Drayton, the former managing director of Advertising.com and the Telegraph Media Group, is leaving the company by mutual agreement at the end of 2008 although he will remain an advisor.
His exit coincides with that of UK chief financial officer Lynne Millar, who has resigned.
Drayton's departure swiftly follows that of the company's chairman, Stephen Heyer, chief operating officer, Virasb Vahidi, and two non-executive directors, David Dorman and Christopher Lawrence, three weeks ago. They left over differences of opinion with chief executive Kent Ertugul.
In the interim Phorm has appointed Nan Richards as deputy chief executive based in London reporting to Ertugrul in New York.
Richards was previously president of Time Warner's Turner Broadcasting System Europe. She will be supported by Nick Barnett, who has been promoted from commercial director to the newly created role of UK managing director.
Andrew Croxson has been is appointed global CFO on an interim basis joining from Ingenious Consulting and replaces Millar.
Phorm has been under fire from bloggers and privacy groups who have attacked its Open Internet Exchange (OIX), which via ISPs profiles uses browsing habits and servers them targeted ads.
Instead of recording user IP addresses OIX assigns every user an identification number. Many advertisers have been wary of using behavioural ad targeting services amid concerns over users' privacy and incorrect ad placement.
Earlier this year the Guardian pulled out of using Phorm, which gives ISPs a cut of revenues in return for supplying browsing data.
Privacy campaigners took exception to BT trialling the system last year without asking its users for their consent and one campaigner is attempting to bring a private prosecution.
Last September the company received a boost from the Government, who said that its technology is legal and more good news arrived this week when Phorm completed a successful trial with BT.
Speaking about his departure Drayton said: "My time with Phorm has been exciting and rewarding.
"In 2009 we expect that Phorm's Open Internet Exchange (OIX) will be commercially deployed and I am very proud that the team we have established is now fully prepared to deliver on the Company's enormous potential."
Ertugrul said: "I thank both Hugo and Lynne for their significant contributions and wish them well in their future endeavours.
"They have helped lay the foundations for a successful commercial launch in the UK and beyond. I am delighted that Hugo will build on his previous achievements with Phorm as an advisor.
"We have made significant progress in the development of partnerships and the testing of our technology.
"I am also pleased that we have completed the trial with BT and look forward to moving to the next stage of development.
"I am confident that we have the right talent at both the bard and executive level to deliver on the huge potential of our technology and the business opportunity that lies ahead.
"I believe that we are now uniquely placed to lead the introduction of privacy-assured behavioural advertising across the whole of the internet."