Paul Greengard Discusses Neuroscience and Winning the Nobel Prize

In a recent video from the series Conversations with Giants in Medicine, Nobel Laureate Paul Greengard discusses his work in neuroscience and the Nobel Prize.

In 2000, Greengard was awarded the Nobel Prize in Physiology or Medicine, along with two other men. His work paved the way for treatments for Parkinson’s disease and other neurological disorders. He established base knowledge for neurotransmitters and slow synaptic transmission that many neuroscientists and neurologists use today.

In the video, Greengard says that he did not get the “bug” of doing scientific research from home because the environment growing up was anti-intellectual. He suspects that going to college was an act of rebellion. Greengard used the G.I. Bill in order to go to college because he served in the military during World War II. He says he studied mathematics and physics. He planned to go to graduate school in order to work in theoretical physics. He states that he changed his mind after the atomic bombs were dropped on Hiroshima and Nagasaki.

He says:

“Almost immediately after the dropping of the atomic bombs on Hiroshima and Nagasaki, I felt that [theoretical physics] was not an area that I wanted to be very involved in, just because I thought there were better ways of spending my life than trying to destroy mankind.”

About that time, he learned about the then-nascent field of medical physics, or biophysics, and became interested in studying that. During this time, he says he decided it would be beneficial to learn about the underlying biochemical and molecular properties of nerve cells. He studied at John Hopkins University for his Ph.D before traveling to England and Holland for five years. He worked for nine years at a pharmaceutical company, which shaped the way Greengard did his research.

He explains:

“It gave me an education of the sort that one might’ve gotten in medical school. At the time I was ready to do advanced studies, I decided not to go to medical school because at that time, it was very much of a hands-on profession where the physicians really couldn’t do very much for the patients. They were brilliant clinicians but there were very limited repertoire of tools that they had.”

He says that his key advance to medical science was discovering that the nervous system responded to neurotransmitters the way the endocrine system responded to hormones.

He states:

“People said unkind things [about the discovery]. Like, ‘This is heretical and nonsense.’ The interesting thing about it was that because it was considered so unlikely to be true, I had basically 15 years… to develop this story. By the time people accepted it, my research group had laid a lot of the foundation of the molecular bases for neurotransmission. So we didn’t have this ultra-heavy competition.”

Greengard mentions that in his conversations with other Nobel Prize winners revealed that they, too, contributed an advance that nobody believed at first.

He explains:

“In many instances it was the same thing: They’ve done something very unconventional and nobody believed them for a while, and it was shown to be true. And if you think about it, it’s more or less the only way the thing could work. If you just did something that was very incremental, it wouldn’t be worthy of a Nobel Prize…. Occasionally there are different types of discoveries, but many of the discoveries that have been made were paradigm shifts where somebody did something that people didn’t accept because it was not consistent with a prevailing paradigm.”

DARPA Awards $3.8 Million Contract to CytoSorbents Corporation (CTSO)

CytoSorbents Corporation (OTCBB: CTSO) is a publicly-traded, critical care focused therapeutic device company using blood purification to treat life-threatening illnesses. Its purification technology is based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Each polymer bead contains millions of pores and channels that can be modified to remove substances as small as drugs, to substances as large as antibodies.

The Company has announced that it has been awarded a technology development contract worth up to $3.8 million by the Defense Advanced Research Projects Agency (DARPA). The contract would be over a period of five years as part of the company’s Dialysis-Like Therapeutics (DLT) program to treat sepsis, pending satisfactory achievement of key milestones. 

DARPA is the U.S. Department of Defense agency responsible for funding cutting-edge programs such as the internet, the global positioning satellite system (GPS), and robotic surgery. In this case, it is funding the development of a portable, artificially intelligent blood purification system that can detect and remove, in real time, substances that can contribute to sepsis, including cytokines, toxins, biowarfare agents, pathogens, and activated cells. The goal is to save the lives of injured warfighters and civilians afflicted with sepsis, where approximately one in every three patients die today, even with the best medical treatment.

Under the terms of this contract, CytoSorbents will develop next-generation broad-spectrum, porous polymers capable of removing cytokines, toxins and certain biowarfare agents from whole blood, with $1.5 million in funding designated for the first year, based upon the achievement of pre-determined milestones.

Dr. Phillip Chan, Chief Executive Officer of CytoSorbents, stated,

"We are delighted to officially begin working with DARPA on this exciting project and are honored to have had our unique core blood purification technology selected for funding. We are one of the industry leaders in the area of blood purification to treat sepsis and other critical care illnesses, with our first-in-class CytoSorb® cytokine filter currently approved and commercialized in the European Union. That being said, under this DARPA program, we are looking to significantly advance our polymer technologies to not only remove cytokines, but also a wide variety of toxins, and do so with little to no anti-coagulation in both high flow and microfluidic systems. The excessive production of cytokines, or 'cytokine storm,' is common in the worst forms of sepsis, and triggers massive inflammation that can lead to organ failure and infection -- the two leading causes of death in the ICU. Meanwhile, toxins produced by bacteria, viruses and other pathogens play an additional devastating role on the body, poisoning or killing cells, leading to widespread tissue destruction and worsened inflammation and sepsis. And the threat of a biowarfare attack with toxins such as ricin and botulinum remains a perennial concern. Our porous polymers are ideally suited to achieve the broad spectrum removal that is needed to counter most of these agents."

Dr. Chan continued,

"Because of the maturity of our technology, we are confident in our ability to meet DARPA's timetable for technology development and strict performance metrics. Over the past several months, we have also collaborated with some of the leading potential systems integrators, to include our technologies into their integration proposals, under a separately funded DARPA DLT solicitation. The role of the systems integrator is to put together the best detection, separation and predictive modeling technologies into a single blood purification system and guide it to human clinical trials within 4 to 5 years. These partnerships are mutually beneficial and will help to contribute to the success of the overall program."

Dr. Chan concluded,

"Just within the recent past, we have seen many high-profile cases of sepsis here in the U.S. including a young woman injured from a fall from a broken homemade zip-line who developed sepsis from a 'flesh-eating' bacterial infection, and a 12-year-old boy who died of unrecognized sepsis after cutting his arm during a basketball game. Unfortunately, these cases are not unusual, with thousands of patients dying silently from sepsis every day in hospitals around the world. The number of sepsis cases in the U.S. alone has doubled in the past decade, and continues to climb due to increased antibiotic resistance, a high rate of hospital-acquired infections, and an aging baby boomer population that is prone to infection due to age, diseases such as diabetes and cancer, and the use of implantable medical devices such as artificial hips and knees. There are currently no approved therapies to treat sepsis in the U.S. or in the European Union. Therapies like CytoSorb® and the device being proposed by DARPA are sorely needed and we are proud to be part of this worthy effort."

Read the full press release here. 

The Crushing Cost of Care @ The Wall Street Journal (CTSO)

In a recent Wall Street Journal article, journalists Janet Adamy and Tom McGinty tell the story of Scott Crawford, a young father who had been healthy his whole life until he was diagnosed with idiopathic dilated cardiomyopathy at age 26. That diagnosis signalled the beginning of a long, painful journey through medication, transplants, surgery, therapy, amputation, and nearly chronic pain, which ended with his death in late 2009. Estimates from Johns Hopkins Hospital in Baltimore, where Mr. Crawford was receiving treatment, put the cost of his Medicare claims at the staggering total of $2.7 million, $766,919 of which remains unpaid. Read the full article here. 

Adamy and McGinty use Mr. Crawford's story as a springboard to discuss Medicare and the shockingly high cost of care in the US. However, something very compelling stands out in Mr. Crawford's story: The frequent mention of sepsis, defined as an overzealous response to a severe infection, as a leading culprit in his downward spiral.

For example, deputy administrator and director for Medicare Jonathan Blum commented that for Mr. Crawford, "a lot of the costs were driven by complications that could have been avoided," citing an early infection as an example. Additionally, after 2 heart transplants, Mr. Crawford developed a severe infenction and had to have his leg above the knee amputated. Shortly before he died, sepsis was again identified as the condition that was overwhelming his system. 

Mr. Crawford isn't the only patient who could have been spared years of pain by catching and treating sepsis early. According to a 2011 brief by the CDC, "an estimated $14.6 billion was spent on hospitalizations for septicemia [In 2008], and from 1997 through 2008, the inflation-adjusted aggregate costs for treating patients hospitalized for this condition increased on average annually by 11.9%. Despite high treatment expenditures, septicemia and sepsis are often fatal. Those who survive severe sepsis are more likely to have permanent organ damage, cognitive impairment, and physical disability. Septicemia is a leading cause of death." Read more here. 

When a person develops sepsis, the body frequently overresponds to the threat by producing a massive excess of cytokines, called cytokine storm. While cytokines normally help the body cope with injury, a cytokine storm "is toxic to the body, driving severe inflammation and a cascade of dangerous changes in the body that cause cell damage, organ failure and often death. It follows that reduction of cytokine storm may limit this cascade of events, thereby reducing the severity of illness, and helping patients recover and survive. Until recently, however, there were no effective ways to reduce cytokine storm broadly."

CytoSorbents Corporation (OTCBB: CTSO) is one company working on a solution, that has until recently has not been possible to do.  Its flagship product, CytoSorb®, is a blood filtration cartridge that works to modulate the immune system by removing excess cytokines in critically-ill patients.  If left unchecked, these inflammatory toxins can lead to deadly inflammation, multiple organ failure, immune dysfunction, and often death in common illnesses such as sepsis, trauma, burn injury, acute respiratory distress syndrome, and pancreatitis. CytoSorb® has demonstrated statistically significant reductions in mortality in septic patients at high risk of death and is now available for sale in Germany for the treatment of critical care illnesses with availability in other E.U. countries planned in the future, assuming adequate and timely funding, and continued positive results from its clinical studies. Read more at cytosorbents.com. 

Unnoticed infection turns unstoppable @ The Irish Times (CTSO)

Rory Staunton was a happy, friendly 12-year old boy who wanted to be a pilot when he grew up. He lived with his parents and younger sister in New York. He was quite healthy until he dove for a basketball in his school gym one day and cut his arm. The next day, he was feverish and vomitting. Two days later, he was dead.

Rory died from Strep A Toxic Shock Syndrome, a commonly misdiagnosed condition. In The Irish Times, journalist Jim Dwyer chronicles the dismaying story of how the severity of Rory's condition could escape the notice of his pediatrician as well as the emergency room at NYU Langone Medical Center. 

He writes,

On the first day of his illness, "partially camouflaged by ordinary childhood woes, Rory’s condition was, in fact, already dire. Bacteria had gotten into his blood, probably through the cut on his arm. He was sliding into a septic crisis, an avalanche of immune responses to infection from which he would not escape."

The rest of the story includes doctor miscommunications, inaccurate diagnoses, and even a 12-minute gap between symptom observation and doctor recommendation that could have caught the sepsis early:

"A screening tool in the Stop Sepsis program, used when a patient first arrives in the emergency room, calls special attention to a person with three symptoms of a possible eight. At the hospital, Rory showed two: he was breathing 20 times per minute and his pulse was 143. 

Two hours later, though, he had three: his temperature had risen to 102, his pulse was 131 and his respiration rate was 22. But by the time those vital signs were recorded, at 9.26pm, they had no bearing on his treatment. In fact, the doctor had already decided that Rory was going home. Rory’s 'ExitCare' instructions, signed by his father, were printed 12 minutes before those readings." Read more at The Irish Times. 

Rory's story serves as yet more evidence that sepsis is a looming health problem for the country, and also that it remains underdiagnosed. In addition to correctly diagnosing the illness, it is also crucial to ensure that solid treatment options are available once sepsis is diagnosed. CytoSorbents Corporation (OTCBB: CTSO) is one company making gains in this space. CytoSorbents Corporation is a critical-care focused therapeutic device company using blood purification to modulate the immune system and fight organ failure in life-threatening illnesses, including sepsis. CytoSorbents is developing novel and advanced blood purification therapies designed to actively prevent, mitigate, or reverse the development of organ failure and infection, thereby potentially reducing illness severity and helping patients to heal and recover faster. Ultimately the goal is to improve patient outcome and save healthcare costs. 

CytoSorbents’ purification technology is covered by 29 issued patents and is based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and adsorption. The technology has been selected for funding by both the U.S. Army and DARPA (Defense Advanced Research Projects Agency) in a Phase I SBIR grant for trauma, and DARPA’s “Dialysis-like Therapeutics” program for the treatment of sepsis, respectively. The technology is also the basis of the Company’s two lead programs, CytoSorb™ and HemoDefend. Read more at cytosorbents.com.

The Coming “Sepsis Boom" and How to Avert it (CTSO)

In the Medical Labratory Observer, contributor Mark H. Oltermann, MD, writes that due to a variety of factors, the generation known as "the Baby Boom is about to become the Sepsis Boom."

He explains,

"We're seeing an unmistakable increase [in sepsis rates] among all age groups, but particularly among the elderly. There are many factors contributing to this trend. Three of the most dynamic are the aging population, underlying conditions that lead to immunosuppression, and the increase in antibiotic resistance."

Coinciding with the increasing rates of sepsis among the elderly is the actual increasing number of elderly Americans relative to other age groups: 

"We are on the front end of an enormous bulge in the population of Americans who will be 65 and older. The first U.S. Baby Boomers [turned] 65 in 2011, inaugurating a rapid increase in the older population during the 2010 to 2030 period. The older population in 2030 is projected to be double that of 2000, growing from 35 million to 72 million...

In fact, this study shows that the trend of the older population growing at a faster pace than the total population will accelerate dramatically from 2010 to 2040. Whereas the total population of the U.S. is expected to increase by nearly 20% in the two decades between 2010 and 2030, the population of U.S. residents 65 years of age and older will increase at nearly four times that rate (78%) in the same time period."

The bottom line is this: In 2030, nearly 1 in 5 Americans will be aged 65 and older, compared with about 1 in 8 in 2010. Of those elderly Americans, many more will be at risk for sepsis than would have been in previous generations. 

However, not all hope is lost. Oltermann proposes 2 changes to be made that could stem the tide of sepsis cases in the coming years:

"The first [is] to require hospitals to make sepsis one of the core measures that would push for standardizing protocols and reporting of mortality rates. Until that happens, sepsis will be one of hundreds of problems competing for scarce resources and priority status. The second step toward improvement would be to adopt screening tests for sepsis such as lactate and procalcitonin as standard blood tests for all elderly patients who are admitted to the hospital. As noted earlier, this population is at increased risk, and they also may not always display the classic SIRS (systemic inflammatory response syndrome) criteria because of comorbid conditions and concomitant medications." Read more here. 

Though not mentioned in the article, a third step to take would be to ensure that there are solid, reliable treatment options available to help treat sepsis once it is diagnosed. In this space, CytoSorbents Corporation (OTCBB: CTSO) is one company making remarkable gains. CytoSorbents Corporation is a critical-care focused therapeutic device company using blood purification to modulate the immune system and fight organ failure in life-threatening illnesses, including sepsis. CytoSorbents is developing novel and advanced blood purification therapies designed to actively prevent, mitigate, or reverse the development of organ failure and infection, thereby potentially reducing illness severity and helping patients to heal and recover faster. Ultimately the goal is to improve patient outcome and save healthcare costs. 

CytoSorbents’ purification technology is covered by 29 issued patents and is based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and adsorption. The technology has been selected for funding by both the U.S. Army and DARPA (Defense Advanced Research Projects Agency) in a Phase I SBIR grant for trauma, and DARPA’s “Dialysis-like Therapeutics” program for the treatment of sepsis, respectively. The technology is also the basis of the Company’s two lead programs, CytoSorb™ and HemoDefend. Read more at cytosorbents.com.

Scientists identify possible drug target for acute pancreatitis ($CTSO)

CytoSorbents Corporation (OTCBB: CTSO) is a critical-care focused therapeutic device company using blood purification to modulate the immune system and fight organ failure in life-threatening illnesses such as sepsis, burn injury, trauma, lung injury and pancreatitis. Its purification technology is based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and absorption. CytoSorbents is currently selling its flagship product, CytoSorb®, in Germany with availability in other European countries.

Acute pancreatitis is the inflammation of the pancreas that results in the local release of digestive enzymes and chemicals that cause severe inflammation, necrosis and hemorrhage of the pancreas and local tissues. Approximately 210,000 people in the U.S. are hospitalized each year with acute pancreatitis with roughly 20% requiring ICU care. Overall ICU mortality of severe acute pancreatitis approaches 20%.

Acute pancreatitis is caused most frequently by a blockage of the pancreatic duct or biliary duct with gallstones, cancer, or from excessive alcohol use. Severe acute pancreatitis is characterized by severe pain, inflammation, and edema in the abdominal cavity, as well as progressive systemic inflammation that can lead to multiple organ failure. High levels of cytokines and digestive enzymes can be found in the blood and are correlated to organ dysfunction.

Aside from trying to unclog the duct with endoscopic techniques, there is little that can be done except for bowel rest, aggressive hydration, antibiotics when indicated, and pain control. However, CytoSorb® may potentially improve the outcome of severe acute pancreatitis by removing a diverse set of toxins from blood.

Some recent data from a report in the June 2012 issue of the Journal of Leukocyte Biology demonstrates that one cytokine in particular, IL-6, is associated with worsened outcomes in mice models of pancreatitis. This report "describes experiments in lean and obese mice that identify the presence of high IL-6 as one of the reasons why the disease is more devastating in obese people." 

John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, stated,

"There is an increasing awareness that obesity and inflammation are connected. Not only does this new report demonstrate an important set of interactions between obesity, pancreatitis, and inflammation, but it also identifies the inflammatory pathway, IL-6, which could represent an important new therapeutic target in these settings." Read more here. 

Amongst its many potential benefits in severe acute pancreatitis, CytoSorb® was clinically proven to reduce IL-6 in critically-ill patients by approximately 50%, and other key cytokines by 30-50%, in CytoSorbents’ European Sepsis Trial that finished last year. CytoSorbents believes severe acute pancreatitis is just one of many life-threatening illnesses that it may be beneficial in.

OxyContin Maker Guards Exclusivity @ WSJ; Dr. Isa Odidi of Intellipharmaceutics Weighs In (IPCI)

Intellipharmaceutics International (NASDAQ: IPCI; TSX: I) is engaged in the research, development, and commercialization of controlled-release and targeted-release pharmaceutical products. Controlled-release means releasing a drug into the bloodstream or at a target site in the body, over an extended period of time or at predetermined times. In some circumstances, controlled-release drug delivery can enhance efficacy and patient compliance as compared to immediate release formats for the same drug.

In a Wall Street Journal article, Timothy W. Martin writes that "OxyContin is set to go off patent next year, but the maker of the powerful and heavily abused prescription painkiller is trying to extend its exclusive rights to the drug, arguing that a new version it spent $100 million to develop might substantially curtail abuse. Whether Purdue Pharma LP will be able to protect its reformulated OxyContin will be decided by the courts."

Purdue Pharma LP argues that its new version of OxyContin, which has patent protection until 2025, is more abuse-resistent than the original formulation, and "generic-drug makers should be prevented from producing the original version of OxyContin." Manufacturers of generic drugs, on the other hand, "say Purdue Pharma is just trying to protect a lucrative market for itself, and that they can make their own abuse-deterrent formulations of the drug." Read the full article here. 

Commenting on the article, Intellipharmaceutics CEO Dr. Isa Odidi stated,

"We expect that any 'generic' of OxyContin will have to have an abuse deterrent technology; this would result in a NDA or NDA 505(b)(2) regulatory path. A pure generic to the original version of OxyContin will not be available; this would be the ANDA regulatory path. The new version of OxyContin from Purdue has additional patent protection to 2025, therefore a generic to this version will be challenging as they have to claim that the change will not merit extending Purdue's patent protection.

Our lead non-generic product under development is Rexista(tm) oxycodone hydrochloride, intended as an abuse- and alcohol-deterrent controlled-release oral formulation of oxycodone hydrochloride for the relief of pain.  Rexista(tm) is a unique dosage form designed to be a deterrent to some of the well-documented abuses associated with some currently marketed controlled-release oxycodone products.  This includes abuse of these drugs by nasal inhalation when crushed or powdered, or by injection when combined with solvents.  Rexista(tm) oxycodone is also designed to resist release of the entire dose when consumed with alcohol, a significant problem with some opioid drugs."

Intellipharmaceutics Announces Second Quarter 2012 Results - $IPCI

Intellipharmaceutics International Inc. (Nasdaq:IPCI) (TSX:I), a pharmaceutical company specializing in the research, development and manufacture of novel and generic controlled-release and targeted-release oral solid dosage drugs, today reported the results of operations for the three and six months ended May 31, 2012. All dollar amounts referenced herein are in United States dollars unless otherwise noted.

The Company recorded a net loss for the three months ended May 31, 2012 of $1.4 million, or $0.08 per common share, compared with a net loss of $2.0 million, or $0.12 per common share for the three months ended May 31, 2011. The net loss for the six months ended May 31, 2012 was $3.3 million, or $0.20 per common share, compared with a net loss of $4.7 million, or $0.33 per common share for the six months ended May 31, 2011. The Company's reduced net loss in the three months ended May 31, 2012, can be attributed to a reduction in the fair value adjustment of derivative liability of $0.8 million and the timing of certain research and development activities. After adjusting for the fair value adjustment of derivative liability, the loss for the three months ended May 31, 2012 was lower by $0.3 million and is discussed below.

Loss from operations for the three months ended May 31, 2012 was $2.0 million compared with $2.4 million for the three months ended May 31, 2011. Research and development expense for the three months ended May 31, 2012 decreased to $1.1 million compared to $1.4 million in the three months ended May 31, 2011. After adjusting for stock-based compensation expense, expenditures for research and development for the three months ended May 31, 2012 were lower by $0.4 million. Selling, general and administrative expenses for the three months ended May 31, 2012 decreased to $0.8 million versus $0.9 million in the prior period. After adjusting for stock-based compensation expense, expenditures for selling, general and administrative expenses for the three months ended May 31, 2012 were lower by $0.2 million.

At May 31, 2012, Intellipharmaceutics' (IPCI) cash and cash equivalents totaled $4.9 million, compared with $2.6 million at February 29, 2012. The increase in cash during the three months ended May 31, 2012 is mainly due to the Company's registered direct common share offering for gross proceeds of $5 million completed on March 14, 2012.

For the three months ended May 31, 2012 net cash flows used in operating activities was effectively unchanged at $1.8 million, as compared to net cash flows used in operating activities for the three months ended May 31, 2011 of $1.9 million. For the three months ended May 31, 2012 net cash flows from financing activities of $4.5 million related mainly to the Company's registered direct common share offering for gross proceeds of $5 million.

Corporate Update

• On March 15, 2012, we closed a registered direct common share offering for gross proceeds of $5 million. The Company sold an aggregate of 1,818,182 shares to U.S. institutional investors at a price of $2.75 per share. After placement agent fees and estimated offering expenses, the Company received net proceeds from the offering of approximately $4.2 million. Intellipharmaceutics is using the net proceeds to file additional abbreviated new drug applications ("ANDAs") with the Food and Drug Administration ("FDA"), to advance clinical trials for its abuse resistant Rexista" technology and/or other New Drug Application ("NDA") 505(b)(2) opportunities, to establish additional partnerships, and for working capital, research, product development and general corporate purposes.
• On May 1, 2012, the Company held a pre-Investigational New Drug ("pre-IND") meeting with the FDA to discuss our Rexista" oxycodone development plan. A panel of the FDA's Center for Drug Evaluation and Research clarified the Company's path going forward for its Rexista" abuse-deterrent oxycodone development plan. Intellipharmaceutics will now advance toward the next goals of its Rexista" program, namely the manufacture of clinical batches of Rexista" abuse-deterrent oxycodone product candidate under current good manufacturing practice ("cGMP") conditions and the commencement of definitive Phase I clinical studies. This follows from the previous proof-of-concept Phase I clinical study completed on a pilot laboratory batch, which yielded positive results. There can be no assurances as to whether or when the FDA will approve any Intellipharmaceutics' application.

About Intellipharmaceutics

Intellipharmaceutics International Inc. is a pharmaceutical company specializing in the research, development and manufacture of novel and generic controlled-release and targeted-release oral solid dosage drugs. The Company's patented Hypermatrix" technology is a multidimensional controlled-release drug delivery platform that can be applied to the efficient development of a wide range of existing and new pharmaceuticals. Based on this technology, Intellipharmaceutics has a pipeline of product candidates in various stages of development, including six ANDAs under review by the FDA, in therapeutic areas that include neurology, cardiovascular, gastrointestinal tract, diabetes, pain and infection.