Mark Wentland

Discovery may lead to further development of compounds to treat nervous system disorders and addiction

For more than 10 years, Mark Wentland professor of chemistry and chemical biology at Rensselaer Polytechnic Institute, led a Rensselaer team in the discovery of a family of novel opioid receptor compounds with the potential to treat nervous system disorders and addiction. The family of compounds was licensed to Alkermes Inc., and the company identified a lead product candidate from the library. Clinical trials with the candidate, known as ALKS 33, began in December 2008. 

Wentland said the “eureka moment” occurred with the realization that an opioid drug that his group discovered had triggered significant, long-acting activity in the targeted area. This breakthrough held unusual promise for treating reward disorders and a number of diseases because of its long-lasting effect in animal tests.

“The broad goal of a medicinal chemist is to discover a drug that gets widespread use to treat human disease with an unmet therapeutic need,” said Wentland, who performs both basic and applied research. With ALKS 33 now in clinical development, the team is one very important step closer to realizing that goal. “Medicinal chemistry, foremost among traditional approaches to drug discovery and development, retains its value in a high-tech world,” noted Wentland, who joined Rensselaer from the pharmaceutical industry in 1994.

“This is a wonderful example of progress under The Rensselaer Plan in the areas of biotechnology and technology transfer that demonstrates Rensselaer’s unique strength in its ability to translate scientific discoveries into practical application,” said Ron Kudla, executive director of the Office of Intellectual Property, Technology Transfer and New Ventures at Rensselaer. “Most importantly, this is a testament to the fact that if the results of your research are going to have an impact on the public, it has to be patented in order to be commercialized.” 

Therapeutic opportunity
In September 2006, Rensselaer signed a licensing agreement granting Massachusetts-based biotechnology company Alkermes exclusive rights to a library of compounds discovered by Wentland and his team. 

According to Alkermes, the library represents an opportunity for the company to develop numerous products as important therapeutics for the treatment of a broad range of diseases and medical conditions, including addiction, pain, and other nervous system disorders. Alkermes screened the library of compounds from Rensselaer and is responsible for the continued research and development of any resulting product candidates.

This year, Alkermes held its Research and Development Day meeting for analysts and investors in Cambridge, Mass., on April 7 and provided an overview of its product candidates, including ALKS 33. Preclinical studies of ALKS 33 suggested that it was not readily metabolized by the liver, a unique advantage over existing oral therapies for addiction. According to the company, initiation of the phase 1 trial of ALKS 33 was based on the compound’s potential for a superior pharmacokinetic profile and the compound’s pharmacological properties relative to other commercial opioid antagonists.   

According to Alkermes, data from the phase 1 study of ALKS 33 showed that the compound is absorbed rapidly into the bloodstream, and has a pharmacokinetic profile that could support once-daily dosing.

“This latest discovery is the result of an interdisciplinary collaboration between chemists and biologists,” Wentland said. “In the process, we are working together to identify novel therapies to treat human diseases and find possible solutions that work. Most importantly, this discovery allows us to see the significant role that biotechnology plays in improving  health, creating new materials for myriads of applications, and addressing some of the world’s most challenging scientific problems. I am pleased to see this exciting technology move from the laboratory toward treating patients.”  

“There are few medications available to help patients struggling to overcome addictions, and new treatment options are desperately needed,” said Elliot Ehrich, M.D., chief medical officer of Alkermes. “We believe that the addiction field will evolve in a similar way to other CNS markets, such as mental illnesses, where treatments include both oral and injectable medications. This flexible approach offers patients and doctors the option to build the most appropriate therapies into treatment programs and fit the needs of individual patients.”

Linking discoveries of the lab and classroom to the marketplace
Historically, American research universities, responsible for so many groundbreaking discoveries and life-saving innovations, did not provide their professors a direct route to move their work to store shelves, medical offices, and industry. Promising discoveries were introduced in the scholarly press, in hopes of drawing bigger grant awards and perhaps the interest of a company willing to spend the money to convert concept into product. Researchers sometimes took their work off campus, establishing their own companies on the side. 

But the Bayh-Dole Act passed in 1980 opened up new avenues by allowing universities to keep discoveries disclosed using federal grants instead of returning them to the government, often to languish. The law brought new incentives to commercialize discoveries, along with bragging rights and, in a few cases, big money. University discoveries — in the United States, Canada, and abroad — have had an impact on everything from health care (the pacemaker from the University of Minnesota, the CAT scan from Georgetown, laser cataract surgery from the University of California-Los Angeles) to better living at home (plexiglass from McGill University, a Kentucky bluegrass hybrid from Rutgers, and even television’s V-Chip from Simon Fraser University), among others. 

Founded in the 1990s, Rensselaer’s Office of Technology Commercialization (OTC), affiliated with the Incubator Program and the Rensselaer Technology Park, helps the Institute protect intellectual property and forges relationships with industry to bring Rensselaer’s discoveries to the marketplace. The OTC also contributes to the local economy by spinning off new companies that are based upon technology developed by university faculty, students, and researchers. Discoveries in nanotechnology, electronics, energy, biotechnology, and terahertz are all part of the Institute’s expanding intellectual property portfolio and reflect Rensselaer’s aggressive, expanding research initiative. 

The initial research leading to Wentland’s latest discovery was funded in 1999 through a $826,000 grant from the National Institutes of Health/National Institute on Drug Abuse (NIH-NIDA) in an effort to discover novel drugs to treat cocaine abuse. In 2002, Wentland’s NIH grant was renewed for an additional $1.6 million, and he was awarded new funding from Albany Molecular Research Inc. for a postdoctoral associate position. In 2007, the NIH grant was renewed again for $1.25 million. 

“My life’s ambition has been to identify a compound that’s actually helping people. That has been my entire focus for the last 39 years,” Wentland said. He had a choice: Go the traditional route of publishing findings in a scientific journal and then seek additional research grants, or try for development and clinical trials through a licensing agreement with a pharmaceutical company. Given that therapeutics are largely developed by such companies, Wentland said the decision wasn’t difficult. He began discussions with the OTC. 

After six years of work, which included the investment in and securing a number of patent applications in the U.S. and overseas, in January 2007, Rensselaer announced a license agreement granting Alkermes rights to the patented and patent pending technologies. Soon after, the Institute began to receive payments for the licensing.

OTC success
With the establishment of the OTC, Rensselaer has staked its claim in the changing landscape of American research universities, where researchers are increasingly encouraged to protect their discoveries and hopefully effectively license them to industry for life-enhancing products. This year, through OTC’s efforts, licensing revenues and patent reimbursements paid to the Institute are expected to be approximately $1,067,000, building upon a steady annual growth since 2002 when Rensselaer only generated $62,000. 

Since 2000, more than 250 inventors have filed patent disclosures with the OTC. In addition, more than 110 patents have been issued and Rensselaer has over 45 active licenses and averages 12 to 15 new deals a year, according to Kudla. 

And thanks to the OTC, Wentland is a step closer to his dream that serves as a promising next step for a medical advance he has been chasing for his entire drug discovery career. The license agreement also culminates years of research work by his team that includes more than 20 undergraduate, graduate and postdoctoral students in Rensselaer’s Department of Chemistry and Chemical Biology, along with Jean Bidlack, professor of pharmacology and physiology at the University of Rochester, and members of her pharmacology group, and funding by the National Institutes of Health.

“I didn’t do it myself,” Wentland said. “With the OTC, it went very smoothly. In the last 39 years I have had many drugs enter the clinic and then fail. And now I’m here again with another chance and I’m absolutely proud of our entire team. The only way academic research collaboration can get a therapeutic into the clinic and approved for human use is to partner with a pharmaceutical company.” 

In the future, Wentland and this team will continue to work with Alkermes to develop the existing family of compounds, as well as identify back-up and/or second-generation drugs for possible application to other diseases.