity and specificity in the range of 85% to 95%.  This test is based on extensive testing in our lab, utilizing in excess of 2,000 CSF samples to differentiate patients diagnosed with AD from patients diagnosed with other forms of dementia and relevant neurological diseases, including major depression, as well as healthy controls.  We are continuing development of our CSF-based diagnostic to reduce the tests incubation time. Our most recent research has sought to further substantiate the utility of the test in the MCI population.  Two studies published in 2007 show the ability of our CSF-based test to be a strong predictor of the decline from MCI to AD.  The September 2007 online edition of Neurobiology of Aging presented a study comparing five of the best-known CSF biomarkers for AD.  Our ptau biomarker was the strongest predictor of the decline from MCI to AD.  The December 2007 issue of Neurology published an internationally based multi-center study that demonstrated our ptau biomarker was a significant predictor of the decline from MCI to AD in a clinically useful time period of 1.5 years.  Studies published in the December 2005 edition of Neuroscience Letters and in the March 2006 journal Neurobiology of Aging support the use of our CSF-based diagnostic test in identifying individuals with MCI who, over time, are most likely to develop AD. Current data seems to suggest that 60% to 80% of individuals with MCI will eventually progress to AD.  As a neurodegenerative disease, it is theorized that early detection of AD could greatly enhance the ability of current and future therapies to better manage the disease.    A study published in the January 2004 edition of Archives of General Psychiatry has shown that detecting phosphorylated tau (“ptau”) proteins in CSF comes closest to fulfilling the criteria of a biological marker for AD.  This publication reported that our CSF-based test exceeded standards for an AD diagnostic test established by the National Institute of Aging and the Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association in a 1998 published “Consensus Report”.  It was determined by that group that a successful biological marker would be one that had a sensitivity level and specificity level of at least 80%.  A Position Paper, “Research Criteria for the Diagnosis of Alzheimer’s Disease: Revising the NINCDS-ADRDA Criteria”, was published in the August 2007 edition of Lancet Neurology that describes suggested revisions to the criteria for the diagnosis of Alzheimer’s disease, including the use of CSF biomarkers, specifically referencing our CSF-based p-tau 231 test.

 
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We are utilizing the knowledge gained during the development of our CSF-based diagnostic test to aid in the development of serum-based diagnostic tests to detect Alzheimer’s disease, specifically a screening test to rule out AD as well as the detection of our ptau biomarker to support the diagnosis of AD.  In January 2006, we entered into a research agreement with Nanosphere, Inc., a nanotechnology-based molecular diagnostics company, to assist us in the development of a serum-based diagnostic test for AD.  Work performed during the research agreement resulted in Nanosphere and APNS scientists achieving a better understanding (in January 2007) of the tools necessary to advance the development of a serum-based AD diagnostic test with our scientifically accepted biomarkers.  We established a project plan and began developing these key tools in early 2007, and targeted to have the first of these tools developed during the first quarter of 2008 to enable us to continue to advance our serum diagnostic development work.

We sought additional expertise and resources by conducting a scientific advisory board meeting that brought together APNS scientists, Dr. Davies and three outside diagnostic experts to assist us in assessing the most effective approaches and resources to advance our diagnostic development programs.  Through 2007, we followed our work plans to develop antibody tools and we achieved a key milestone in the first quarter of 2008 by identifying several high affinity antibodies that meet our requirements.  These tools will support advancing development of a “rule out” serum based test for AD.  Additional back up tool options to support a “rule out” test are also in development.  In addition, tools directed toward the development of a ptau biomarker based test in serum that could support the early identification of AD are targeted for completion in the second quarter 2008.  Throughout the tool development process we have been identifying specialized technologies that may enable us to advance our diagnostic development programs.  Technology assessments have been initiated.  Currently there is no FDA-approved diagnostic test to detect AD.

While continuing development of our diagnostic programs, we are seeking appropriate partnerships and expertise to assist us in advancing towards commercialization.  We are having discussions with experts and companies regarding various approaches and opportunities for collaboration and to assist us in advancing our diagnostic programs towards commercialization.

·  
Transgenic Mice To date, no widely accepted animal model that exhibits both AD pathologies has been developed.  Dr. Peter Davies, through collaboration with a researcher at Nathan Klein Institute (“NKI”), has developed a transgenic mouse containing the human tau gene that develops human paired helical filaments, the building blocks of the neurofibrillary tangles, which are known to be involved in the pathology of Alzheimer’s disease. The pathology in these mice is Alzheimer-like, with hyperphosphorylated tau accumulating in cell bodies and dendrites as neurofibrillary tangles.  In addition, these transgenic mice have exhibited extensive neuronal death that accompanies the tau pathology.  These transgenic mice could be used for testing the efficacy of therapeutic compounds.  AECOM and the New York State Office of Mental Health, the agency that oversees NKI, each have an interest in these transgenic mice.  Through our agreements with AECOM, we have license rights to AECOM’s interest in these transgenic mice.  In 2006, we entered into additional license agreements that provide us with the exclusive rights to sell these mice.  The mice are currently available through Jackson Laboratories.  In December 2006, we entered into an agreement to sell a breeding pair of these mice.

 
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As we currently do not have any approved products in the marketplace, we do not have a time frame for generating significant revenues from our research and development activities.

As of December 31, 2007, we had a cash balance of $2,960,141.  We anticipate that our cash balance at December 31, 2007, coupled with our annual R & D support from Eli Lilly and Company, should be sufficient to fund our current planned development activities and operating expenses through the first quarter of 2009.  We will need additional funding during the first quarter of 2009 to continue our research, product development and our operations.  We intend to seek such additional funding through private and/or public financing, through exercise of currently outstanding stock options and warrants or through collaborative or other arrangements with partners.  If we need to sell additional shares of common stock in order to raise such additional funding, we will in all likelihood amend our certificate of incorporation to increase the number of authorized shares of common stock.  This amendment would require the approval of our stockholders.  The cash on hand will be used for ongoing research and development, working capital, general corporate purposes and possibly to secure appropriate partnerships and expertise.

We do not anticipate the purchase, lease or sale of any significant property and equipment during 2008.  We do not anticipate any significant changes in our employee count during 2008.

Plan of Operation

Our strategic plan involves focusing our resources, and establishing priorities, to maximize the return to the shareholders.  In order to accomplish this objective, it is expected that we will focus on advancing our therapeutic collaboration with Eli Lilly and Company and developing the projects in our diagnostic pipeline to detect AD, including our CSF-based test and serum-based tests, toward commercialization.

In November 2006, we entered into an agreement with Eli Lilly and Company (“Lilly”) to develop therapeutics to treat AD.  Pursuant to the terms of the agreement, we received $2 million in cash, including an equity investment of $500,000, from Lilly, plus we will receive annual research and development support for the duration of the collaboration agreement.  In addition, Lilly will, based on the achievement of certain defined milestones, provide us over time with up to $20 million in milestone payments for advancing our proprietary target to a therapeutic compound.  The collaboration has also made progress on other targets that are part of the collaboration that could provide milestone payments to us over time of up to $10 million for advancing each of these other targets to a therapeutic compound.  There is no limit to the number of targets that we could receive milestone payments from Lilly.  Royalties are to be paid to us for AD drug compounds brought to market that result from the collaboration.  There is no limit on the number of drug compounds for which royalty payments may be due to us.  Lilly received the exclusive worldwide rights to the intellectual property related to our expertise in understanding the molecular neuropathology of AD as it pertains to the formation of neurofibrillary tangles in the development of AD therapeutics.  Lilly will fund the vast majority of all pre-clinical research and development and will fully finance the clinical testing, manufacturing, sales and marketing of AD therapeutics developed from our collaboration.

Our product farthest along in development is a CSF-based diagnostic test to detect whether a person has AD.  We are planning to continue development to reduce the tests incubation time.  We are utilizing the knowledge gained during the development of our CSF-based diagnostic test to aid in the development of serum-based diagnostic tests to detect Alzheimer’s disease, specifically a screening test to rule out AD as well as the detection of our ptau biomarker to support the diagnosis of AD.  In January 2006, we entered into a research agreement with Nanosphere, Inc., a nanotechnology-based molecular diagnostics company, to assist us in the development of a serum-based diagnostic test for AD.  Work performed during the research agreement resulted in Nanosphere and APNS scientists achieving a better understanding (in January 2007) of the tools necessary to advance the development of a serum-based AD diagnostic test with our scientifically accepted biomarkers.  We established a project plan and began developing these key tools in early 2007, and targeted to have the first of these tools developed during the first quarter of 2008 to enable us to continue to advance our serum diagnostic development work.

 
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We sought additional expertise and resources by conducting a scientific advisory board meeting that brought together APNS scientists, Dr. Davies and three outside diagnostic experts to assist us in assessing the most effective approaches and resources to advance our diagnostic development programs.  Through 2007, we followed our work plans to develop antibody tools and we achieved a key milestone in the first quarter of 2008 by identifying several high affinity antibodies that meet our requirements.  These tools will support advancing development of a “rule out” serum based test for AD.  Additional back up tool options to support a “rule out” test are also in development.  In addition, tools directed toward the development of a ptau biomarker based test in serum that could support the early identification of AD are targeted for completion in the second quarter 2008.  Throughout the tool development process we have been identifying specialized technologies that may enable us to advance our diagnostic development programs.  Technology assessments have been initiated.

In order to maximize the value, and minimize the time to market, of our diagnostic programs, we are seeking some form of partnering, including collaborations, strategic alliance and/or licensing opportunities.

We will need additional funding prior to the end of the first quarter 2009 to cover operations, and to fund the costs of any diagnostic products in development.  Eli Lilly and Company funds the vast majority of our therapeutic program through our collaboration.  If additional funding is not obtained, we will not be able to fund any programs in development, and we may have to discontinue all our product development and/or our operations.

Critical Accounting Policies and Estimates

Our consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America.  The consolidated financial statements include the accounts of APNS and its wholly-owned subsidiaries prior to our dissolution of our subsidiaries in 2004.  All significant intercompany balances and transactions have been eliminated.  The preparation of these financial statements requires our management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenues and expenses during the reporting period.

On an on-going basis, our management evaluates its estimates and judgments, including those related to tax valuation and equity compensation.  Our management bases its estimates and judgments on historical experience and on various other factors that are believed to be reasonable under the circumstances.  Actual results may differ from these estimates under different assumptions or conditions.  Our management believes the following critical accounting policies, among others, affect our more significant judgments and estimates used in preparation of these consolidated financial statements.

Revenue Recognition

We generate revenues from research agreements and collaborations, and in the past, we also generated revenues from grants, and recognize these revenues when earned.  Grant revenues represent funds received from certain government agencies for costs expended to further research on the subject of the grant.  In accordance with EITF 00-21 “Revenue Arrangements with Multiple Deliverables”, for arrangements that contain multiple deliverables, we separate the deliverables into separate accounting units if they meet all of the following:  a) the delivered items have stand-alone value to the customer; b) the fair value of any undelivered items can be reliably determined; and c) if the arrangement includes a general right of return, delivery of the undelivered items if probable and substantially controlled by the seller.  Deliverables that do not meet these criteria are combined with one or more other deliverables into one accounting unit.  Revenue from each accounting unit is recognized based on the applicable accounting literature, primarily Staff Accounting Bulletin No. 104 (SAB 104), "Revenue Recognition".

Research and Development

All research and development costs are expensed as incurred and include salaries of, and expenses related to, employees and consultants who conduct research and development.  We have, from time to time, entered into arrangements whereby we will obtain research reimbursement in the form of funds received to partially reimburse us for costs expended.

Net Deferred Tax Asset Valuation Allowance

 
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We record our net deferred tax assets in the amount that we expect to realize based on projected future taxable income.  In assessing the appropriateness of the valuation, assumptions and estimates are required such as our ability to generate future taxable income.  In the event that we were to determine that we would be able to realize our deferred tax assets in the future in excess of our net recorded amount, an adjustment to the deferred tax asset would increase income in the period such determination was made.  Since inception, we have concluded that the more likely than not criteria of Statement of Financial Accounting Standard No. 109, Accounting for Income Taxes, has not been met and accordingly, we have recorded a valuation allowance for all our deferred income taxes for all periods presented.

For the year ended December 31, 2007, we adopted Financial Accounting Standards Board (FASB) Interpretation 48, Accounting for Uncertainty in Income Taxes an Interpretation of FASB Statement No. 109, (FIN 48), which clarifies the accounting for uncertain income tax positions.  This interpretation prescribes a financial statement recognition threshold and measurement attribute for any tax position taken, or expected to be taken, in a tax return. The interpretation also provides guidance on derecognition, classification, interest and penalties, accounting in interim periods, disclosure and transition.  Upon adoption, there was not any unrecognized income tax benefits and the adoption of FIN 48 had no effect on shareholders’ equity.  We do not expect any reasonably possible material changes to the estimated amount in our liability associated with our uncertain tax position through December 31, 2007.

Equity Compensation

Effective January 1, 2006, we adopted Statement No. 123R, Share-Based Payment (SFAS 123R), which requires companies to measure and recognize compensation expense for all stock-based payments at fair value.  SFAS 123R is being applied on the modified prospective basis.  Prior to the adoption of SFAS 123R, we accounted for our stock-based compensation plans under the recognition and measurement principles of Accounting Principles Board (APB) Opinion No. 25, Accounting for Stock Issued to Employees, and related interpretations, and accordingly, recognized no compensation expense related to the stock-based plans.

Under the modified prospective approach, SFAS 123R applies to new awards and to awards that were outstanding on January 1, 2006 that are subsequently modified, repurchased, cancelled or vest.  Under the modified prospective approach, compensation cost recognized in 2006 includes compensation cost for all share-based payments granted prior to, but not yet vested on, January 1, 2006, based on the grant-date fair value estimated in accordance with the provisions of SFAS 123R, and compensation cost for all shared-based payments granted subsequent to January 1, 2006, based on the grant-date fair value estimated in accordance with the provisions of SFAS 123R.  Prior periods were not restated to reflect the impact of adopting the new standard.

We apply Statement of Financial Accounting Standards (SFAS) No. 123 and EITF 96-18 Accounting for Equity Instruments That are Issued to Other Than Employees for Acquiring, or in Conjunction with Selling, Goods or Services, for our options awarded to non-employee consultants.  To determine fair value, management is required to make assumptions such as the expected volatility and expected life of the instruments.


Results of Operations

The following discussion of the financial condition and results of operations should be read in conjunction with the consolidated financial statements and notes thereto included in Item 7.


Year Ended December 31, 2007 Compared to Year Ended December 31, 2006

Revenues

We recognized $1,083,333 of revenues in 2007 from the completion of one research agreement and the recognition of twelve months of our initial funds received from our collaboration with Eli Lilly and Company.  We recognized $251,634 of revenues in 2006 from the completion of two research agreements and the recognition of approximately one month of our initial funds received from our collaboration with Eli Lilly and Company,

Research and development

Research and development expenses consist primarily of compensation of personnel and related benefits and taxes, funding of research related to license agreements, scientific consultant expenses, laboratory supplies and overhead costs.  Research and development expenses for the year ended December 31, 2007 decreased 22% or $460,173 to $1,659,258 from $2,119,431 for the year ended December 31, 2006.  Below is a summary of our most significant research and development expenses:

 
71

 
               
Increase
 
Expense
 
2007
   
2006
   
(Decrease)
 
Compensation, taxes and benefits
  $ 786,961     $ 885,127     $ (98,166 )
Program R & D funding, license fees and consulting
    791,890       871,575       (79,685 )
Rent, telephone and utilities
    107,342       110,645       (3,303 )
Stock option compensation expense
    3,423       230,018       (226,595 )
Other research and development expenses, net of reimbursements
    (30,358 )     22,066       (52,424 )
Total Research and Development Expenses
  $ 1,659,258     $ 2,119,431     $ (460,173 )

This decrease in 2007 is primarily due to non-cash costs associated with expensing stock options, a decrease in research funding, license fees and consulting and a decrease in compensation related expenses.  Beginning January 1, 2006, SFAS 123R requires companies to measure and recognize compensation expense for all stock based payments at fair value.  Expense included in 2007 was $3,423 while expense included in 2006 was $230,018, which was comprised of $112,558 primarily due to option grants prior to 2006 and a non-cash expense of $117,460 for unrecognized compensation costs for options granted in 2005 that were subsequently cancelled in June 2006.  We also had a decrease in research funding, licensing and consulting of $79,685 due to our agreement with Nanosphere in 2006 and expense for regulatory consultants in 2006, which was offset by an increase in our payments to AECOM, license fees incurred, costs of our scientific advisory meeting, and an increase in our direct costs for R & D programs in 2007.  Our compensation related expenses decreased due to a reduction in one of our lab technicians in the second half of 2006, an additional reduction due to a restructuring of our VP-R & D position in the fourth quarter of 2007 and a $45,000 reduction in benefit expense in 2007.  We estimate that we may incur costs of approximately $150,000 to $180,000 per month on research and development activities going forward.  This excludes the non-cash effect of accounting for equity instruments included in the annual amounts mentioned above.  These expenditures, however, may fluctuate from quarter-to-quarter and year-to-year depending upon the resources available, our development schedule, and our progress.  Results of preclinical studies, clinical trials, regulatory decisions and competitive developments for our diagnostic programs may significantly influence the amount of our research and development expenditures.  In addition, if we incur clinical development costs of any diagnostic program, research and development spending will significantly increase.

General and administrative

General and administrative expenses consist primarily of compensation of personnel and related benefits and taxes, legal and accounting expenses, and occupancy related expenses.  General and administrative expenses for the year ended December 31, 2007 decreased 10% or $224,500 to $2,000,439 from $2,224,939 for the year ended December 31, 2006.  Below is a summary of our most significant general and administrative expenses:

               
Increase
 
Expense
 
2007
   
2006
   
(Decrease)
 
Compensation, taxes and benefits
  $ 753,513     $ 502,614     $ 250,899  
Consulting
    138,603       212,459       (73,856 )
Professional fees
    319,960       552,366       (232,406 )
Rent, telephone and utilities
    44,876       50,317       (5,441 )
Stock option compensation expense
    532,917       687,929       (155,012 )
Other general and administrative expenses
    210,570       219,254       (8,684 )
Total General and Administrative Expenses
  $ 2,000,439     $ 2,224,939     $ (224,500 )

This decrease in 2007 is primarily due to non-cash costs associated with expensing stock options and decreases in professional fees and consulting costs partially offset by an increase in compensation costs.  Beginning January 1, 2006, SFAS 123R requires companies to measure and recognize compensation expense for all stock based payments at fair value.  Expense included in 2006 was $687,929 while it was $532,917 in 2007.  The expense in 2006 was greater due to larger grants in 2006, primarily to our new CEO and Chairman who was appointed in June 2006.  The decrease in professional fees is primarily related to costs incurred to retain an executive search firm to assist us in hiring Ellen R. Hoffing as President and CEO in August 2006, plus additional legal time spent on specific projects in 2006, including our stockholders’ meeting, numerous licensing agreements and SEC filings.  Consulting costs decreased in 2007 primarily due to a reduction in consulting projects and a reduction in PR expense.  In 2006, we contracted with a business development consultant and with operational review consultants for specific projects.  The increase in compensation expense is primarily due to the hiring of Ms. Hoffing in August 2006.  We estimate that we may incur costs of approximately $100,000 to $150,000 per month on general and administrative activities going forward.  This excludes the non-cash effect of accounting for equity instruments included in the annual amounts mentioned above.  These expenditures, however, may fluctuate from quarter-to-quarter and year-to-year depending upon the resources available, SEC requirements, and our development schedule.

 
72

 
Other income and expense

Interest expense for the year ended December 31, 2007 was $12,159 due to non-cash amortization of debt discount related to the bridge loan.  Interest expense for the year ended December 31, 2006 was $218,740, primarily due to $189,707 non-cash amortization of debt discount and $29,000 accrued interest related to the bridge loan.    Interest income for the year ended December 31, 2007 increased 172% or $38,011, to $60,160 from $22,149 for the year ended December 31, 2006.  The increase is primarily due to higher average invested balances and a higher rate of return.

We currently do not hedge foreign exchange transaction exposures.  As of December 31, 2007, we do not have any assets and liabilities denominated in foreign currencies.

Net loss

We incurred a net loss of $2,528,363 for the year ended December 31, 2007 compared to a net loss of $4,289,327 for the year ended December 31, 2006.  The primary reasons for the $1,760,964 decrease in the net loss in 2007 were the $831,699 increase in revenues; the $381,607 decrease in stock based compensation expense; the $306,262 decrease in professional fees and consulting; and the $244,592 net decrease in interest expense/income.

Capital resources and liquidity

To date, we have raised equity and convertible debt financing and received research agreement revenues, collaboration revenues and grant revenues to fund our operations, and we expect to continue this practice to fund our ongoing operations.  Since inception, we have raised net proceeds of approximately $42.1 million from private equity and convertible debt financings.  We have also received approximately $3.9 million from research agreements, collaboration revenues and grant revenues.

Our cash and cash equivalents were $2,960,141 and $1,433,250 at December 31, 2007 and 2006, respectively.  The increase in our cash balance is due to the $4.6 million in funds raised in 2007 less repayment of the $500,000 July 2006 bridge loan in January 2007 less the excess cash used in operations.

We used cash in operating activities of $2,565,860 for the year ended December 31, 2007 versus cash used in operating activities of $1,809,803 for the year ended December 31, 2006.  This increase primarily reflects the funds received from Eli Lilly and Company in December 2006 net of the increase in non-cash equity and interest expense in 2006.  Improved cash flow in 2007 due to funds received in financings allowed us to pay down liabilities during 2007.  Cash used in investing activities was negligible in 2007 and 2006.  Net cash provided by financing activities was $4,097,539 for the year ended December 31, 2007 versus net cash provided by financing activities of $1,581,299 for the year ended December 31, 2006.  This increase primarily reflects additional funds raised through sale of stock and exercise of warrants in 2007.  The bridge loan funds received in 2006, were repaid, plus accrued interest, in January 2007.

We have incurred recurring losses since our inception and expect to incur substantial additional research and development costs prior to reaching profitability.  We incurred research and development costs of $1,655,835 in 2007 and $1,889,413 in 2006, excluding non-cash costs related to accounting for stock options and other costs associated with the issuance of equity instruments.  Through 2007, virtually all of our research and development costs were internal costs and license costs which were not specifically allocated to any of our research and development projects.  Beginning in 2008, an increasing amount of our research and development costs are being specifically allocated to our research and development projects.  Through a restructuring, we eliminated a senior scientist position in November 2007.  The compensation that had been utilized for the senior scientist is now being allocated to direct R & D projects and working with outside companies and consultants to obtain specific expertise and technologies to assist us in advancing our programs.  We anticipate that our cash balances as of December 31, 2007, coupled with anticipated funds to be received from operations, will be sufficient to cover our planned research and development activities and general operating expenses through the first quarter 2009.  We will need additional funding prior to the end of the first quarter 2009 to cover operations.  If additional funding is not obtained, we will not be able to fund the costs of any programs in development.  This would have a material adverse effect on our operations and our prospects.
 
 
73

 
As we currently do not have any approved products in the marketplace, we do not have a time frame for generating significant revenues from our research and development activities.

We currently do not have sufficient resources to maintain operations and complete the development of our proposed research projects.  Therefore, we will need to raise substantial additional capital prior to the end of the first quarter 2009 to fund our operations.  We cannot be certain that any financing will be available when needed, or on terms acceptable to us.  If we fail to raise additional financing as we need it, we may have to delay or terminate our own product development programs or pass on opportunities to in-license or otherwise acquire new products and/or technologies that we believe may be beneficial to our business.  We may spend capital on:

·  
research and development programs;
·  
pre-clinical studies and clinical trials; and
·  
regulatory processes.

The amount of capital we may need will depend on many factors, including the:

·  
progress, timing and scope of research and development programs;
·  
progress, timing and scope of our pre-clinical studies and clinical trials;
·  
time and cost necessary to obtain regulatory approvals;
·  
time and cost necessary to seek third party manufacturers to manufacture our products for us;
·  
time and cost necessary to seek marketing partners to market our products for us;
·  
time and cost necessary to respond to technological and market developments; and
·  
changes made to, or new developments in, our existing collaborative, licensing and other commercial relationships; new collaborative, licensing and other commercial relationships that we may establish.

Commitments

We have several financial commitments, including those relating to our license agreements with Albert Einstein College of Medicine (“AECOM”).

Under our license agreements with AECOM, we are required to:

·  
pay semi-annual maintenance payments in January and July each year;
·  
pay quarterly funding payments in February, May, August and November each year as long as the license agreements are in place; and
·  
pay the costs of patent prosecution and maintenance of the patents included in the agreement.

Our fixed expenses, such as rent, license payments and other contractual commitments, may increase in the future, as we may:

·  
enter into additional leases for new facilities and capital equipment;
·  
enter into additional licenses and collaborative agreements; and
·  
incur additional expenses associated with being a public company.

In addition to the commitments to AECOM, we also have consulting agreements and minimum annual lease payments.

The following table summarizes the timing of these future long term contractual obligations and commitments for the next five years ending December 31:

   
2008
Year 1
   
2009
Year 2
   
2010
Year 3
   
2011
Year 4
   
2012
Year 5
   
Total
 
Operating Leases
  $ 99,375     $ 99,375     $ 37,266     $ -     $ -     $ 236,016  
Consulting Agreements with initial terms greater than one year
      99,000         -         -         -         -         99,000  
Commitments Under License Agreement with AECOM
    500,000       500,000       500,000       500,000       500,000       2,500,000  
Total Contractual Cash Obligations
  $ 698,375     $ 599,375     $ 537,266     $ 500,000     $ 500,000     $ 2,835,016  

 
74

 
We are obligated to continue to pay AECOM $500,000 for each year in which the Agreements are still in effect.  In addition, we are obligated to pay AECOM a percentage of all revenues we receive from selling and/or licensing aspects of the AD technology licensed under the Agreements that exceeds the minimum obligations reflected in the annual license maintenance payments.

Recently issued accounting pronouncements

In July 2006, the FASB issued Interpretation No. 48, “Accounting for Uncertainty in Income Taxes” (“FIN 48”). FIN 48 prescribes a recognition threshold and measurement attribute for the financial statement recognition and measurement of a tax position taken or expected to be taken in its tax return. FIN 48 also provides guidance on derecognition, classification, interest and penalties, accounting in interim periods, disclosure and transition. FIN 48 is effective in fiscal years beginning after December 15, 2006. The provisions of FIN 48 are to be applied to all tax positions upon initial adoption, with the cumulative effect adjustment reported as an adjustment to the opening balance of retained earnings. Upon adoption, there were no unrecognized income tax benefits and the adoption of FIN 48 had no effect on shareholders’ equity.

In February 2007, the FASB Board issued SFAS No. 159, “The Fair Value Option for Financial Assets and Financial Liabilities” (“SFAS 159”). This statement permits entities to choose to measure many financial instruments and certain other items at fair value. SFAS 159 is effective for fiscal years beginning after November 15, 2007.  We are currently assessing the effect that SFAS 159 will have on our results of operations and financial position.

In December 2007, the FASB issued SFAS No. 160, “Noncontrolling Interests in Consolidated Financial Statements an amendment of ARB No. 51” (“SFAS 160”).  This statement establishes accounting and reporting standards for noncontrolling interests in subsidiaries and for the deconsolidation of subsidiaries and clarifies that a noncontrolling interest in a subsidiary is an ownership interest in the consolidated entity that should be reported as equity in the consolidated financial statements.  This Statement also requires expanded disclosures that clearly identify and distinguish between the interests of the parent owners and the interests of the noncontrolling owners of a subsidiary.  SFAS 160 is effective for fiscal years beginning on or after December 15, 2008.  We do not believe that the adoption of SFAS 160 will have a material effect on our results of operations or financial position.

In December 2007, the FASB issued SFAS No. 141 (Revised 2007), “Business Combinations” (“SFAS 141 (Revised 2007)”).  While this statement retains the fundamental requirement of SFAS 141 that the acquisition method of accounting (which SFAS 141 called the  purchase method ) be used for all business combinations, SFAS 141 (Revised 2007) now establishes the principles and requirements for how an acquirer in a business combination:  1) recognizes and measures in its financial statements the identifiable assets acquired, the liabilities assumed, and any noncontrolling interests in the acquiree; 2) recognizes and measures the goodwill acquired in the business combination or the gain from a bargain purchase; and 3) determines what information should be disclosed in the financial statements to enable the users of the financial statements to evaluate the nature and financial effects of the business combination.   SFAS 141 (Revised 2007) is effective for fiscal years beginning on or after December 15, 2008.  We do not believe that the adoption of SFAS 141 (Revised 2007) will have a material effect on our results of operations or financial position.

CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE.

None.


DIRECTORS, EXECUTIVE OFFICERS, PROMOTERS AND CONTROL PERSONS

The Directors, executive officers, and certain key scientists and advisors of the Company and their ages, as of May 5, 2008, are as follows:

Ellen R. Hoffing
51
President, Chief Executive Officer, Chairman of the Board of Directors & Class II Director
Alan L. Heller (2), (3)
54
Class III Director
Jay B. Langner (1)
78
Class II Director
David C. Tiemeier (3)
61
Class I Director
Robert S. Vaters (1)(2)
47
Class III Director
David Ellison
46
Chief Financial Officer & Corporate Secretary
 
 
75

 
(1)    Member of the Audit Committee
(2)    Member of the Compensation Committee
(3)    Member of Nominating and Governance Committee

On December 31, 2007, Mr. Bruce Barron’s resignation from the Board of Directors became effective.  On April 20, 2007, Dr. Michael Sorell, a Class III director, passed away.  We have not filled the vacancy resulting from Mr. Barron’s resignation and Dr. Sorell’s untimely passing.

Ellen R. Hoffing, a Class II director, was appointed Chairman of the Board of Directors in December 2007 and has been President, Chief Executive Officer and a Director since August 29, 2006.  Since 2005, she has been a consultant to healthcare focused companies.  In 2005, Ms. Hoffing was Vice President, Strategic Planning at American Pharmaceutical Partners, a publicly traded specialty pharmaceutical company focused on injectable oncology, anti-infective and critical care products.  From 2002 to 2005, Ms. Hoffing was Vice President, Renal Pharmaceuticals at Baxter Healthcare, a New York Stock Exchange listed company. From 2001 to 2002, she was Vice President, Strategy and Acquisitions, at Merisant (the maker of Equal®) and from 2000 to 2001, Ms. Hoffing was a strategy and management consultant to healthcare focused companies. Prior to 2000, Ms. Hoffing took on roles of increasing responsibility in her 17 years at the Searle division of Monsanto, which culminated in her position as Vice President, Global Analytics.

Alan L. Heller, a Class III director, has been a director since September 2006.  Since March 2006, Mr. Heller has been an Operating Partner at a private equity firm, Water Street Capital Partners.  Mr. Heller currently serves on the Board of Directors of two public companies: Savient Pharmaceuticals, Inc. and Northfield Laboratories Inc.  From November 2004 to November 2005, Mr. Heller was President and Chief Executive Officer of American Pharmaceutical Partners, Inc., a company that develops, manufactures and markets branded and generic injectable pharmaceutical products.  From January 2004 to November 2004 Mr. Heller served as an investment advisor on life science transactions to One Equity Partners, a private equity arm of JP Morgan Chase.  From 2000 to 2004, Mr. Heller also served as Senior Vice President and President Global Renal operations at Baxter Healthcare Corporation.  Prior to joining Baxter, Mr. Heller spent 23 years at G.D. Searle. He served in several senior level positions including Co-President and Chief Operating Officer, with responsibility for all commercial operations worldwide, and Executive Vice President and President, Searle Operations.

Jay B. Langner, a Class II director, was appointed as a director in July 2005.  Since 1985, Mr. Langner has served as the Chairman of the Board of Trustees of Montefiore Medical Center. Located in The Bronx, NY, Montefiore Medical Center is the University Hospital for the Albert Einstein College of Medicine (AECOM) and one of the largest health care systems in the United States. From 1961 to 2003, he served as Chairman and CEO of the Hudson General Corporation, which was sold to Luftansa Airlines in 1999. Mr. Langner began his career in 1954, serving as president of Langner Leasing Corporation.

David C. Tiemeier, Ph.D., a Class I director, has been a director since October 2007.  He is currently serving as Deputy Director of UChicagoTech, the University of Chicago’s Office of Technology and Intellectual Property.  Previously, Dr. Tiemeier pursued postdoctoral studies in molecular genetics at the National Institutes of Health before joining the faculty of the University of California, Irvine, Medical School.  He joined Monsanto Co. (NYSE:MON) as the head of Molecular Genetics, and continued his career in Monsanto’s pharmaceutical division as Senior Director of Immunoinflammatory and Infectious Diseases and took on roles of increasing responsibility including General Manager of the Global New Business Franchise and Vice President of Global Business Development.  He subsequently held senior positions in Pharmacia Corporation and Pfizer Inc. (NYSE:PFE).  Following his retirement from Pfizer, Dr. Tiemeier held senior management positions with NeoPharm, Inc. (Nasdaq:NEOL), Immtech Pharmaceuticals, Inc. (Amex:IMM) and Kalypsys, Inc.

Robert S. Vaters, a Class III director, has been a Director of the Company since October 2005.  Mr. Vaters was Chairman of the Board of Directors from July 2006 until December 2007.  Mr. Vaters is currently a General partner in Med Opportunity Partners, a New York based private equity firm. Previously, Mr. Vaters was Executive Vice President, Strategy and Corporate Development of Inamed Corporation from November 2004 to March 2006 after serving as Inamed's Chief Financial Officer from August 20, 2002 to November 2004. From September 2001 to August 2002, Mr. Vaters worked on a variety of private merchant banking transactions. He was Executive Vice President and Chief Operating Officer at Arbinet Holdings, Inc., a leading telecom capacity exchange from January 2001 to July 2001. He served as Chief Financial Officer at Arbinet from January 2000 to December 2000. Prior to that he was at Premiere Technologies from July 1996 through January 2000, where he held a number of senior management positions, including Executive Vice President and Chief Financial Officer, Managing Director of the Asia Pacific business based in Sydney, Australia and Chief Financial Officer of Xpedite Systems Inc., formerly an independent public company that was purchased by Premiere. Additional experience includes Senior Vice President, Treasurer of Young and Rubicam Inc., a global communications firm with operations in 64 countries. From 1995 to 1998, Mr. Vaters was also an independent board member and chairman of the audit committee of Rockford Industries, a public company providing healthcare equipment financing.

 
76

 
David Ellison, CPA, has been Chief Financial Officer of the Company since May 1996 and Corporate Secretary since August 1999.  He had been Chief Financial Officer of a long-term care facility specializing in Alzheimer’s care and prior to that he was a senior manager in a Chicago-area public accounting firm.

There are no family relationships between any of the officers and directors.
 
Director Independence

We currently have four “independent directors” as determined by our Board of Directors, and one non-independent director.  In assessing director independence, we follow the criteria of the Nasdaq Stock Market (Marketplace Rule 4200(15)).  Our current independent directors are Alan L. Heller, Jay B. Langner, David C. Tiemeier and Robert S. Vaters.

EXECUTIVE COMPENSATION

The following table sets forth all compensation awarded to, earned by, or paid for services in all capacities during 2007 and 2006 by our President and Chief Executive Officer, Chief Financial Officer, and Chief Scientific Officer.

Name and
Principal Position
 
Year
 
Salary
 
Bonus
Stock
Awards
Option
Awards
All Other
Compensation
 
Total
 
Ellen R. Hoffing
President & CEO (1)
 
2007
2006
 
    $301,250
        92,115
 
    $120,000
        40,000
 
    $20,761
      39,805
 
    $         0
    718,685
 
    $        0
              0
 
    $442,011
      890,605
 
David Ellison
CFO (2)
 
2007
2006
 
    $195,339
      187,529
 
    $           0
                 0
 
    $         0
               0
 
    $         0
               0
 
    $        0
              0
 
    $195,339
      187,529
 
John F. DeBernardis
Chief Scientific Officer Former Pres. and CEO (3)
 
2007
2006
 
    $291,526
      303,326
 
    $           0
                 0
 
    $         0
               0
 
    $         0
               0
 
    $ 1,000
       4,263
 
    $292,526
      307,589

(1)           Ms. Hoffing began employment as President and Chief Executive Officer of the Company in September 2006.  Her minimum annual base salary per her employment agreement is $300,000.  On August 29, 2006, The Company’s Board of Directors approved a grant of 6,000,000 stock options to Ms. Hoffing.  This option grant was made pursuant to her employment agreement and was not made under the Company’s 2003 stock option plan.  On August 29, 2006, the Company granted to Ms. Hoffing of 400,000 shares of restricted stock.  On October 23, 2007, the Company granted Ms. Hoffing 526,316 shares of restricted stock.  Both restricted stock grants were made pursuant to her employment agreement.  In January 2007, the Company’s Board of Directors approved a $40,000 bonus for 2006 to Ms. Hoffing.  In February 2008, the Company’s Board of Directors approved a $120,000 bonus for 2007 to Ms. Hoffing.  The bonuses were made pursuant to her employment agreement.  In December 2007, Ms. Hoffing was appointed as Chairman of the Company’s Board of Directors.  Effective December 1, 2007, the Company’s Board of Directors approved an increase in Ms. Hoffing’s annual base salary to $315,000.
 
(2)           Mr. Ellison was employed as Chief Financial Officer of the Company pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $174,000 per year, with an annual cost of living increase.  Mr. Ellison had not received an increase in his base salary of $183,000 since April 2005.  Mr. Ellison’s agreement also provided a minimum monthly non-accountable allowance of $300 for automobile and cell phone expenses.  This allowance was increased to $400 per month in April 2005.  In July 2007, the Company gave Mr. Ellison timely notice that his employment agreement was not being renewed.  On October 31, 2007, the Company paid Mr. Ellison $13,201, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Since November 1, 2007, Mr. Ellison has continued in his current position with the Company as an at-will employee with an annual base salary of $205,000.
 
(3)           Dr. DeBernardis was President and CEO of the Company from October 2004 through August 2006.  Dr. DeBernardis was employed as Chief Scientific Officer of the Company pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $282,000 per year, with an annual cost of living increase.  Dr. DeBernardis had not received an increase in his base salary of $296,000 since April 2005.  Dr. DeBernardis’s agreement also provided a minimum monthly non-accountable allowance of $1,000 for automobile and cell phone expenses.  This allowance was increased to $1,150 per month in April 2005.  Dr. DeBernardis’s employment agreement provided for the Company to pay for a life insurance policy, in addition to the life insurance policy provided through the Company’s group health plan.  The annual premium is included in All Other Compensation.  This additional life insurance policy was cancelled in April 2007.  In July 2007, the Company gave Dr. DeBernardis timely notice that his employment agreement was not being renewed.  On October 31, 2007, the Company paid Dr. DeBernardis $21,352, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Since November 1, 2007, Dr. DeBernardis has continued in his current position with the Company as an at-will employee with an annual base salary of $185,000.
 

 
77

 
OUTSTANDING EQUITY AWARDS AT FISCAL YEAR-END


Option Awards
 
Stock Awards
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name
 
Number of Securities Underlying Unexercised Options (#) Exercisable
   
 
 
 
 
 
 
 
 
 
 
 
Number of Securities Underlying Unexercised Options (#) Unexercisable
   
 
Equity Incentive Plan Awards: Number of Securities Underlying Unexercised Unearned Options
(#)
   
 
 
 
 
 
 
 
 
 
 
 
 
 
Option Exercise Price
($)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Option Expiration Date
 
 
 
 
 
 
 
 
 
 
 
Number of Shares or Units of Stock That Have Not Vested
(#)(1)
   
 
 
 
 
 
Market Value of Shares or Units of Stock That Have Not Vested
($)
   
Equity Incentive Plan Awards: Number of Unearned Shares, Units or Other Rights That Have Not Vested
(#)
   
Equity Incentive Plan Awards: Market or Payout Value of Unearned Shares, Units or Other Rights That Have Not Vested
($)
 
                                                   
Ellen R. Hoffing
    2,666,670       3,333,330       -     $ 0.230  
08/29/2016
    266,666     $ 27,096       -     $ -  
                                                                   
David Ellison
    9,876       -       -     $ 0.150  
04/01/2008
    -       -       -     $ -  
      69,132       -       -     $ 0.150  
11/16/2010
                               
      164,599       -       -     $ 0.150  
1/01/2011
                               
      35,656       -       -     $ 0.150  
06/01/2012
                               
      500,000       -       -     $ 0.150  
09/02/2013
                               
                                                                   
John F.
 DeBernardis
       65,840                     $ 0.150  
 
 
04/01/2008
       -          -          -     $  -  
      233,731                     $ 0.150  
11/16/2010
                               
      427,957                     $ 0.150  
11/01/2011
                               
      120,402                     $ 0.150  
06/01/2012
                               
      1,500,000                     $ 0.150  
09/02/2013
                               
                                                                   

(1)           Ms. Hoffing’s unexercised stock options as of December 31, 2007 will become exercisable as follows:  166,667 options will become exercisable each month thereafter through July 29, 2009 and 166,657 options will become exercisable on August 29, 2009.  Ms. Hoffing’s restricted common stock will become exercisable as follows:  308,772 shares of restricted common stock vests on August 29, 2008, 308,772 shares of restricted common stock vests on August 29, 2009, and 175,438 shares of restricted common stock vests on August 29, 2010.

Employment agreement

Under the terms of her employment agreement, Ellen R. Hoffing, the Chairman, President and CEO, receives a minimum base salary of $300,000 per year, plus a bonus of up to 40% of Ms. Hoffing’s base salary upon attainment of performance objectives established by the our Board of Directors and acceptable to Ms. Hoffing.    On August 29, 2006, we granted Ms. Hoffing a stock option to purchase 6,000,000 shares of our common stock at an exercise price of $0.23 (which was the closing price of the common stock on the over-the-counter market on the date of grant). The option vests as to 1,000,000 shares of common stock on the sixth month anniversary of the grant, and then will vest as to an additional 166,667 shares for each month thereafter until the option is vested in full (which will be on the third anniversary of the date of grant).  On August 29, 2006, we also granted Ms. Hoffing 400,000
 
 
78

 
shares of restricted stock ($100,000 at $0.25 per share, which was the high price of the common stock on the over-the-counter market on the date of grant), which vests as to 133,334 shares on the first anniversary of the date of grant and 133,333 shares on the second and third anniversaries of the date of grant.  On October 23, 2007, we granted Ms. Hoffing 526,316 shares of restricted stock ($100,000 at $0.19, which was the closing price of the common stock on the over-the-counter market on the day prior to the grant), which vests as to 175,439 shares on August 29, 2008 and 2009 and 175,438 shares on August 29, 2010.  In addition, Ms. Hoffing will receive $100,000 worth of shares of restricted stock on her two-year anniversary with the Company (August 29, 2008).  If Ms. Hoffing’s employment is terminated by us without cause, she is entitled to her base salary and benefits for a period of 12 months after such termination, and the portion of her options and restricted stock that would have vested during the 12 months following such termination will immediately vest.  If Ms. Hoffing’s employment is terminated upon or in connection with a change of control of the Company, then Ms. Hoffing will be paid the equivalent of one year’s base salary and any unvested shares of restricted stock and stock options will immediately vest in full upon such “change in control”.

Prior Employment Agreements

David Ellison, the Chief Financial Officer and Corporate Secretary, was employed pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $174,000 per year, with an annual cost of living increase.  Mr. Ellison had not received an increase in his base salary since April 2005.  Included in general and administrative expense is $8,672 and $4,529 for 2007 and 2006, respectively, representing his earned, but not yet paid, cost of living increase from April 2006 to October 2007.  Mr. Ellison’s agreement also provided a minimum monthly non-accountable allowance of $300 for automobile and cell phone expenses.  This allowance was increased to $400 per month in April 2005.  In July 2007, we gave Mr. Ellison timely notice that his employment agreement was not being renewed.  On October 31, 2007, the Company paid Mr. Ellison $13,201, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Since November 1, 2007, Mr. Ellison has continued in his current position with the Company as an at-will employee with an annual base salary of $205,000.

John F. DeBernardis, Ph.D., Chief Scientific Officer, was employed pursuant to an agreement through October 31, 2007 that provided for a minimum base salary of $282,000 per year, with an annual cost of living increase.  Dr. DeBernardis had not received an increase in his base salary since April 2005.  Included in research and development expense is $14,026 and $7,326 for 2007 and 2006, respectively, representing his earned, but not yet paid, cost of living increase from April 2006 to October 2007.  Dr. DeBernardis’s agreement also provided a minimum monthly non-accountable allowance of $1,000 for automobile and cell phone expenses.  This allowance was increased to $1,150 per month in April 2005.  In addition, we also provided Dr. DeBernardis, at our expense, a term life insurance policy in the amount of $600,000.  This additional life insurance policy was cancelled in April 2007.  In July 2007, we gave Dr. DeBernardis timely notice that his employment agreement was not being renewed.  On October 31, 2007, we Company paid Dr. DeBernardis $21,352, representing his earned, but unpaid, cost of living increase for the period April 2006 through October 2007.  Since November 1, 2007, Dr. DeBernardis has continued in his current position with the Company as an at-will employee with an annual base salary of $185,000.

Compensation of directors

Prior to 2008, Directors received annual option grants upon becoming directors and received additional option grants from time to time as compensation for their service as members of the board of directors.  In March 2008, the Board of Directors approved a compensation plan for independent Directors effective as of January 1, 2008.  Each independent Director will receive annually a $5,000 cash retainer plus $1,000 for each in-person Board meeting attended, $500 for each telephonic Board meeting attended and $500 for each committee meeting attended.  The total annual cash compensation for each Director cannot exceed $10,000.  In addition, each independent Director will receive an annual stock option grant as of the first Board meeting of the year, valued at $5,000, calculated using a Black-Scholes valuation on the date of the grant.  The stock options will have an exercise price equal to the closing price of our common stock on the day prior to the grant and will vest on the first business day of January in the following year.  Directors are reimbursed for reasonable out-of-pocket expenses incurred in the performance of their duties and the attendance of board meetings and any meeting of stockholders.  Mr. Barron was paid $38,708 as compensation for services rendered to the Company as Chairman in 2006.  Mr. Barron was compensated as an employee of the Company and received health benefits and participated in the Company’s 401(k) retirement plan in 2006.  In connection with Mr. Barron’s resignation as Chairman in June 2006, the Company and Mr. Barron agreed to reduce the monthly payments that Mr. Barron received under his employment agreement to $2,479.74.  Such payments were made through December 31, 2006, and represent Mr. Barron’s contributions for the coverage of Mr. Barron and his family under the Registrant’s group health insurance plan and Mr. Barron’s contributions to the Registrant’s 401(k) plan. In the event that the Company during its 2007 fiscal year raised at least $2 million in additional funding, the Company agreed to make six additional payments to Mr. Barron, each in the amount of $2,479.74.  In September 2007, the Company raised more than $2 million and the Company made the six payments in one lump sum to Mr. Barron in October 2007.  The Company also agreed to convert Mr. Barron’s incentive options into non-qualified options immediately upon his resignation as a Director in December 2007.  Mr. Vaters, who became Chairman in June 2006 and stepped down as Chairman in December 2007, was paid $48,000 and $20,000 for consulting services rendered to the Company as Chairman in 2007 and 2006, respectively.

 
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DIRECTOR COMPENSATION
 
 
 
 
 
 
Name
 
 
 
 
Fees Earned or Paid in Cash ($)
   
 
 
 
Stock Awards ($)
   
 
 
 
 
Option Awards ($)
   
 
 
Non-Equity Incentive Plan Compensation ($)
   
Change in Pension Value and Non-Qualified Deferred Compensation Earnings
   
 
 
 
All Other Compensation ($)
   
 
 
 
 
 
Total ($)
 
                                           
 
Robert S. Vaters
  $ 48,000     $ -     $ -     $ -     $ -     $ -     $ 48,000  
                                                         
Bruce N. Barron
  $ 14,878     $ -     $ -     $ -     $ -     $ -     $ 14,878  
                                                         
Jay B. Langner
  $ -     $ -     $ -     $ -     $ -     $ -     $ -  
                                                         
Alan L. Heller
  $ -     $ -     $ -     $ -     $ -     $ -     $ -  
                                                         
David C. Tiemeier
  $ -     $ -     $ 24,655     $ -     $ -     $ -     $ 24,655  
                                                         


SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT

The following table sets forth the beneficial ownership of our securities as of May XX, 2008, by (a) each person known by us to be the beneficial owner of more than 5% of any class of our securities, (b) our directors, (c) our executive officers, and (d) all directors and executive officers as a group.  Except as listed below, the address of all owners listed is C/O Applied NeuroSolutions, Inc., 50 Lakeview Parkway, Suite 111, Vernon Hills, Illinois 60061.  As of May 5, 2008, a total of 130,217,808 shares of our common stock was outstanding.


 
 
Nature of Beneficial Owner
Amount and nature
of beneficial
ownership
 
Percent of
Class (1)
     
SF Capital Partners Ltd.
c/o Stark Offshore Management LLC
235 Pine Street, Suite 1175
San Francisco, CA 94104
 26,928,572  (5)
19.7%
Ellen R. Hoffing (2)
     4,809,655  (6)
3.6%
Jay B. Langner (3)
        650,000  (7)
*
Robert S. Vaters (3)
     2,666,667  (8)
2.0%
David Ellison (4)
         779,263  (9)
*
Alan L. Heller (3)
         350,000 (10)
*
David C. Tiemeier (3)
         200,000 (11)
*
Benjamin Family Trusts
      8,307,780 (12)
6.4%
All Directors and Officers as a group
            (6 persons)
      9,455,585 (13)
 
6.8%


 
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*  Less than 1.0%

 
(1)  Based on 130,217,808 shares of common stock outstanding as of May XX, 2008, plus each person’s warrants or options that are currently exercisable or that will become exercisable within 60 days of May XX, 2008. 
 
(2)  Director and officer.
 
(3)  Director.
 
(4)  Officer.
 
(5)  Consists of 20,714,286 of common stock and 6,214,286 shares of common stock issuable upon the exercise of warrants held by SF Capital Partners Ltd. (“SF Capital”).  Brian J. Stark and Michael A. Roth (the “Reporting Persons”) are the Managing Members of Stark Offshore Management, LLC, (“Stark Offshore”) which acts as investment manager and has sole power to direct the management of SF Capital.  Through Stark Offshore, the Reporting Persons possess voting and dispositive power over the shares of common stock held by SF Capital.
 
(6)  Consists of 50,000 shares of common stock, 3,833,339 shares of common stock issuable upon the exercise of currently exercisable stock options and 926,316 shares of restricted stock, of which 133,334 shares have vested as of May 5, 2008.
 
 
(7)  Consists of 350,000 shares of common stock and 300,000 shares of common stock issuable upon the exercise of currently exercisable stock options.
 
(8)  Consists of 2,666,667 shares of common stock issuable upon the exercise of currently exercisable stock options.
 
(9)  Consists of 779,263 shares of common stock issuable upon the exercise of currently exercisable stock options.
 
(10)  Consists of 100,000 shares of common stock and 250,000 shares of common stock issuable upon the exercise of currently exercisable stock options.
 
(11)  Consists of 200,000 shares of common stock issuable upon the exercise of currently exercisable stock options.
 
(12)  Consists of 8,207,780 shares of common stock held by various family trusts and 100,000 shares of common stock held by a family member.  The trustees of these various family trusts is Bank of America Corporation, 100 North Tryon Street, Floor 25, Bank of America Corporate Center, Charlotte, NC 28255.
 
(13)  Consists of 500,000 shares of common stock, 8,029,269 shares of common stock issuable upon the exercise of currently exercisable stock options and 926,316 shares of restricted stock, of which 133,334 shares have vested as of May 5, 2008.


CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS

During 2003, 2002 and 2001, due to cash constraints, officers of the Company deferred compensation, loaned funds to the Company and personally paid for some Company expenses.  In June 2002, $215,000 of the amount due to these officers was converted to shares of common stock at the merger adjusted market price of $0.228 per share.  The balance due to these officers was paid in February 2004.

In 2003, Richard Stone, one of our directors until September 2004, invested $100,000 in our convertible bridge debt, which earned interest at rate of 6% per annum.  Mr. Stone’s investment, including accrued interest, was converted, at rate of $0.25 per unit of one share and 1.1 warrant, to 413,819 shares of common stock and 455,201 warrants to purchase shares of common stock at an exercise price of $0.30 per share in the debt conversion in conjunction with the February 2004 private placement.  The conversion rate was the same offered to all holders of the bridge debt.

We believe that each of the transactions set forth above were entered into on (i) terms as fair as those that could be obtained from independent third parties, and (ii) were ratified by a majority (but no less than two) of our independent directors who did not have an interest in the transaction and who had access to our counsel at our expense.


DISCLOSURE OF COMMISSION POSITION OF INDEMNIFICATION FOR SECURITIES ACT LIABILITIES

Our Certificate of Incorporation, as amended and restated, incorporates certain provisions permitted under the General Corporation Law of Delaware relating to the liability of Directors.  The provisions eliminate a Director's liability for monetary damages for a breach of fiduciary duty, including gross negligence, except in circumstances involving certain wrongful acts, such as the breach of a Director's duty of loyalty or acts or omissions which involve intentional misconduct or a knowing violation of law.  These provisions do not eliminate a Director's duty of care.  Moreover, the provisions do not apply to claims against a Director for violations of certain laws, including federal securities laws.

 
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Our Certificate of Incorporation, as amended and restated, also contains provisions to indemnify the Directors, officers, employees or other agents to the fullest extent permitted by the General Corporation Law of Delaware.  These provisions may have the practical effect in certain cases of eliminating the ability of shareholders to collect monetary damages from Directors.  Applied NeuroSolutions believes that these provisions will assist it in attracting or retaining qualified individuals to serve as Directors.

Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to our Directors, officers and controlling persons pursuant to the foregoing provisions, or otherwise, we have been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Act and is, therefore, unenforceable.





 
82 

 


APPLIED NEUROSOLUTIONS, INC.
 
PROSPECTUS
 
TABLE OF CONTENTS
 

Prospectus Summary
1
Special Note Regarding Forward Looking Statement
3
Risk Factors
3
Use of Proceeds
14
Selling Security Holders
14
Plan of Distribution
22
Description of Securities
 24
Interest of Named Experts and Counsel
 28
Description of Business
 28
Description of Property
 38
Legal Proceedings
 38
Market for Common Equity and Related Stockholder Matters
 38
Financial Statements
 41
Management’s Discussion and Analysis of Financial Condition and Results of Operations
 67
Changes In and Disagreements with Accountants on Accounting and Financial Disclosure
 75
Directors, Executive Officers, Promoters and Control Persons
 75
Executive Compensation
 77
Security Ownership of Certain Beneficial Owners and Management
 80
Certain Relationships and Related Transactions
 81
Disclosure of Commission Position of Indemnification for Securities Act Liabilities
 81















May 22, 2008
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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