Targacept’s (NASDAQ:TRGT) top business executive, who succeeded in landing potentially lucrative deals with big pharmas GlaxoSmithKline (NYSE:GSK) and AstraZeneca (NYSE:AZN) only to see those partnerships fail to yield any successful drugs, is leaving the company.

Jeffrey Brennan, senior vice president, business and commercial development and chief business officer, will leave at the end of March “to pursue other opportunities,” the company said in a statement released after the markets closed. No other details on Brennan’s departure or plans were disclosed.

In 2005, Brennan helped Targacept secure a drug development partnership with AstraZeneca on an Alzheimer’s disease candidate. That deal paid Targacept $10 million up front and granted AstraZeneca exclusive development and worldwide rights. The companies expanded their relationship in 2009 with a deal that paid Targacept $200 million up front and promised an additional $540 million if the company’s drug programs hit milestones. The centerpiece of the deal was a Targacept compound being developed as a depression treatment. Targacept stood to collect up to $500 million in sales-related milestones.

But last year, the depression candidate failed in phase III clinical trials. AstraZeneca had previously declined to license other partnered with Targacept, including a compounds being studied in indications such as schizophrenia. Earlier this month, the partners restructured the terms of the partnership. AstraZeneca may still license some of the drugs that Targacept is developing but Targacept is also taking back some drug candidates, removing the big pharma’s contractual obligations for those compounds. Targacept’s drug pipeline currently includes several compounds in mid-stage clinical trials, including the Alzheimer’s disease candidate that initially piqued AstraZeneca’s interest in 2005. That compound is one of those whose rights now return to Targacept.

Brennan also helped Targacept land a 2007 partnership with GSK to develop new drugs for pain, smoking cessation, addiction, obesity and Parkinson’s disease. Targacept received a$35 million up-front payment from GSK and the company was eligible to receive up to $1.5 billion in additional milestones.

But in 2010, London-based GSK, which has its U.S. headquarters in Research Triangle Park, announced changes in its neurosciences operations as it withdrew from some neuroscience areas and focused its R&D efforts in other areas. Those changes led to the decision to end the Targacept partnership.

Brennan has worked at Targacept since 2003, when he joined to become the company’s vice president, business and commercial development. He had previously served as vice president, business development at Sanofi-Synthelabo.

In other changes, Targacept announced departures from to its board of directors. M. James Barrett and G. Steven Burrill have resigned their seats, effective May 31. They joined in 2002 and 2000 respectively at the time of venture capital investments made in the company by funds that they were affiliated with. Also, Dr. Ralph Snyderman has decided not to stand for reelection and he will retire from Targacept’s board, also effective May 31. Snyderman joined the board in 2007 and he has reached the retirement age set in Targacept’s corporate governance guidelines.

Targacept said that the board changes did not arise from any disagreements with the company. The departures will leave Targacept’s board with seven members, comprised of president and CEO Stephen Hill and six independent directors.