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SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 10-K

FOR ANNUAL AND TRANSITION REPORTS

PURSUANT TO SECTIONS 13 OR 15(d) OF THE

SECURITIES EXCHANGE ACT OF 1934

(Mark One)

For the year ended December 31, 2003

OR

For the transition period from              to             

Commission File Number: 0-50564

RENOVIS, INC.

(Exact name of registrant as specified in its charter)

(650) 266-1400

(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act:

Securities registered pursuant to Section 12(g) of the Act: Common Stock, par value $0.001 per share

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

Aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant, based on the last sale price for such stock on June 30, 2003: Not applicable because trading of the registrant’s common stock on the NASDAQ National Market did not commence until February 5, 2004.

The number of outstanding shares of the registrant’s common stock, par value $0.001 per share, as of March 25, 2004 was 24,546,150.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s definitive Proxy Statement to be filed with the Securities and Exchange Commission within 120 days after registrant’s fiscal year end December 31, 2003 are incorporated by reference into Part III of this report.

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RENOVIS, INC.

FORM 10-K — ANNUAL REPORT

FOR THE YEAR ENDED DECEMBER 31, 2003

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PART I

Item 1. Business

Overview

We are a biopharmaceutical company developing drugs to treat neurological diseases and disorders. We were incorporated in Delaware in January 2000. In December 2002, we acquired the pharmaceutical assets of Centaur Pharmaceuticals, Inc. (Centaur), including the product candidates Cerovive^® and REN-1654. Our research and development programs currently focus on major medical needs in the areas of pain, trauma and stroke and neurodegenerative diseases. Within these areas we are pursuing eight distinct programs, including three product candidates in clinical development. Our most advanced product candidate is Cerovive, an intravenous drug for acute ischemic stroke. Cerovive is being evaluated in a Phase III clinical trial program that is planned to involve approximately 4,000 patients by our exclusive licensee, AstraZeneca. We are independently developing two clinical candidates for the treatment of pain: REN-1654, an oral drug for neuropathic pain in Phase II clinical trials, and REN-213, an intravenous drug for acute post-operative pain also in Phase II clinical trials. Beyond these clinical trials, our goal is to file one investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) in 2004 and another in 2005.

Our Product Pipeline

The following table summarizes our product candidates in clinical development and our research programs:

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Cerovive

Cerovive (NXY-059) is our intravenous drug for the treatment of acute ischemic stroke which is being evaluated in Phase III clinical trials by AstraZeneca. Stroke is the third leading cause of death in the United States and Western Europe and the most common cause of adult long-term disability in the United States. Cerovive works as a “neuroprotectant” to protect brain cells from damage triggered by a stroke. We believe that if Cerovive demonstrates neuroprotective benefits in stroke patients, the drug may also prove useful to treat a range of other brain injuries.

Market Opportunity

Stroke is an acute medical condition involving the death of brain tissue caused by blockage or rupture of the blood vessels leading to or within the brain. There are two major types of strokes. According to the Foundation for Education and Research in Neurological Emergencies, ischemic strokes account for approximately 85% and hemorrhagic strokes account for approximately 15% of all strokes in the United States. Ischemic strokes are caused by a blockage, called an occlusion, within an artery leading to or within the brain, while hemorrhagic strokes are caused by the sudden rupture or bursting of such an artery. When either kind of stroke occurs, blood flow and the supply of oxygen to an area of the brain are interrupted, leading to death of brain tissue. Although initial damage to brain tissue occurs within the first hour, much of the damage occurs subsequently up to three days after the stroke.

Existing treatment options, called thrombolytics, focus on restoring blood flow in patients with acute ischemic stroke and must be administered no more than three hours after the stroke. For a thrombolytic, such as recombinant tissue plasminogen activator (tPA), to be administered safely, a patient must receive a computerized tomography (CT) scan within three hours of the onset of symptoms to verify that the stroke did not result from bleeding in the brain (a hemorrhagic stroke), a condition that would be worsened by administration of a thrombolytic. In addition, thrombolytics may induce brain hemorrhage in ischemic stroke patients. According to the American Heart Association, only 3% to 5% of stroke patients receive tPA for acute ischemic stroke, which we believe is due to the treatment restrictions associated with thrombolytics.

The only neuroprotectant drug approved for treatment of stroke patients is edaravone, which is approved only in Japan. Edaravone was approved by Japanese regulatory authorities based on positive results from a 252-patient Phase III trial. In its first full year on the market in Japan (2002-2003), edaravone achieved sales in excess of $275 million and was administered to more than 125,000 patients. However, following its approval and introduction to the market, edaravone was associated with infrequent serious adverse events, including deaths, in a number of patients with kidney dysfunction. Given these safety concerns, sales growth in Japan has fallen significantly, and we believe it is unlikely that this drug will be approved in the United States or Europe. Edaravone is a free radical scavenger (see below) that differs from Cerovive in both structure and metabolism. Accordingly, we believe that the safety concerns with edaravone are not predictive of the safety of Cerovive.

According to the American Heart Association, the annual cost of stroke-related care in the United States exceeds $51 billion. Based on figures reported by Datamonitor, a business information company, more than two million strokes occur each year in the world’s major industrialized countries, and, according to the American Heart Association, 700,000 of such strokes occur in the United States. The leading product for stroke is tPA, which, due to its treatment restrictions, is used to treat only 3% to 5% of stroke patients annually. According to data published by Frost & Sullivan, a marketing, consulting and training company, tPA accounts for approximately $200 million in annual sales. We believe that a neuroprotectant drug capable of reducing stroke-related mortality and disability that can be administered for six hours after stroke without significant safety concerns would be used to treat a substantially broader population of stroke victims.

Scientific Overview

Cerovive is a novel compound of the nitrone class, a neuroprotectant that binds to and inactivates (by scavenging or trapping) cell-damaging free radicals. Free radicals are toxic molecules that the body produces in

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response to tissue injury, in particular after a stroke. As a neuroprotectant with free radical trapping properties, Cerovive acts to neutralize the free radicals and protects brain cells from further damage and death.

An acute ischemic stroke causes the nerve cells (called neurons) in the immediate area, the core infarct, to be cut off from their much-needed supply of blood and oxygen. Without oxygen, these neurons die within minutes to hours. When neurons in the core infarct die, they release chemicals that set off a chain reaction called the “stroke cascade”. This chain reaction, which lasts for hours to days, endangers neurons in a much larger area surrounding the core infarct by creating an area of brain tissue for which the blood supply is compromised but not completely cut off. Tissue within this much larger area of the brain, called the penumbra, will also die over hours to days. As additional neurons die, the penumbra expands progressively outward from the initial infarct, and additional neurological damage occurs. As neurons in an area of the brain die, the abilities and function once controlled by those neurons are compromised or lost. This may include functions such as speech, movement and memory. Ultimately, the loss of brain tissue can result in death. A neuroprotectant drug that can halt the stroke cascade at a key step has the potential of preserving brain tissue in the penumbra and limiting the loss of neurological function.

Because the death of neurons and expansion of the penumbra occur over a period of many hours to several days, there are windows of opportunity (clinically called therapeutic windows) for intervening at key steps in the stroke cascade with various neuroprotectant drugs. An early step in this cascade is associated with “glutamate excitotoxicity”, a mechanism that provides a short therapeutic window, typically within the first 60 minutes after a stroke. This early step in the cascade leads to damage to mitochondria, the key structures within the neuron that regulate energy.

In a later stage in the cascade, the damaged mitochondria generate free radicals, which damage both the affected neuron and surrounding neurons, ultimately leading to the death of these neurons hours to days later. This free radical generation provides a longer and therefore more clinically relevant therapeutic window during the first 12 hours after stroke.

During the 1990s, a number of potential neuroprotectant drugs that block glutamate excitotoxicity were tested. In animal models of acute ischemic stroke, many of these drugs were effective in mitigating further damage caused by the stroke cascade when given within 30 minutes, and occasionally up to two hours, after stroke. However, when subsequently tested in human patients up to 12 hours after stroke, they did not demonstrate statistically significant efficacy. Thus, the therapeutic window to block glutamate excitotoxicity, the target of these drugs, was too short (less than two hours) to be clinically useful for a significant number of stroke patients. Moreover, some of these drugs had serious side effects, which required testing in human patients at doses lower than those levels that had demonstrated efficacy in preclinical animal models.

Given the history of failed clinical trials for stroke drugs, an industry/academic roundtable group was convened in the late 1990s to establish a stringent set of preclinical and clinical criteria designed to guide the successful development of neuroprotectant drugs. This group published the Stroke Therapy Academic Industry Roundtable criteria (the STAIR criteria) in 1999 in order to improve the selection process for a drug to enter pivotal human clinical trials. Based on our research and review of published data, we believe Cerovive is the only stroke drug that has met all of the STAIR criteria.

The Cerovive Solution

Cerovive binds to and inactivates (or traps) free radicals thereby protecting brain cells from damage caused by a stroke, but, unlike a thrombolytic, it does not restore blood flow. It has been shown to reduce the death and damage of neurons in animal models of stroke. The functional improvement seen in these models shows the potential to preserve functions such as speech, movement and memory in stroke patients. By trapping free radicals, Cerovive targets a more clinically relevant therapeutic window than many drugs previously tested. Cerovive may also have mechanisms of action that protect neurons beyond its function as a free radical trap. We believe that Cerovive is positioned to be the first neuroprotectant drug marketed for stroke in the United States and Europe.

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Cerovive represents the first use of a class of compounds called nitrones to be developed in the clinic for stroke. Cerovive demonstrates neuroprotective efficacy in both transient and permanent occlusion ischemic stroke models and hemorrhagic stroke models in rats, in permanent occlusion ischemic stroke models in monkeys and in another stroke model in rabbits. It has been shown to substantially lessen both motor and cognitive disability and to reduce infarct volume in monkeys when administered four hours after the onset of an ischemic stroke.

We believe that Cerovive may have another therapeutic value for stroke patients as well. When blocked arteries are unblocked, either spontaneously or by a thrombolytic drug, a rapid increase in blood flow, called reperfusion, occurs resulting in further brain damage, called reperfusion injury. Much of the reperfusion injury involves a sudden increase in free radicals. Following many ischemic strokes, there is spontaneous unblocking of arteries (thrombolysis). About half of stroke patients spontaneously reperfuse within three to four days. We believe that the continuous intravenous administration of Cerovive for 72 hours will continue to protect the brain of stroke patients against the damage that occurs from the production of free radicals during both spontaneous reperfusion and reperfusion induced by thrombolytic drugs. If Cerovive receives marketing approval, we believe it may be used both as a monotherapy as well as in combination with tPA and other thrombolytic (blood flow increasing) therapies that are currently being developed.

Prior Clinical Trials

A total of ten clinical trials have been performed with Cerovive, two trials in subjects with acute ischemic or hemorrhagic stroke (184 subjects exposed to Cerovive), seven in healthy subjects (286 subjects exposed to Cerovive) and one in subjects with kidney impairment (24 subjects exposed to Cerovive). Four double-blinded, placebo controlled trials have been performed in healthy volunteers to explore safety, tolerability, absorption, metabolism, distribution and excretion of Cerovive administered intravenously (i.v.) for eight to 72 hours in increasing doses. The adverse events that occurred were not considered clinically significant and Cerovive was hence judged to be well tolerated in healthy volunteers in these trials.

Two Phase IIa trials were performed to evaluate safety and tolerability of 72-hour infusions of Cerovive in subjects with acute stroke. The first trial enrolled 135 subjects with ischemic stroke and fifteen subjects with hemorrhagic stroke. The second trial enrolled 135 subjects with symptoms of acute ischemic stroke. The study drug was initiated within 24 hours of symptom onset. Cerovive was well tolerated with no concerns raised by the safety evaluation.

These Phase IIa clinical trials were primarily designed to examine the safety of Cerovive. In May 2003, AstraZeneca advanced Cerovive into Phase III clinical trials. We believe Cerovive is a strong Phase III product candidate based on the Phase II data, when combined with all of the other clinical safety data, the compelling efficacy shown in preclinical animal models in monkeys and rodents, and our belief, based on our research and review of published data, that Cerovive is the only neuroprotectant drug to have passed the STAIR criteria.

We believe that Cerovive enters Phase III clinical trials with strong preclinical and clinical data on safety and efficacy. Our belief, based on our research and review of published data, is that Cerovive is the only neuroprotectant that has met the STAIR criteria, and is the only drug that has been shown to substantially decrease both motor and cognitive disability in primates when given four hours after stroke.

Current Clinical Trials

AstraZeneca is conducting two multi-national, multicenter, randomized, double-blinded studies to test Cerovive (NXY-059) versus a placebo. “Double-blind” means neither the researcher nor the patient knows whether the patient has received the drug or the placebo. “Randomized” means that patients are randomly assigned to receive the drug treatment or the placebo. These two Stroke-Acute Ischemic-NXY Treatment (SAINT) trials are currently underway. The first trial, SAINT-I, is being conducted in Europe, Australia, South Africa and Asia and is planned to include more than 1,500 subjects. It will involve more than 200 centers across

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24 countries. The second trial, SAINT-II, is being conducted in the United States, Canada and South America and is planned to include more than 1,500 subjects at more than 200 sites. The first patient was dosed in May 2003. A global safety trial scheduled to commence in 2004 is planned to include approximately 600 subjects with acute hemorrhagic stroke. Patient recruitment is proceeding consistent with the goal announced by AstraZeneca to request regulatory approval in 2006.

The Phase III trials are designed to determine the efficacy and evaluate the safety of Cerovive when administered up to six hours after the onset of symptoms. The drug is being administered as a one-hour i.v. loading-dose infusion followed by a 71-hour i.v. maintenance dose. Phase III clinical trials are being conducted with similar drug exposure and time window for which behavioral efficacy has been shown in primates. The mean time for the start of drug administration for each trial in acute ischemic stroke, and for all centers within these trials, is four hours after the onset of symptoms. In addition to this time limitation, to be enrolled in the SAINT trials, patients must show symptoms of acute ischemic stroke with limb weakness and have had full functional independence before stroke. The primary outcome will be measured three months after stroke by examining functional deficit (overall recovery and recovery of motor function) as measured by a standard neurological scoring system called the modified Rankin Scale.

The SAINT-I and SAINT-II clinical trials were designed with several interim analyses. At each interim analysis, an independent data and safety monitoring board will review patient data to evaluate the safety or efficacy of Cerovive. At such time, a decision can be made to either stop or continue the clinical trials.

Commercialization

Renovis has licensed to AstraZeneca the rights to develop, market and sell Cerovive worldwide. Pursuant to a license agreement, AstraZeneca made milestone payments totaling $4.5 to Renovis in February 2003 when it received FDA approval to commence the Phase III clinical trials. AstraZeneca may be required to make additional milestone payments to Renovis in the future upon regulatory filings and marketing approvals of Cerovive in the United States and other territories. Furthermore, Renovis is entitled to receive mid-teen percentage royalties on worldwide net sales of Cerovive. AstraZeneca has announced a goal to request regulatory approval of Cerovive in 2006.

If Cerovive meets its target product profile, we believe this product will be adopted rapidly by physicians in an area with a significant medical need due to the limitations of existing therapies and the severe nature of the disabilities suffered by many stroke patients. As one of the world’s leading pharmaceutical companies, AstraZeneca’s global regulatory, sales and marketing capabilities should allow it to drive rapid product adoption and use throughout the world. In addition, AstraZeneca is well positioned to potentially broaden the clinical uses and tests of the drug in related indications involving brain injury.

REN-1654

REN-1654 is an oral drug that we are evaluating in Phase II clinical trials for the treatment of certain types of neuropathic pain. Despite the wide assortment of prescription pain relievers already available, a number of specific types of pain, including neuropathic pain, remain inadequately treated. REN-1654 has been shown to decrease inflammatory signaling that we believe plays a significant role in the damage of nerve cells underlying certain forms of neuropathic pain.

Market Opportunity

Neuropathic pain is a form of pain that results from damage to nerves. The damage may result from a variety of causes, including illness, injury, and exposure to the toxic effects of chemotherapy drugs. Regardless of its original cause, neuropathic pain may persist for months or years after the original nerve damage occurs. We believe that an anti-inflammatory drug for the nervous system could be used following illness or injury to prevent the onset of, or reduce, many forms of neuropathic pain.

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According to Pharmaprojects, a healthcare publication, each year approximately 26 million people worldwide suffer from some form of neuropathic pain. Several of the common forms of neuropathic pain can be traced to inflammation of peripheral nerves, including post-herpetic neuralgia (PHN) and sciatica. PHN is a complication of “shingles”, a recurrence in adults of a severe skin rash caused by the virus herpes zoster. Sciatica is a common type of back and leg pain characterized by compression and inflammation of the sciatic nerve.

Conventional analgesics, or pain relievers, are typically ineffective in treating neuropathic pain. As a result, drugs originally developed as anti-depressants and anti-convulsants, are frequently prescribed for neuropathic pain. One of these drugs, gabapentin, was originally approved as an anti-convulsant for the treatment of epilepsy and later became approved for treatment of PHN. Based on figures reported by Datamonitor, in 2002, sales of gabapentin exceeded $2.2 billion, a significant portion of which related to use of the drug to treat PHN and other forms of neuropathic pain. Gabapentin and other drugs currently prescribed for neuropathic pain are not effective in a high proportion of patients and, even where effective, frequently provide only modest pain relief at the expense of adverse side effects. Accordingly, there is a significant need for improved neuropathic pain therapies.

Scientific Overview

Inflammation in the nervous system is a common cause of multiple types of neuropathic pain. REN-1654 reduces inflammation in the nervous system by decreasing the release of tumor necrosis factor a (TNFa), a signaling molecule used by the immune system and certain cells in the nervous system. During inflammation, TNFa is thought to play a key role both in directly causing an increase in pain signaling and in damaging nerves by increasing the inflammatory response. Examples of neuropathic pain that involve inflammation include PHN and chemotherapy- induced neuropathy. In addition, long-term neuropathies can develop in other inflammatory pain conditions such as sciatica, lower back pain, neck pain and carpal tunnel syndrome.

The potential utility of TNFa inhibition as a strategy for treating certain types of neuropathic pain has been demonstrated in human studies. Drugs such as infliximab, which act by inhibiting TNFa, have demonstrated therapeutic potential in pilot studies of patients with sciatica. While cost and route of administration significantly limit the practical utility of these and other similar injectable drugs as treatments for neuropathic pain, they validate TNFa inhibition as a therapeutic strategy for these common types of neuropathic pain involving significant nerve inflammation.

The REN-1654 Solution

REN-1654 is an oral, small molecule drug that we believe will be effective as a treatment for certain types of neuropathic pain in which nerve inflammation plays a significant role. REN-1654 penetrates into the nervous system effectively and has a half-life which facilitates once-daily dosing. It has been shown to inhibit the release of TNFa by certain cell types. By decreasing the amount of TNFa in and around neurons, REN-1654 should reduce the nerve signaling and resulting pain caused by TNFa and decrease the amount of inflammation which leads to nerve damage. REN-1654 has demonstrated efficacy in preclinical models of neuropathic pain involving inflammation.

Clinical Trials

In ten previous safety trials REN-1654 was orally administered to approximately 300 subjects, establishing the safety of the drug for further clinical development. In July 2003, we submitted a new IND to the FDA to commence trials for neuropathic pain. We initiated a Phase II clinical program for REN-1654 in October 2003. Our first clinical trial is a double-blinded, randomized trial versus a placebo designed to evaluate the effect of REN-1654 on pain in response to localized skin inflammation in healthy volunteers. The second trial underway with REN-1654 is intended to evaluate the efficacy of the drug candidate in patients with or at risk for PHN. This is also a multi-center, double-blinded, randomized trial versus a placebo. We are conducting a third trial designed to explore the effectiveness of REN-1654 for treatment of sciatica. We expect to complete these Phase II trials and report preliminary results during the fourth quarter of 2004.

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Commercialization

Our current plan is to independently develop REN-1654 through at least Phase II trials. Thereafter, we may seek strategic partners in international markets and potentially the United States. We currently plan to retain U.S. co-promotion rights, at a minimum, as part of any collaboration we establish for development and commercialization of REN-1654. We hold exclusive worldwide rights to patents covering REN-1654. We hold composition-of-matter and method-of-use patents which protect REN-1654 in the United States and other territories.

REN-213

REN-213 is an intravenous drug for acute post-operative pain that is in Phase II clinical trials. REN-213 is a patented combination of two marketed, off-patent drugs: nalbuphine, used for pain during labor and delivery, and naloxone, used to treat opiate overdose. Human patients treated with a precise, patented ratio of nalbuphine and naloxone in investigator-initiated studies have reported pain relief comparable to the relief provided by morphine without reporting the constipation, respiratory depression, nausea and cognitive impairment frequently associated with the use of morphine. We believe that REN-213, if approved for commercialization, has the potential to capture a significant share of the post-operative pain market.

Market Opportunity

According to data published in the Cleveland Clinic Journal of Medicine, there are more than 31 million surgeries performed in the United States each year that require drugs for post-operative pain. When tissues are damaged as a result of surgery, electrical “pain” signals are transmitted from the injured tissues through nerve fibers into the spinal cord and up to the brain.

Transmission of pain signals is decreased (producing a decrease in pain, or analgesia) by drugs that bind specifically to opioid receptors, molecules located on the surface of nerve cells. Such drugs are termed opioid receptor agonists. There are at least three types of opioid receptors (mu, kappa and delta), each of which produces analgesia when activated. Frequently prescribed narcotic analgesics (e.g., morphine, fentanyl, oxydodone and hydrocodone) bind to and activate mu-opioid receptors in the brain and spinal cord and are known as mu-opiates.

Morphine and other existing narcotic mu-opiates are presently the standard-of-care for post-operative acute pain. Unfortunately, these narcotics have serious side effects including constipation, respiratory depression (a dangerous slowing of breathing, especially common among elderly patients), nausea, itching, confusion and addiction (when given for chronic pain). These side effects may delay recovery and hospital release and frequently limit dosages that can be administered, such that optimal control of pain is not achieved. In addition, because mu-opiates have the potential to cause addiction and be abused, drugs like morphine are regulated by the U.S. Drug Enforcement Agency (DEA).

Scientific Overview

REN-213 is an injectable analgesic product that combines two approved off-patent drugs formulated in a specific, patent-protected ratio. REN-213 combines nalbuphine, a kappa-opiate, with naloxone, an opiate antagonist (which binds to and blocks opiate receptors). Unlike morphine and other mu-opiate narcotics, neither nalbuphine nor naloxone is designated as a controlled drug by the DEA. For decades, pharmaceutical companies, doctors and other healthcare professionals have been searching for an alternative to morphine and other mu-opiates that do not have the side effects of these drugs. Historically, one attractive alternative to mu-opiates were the kappa-opioid receptor agonists, or kappa-opiates, such as nalbuphine (which is a kappa-opiate agonist and also a weak mu-opiate antagonist). Researchers found that compounds activating kappa-opioid receptors also produce analgesia but with minimal side effects in animal testing. Studies in animals and humans also suggested that drugs activating the kappa-opioid receptors are unlikely to cause addiction. However, kappa-opiates

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produced a significant, unexpected side effect in humans that had not been seen in preclinical animal tests: increased pain, or anti-analgesia, most acutely in men. The increased pain caused by kappa-opiates has previously prevented the development of such compounds into widely-used analgesic drugs.

The REN-213 Solution

REN-213 eliminates the previously described anti-analgesic side effect by combining nalbuphine, a kappa-opiate, with naloxone, an opiate antagonist, at a fixed ratio. The anti-analgesic side effect of kappa-opiates is only observed in humans and not other animals. Because REN-213 has this property, it was developed by an academic physician-scientist exclusively in human clinical studies. We believe REN-213 may provide equal or superior pain control as compared to morphine and other mu-opiate analgesics but without significant side effects such as constipation, respiratory depression, nausea, itching and confusion.

Prior Clinical Studies

REN-213 was invented by an academic physician-scientist based on human clinical studies as part of his research to determine why kappa-opiates produced pain in humans and most acutely in men. He hypothesized that these anti-analgesic properties were being generated via another opioid receptor. This hypothesis was verified when he determined that co-administration of a low dose of naloxone, an opiate receptor antagonist which had no analgesic action alone, reversed the pain-enhancing effect of nalbuphine and produced long-lasting, enhanced analgesia in both men and women. These studies involved more than 370 patients who had undergone major dental surgery.

Current Clinical Trials

We completed a Phase I clinical trial for REN-213 in December 2003. We are currently conducting two Phase II clinical trials of REN-213 in patients following dental and abdominal surgery, respectively. We plan to commence an additional Phase II trial in post-surgical dental pain patients during the second quarter of 2004. Including these ongoing trials, we plan to conduct a total of eight Phase II and Phase III clinical trials on REN-213 over the next two years. Two of the eight clinical trials will be conducted in healthy volunteers, two trials in dental surgery patients with post-operative pain, one trial in adults with polysubstance abuse, and three trials in post-operative patients immediately after non-dental surgery requiring general anesthesia. We believe this entire clinical program can be completed by 2006.

Commercialization

We plan to develop REN-213 through all phases of its clinical development and to sell and market the drug in the United States. At the appropriate time in the development of REN-213, we plan to build a specialized sales and marketing organization to sell our products to hospitals, surgeons, oncologists and pain management specialists. As part of our strategy for commercializing REN-213, we are testing a nasal formulation of the product candidate called REN-214 that would enable treatment of acute post-operative pain patients following their release from the hospital. We intend to enter into strategic marketing agreements with, and grant additional licenses to, pharmaceutical companies to gain access to broader market segments, including general practitioners and international markets. We have the exclusive worldwide license to the U.S. patent for REN-213 and its follow-on patent applications for the development and commercialization of REN-213.

Research Programs

Our research is focused on developing new drugs to treat neurological diseases and disorders. According to data published by Frost & Sullivan, drugs that target central nervous system diseases and disorders represent the second largest sector of the worldwide drug market, accounting for more than $55 billion in worldwide drug sales in 2002. Our research in neurological diseases and disorders is focused in three therapeutic areas: pain,

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trauma and stroke and neurodegenerative diseases. We pursue research programs in each of these therapeutic areas. Our neurobiology expertise includes broad capabilities in assay development, screening, lead optimization and target identification and validation. Our medicinal chemistry expertise includes the use of state-of-the-art technologies to turn initial promising compounds generated by our neuroscientists into drug candidates. Given progress with REN-214 and the research programs outlined below, our goal is to file one new IND in 2004 and another in 2005.

Pain

Pain, the unpleasant sensation associated with actual or potential tissue damage, comes in two forms: acute and chronic. Both forms of pain represent major medical needs.

VR1 Antagonist Program.    Key mediators of pain signaling are ion channels, which regulate the flow of different ions (charged atoms) between the inside and outside of neurons. The transient receptor potential (TRP) ion channels constitute a large and diverse family, several of which are thought to mediate pain signaling and are attractive targets for drug discovery. The best known of these is the vanilloid receptor 1 (VR1).

We believe that a drug that blocks VR1, preventing it from activating nerve cell signaling, could provide a non-narcotic analgesic and would also be useful for treating non-neurological conditions such as inflammatory bowel disorders and asthma. We have several lead development candidates and commenced preclinical development of one of these compounds in 2004. To date, we retain all commercial rights to the VR1 antagonist program.

Nitrone Analgesic Program.    In a parallel program, we are working on a different proprietary class of non-opiate analgesics for acute and chronic pain. We have developed a series of nitrone-based analgesic agents which are active in rat and mouse models of neuropathic pain. To date, we retain all commercial rights to this program.

Trauma and Stroke

Trauma and stroke include conditions in which the nervous system is physically injured (trauma), as well as conditions in which the blood supply to nervous system tissue is disrupted (stroke), both leading to acute neurological damage. In trauma and stroke, free radical generation plays a key role in generating damage to nervous system tissue above and beyond the damage directly caused by the physical injury or lack of oxygen and nutrients.

Next-Generation Neuroprotectant Program.    Compounds that reduce free radicals (e.g., free radical trapping agents such as Cerovive) protect tissues against the damage caused by free radicals that occurs during trauma and stroke. Cerovive, the first nitrone-based neuroprotectant to be developed in the clinic for the indication of stroke, is administered via intravenous injection. We are developing next generation orally active nitrone-based compounds for the treatment of trauma, stroke and other related neurological diseases. AstraZeneca may have the right to license certain compounds developed through this program.

Other Programs.    We have identified potential protein biotherapeutics that may facilitate nerve regrowth, repair and restoration of function following damage to the nervous system arising from spinal cord injury and other neurological diseases and disorders. We have entered into a collaboration with Genentech to pursue certain of these opportunities.

Neurodegenerative Diseases

Neurodegenerative diseases are characterized by progressive nervous system dysfunction in which neurons in particular structures or regions of the brain deteriorate or die over time. Such conditions include Alzheimer’s Disease and Parkinson’s Disease, as well as disorders such as Multiple Sclerosis, which is a nervous system

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“autoimmune disease” in which cells from the immune system inappropriately attack the body’s own tissues. While the first cause of each disease is debated among scientists and clinicians, it is clear that inflammation plays a large role in the progression of these diseases.

Leukocyte Trafficking Inhibitor Program.    In neurodegenerative diseases, leukocytes (white blood cells) from both inside and outside the nervous system cause inflammatory damage. We have commenced preclinical development of an orally active small molecule lead drug from a series of proprietary compounds that acts as an inhibitor of leukocyte trafficking, blocking the entry of these damage-inducing leukocytes into the nervous system. These compounds may also be useful for inflammation-related neurodegenerative disorders such as Multiple Sclerosis. We currently retain all commercial rights to this program.

TNFa Release Inhibitor Program.    Tumor necrosis factor a (TNFa) is a leukocyte signaling molecule that is capable of directly damaging tissue in the nervous system and increasing the activation of leukocytes at the site of nervous system inflammation. We are developing proprietary small molecule compounds that block the release of TNFa in the nervous system. To date, we retain all commercial rights to this program.

Strategy

Our goal is to become the leading biopharmaceutical company focused on discovering, developing and commercializing novel drugs to treat neurological diseases and disorders. The key elements of our strategy for achieving this goal are to:

Build a balanced portfolio of product candidates based on neurological diseases and disorders.    

We believe that our scientific expertise is broadly applicable to a wide range of neurological diseases and disorders and that expanding our product portfolio will mitigate some of the risks associated with drug development. We currently have eight distinct programs in various stages of research and development in the areas of pain, trauma and stroke and neurodegenerative diseases. The development and commercialization of one of these programs, Cerovive, is the responsibility of our exclusive licensee AstraZeneca. We intend to advance the other seven programs through research, development and commercialization as rapidly as practicable, while taking an opportunistic approach to acquiring or in-licensing additional product candidates. We believe our scientific expertise enables us to effectively identify and capitalize on external product opportunities as evidenced by our acquisition of product candidates from Centaur and our in-licensing of REN-213 from a research institution. We also intend to undertake new discovery projects to identify novel product opportunities for internal development or collaboration.

Independently pursue significant market opportunities in indications that can be tested in clinical trials that involve clear patient outcomes and short periods of patient follow-up, such as acute post-operative pain.    We focus our internal clinical development efforts on product opportunities that we believe can be commercialized or partnered based on results from rapid and cost-effective clinical programs. Such programs generally have clear efficacy endpoints and relatively brief periods of treatment and patient follow-up. Our first product candidates for pain, REN-1654 and REN-213, fit these parameters.

Establish selective corporate collaborations to assist in the development and commercialization of our products while retaining significant commercial rights.    We leverage the development, regulatory and commercialization expertise of AstraZeneca to mitigate risk and accelerate the development of Cerovive. We intend to selectively form additional corporate collaborations to further leverage our internal resources to undertake projects that are beyond our resources while retaining co-promotion or commercial rights in the United States. Such projects include establishing an international sales capability and completing large and costly clinical trials.

Develop a specialized U.S. sales and marketing organization to commercialize our lead products in pain.    We intend to retain all or a significant portion of U.S. commercialization rights to our most advanced, internally developed product candidates, REN-1654 and REN-213. At the appropriate time in the development of REN-213, we intend to build a focused sales and marketing organization to promote

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REN-213 to physicians who frequently prescribe medications to treat acute post-operative pain. Because these physicians are primarily hospital-based and concentrated in major metropolitan areas, we believe that we can effectively promote REN-213 with a focused sales and marketing organization. Similarly, we believe that a relatively small number of specialist physicians (e.g., neurologists and pain specialists) frequently prescribe medications for neuropathic pain and influence the practice and prescribing habits of broader groups of physicians. We intend to leverage the sales and marketing organization built to support REN-213 to also reach these high-prescribing specialist physicians with information about the appropriate use of REN-1654. We believe that developing a specialized internal sales capability in the future will be an essential component of achieving our goal to become the leading, fully-integrated biopharmaceutical company focused on developing and commercializing drugs to treat neurological diseases and disorders.

Strategic Alliances

AstraZeneca

Our agreement with AstraZeneca grants them exclusive worldwide rights to develop, manufacture and market Cerovive. Under the agreement, we are entitled to receive future milestone payments upon occurrence of each of the following events: filing of a marketing authorization application with European or Japanese regulatory authorities, approval of such marketing authorization application, filing of an NDA with the FDA and approval of such NDA. We are also entitled to mid-teen percentage royalties on worldwide net sales of Cerovive. AstraZeneca has responsibility for all aspects of clinical development under the agreement, including all costs. The agreement also establishes AstraZeneca’s and our rights and obligations involving defined product opportunities that may arise in the future from our nitrone chemical platform.

If we identify any nitrone-based drug candidate similar to Cerovive (i.e., that functions as a specific type of free radical trap) as a development candidate for stroke or stroke pain, traumatic brain injury or certain types of dementia, AstraZeneca would be entitled to license the compound from us on the terms and conditions of the Cerovive agreement. If we identify a compound of the same type in the areas of neurodegenerative diseases or psychiatric disorders outside the areas identified above, which we choose to partner with a third party, we are obligated to notify AstraZeneca and consider in good faith any interest it may have in such partnership opportunity. If we commercialize a compound with a third party in the areas of neurodegenerative diseases or psychiatric disorders (and, in the event AstraZeneca relinquishes its rights to products for stroke, stroke pain, traumatic brain injury or certain types of dementia), we will be required to pay AstraZeneca a low single-digit percentage royalty on worldwide net sales of that product.

Our agreement with AstraZeneca expires on the later of fifteen years after the first commercial sale of a licensed product, or the expiration of applicable patents, on a country-by-country basis. Additionally, AstraZeneca can terminate the agreement either in whole or in part, without cause, upon 12 months notice.

Genentech

In December 2003, we entered into a collaborative research, development and license agreement with Genentech for the discovery and development of drugs that inhibit pathological or tumor angiogenesis and promote nerve re-growth following nervous system injury. Under the terms of the agreement, Genentech paid us an upfront license and technology access fee of $5.25 million in January 2004 and made a $3.0 million equity purchase concurrent with our initial public offering. In addition, we are eligible to receive future milestone and royalty payments on therapeutic products emerging from the collaboration that are developed and commercialized by Genentech. In exchange, Genentech obtained exclusive worldwide rights to research, develop, manufacture and commercialize protein-based therapeutics and other drug compositions for the treatment of cancer and other diseases in which mechanisms underlying new blood vessel growth play a significant role. Under the collaboration, we will be responsible for evaluating protein biotherapeutic candidates in preclinical models of spinal cord injury. Unless Genentech exercises certain rights and makes additional payments to us, we will have the right to develop and commercialize products arising from the collaboration that

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are specifically useful for the treatment of central and peripheral nervous system diseases and conditions. We are required to make royalty payments, and in certain cases milestone payments, to Genentech on therapeutic products that we develop and commercialize under the collaboration.

Merck

In July 2003, we entered into a patent license and research collaboration agreement with Merck. Under this agreement, we are collaborating with Merck to ascertain whether certain drug compounds provided by Merck may have utility in certain conditions affecting the central nervous system. We hold method-of-use patents for the class of drugs being evaluated. The term of the agreement is nine months. We anticipate our expenses related to research programs under this agreement to be approximately $500,000. Based upon the experimental results obtained during this pilot collaboration, we and Merck do not expect to extend the agreement beyond the original term.

Intellectual Property

Patents, Trade Secrets and Licenses

The following factors are important to our success:

We actively seek, when appropriate, protection for our products, technologies and proprietary information through U.S. and foreign patents. In addition, we rely upon trade secrets and contractual arrangements to protect our proprietary information.

As of January 1, 2004, we own more than 30 U.S. patents, 15 U.S. patent applications, 55 foreign patents and 90 foreign patent applications related to our technologies, compounds and their applications in pharmaceutical development or their use as pharmaceuticals. In particular, we own patents and patent applications which materially relate to our ability to develop and commercialize our product candidate REN-1654. As of January 1, 2004, we have licensed, from institutions such as the Oklahoma Medical Research Foundation (OMRF), the University of Kentucky Research Foundation (UKRF), the Regents of the University of California (the Regents) and others, the exclusive rights to more than 35 U.S. patents, 20 U.S. patent applications, 100 foreign patents and 55 foreign patent applications related to our technologies, compounds and their applications in pharmaceutical development or their use as pharmaceuticals. We face the risk that one or more of the above patent applications may be denied. We also face the risk that our issued patents may be challenged or circumvented or may otherwise not provide protection for any commercially viable products we develop. We also note that U.S. patents and patent applications may be subject to interference proceedings and U.S. patents may be subject to reexamination proceedings in the U.S. Patent and Trademark Office (and foreign patents may be subject to opposition or comparable proceedings in the corresponding foreign patent office), which proceedings could result in either loss of the patent or denial of the patent application or loss or reduction in the scope of one or more of the claims of the patent or patent application. In addition, such interference, reexamination and opposition proceedings may be costly. In the event that we seek to enforce any of our owned or exclusively licensed patents against an infringing party, it is likely that the party defending the claim will seek to invalidate the patents we assert, which, if successful, would result in the entire loss of our patent or the relevant portion of our patent and not just with respect to that particular infringer. Any litigation to enforce or defend our patent rights, even if we were to prevail, could be costly and time-consuming and would divert the attention of our management and key personnel from our business operations.

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In addition, our ability to assert our patents against a potential infringer depends on our ability to detect the infringement in the first instance. Many countries, including certain European countries, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties in some circumstances (for example, the patent owner has failed to “work” the invention in that country, or the third party has patented improvements). In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of the patent. Compulsory licensing of life saving drugs is also becoming increasingly popular in developing countries either through direct legislation or international initiatives. Such compulsory licenses could be extended to include some of our product candidates, which could limit our potential revenue opportunities. Moreover, the legal systems of certain countries, particularly certain developing countries, do not favor the aggressive enforcement of patent and other intellectual property protection which makes it difficult to stop infringement.

Our success will also depend in part upon our not infringing patents issued to others. If our product candidates are found to infringe the patents of others, our development, manufacture and sale of such potential products could be severely restricted or prohibited. In this regard, we have received correspondence from a third party that alleges that certain of our compositions and methodologies fall within the scope of patents owned by this individual. Although we do not believe that these patents seriously harm our ability to develop and commercialize our products, we cannot be certain of this. We are also aware of certain third party patents relating to the use of certain opioid agonists in conjunction with certain opioid antagonists that are the subjects of re-examination proceedings on the basis that the claims of such patents are invalid. Although we believe that these claims are indeed invalid and/or not infringed and will not seriously harm our ability to develop and commercialize our products, we cannot be certain of this. It is likely that in the future we will encounter other similar situations which will require us to determine whether we need to license a technology or face the risk of defending an infringement claim.

Patent litigation can involve complex factual and legal questions and its outcome is uncertain. Any claim relating to infringement of patents that is successfully asserted against us may require us to pay substantial damages. Even if we were to prevail, any litigation could be costly and time-consuming and would divert the attention of our management and key personnel from our business operations. Furthermore, as a result of a patent infringement suit brought against us or our strategic partners or licensees, we or our strategic partners or licensees may be forced to stop or delay developing, manufacturing or selling potential products that are claimed to infringe a third party’s intellectual property unless that party grants us or our strategic partners or licensees rights to use its intellectual property. In such cases, we may be required to obtain licenses to patents or proprietary rights of others in order to continue to commercialize our products. However, we may not be able to obtain any licenses required under any patents or proprietary rights of third parties on acceptable terms, or at all. Even if our strategic partners, licensees or we were able to obtain rights to the third party’s intellectual property, these rights may be non-exclusive, thereby giving our competitors access to the same intellectual property. Ultimately, we may be unable to commercialize some of our potential products or may have to cease some of our business operations as a result of patent infringement claims, which could severely harm our business.

Much of our technology and many of our processes depend upon the knowledge, experience and skills of our scientific and technical personnel. To protect rights to our proprietary know-how and technology, we generally require all employees, contractors, consultants, advisors, visiting scientists and collaborators as well as potential collaborators to enter into confidentiality agreements that prohibit the disclosure of confidential information. The agreements with employees and consultants also require disclosure and assignment to us of ideas, developments, discoveries and inventions. These agreements may not effectively prevent disclosure of our confidential information or provide meaningful protection for our confidential information.

Many of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although no claims against us are currently pending, we may be subject to claims that these employees or we have inadvertently or otherwise used or

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disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management. If we fail in defending such claims, in addition to paying money claims, we may lose valuable intellectual property rights or personnel.

We also use as advisors and consultants individuals who are currently employed by universities. Most of these individuals are parties to agreements pursuant to which some of the work product created by these individuals belongs to their respective universities. While we and these individuals try to maintain records which make it clear that the work these individuals do for us is not subject to their agreements with universities, it is always possible that a university will assert an ownership claim to the work of one or more of these individuals.

OMRF and UKRF.    We hold the exclusive, worldwide license to specified intellectual property related to Cerovive owned by OMRF and UKRF pursuant to a license agreement entered into in July 1992. In consideration for this technology license, we are obligated to pay OMRF and UKRF low-single digit royalties on any future net sales of products relating to our license, subject to a minimum annual royalty payment of $25,000 through the year the FDA first approves an NDA and $100,000 annually thereafter. The license agreement terminates upon the later of the expiration of the last of any patent rights to licensed products that are developed under the agreement or 15 years from the effective date of the agreement. We may terminate the license agreement for any reason following six months written notice to OMRF and UKRF.

OMRF.    We hold the exclusive, worldwide license to specified intellectual property related to nitrones that are potential therapeutics owned by OMRF pursuant to a license agreement entered into in January 1998. In consideration for this technology license, we are obligated to pay OMRF royalties on any future net sales of products relating to our license, subject to minimum annual royalty payments of $10,000. In addition, we are obligated to pay OMRF milestone payments if we reach certain regulatory milestones. The license agreement terminates upon the later of the expiration of the last to expire of any patent rights to licensed products that are developed under the agreement or 15 years from the effective date of the agreement. We may terminate the license agreement for any reason following six months written notice to OMRF.

The Regents of the University of California.    We hold the exclusive, worldwide license to specified intellectual property related to REN-213 owned by the Regents pursuant to a license agreement entered into in December 2002. In consideration for this technology license, we paid a license fee to the Regents which requires additional annual payments in 2003 and 2004. We are also obligated to pay the Regents royalties on any future net sales of products relating to our license. In addition, we are obligated to make payments to the Regents based on meeting certain regulatory and clinical milestones. The license agreement terminates upon the expiration of all patent rights licensed thereunder. We may terminate the license agreement for any reason following 60 days written notice to the Regents.

We hold two exclusive, worldwide licenses to specified intellectual property related to targets and potential protein biotherapeutics relevant for inhibition of tumor angiogenesis and other pathological diseases and for nerve regeneration and repair, owned by the Regents pursuant to license agreements entered into in June 2001 and November 2002, respectively, each as amended in December 2003. In consideration for these technology licenses, we paid license fees to the Regents. We are required to make additional annual payments on the November 2002 license. We are also obligated to pay the Regents royalties on any future net sales relating to our licenses subject to specified minimum annual royalty payments of $25,000 for products developed under the June 2001 license and $50,000 for products developed under the November 2002 license. In addition, we are obligated to make payments to the Regents based on meeting certain regulatory and clinical milestones. The June 2001 license automatically terminates upon the date of expiration of the last to expire patent under the license. The November 2002 license automatically terminates on or after December 31, 2018.

Cutanix.    In December 2002, Centaur assigned all of its rights and obligations under an agreement with Cutanix Corporation (Cutanix) to us. Pursuant to this agreement entered into in January 1998, Cutanix received

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the right to exclusively develop and commercialize individual compounds for use in the fields of dermatology and cosmetics and other skin care applications. In September 2002, the agreement with Cutanix was amended to clarify and modify the scope of technology to which Cutanix had rights, redefine the criteria allowing Centaur and Cutanix to claim certain exclusive rights to develop and commercialize compounds within the Centaur compound library licensed under the agreement, as well as provide a defined mechanism for access by Cutanix of certain proprietary technology and compound samples. Resulting modifications included limitation of the license granted to Cutanix to cover only technology existing as of July 31, 2002, the termination of the right for Centaur to be the exclusive supplier of active compounds to Cutanix and the explicit exclusion of certain compounds under development by Centaur and Cutanix as long as they continue to be in development. There are no ongoing fees or expenses payable by us under this agreement.

Government Regulation

The FDA and comparable regulatory agencies in state and local jurisdictions and in foreign countries impose substantial requirements upon the clinical development, manufacture and marketing of pharmaceutical products. These agencies and other federal, state and local entities regulate research and development activities and the testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion of our products.

The process required by the FDA before product candidates may be marketed in the United States generally involves the following:

The testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any new approvals for our products will be granted on a timely basis, if at all.

Prior to commencing the first clinical trial, we must submit an IND to the FDA. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the clinical trial. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Our submission of an IND may not result in FDA authorization to commence a clinical trial. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development, and the FDA must grant permission for each clinical trial to start and continue. Further, an independent institutional review board for each medical center proposing to conduct the clinical trial must review and approve the plan for any clinical trial before it commences at that center. Regulatory authorities or an institutional review board or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects or patients are being exposed to an unacceptable health risk.

For purposes of NDA approval, human clinical trials are typically conducted in three sequential phases that may overlap.

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The FDA may require, or companies may pursue, additional clinical trials after a product is approved. These so-called Phase IV studies may be made a condition to be satisfied after a drug receives approval. The results of Phase IV studies can confirm the effectiveness of a product candidate and can provide important safety information to augment the FDA’s voluntary adverse drug reaction reporting system.

The results of product development, preclinical studies and clinical trials are submitted to the FDA as part of an NDA, or as part of an NDA supplement. The FDA may deny approval of an NDA or NDA supplement if the applicable regulatory criteria are not satisfied, or it may require additional clinical data and/or an additional pivotal Phase III clinical trial. Even if such data are submitted, the FDA may ultimately decide that the NDA or NDA supplement does not satisfy the criteria for approval. Once issued, the FDA may withdraw product approval if ongoing regulatory standards are not met or if safety problems occur after the product reaches the market. In addition, the FDA may require testing and surveillance programs to monitor the effect of approved products which have been commercialized, and the FDA has the power to prevent or limit further marketing of a product based on the results of these post-marketing programs.

Satisfaction of FDA requirements or similar requirements of state, local and foreign regulatory agencies typically takes several years and the actual time required may vary substantially based upon the type, complexity and novelty of the product or disease. Typically, if a drug product is intended to treat a chronic disease, as is the case with some of the product candidates we are developing, safety and efficacy data must be gathered over an extended period of time, which can range from six months to three years or more. Government regulation may delay or prevent marketing of product candidates or new diseases for a considerable period of time and impose costly procedures upon our activities. The FDA or any other regulatory agency may not grant approvals for new indications for our product candidates on a timely basis, if at all. Success in early stage clinical trials does not ensure success in later stage clinical trials. Data obtained from clinical activities is not always conclusive and may be susceptible to varying interpretations, which could delay, limit or prevent regulatory approval. Even if a product candidate receives regulatory approval, the approval may be significantly limited to specific disease states, patient populations and dosages. Further, even after regulatory approval is obtained, later discovery of previously unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product from the market. Delays in obtaining, or failures to obtain, additional regulatory approvals for Cerovive, REN-1654 or REN-213 would harm our business. In addition, we cannot predict what adverse governmental regulations may arise from future U.S. or foreign governmental action.

Any products manufactured or distributed by us pursuant to FDA approvals are subject to continuing regulation by the FDA, including record-keeping requirements and reporting of adverse experiences with the drug. Drug manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with good manufacturing practices, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. We cannot be certain that we or our present or future suppliers will be able to comply with the good manufacturing practices regulations and other FDA regulatory

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