AstraZeneca's Chief Financial Officer Jon Symonds, who lost out in a 2005 race for the CEO
job, is to leave the company at the end of July to join investment bank Goldman Sachs.
The move, announced on Wednesday, marks a new blow for the Anglo-Swedish drugmaker, which has suffered a series of setbacks with experimental medicines and has struggled to regain investor confidence by acquiring biotech companies.
AstraZeneca said an external search was underway to find a successor.
Paul Diggle, an industry analyst with Nomura Code Securities, said the loss of Symonds was damaging.
"I don't think it will be very well taken -- especially as (new CEO) Brennan has not gone down brilliantly in the City. He (Symonds) is still the face of AstraZeneca that people trust," Diggle said.
"On a more practical level, people may also wonder whether the regime of tight cost control that he has managed terribly well is going to be that easy to continue."
Symonds was passed over in favour of U.S. operations head David Brennan for the top job at AstraZeneca in July 2005.
Brennan formally took over as CEO at the start of 2006.
Shares in the London-based group, which have been in decline since it clinched a poorly received deal to buy U.S. biotech firm MedImmune for $15.6 billion in April, fell to their lowest level since February 2006 in early trade.
The stock later recovered to stand 0.2% percent higher.
Symonds joined Zeneca in 1997 and within months was involved in the merger negotiations with Sweden's Astra. He quickly won respect from analysts and adopted a higher profile in running the business than many drug firm finance directors.
"I regret Jon's decision to leave AstraZeneca, however, the move to Goldman Sachs represents an exciting career challenge," AstraZeneca Chairman Louis Schweitzer said in a statement.
Symonds will take up his new position as a managing director at Goldman Sachs in mid-September.
The loss of a pivotal management figure may rekindle takeover speculation around AstraZeneca, according to some analysts.
The company has long been seen as a possible target for larger rivals, who might be interested in acquiring its expertise in fields such as cancer medicine, despite the group's weak pipeline of new drugs.
GlaxoSmithKline and Novartis have both been mentioned in the past as possible buyers, although the chief executives of both have played down their interest in large takeovers in recent months.
AstraZeneca's chunky tender offer for MedImmune, which it successfully completed on Tuesday, might also deter predators.
Nomura Code's Diggle was sceptical whether the departure of Symonds had any implications for a possible mega-merger, since the respected AstraZeneca CFO would have been in a strong
position to claim the top finance job in any enlarged group.