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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

For the fiscal year ended December 31, 2004.

OR

For the transition period from              to             .

Commission file number: 0-21643

CV THERAPEUTICS, INC.

(Exact name of Registrant as specified in its charter)

3172 Porter Drive, Palo Alto, California 94304

(Address of principal executive offices, including zip code)

Registrant’s telephone number, including area code: (650) 384-8500

Securities registered pursuant to Section 12(b) of the Act: None

Securities registered pursuant to Section 12(g) of the Act: Common Stock, $.001 Par Value

Indicate by check whether the Registrant (1) has filed all reports to be filed by Section 13 or 15(d) of the Securities and Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes  x    No  ¨

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained to the best of the Registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K.    x

Indicate by check mark whether the Registrant is an accelerated filer (as defined in Rule 12b-2 of the Act). Yes  x    No  ¨

The aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold, or the average bid and asked price of such common equity, was $525,578,315 as of June 30, 2004.

The number of shares of Common Stock outstanding as of February 24, 2005 was 36,020,979.

DOCUMENTS INCORPORATED BY REFERENCE

Certain portions of the Registrant’s Definitive Proxy Statement in connection with the Registrant’s 2005 Annual Meeting of Stockholders are incorporated herein by reference into Part III of this report.

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CV THERAPEUTICS, INC.

FORM 10-K

TABLE OF CONTENTS

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PART I

Forward-Looking Statements

This Annual Report on Form 10-K and the information incorporated herein by reference contain forward-looking statements that involve a number of risks and uncertainties. Although our forward-looking statements reflect the good faith judgment of our management, these statements can only be based on facts and factors currently known by us. Consequently, forward-looking statements are inherently subject to risks and uncertainties, and actual results and outcomes may differ materially from results and outcomes discussed in the forward-looking statements.

Forward-looking statements can be identified by the use of forward-looking words such as “believe,” “expect,” “hope,” “may,” “will,” “plan,” “intend,” “estimate,” “could,” “should,” “would,” “continue,” “seek,” “pro forma” or “anticipate,” or other similar words (including their use in the negative), or by discussions of future matters such as our future clinical or product development, regulatory review of our products or product candidates, commercialization of our products, our financial performance, possible changes in legislation and other statements that are not historical. These statements include but are not limited to statements under the captions “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and “Business” as well as other sections in this report. You should be aware that the occurrence of any of the events discussed under the heading “Item 1. Business-Risk Factors” and elsewhere in this report could substantially harm our business, results of operations and financial condition and that if any of these events occurs, the trading price of our common stock could decline and you could lose all or a part of the value of your shares of our common stock.

The cautionary statements made in this report are intended to be applicable to all related forward-looking statements wherever they may appear in this report. We urge you not to place undue reliance on these forward-looking statements, which speak only as of the date of this report. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.

Item 1.    Business

Overview

CV Therapeutics, Inc., headquartered in Palo Alto, California, is a biopharmaceutical company focused on the discovery, development and commercialization of new small molecule drugs for the treatment of cardiovascular diseases. We apply advances in molecular biology and genetics to identify mechanisms of cardiovascular diseases and targets for drug discovery. We have four clinical development drug candidates, including our lead drug candidate Ranexa^™ (ranolazine) for the potential treatment of chronic angina, which is subject to an approvable letter from the United States Food and Drug Administration, or FDA. We also have several preclinical programs whose objectives are to bring additional drug candidates into human clinical testing. In addition, we have entered into an agreement to co-promote ACEON^® (perindopril erbumine) Tablets, an angiotensin converting enzyme inhibitor, or ACE inhibitor, with our partner Solvay Pharmaceuticals, Inc. in the United States.

In December 2004, the Company signed a co-promotion agreement with Solvay Pharmaceuticals to co-promote ACEON^® in the United States. ACEON^® is an ACE inhibitor with tissue activity approved in the United States for the treatment of hypertension. Also in December 2004, Solvay Pharmaceuticals submitted a supplemental new drug application, or sNDA, for ACEON^® to the FDA seeking approval to market the product under a proposed label expansion. The FDA has granted priority review for the sNDA, with a regulatory action date in June 2005. The proposed label expansion is based on the EUROPA (EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease) study which

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assessed the ability of perindopril to reduce cardiovascular death, nonfatal myocardial infarction and cardiac arrest in a broad population of patients who had stable coronary artery disease but not heart failure or substantial hypertension. In the EUROPA study, perindopril significantly reduced relative cardiovascular risk by 20% as assessed by the primary combined study endpoint of cardiovascular death, non-fatal myocardial infarction and cardiac arrest.

We are developing our lead drug candidate, Ranexa, for the potential treatment of chronic angina. Unlike current anti-anginal drug therapies, Ranexa appears to exert its anti-anginal activity without depending on reductions in heart rate or blood pressure. If approved by the FDA, Ranexa would represent the first new class of anti-anginal therapy in the United States in more than 25 years. In October 2003, the FDA sent us an approvable letter indicating that Ranexa is approvable, that there is evidence that Ranexa is an effective anti-anginal, and that additional clinical information is needed prior to approval. In June 2004, we reached written agreement with the FDA on a protocol for a clinical trial of Ranexa which, if successful, could support the approval of Ranexa for the treatment of chronic angina in a restricted patient population. This agreement was reached under the FDA’s special protocol assessment, or SPA, process. We initiated this potentially approval-enabling study, called the Evaluation of Ranolazine In Chronic Angina, or ERICA, in August 2004 and completed patient enrollment in November 2004. Initial data from the ERICA study are expected in the second quarter of 2005. If the study is successful, we would expect to submit an amendment to our new drug application for Ranexa in the second half of 2005, seeking product approval from the FDA in a restricted patient population. In order to potentially broaden the product labeling for Ranexa, if any, over time, we also reached written agreement with the FDA in August 2004 on a separate SPA agreement for a study of Ranexa which could support potential approval of Ranexa as first-line therapy for patients suffering from chronic angina. In order to obtain potential approval as first-line angina therapy, under the SPA we also need to perform a separate successful clinical evaluation of higher doses of Ranexa. The study, if positive, also could result in the approval of Ranexa for the treatment and long-term prevention of acute coronary syndromes. The study, known as Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes, or MERLIN TIMI-36, began enrollment in October 2004 and is being conducted by the Harvard-based TIMI Study Group.

In March 2004, we filed a Marketing Authorization Application, or MAA, with the European Medicines Agency seeking approval of ranolazine for the treatment of chronic angina. The MAA was filed for review under the European regulatory authorities’ centralized procedure by our European subsidiary, CV Therapeutics Europe Limited.

Another one of our late stage compounds is regadenoson, a selective A_2A-adenosine receptor agonist for potential use as a pharmacologic agent in myocardial perfusion imaging studies. We initiated a second double-blind Phase III clinical trial of regadenoson in April 2004. Data from one Phase III trial are expected in the third quarter of 2005, and data from the other Phase III trial are expected by the end of 2005.

Tecadenoson is a selective A₁-adenosine receptor agonist for the potential reduction of rapid heart rate during atrial arrhythmias. Adentri^™ is a selective A₁-adenosine receptor antagonist for the potential treatment of congestive heart failure, and has been licensed to Biogen Inc. (now Biogen Idec Inc.). In addition, we have several on-going research and preclinical development programs whose objectives are to bring additional drug candidates into human clinical testing.

Business Strategy

Despite the development during the past 25 years of significant new therapies for patients with cardiovascular disease, heart disease remains one of the leading causes of death in the United States, claiming almost 1,000,000 lives in 2002. Cardiovascular diseases, including atherosclerosis (hardening of the arteries), hypertension (high blood pressure), and ischemia (lack of sufficient oxygen to the cells), may cause permanent damage to the heart and blood vessels, leading to angina, heart failure and myocardial infarction (heart attack).

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Molecular cardiology is providing new insight into the mechanisms underlying cardiovascular diseases and creating opportunities for improved therapies. The key elements of our business strategy are as follows:

Identify, develop and commercialize drugs primarily within a single therapeutic area—cardiovascular disease

By focusing primarily on this single therapeutic area, we believe that we can be relatively efficient in our drug discovery, development and commercialization efforts. Our concentrated focus on cardiovascular disease enhances our efforts in the following areas:

Focus on small molecule drug candidates

Small molecule therapeutics can frequently be administered orally on an outpatient basis. By contrast, “large molecule” therapeutics, such as proteins or monoclonal antibodies, can very rarely be formulated to accommodate oral outpatient administration. In addition, our emphasis on small molecule therapeutics means that our drug candidates can be produced by conventional pharmaceutical manufacturing methods, using the established production capabilities of the contract pharmaceutical manufacturing industry.

In-licensing cardiovascular products with unique potential

We believe it is important to explore in-licensing opportunities to complement our expertise in cardiology. In December 2004, we entered into an agreement with Solvay Pharmaceuticals to co-promote ACEON^® (perindopril erbumine) Tablets in the United States. ACEON^® is an ACE inhibitor that is currently approved for the treatment of hypertension, and a supplemental new drug application has been submitted to the FDA for a label expansion based on data from the EUROPA outcomes study. We expect to continue to evaluate additional products for potential in-licensing or co-promotion.

Commercialize products, in part, through a concentrated sales and marketing effort using a cardiovascular specialty sales force

A focused commercialization effort can provide sales and marketing efficiencies. Patients that have severe cardiovascular conditions are often treated by cardiologists and other specialists. We believe that a relatively small number of specialists are responsible for a significant portion of the patient visits associated with prescriptions written for important cardiovascular conditions. We believe these market dynamics may make it possible to market and sell our products with a focused commercialization effort using a cardiovascular specialty sales force.

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Product Portfolio

We have the following portfolio of product and product candidates:

In the table, under the heading “Development Status,” “Approvable letter” indicates that the FDA has reviewed the NDA and has issued an approvable letter, and that additional work is required before marketing approval can be obtained; “sNDA submitted” indicates that a supplemental new drug application seeking an expansion to the existing approved label has been submitted to the FDA, “Phase III” indicates evaluation of clinical efficacy and safety within an expanded patient population at geographically dispersed clinical trial sites; “Phase II” indicates clinical safety testing, dosage testing and initial efficacy testing in healthy volunteers and/or a limited patient population; “Phase I” indicates initial clinical safety testing in healthy volunteers or a limited patient population, or studies directed toward understanding the mechanisms or metabolism of the drug; “Preclinical” indicates the program has not yet entered human clinical trials. For purposes of the table, “Development Status” indicates the most advanced stage of development that has been completed or is in process.

Approved Product

ACEON^® (perindopril erbumine) Tablets

ACEON^® is an angiotensin converting enzyme inhibitor, or ACE inhibitor, with tissue activity. It is approved in the United States for the treatment of hypertension. ACEON^® offers continuous 24-hour blood pressure control with once-daily dosing. ACEON^® may be used alone or with other classes of antihypertensives.

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Hypertension

In 2002, 65 million people in the United States were diagnosed with hypertension. Based on data collected in 1999-2000, approximately 70% of individuals with hypertension are aware of their condition, 60% are treated with drugs but only about 35% are controlled (meaning that their systolic blood pressure is less than 140 mmHg and their diastolic blood pressure is less than 90 mmHg). In the United States hypertension prevalence is expected to grow due to an aging population and increasingly sedentary life styles. Recent data from the Framingham Heart Study suggest that individuals who have normal blood pressure at age 55 have a 90% life-time risk for developing hypertension.

Current Pharmaceutical Approaches to Hypertension Treatment

Clinical outcomes trial data show that lowering blood pressure using several classes of drugs, including ACE inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers and thiazide-type diuretics, in addition to lifestyle modifications, such as physical activity, weight loss, and a healthy diet, will reduce the complications of hypertension. Since as many as two thirds of patients cannot achieve adequate blood pressure control with one drug, physicians frequently prescribe multiple drugs from different classes.

ACE Inhibitors

ACE inhibitors act to reduce hypertension by interfering with the conversion of angiotensin I in plasma to artery-constricting angiotensin II. Blocking the production of angiotensin II results in arterial vasodilation and an accompanying reduction in blood pressure. However, angiontensin II is also found in the lining of tissue, including blood vessels and the heart, and is believed to have additional effects on the pathology of coronary artery disease, beyond its effect on blood pressure. In fact, more than 90% of ACE is tissue-bound, with less than 10% of ACE found in plasma. The local production of angiotensin II in the inner lining of vessels is increased in response to injury, such as in the presence of high cholesterol, high blood pressure, diabetes, smoking, and during the aging process. Excess amounts of tissue angiotensin II produces oxidative stress in the vessel and can lead to a cascade of effects, including vasospasm, smooth muscle proliferation, thrombosis, inflammation and atherosclerosis.

While all ACE inhibitors block the renin-angiotensin system, certain ACE inhibitors, including ACEON^®, have been shown to also have an enhanced affinity for tissue ACE. Tissue ACE inhibitors like ACEON^® have physical and chemical properties that allow them to penetrate the fatty environment of atherosclerotic plaque more easily than ACE inhibitors which lack this quality.

ACE inhibitors currently are recommended as first-line therapy for hypertension in certain patient populations, because of their safety and efficacy. Recently, the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has recommended ACE inhibitors as one of the initial therapy choices for patients with hypertension and additional compelling co-morbidities such as heart failure, postmyocardial infarction, high coronary disease risk, diabetes, chronic kidney disease and recurrent stroke prevention. ACEON^® is indicated only for the treatment of hypertension.

ACEON^®

ACEON^® is an ACE inhibitor indicated for the treatment of hypertension. It offers continuous 24-hour blood pressure control with once-daily dosing for hypertensive patients. ACEON^® may be used alone or with other classes of antihypertensives. It is contraindicated in patients known to be hypersensitive to the product or to any other ACE inhibitors, and in patients with a history of angioedema related to previous treatment with an ACE inhibitor. ACEON^® should not be used during pregnancy.

Tissue ACE inhibitors like ACEON^® have physical and chemical properties that allow them to penetrate the fatty environment of vascular tissue and atherosclerotic plaque more easily than ACE inhibitors without this quality.

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Under the terms of our co-promotion agreement with Solvay Pharmaceuticals, we are responsible for brand marketing activities and for establishing a cardiovascular specialty sales force to promote ACEON^® in the United States. Solvay Pharmaceuticals will continue to handle the manufacturing and distribution of the product, and its primary care sales force also will continue to promote the product.

In Europe, perindopril is marketed under several brand names, including Coversyl^®.

ACEON^® Development Status

Perindopril has been launched in more than 100 countries. FDA approval for ACEON^® was granted in December 1993 for the treatment of patients with hypertension either as monotherapy or in combination with other classes of anti-hypertensives, especially thiazide diuretics.

The EUROPA trial (EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease), was a multicenter, randomized, double-blind, placebo-controlled outcomes trial in 12,218 patients with stable coronary disease and without heart failure or substantial hypertension. The study was designed to assess the ability of perindopril to reduce cardiovascular death, myocardial infarction, and cardiac arrest.

EUROPA showed that in this low-risk population with stable coronary heart disease and no apparent heart failure, perindopril significantly reduced relative cardiovascular risk by 20% as assessed by the primary combined study endpoint of cardiovascular death, non-fatal myocardial infarction and cardiac arrest. Treatment benefit was observed in patients taking lipid lowering therapy and beta-blockers.

The results of EUROPA were presented at the annual meeting of the European Society of Cardiology in 2003, and published in The Lancet in September 2003. In December 2004, Solvay Pharmaceuticals submitted a supplemental new drug application, or sNDA, for ACEON^® to the FDA seeking approval to market the product under a proposed label expansion. FDA has granted priority review for the sNDA, with a regulatory action date in June 2005.

The Anglo-Scandinavian Cardiac Outcomes Trial, or ASCOT, was a multi-national study evaluating the effectiveness of a treatment regimen with the calcium channel blocker amlodipine with the ACE inhibitor perindopril compared to a treatment regimen with the beta blocker atenolol and the diuretic bendroflumethiazide in more than 19,000 patients with hypertension. The study was initiated in 1997 and was terminated prior to completion in December 2004 by the data safety monitoring board due to significant benefits observed in the amlodipine plus perindopril arm of the study. Preliminary results were presented at the 2005 American Congress of Cardiology Scientific Sessions. The study was not funded or conducted by us or by Solvay Pharmaceuticals.

Commercialization of ACEON^®

In accordance with our co-promotion agreement with Solvay Pharmaceuticals, we plan to hire a cardiovascular specialty sales force to promote ACEON^® in the United States, consisting of approximately 150-200 field sales personnel. We have already developed a senior sales and marketing team that has begun building and implementing portions of the key infrastructure that serves as the foundation for our field sales organization.

Clinical Product Candidates in Development

Ranexa^™ (ranolazine)

Ranexa, or ranolazine, is a novel small molecule for the potential treatment of chronic angina. Unlike current anti-anginal drug therapies, ranolazine appears to exert its anti-anginal activity without depending on reductions in heart rate or blood pressure. We are developing Ranexa for the potential treatment of chronic

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angina because we believe Ranexa is safe and effective in treating angina and may reduce the frequency of angina attacks as well as the number of doses of short-acting nitroglycerin needed to relieve angina pain and discomfort. Ranexa does not appear to produce clinically meaningful changes in blood pressure or heart rate, and as a result, Ranexa may provide significant benefits for some patients. Based on the anti-ischemic properties we have observed in previous studies of Ranexa, we also are evaluating Ranexa for potential treatment and long-term prevention of acute coronary syndromes. Ranexa has not been approved for marketing by the FDA or any other regulatory authorities.

We have exclusive license rights to Ranexa in the United States and specified foreign territories outside Asia for use in all cardiovascular indications, including chronic angina, from Syntex (U.S.A.) Inc. (now Roche Palo Alto LLC).

Chronic Angina

Cardiovascular disease results from the accumulation of disease to the heart and vessels that may take decades to develop. Beginning in the early years of life, the impact of cardiovascular risk factors such as smoking, lipid disorders, physical inactivity, obesity and others may eventually cause the heart to become unable to respond adequately to the energy demands placed on it. For some patients with heart disease, this continuum of progressive events may ultimately result in premature death. Chronic angina is an overt—and often the first physically evident—manifestation of the heart disease continuum. The atherosclerotic plaque of coronary artery disease narrows the vessels that carry blood throughout the heart. Myocardial ischemia ensues, making the heart unable to receive enough oxygen-rich blood to respond to increased energy demands caused by physical activity or emotional stress. The debilitating pain or discomfort that many patients with chronic angina can experience may negatively impact physical functioning and, in turn, lead to reduced activity and decreased quality of life.

Chronic angina is a growing health problem, affecting millions of people, generally over the age of 55. Annually, it costs the United States tens of billions of dollars in healthcare services and lost work. According to the American Heart Association, 6.4 million people in the United States live with chronic angina, with an additional 400,000 people newly diagnosed each year. The U.S. Census Bureau projects that the over 55 population the group most at-risk for angina—will increase by approximately 70% over the next 25 years.

Current Pharmaceutical Approaches to Chronic Angina Treatment

Currently available drugs to treat chronic angina include beta-blockers, calcium channel blockers and long-acting nitrates, all of which decrease the heart’s demand for oxygen by lowering either heart rate, blood pressure and/or the strength of the heart’s contraction. These effects can limit or prevent the use of currently available drugs in patients whose blood pressure or cardiac function is already decreased, and can have negative impact on patients’ quality of life, especially when these drugs are used in combination.

Despite the use of currently available therapies, up to three-fourths of chronic angina patients in the United States still have angina symptoms, and some patients on multiple drugs continue to experience angina attacks. Adverse effects of drug therapy may include lower extremity edema associated with calcium channel blockers, impotence and depression associated with beta-blockers, and headaches associated with nitrates. Consequently, for some patients and physicians, presently available medical treatment may not relieve angina without unacceptable effects.

Ranexa—A Potential New Approach Without Depending On Reductions In Heart Rate Or Blood Pressure

The treatment of angina is suboptimal in many patients who cannot tolerate the currently available anti-anginal agents at doses sufficient to treat their symptoms fully, either because of their concomitant diseases, or because of the adverse effects intrinsic to the drugs themselves. We believe that a well tolerated anti-anginal drug which provides efficacy either by itself or in addition to that provided by existing agents, without further

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reducing blood pressure, heart rate and/or contractile function, would be a useful new tool to alleviate the burden of chronic angina. Such a drug would provide physicians with an additional option to treat patients who are symptomatic with angina but cannot tolerate reductions in blood pressure, heart rate or contractile performance or the slowing of atrio-ventricular nodal conduction caused by existing anti-anginals.

Preclinical research indicates that Ranexa is a selective late sodium current blocker. Because of Ranexa’s action to significantly reduce the late sodium current, it is believed to prevent sodium overload and subsequent calcium overload in the heart, which occur during both ischemia and heart failure but not under other conditions or in the normal heart. This in turn can preserve energy and mitochondrial function, improve contractility and diastolic function, and preserve proper ion balance during ischemia and/or heart failure. To our knowledge, Ranexa is the first selective late sodium current blocker in cardiovascular development. In our Phase III clinical trials of Ranexa, Ranexa did not produce clinically meaningful reductions in heart rate or blood pressure.

Ranexa Development Status

Our new drug application, or NDA, for Ranexa seeking FDA approval for the treatment of chronic angina was submitted to the FDA in December 2002. The NDA contained data from more than 3,300 angina patients and subjects, and from more than 25,000 electrocardiograms. Our two Phase III clinical trials of Ranexa, the Monotherapy Assessment of Ranolazine in Stable Angina trial, or MARISA, and the Combination Assessment of Ranolazine in Stable Angina trial, or CARISA, were randomized, double-blind, placebo controlled trials. MARISA evaluated Ranexa when used in patients who were not receiving other anti-anginal drugs. CARISA evaluated Ranexa when used in patients who were receiving either a beta-blocker or a calcium channel blocker. In both of these trials, Ranexa statistically significantly increased patients’ symptom-limited exercise duration at trough drug concentrations compared to placebo. Additionally, in CARISA, Ranexa significantly reduced the frequency of angina attacks and the use of nitroglycerin to relieve angina pain, both secondary endpoints of the study. In both of these trials, Ranexa had no clinically meaningful impact on heart rate or blood pressure, either at rest or following exercise. In these trials, the most common adverse events included dizziness, constipation, nausea, asthenia (weakness), headaches and dyspepsia (indigestion). Adverse event frequency increased as dose increased. In addition, small but statistically significant increases in the corrected QT measurement on the electrocardiogram, or QTc, were observed compared to placebo.

On October 30, 2003 we received an approvable letter from the FDA for our NDA for Ranexa for the treatment of chronic angina. In the approvable letter, the FDA indicated that Ranexa is approvable, that there is evidence that Ranexa is an effective anti-anginal, and that additional clinical information is needed prior to approval. After a meeting with the FDA’s Cardiovascular and Renal Drugs Advisory Committee of the FDA and subsequent discussions with the FDA, we reached written agreement with the FDA in June 2004 on a protocol for a clinical trial of Ranexa which, if successful, could support the approval of Ranexa for the treatment of chronic angina in a restricted patient population. This agreement was reached under the FDA’s special protocol assessment, or SPA, process.

The SPA process creates a written agreement between the sponsoring company and the FDA concerning clinical trial design, clinical endpoints, study conduct, data analysis and other clinical trial issues. It is intended to provide assurance that if pre-specified trial results are achieved, they may serve as the primary basis for an efficacy claim in support of a new drug application. In general, these assessments are considered binding on the FDA as well as the sponsor unless public health concerns unrecognized at the time the SPA is entered into become evident or other new scientific concerns regarding product safety or efficacy arise. However, even with an SPA in place, the FDA retains broad discretion in interpreting the data and making regulatory decisions, and there is no guarantee of regulatory approval.

We initiated this potentially approval-enabling clinical study, known as the Evaluation of Ranolazine In Chronic Angina, or ERICA, in August 2004 and completed patient enrollment in November 2004. Initial data from the ERICA study are expected in the second quarter of 2005. ERICA is a multi-national, double-blind,

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randomized, placebo-controlled, parallel group study to evaluate the effectiveness of Ranexa (1000 mg twice daily) in approximately 500 patients with chronic angina who remain symptomatic despite daily treatment with the maximum labeled dose of amlodipine (10 mg daily), a calcium channel blocker approved for the treatment of chronic angina. Eligible patients were randomized to receive Ranexa 1000 mg or placebo twice daily, in addition to a daily dose of 10 mg of amlodipine, during a six week assessment period. Prior to entering the study, patients were required to have had at least two weeks of treatment with amlodipine 10 mg daily, with the discontinuation of other anti-anginal therapy for at least five days. Eligible patients must have had documented evidence of coronary artery disease or prior myocardial infarction, in addition to a diagnosis of chronic angina. Physicians were able to include long-acting nitrates as background therapy at the start of the study.

The primary efficacy endpoint of ERICA is angina frequency. Based on the reduction in angina frequency observed in the Phase III CARISA study, ERICA is estimated to be 95 percent powered to detect a statistically significant reduction in angina frequency due to Ranexa. In CARISA, Ranexa (1000 mg) reduced the frequency of angina by an average of 1.2 attacks per week, compared to placebo, in a secondary endpoint of the CARISA study.

Other objectives of ERICA are to gather additional data on the safety and tolerability of Ranexa and to learn more about the effect of Ranexa on nitroglycerin consumption during angina attacks and on quality of life.

If the ERICA study is successful, we would expect to submit an amendment to our Ranexa NDA to the FDA in the second half of 2005, seeking approval of Ranexa for the treatment of chronic angina in a restricted patient population.

In July 2004, we also reached written agreement with the FDA on a second, separate SPA for a study, the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes study, or MERLIN TIMI-36. This SPA agreement defines a path to potential approval of Ranexa as first-line therapy in the chronic angina population. Under the SPA agreement, if statistical significance on the primary endpoint is achieved, Ranexa could gain approval for hospital-based and long-term prevention of acute coronary syndromes. In addition, under the same SPA agreement, if treatment with Ranexa is not associated with an adverse trend in death or arrhythmia compared to placebo, the study could support potential approval of Ranexa as first-line chronic angina therapy, even if statistical significance on the primary endpoint is not achieved. However, in order to obtain potential approval as first-line angina therapy, under the SPA we also need to perform a separate successful clinical evaluation of higher doses of Ranexa.

The MERLIN TIMI-36 study was initiated in October 2004 and is being conducted by the Harvard-based TIMI Study Group.

MERLIN TIMI-36 is a multi-national, double-blind, randomized, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of Ranexa during acute and long-term treatment in approximately 5,500 patients with non-ST elevation acute coronary syndromes treated with standard therapy. The primary efficacy endpoint in MERLIN TIMI-36 is time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction or recurrent ischemia in patients with non-ST elevation acute coronary syndromes receiving standard therapy. The study also is evaluating the safety of long-term treatment with Ranexa compared to placebo.

Within 48 hours of the onset of angina due to acute coronary syndromes, eligible hospitalized patients are enrolled in the study and randomized to receive intravenous Ranexa or placebo, followed by long-term outpatient treatment with oral Ranexa or placebo. All patients also receive standard therapy during both hospital-based and outpatient treatment. The oral doses of Ranexa used in MERLIN TIMI-36 have been studied in previous Phase III clinical trials.

In addition to performing periodic safety assessments, an independent data safety monitoring board overseeing MERLIN TIMI-36 will conduct a blinded interim efficacy analysis, based on the endpoint of

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cardiovascular death, which is anticipated to occur after approximately half of the specified cardiovascular events have been observed. A p-value of 0.001 would be required to stop the study early at the time of the interim efficacy analysis. We believe it would be unlikely for MERLIN TIMI-36 to achieve this with only approximately half of the patients enrolled, and so we do not expect the study to be stopped at the time of the interim efficacy analysis. In addition, a blinded interim assessment of sample size also will occur, which will permit the overall study size to expand to approximately 6,500 patients if the overall mortality rate needed to complete the study is significantly lower than anticipated.

The study’s duration will be event driven. It is expected to continue until 730 cases of cardiovascular death, myocardial infarction or severe recurrent ischemia have been observed, and 310 deaths from any cause have occurred. Approximately 500 to 600 study sites worldwide are expected to enroll patients. Based on historical clinical trial information from the TIMI Study Group, preliminary data could be available by the end of 2006.

In March 2004, we filed a Marketing Authorization Application, or MAA, seeking approval of ranolazine for the treatment of chronic angina with the European Medicines Agency. The MAA was filed for review under the European regulatory authorities’ centralized procedure by our European subsidiary, CV Therapeutics Europe Limited.

While we believe that the safety and efficacy of Ranexa have been well characterized as part of our clinical development program, the final determination of the safety and efficacy of Ranexa will be made by the FDA and other relevant health authorities. Ranexa has not been determined by the FDA or any other regulatory authorities to be safe or effective in humans for any use.

Potential Commercialization of Ranexa

We have exclusive license rights to Ranexa in the United States and specified foreign territories outside Asia, for use in all cardiovascular indications. If approved, we expect to commercialize Ranexa in the United States. Our European subsidiary is assessing commercial strategies in the various European markets.

Regadenoson

The diagnosis of coronary artery disease can present challenges to cardiologists and other practitioners. One of the most common methods for diagnosing coronary artery disease is the exercise treadmill test, during which patients exercise on a treadmill to stress the heart while connected to an electrocardiogram. The observation of specific changes in the electrocardiogram, with or without the development of chronic angina pain or discomfort, signals the need for additional testing to confirm the presence of coronary artery disease. The ability of some patients to complete an exercise treadmill test may be limited because of long-term physical inactivity and/or concomitant illness such as arthritis, peripheral vascular disease, or heart failure. Myocardial perfusion imaging stress tests offer an effective alternative for the diagnosis of coronary artery disease in these types of patients. Regadenoson is an A_2A-adenosine receptor agonist for potential use as a pharmacologic stress agent in myocardial perfusion imaging test, or MPI stress tests.

Myocardial Perfusion Imaging Studies

MPI stress tests are usually performed in a nuclear medicine clinic. Medication is administered to the patient that temporarily increases coronary blood flow through the heart, mimicking the heart’s physical response to the increased energy demand caused by exercise. Once the equivalent of maximal exercise is reached, a small amount of a radioactive substance is injected into the bloodstream to highlight the vessels. A photograph of the area is then taken by a camera that specifically detects the distribution of radioactive substance in the heart during stress. Additional photographs are taken of the heart “at rest.” If the photographs of the heart during stress and at rest show the same level of perfusion through the heart, then the test result is normal. However, if a perfusion defect is seen in the photograph of the stressed heart while the photograph of the heart at rest appears

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normal, then it is possible the defect is the result of a partial blockage caused by an atherosclerotic plaque associated with coronary artery disease, signaling the need for additional testing to confirm the diagnosis. In 2002, approximately 7.8 million patients underwent MPI stress tests. Of those, approximately 3.4 million, or more than 40%, required a pharmacologic agent to generate maximum coronary blood flow because peripheral vascular disease, arthritis or other limiting medical conditions prevented them from exercising on the treadmill. There are other approaches for diagnosing coronary artery disease, including electrocardiogram, electron beam computed tomography (for detecting and quantifying coronary calcification), echocardiography (echo), and coronary angiography.

Current Approaches to Increasing Coronary Blood Flow During Myocardial Perfusion Imaging Studies

MPI stress tests use pharmacological agents to increase coronary blood flow of the heart as if it were responding to the demands of physical exercise. Traditional agents used have included dipyridamole and adenosine. Both agents are administered to patients by intravenous infusion with the aid of a pump. Both of these agents act nonspecifically on the heart. While they are very effective at increasing coronary blood flow, their nonspecificity may also produce undesirable and uncomfortable side effects. For example, dipyridamole is most commonly associated with chest pain, headache, and dizziness. The long half-life of dipyridamole requires lengthy patient monitoring following the procedure. Adenosine, while it has a short half-life, activates all adenosine receptor subtypes and, as a result, may cause flushing, dyspnea, and headache. The activation of other adenosine receptor subtypes may also cause sustained decreases in blood pressure (hypotension), reduced heart rate, and heart block. Adenosine is contraindicated in patients with asthma because of the risk of bronchoconstriction with the use of this agent.

Potential Treatment with Regadenoson

Regadenoson is a selective A_2A-adenosine receptor agonist administered by an intravenous bolus (without the use of a pump) that stresses the heart by increasing coronary blood flow as if the heart were responding to the demands of physical exercise. Importantly, the selective and specific action of regadenoson on the A_2A-adenosine receptor potentially avoids the side effects caused by the less specific action of traditional agents. Bolus administration of regadenoson as well as its short half-life may also allow for more efficient administration of the MPI stress test.

Regadenoson Development Status

We announced the results of a Phase II open-label study designed to evaluate the effect of a single, rapid intravenous bolus of various doses of regadenoson on coronary blood flow velocity at the 2002 American Heart Association Scientific Sessions. Regadenoson caused a dose-dependent increase in coronary blood flow velocity that was at, or near, peak within 30 to 40 seconds of administration. The doses of regadenoson producing the maximal response similar to adenosine were also determined. Regadenoson was generally well-tolerated. Associated side effects were mild and self-limiting, and included chest discomfort, headaches, increased heart rate, dizziness, hypotension, flushing, and shortness of breath.

The results of a second Phase II trial of regadenoson were announced at the 2003 American Heart Association Scientific Sessions. This study was designed to evaluate the ability of regadenoson to produce an increase in coronary blood flow and to accurately detect the presence of coronary artery disease, compared with adenosine. MPI stress tests were performed in all subjects under stress and at rest with both agents. The results of adenosine and regadenoson tests were similar in both visual and quantitative methods for detecting myocardial ischemia, and a dose-dependent effect by regadenoson was not observed.

In October 2003, we initiated a pivotal Phase III trial of regadenoson. This on-going study is a double-blind trial of regadenoson in patients undergoing a myocardial perfusion imaging study. We initiated a second double-blind Phase III clinical trial of regadenoson in April 2004. Data from one Phase III trial are expected in the third quarter of 2005, and data from the other Phase III trial are expected by the end of 2005.

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Regadenoson has not been determined by the FDA or any other regulatory authorities to be safe or effective in humans for any use.

Tecadenoson

Tecadenoson is a selective A₁-adenosine receptor agonist for the potential reduction of rapid heart rate during acute atrial arrhythmias. Atrial arrhythmias are characterized by abnormally rapid heart rates, and include the conditions of atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardias, or PSVT. Tecadenoson acts selectively on the conduction system of the heart to slow electrical impulses and may offer a new approach to rapid and sustained control of acute atrial arrhythmias by reducing heart rate without lowering blood pressure. We have completed a Phase III trial of tecadenoson in patients with PSVT and have conducted Phase II trials in patients with atrial fibrillation and atrial flutter.

Tecadenoson Development Status

We have completed a Phase III trial of patients with paroxysmal supraventricular tachycardias, or PSVT, who were given tecadenoson. In this Phase III trial, all five dosing regimens of tecadenoson tested converted patients with PSVT back into a normal heart rhythm (p<0.0005 versus placebo). The most frequent adverse symptom was paresthesia, a tingly sensation, and there was no apparent dose-dependent increase in any adverse symptom following administration of tecadenoson. In an earlier Phase II trial of patients with atrial fibrillation or flutter, tecadenoson appeared to reduce heart rate from baseline without clinically meaningful changes in blood pressure. As expected, based on the pharmacology of the study drug, dose dependent, transient and clinically insignificant atrial ventricular block was observed shortly after conversion across the highest three doses of tecadenoson. Hemodynamic parameters such as blood pressure and heart rate were not adversely affected by tecadenoson.

We are currently involved in very limited development activity with tecadenoson. Tecadenoson has not been determined by the FDA or any other regulatory authorities to be safe or effective in humans for any use.

Adentri^™ Program

Adentri^™ is a selective A₁-adenosine receptor antagonist for the potential treatment of heart failure. Heart failure occurs when a diseased heart is so weak that the ventricle is unable to effectively fill with blood or pump blood to the rest of the body. Fatigue, shortness of breath, and fluid accumulation are common symptoms of heart failure. The corresponding reduction in blood flow through the body can also impair the ability of the kidneys to clear fluid wastes. The left ventricle is most commonly affected, and coronary artery disease is a common cause of heart failure.

Some currently available therapies for heart failure may also tend to negatively impact kidney function. Preclinical and clinical trials indicate that A₁-adenosine receptor antagonists may increase the kidneys’ ability to clear fluid wastes without decreasing other kidney functions. Thus, we believe that A₁-adenosine receptor antagonists have the potential to be a new type of therapy for the treatment of heart failure.

In March 1997, we licensed the rights to our A₁-adenosine receptor antagonist technology, patents and compounds to Biogen, Inc. (now Biogen Idec Inc.). Biogen’s efforts in this area are referred to as the Adentri^™ program. Under these agreements, Biogen has an exclusive worldwide license to develop, manufacture and commercialize any A₁-adenosine receptor antagonists developed either by Biogen or us based on our patents or our technology. Under the license, Biogen is responsible for funding all development and commercialization expenses related to the Adentri program.

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Adentri Development Status

Biogen has conducted Phase I and Phase II studies of BG9928, a backup licensed compound, in both oral and intravenous formulations for the potential treatment of acute and chronic heart failure. We understand that Biogen is exploring additional studies under its development program.

Under the Adentri program to date, no licensed compound has been determined by the FDA or any other regulatory authorities to be safe or effective in humans for any use.

Preclinical Research and Development

Our research and development team is working to create new product opportunities through our expertise in molecular cardiology, and we have several preclinical research programs.

Adenosine Receptors

Adenosine is a small molecule that is naturally present in the body and has many actions in many different organs. Its effects on cells are the responses to activation by adenosine of cell-surface proteins called receptors. There are four types of adenosine receptors: A₁, A_2A, A_2B and A₃. Activation of these receptors initiates cascades of cellular biochemical events that result in specific changes of important cell functions, such as ion transport, electrical and contractile activity, and secretion of hormones and other small molecules.

The effects of adenosine on the heart are protective and serve as the basis for our regadenoson and tecadenoson programs. Adenosine’s effect to decrease the release of fatty acids from adipose tissue serves as the rationale for our program to investigate the use of an adenosine-like drug to decrease free fatty acids and blood triglyceride levels. Adenosine’s effects to increase inflammatory responses in the asthmatic lung and in relation to addictive behavior and withdrawal are the basis for our programs to design antagonists of these actions for treatment of inflammatory lung diseases and addiction, respectively. The goal of our adenosine programs is to further investigate additional therapeutic effects of both activation and blockade of adenosine receptors.

Late Sodium Current

We believe that inhibition of the late sodium current can reduce sodium overload and minimize calcium overload. This in turn can preserve energy and mitochondrial function, restore contractility and diastolic function, and preserve proper ion balance. We are building upon our scientific knowledge in this field to identify novel, orally bioavailable blockers of the late sodium current that may be effective in the treatment of chronic angina and the acute and chronic treatment of HF. We have discovered several novel, proprietary compounds under this program. The goal of our late sodium current program is to further characterize the therapeutic potential and to discover new, proprietary potential products.

Reverse Cholesterol Transport

Our scientists and collaborators were one of several laboratories to discover that the ABCA1 protein is the rate limiting protein responsible for removal of cholesterol from the walls of blood vessels and atherosclerotic plaque, a process called reverse cholesterol transport. The activation of ABCA1 leads to an increase in high density lipoprotein, or HDL. Roughly one half of heart attacks occur in patients with low levels of HDL, known as the “good” form of cholesterol. The goal of our reverse cholesterol transport program is to discover a new proprietary potential product that will reduce the overall atherosclerotic burden in patients with cardiovascular disease.

Collaborations and Licenses

We have established, and intend to continue to establish, strategic partnerships to potentially expedite the development and commercialization of our products. In addition, we have licensed, and intend to continue to

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license, chemical compounds from academic collaborators and other companies. Our key collaborations and licenses currently in effect include:

University of Florida Research Foundation

In June 1994, we entered into a license agreement with the University of Florida Research Foundation, Inc. under which we received exclusive worldwide rights to develop A₁-adenosine receptor antagonists and agonists for the detection, prevention and treatment of human and animal diseases. In consideration for the license, we paid an initial license fee and are obligated to pay royalties based on net sales of products that utilize the licensed technology. Under this agreement, we must exercise commercially reasonable efforts to develop and commercialize one or more products covered by the licensed technology. In the event we fail to reach certain milestones under the agreement, the University of Florida Research Foundation may convert the exclusive license into a non-exclusive license. In March 1997, we sublicensed our rights under this license that relate to A₁-adenosine receptor antagonists to Biogen.

Roche

In March 1996, we entered into a license agreement with Syntex (U.S.A.) Inc. (now Roche Palo Alto LLC) covering United States and foreign patent rights to ranolazine and related know how for the treatment of angina and other cardiovascular indications. Roche provided initial quantities of the compound for use in clinical trials and related development activities. The license agreement is exclusive and worldwide except for the following countries which are licensed exclusively to Kissei Pharmaceuticals, Ltd. of Japan: Japan, Korea, China, Taiwan, Hong Kong, the Philippines, Indonesia, Singapore, Thailand, Malaysia, Vietnam, Myanmar, Laos, Cambodia and Brunei.

Under our license agreement, we paid an initial license fee, and are obligated to make certain payments to Roche, upon receipt of the first and second product approvals for Ranexa in any of the following major market countries: France, Germany, Italy, the United States and the United Kingdom. As of December 31, 2004, we had not terminated this agreement and therefore will be required to pay Roche, by March 31, 2005, $7.0 million plus interest accrued thereon from May 1, 2002, until the date of payment. As of December 31, 2004, we accrued the $7.0 million payment and associated $3.1 million accrued interest. These amounts are included within the consolidated statement of operations as research and development expenses. Unless the agreement is terminated, if the second product approval in one of the major market countries occurs after May 1, 2004, but before March 31, 2006, we will make a second payment of $7.0 million plus interest accrued thereon from May 1, 2004, until the date of payment. Unless the agreement is terminated, if the second product approval in one of the major market countries has not occurred by March 31, 2006, we will pay Roche $3.0 million on or before March 31, 2006, and if we receive the second product approval after March 31, 2006, we will pay Roche $4.0 million within 30 days after the date of such second product approval. No amounts have been accrued at December 31, 2004 beyond the first payment discussed above. In addition, we will owe royalty payments based on net sales of products, if approved, that utilize the licensed technology. We are required to use commercially reasonable efforts to develop and commercialize the product for angina.

We or Roche may terminate the license agreement for material uncured breach, and we have the right to terminate the license agreement at any time on 120 days notice if we decide not to continue to develop and commercialize ranolazine.

Biogen Idec

In March 1997, we entered into research collaboration and license agreements with Biogen, Inc. (now Biogen Idec Inc.) which grant Biogen the exclusive worldwide right to develop and commercialize any products that are produced based on our A₁-adenosine receptor antagonist patents or technologies (including our rights under the University of Florida Research Foundation license) for all indications. Biogen’s efforts in this area are

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referred to as the Adentri^™ program. In February 2000, based on results of a Phase II clinical trial, Biogen announced its intention to continue with the Adentri program, but with a backup licensed compound. Biogen owes certain milestone payments in connection with the successful completion of certain development and commercialization milestones relating to licensed products, and is obligated to pay royalties on any sales of licensed products covered by the agreements. Biogen has control and responsibility for conducting, funding and pursuing all aspects of the development, submissions for regulatory approvals, manufacture and commercialization of licensed products under the agreements.