**Exhibit 4.2.4**

**Private & Confidential**

Dr Jerry Karabelas

129 Hodge Road

Princeton

New Jersey 08540-3013

USA

Dated as of 2nd February 2006

Dear Jerry

I am writing to set out the terms of your appointmentas Non-Executive Chairman of SkyePharma PLC. It is agreed that this is acontract for services and is not a contract of employment.

**Appointment**

Your appointment as Non-Executive Chairman will be fora term of three years commencing on 2nd February 2006,unless otherwise terminated earlier by and at the discretion of either partyupon one month’s written notice. Continuation of your contract of appointmentis contingent on satisfactory performance and re-election at forthcoming AGMs.

**Timecommitment**

We anticipate a significant time commitment which willnormally include attendance at monthly board meetings, the AGM and at least onesite visit per year. In addition, you will be expected to devote appropriatepreparation time ahead of each meeting.

By accepting this appointment, you have confirmed thatyou are able to allocate sufficient time to meet the expectations of your role.

**Role**

The Board of the Company as a whole is collectivelyresponsible for the success of the company. The Board:

·                  provides entrepreneurialleadership of the Company within a framework of prudent and effective controlswhich enable risk to be assessed and managed;

·                  sets the Company’sstrategic aims, ensures that the necessary financial and human resources are inplace for the Company to meet its objectives, and reviews management performance;and

·                  sets the Company’svalues and standards and ensure that its obligations to its shareholders andothers are understood and met.

All directors must take decisions objectively in theinterests of the Company. In addition it is the responsibility of the Chairmanto:

·                  run the Boardand set its agenda. The agenda should take full account of the issues and theconcerns of all Board members. Agendas should be forward looking andconcentrate on strategic matters rather than formulaic approvals of proposalswhich can be subject to appropriate delegated powers to management;

·                  ensure that themembers of the Board receive accurate, timely and clear information, inparticular about the Company’s performance, to enable the Board to take sounddecisions, monitor effectively and provide advice to promote the success of theCompany;

·                  ensure effectivecommunication with shareholders and ensure that the members of the Boarddevelop an understanding of the views of the major investors;

·                  manage the Boardto ensure that sufficient time if allowed for discussion of complex orcontentious issues, where appropriate arranging for informal meetingsbeforehand to enable thorough preparation for the Board discussion. It isparticularly important that Non-Executive Directors have sufficient time toconsider critical issues and are not faced with unrealistic deadlines fordecision-making;

·                  take the lead inproviding a properly constructed induction for new directors that iscomprehensive, formal and tailored, facilitated by the Company Secretary;

·                  take the lead inidentifying and meeting the development needs of individual directors, with theCompany Secretary having a key role in facilitating the process. It is theresponsibility of the Chairman to address the development needs of the Board asa whole with a view to enhancing its overall effectiveness as a team;

·                  ensure that theperformance of the individuals and of the Board as a whole and its committeesis evaluated at least once a year; and

·                  encourage activeengagement by all the members of the Board.

**Fees**

You will be paid a fee of £70,000 gross per annumwhich will be paid monthly in arrears and which will be subject to an annualreview by the board.

The Company will reimburse you for all reasonable andproperly documented expenses you incur in performing the duties of your office.

**Outsideinterests**

It is accepted and acknowledged that you have businessinterests other than those of the Company and have declared any conflicts thatare apparent at present. In the event that you become aware of any potentialconflicts of interest, these should be disclosed to the Board and CompanySecretary as soon as apparent.

**Confidentiality**

All information acquired during your tenure is confidentialto the Company and should not be released, either during your appointment orfollowing termination (by whatever means), to third parties without priorclearance from the Board.

Your attention is also drawn to the requirements underboth legislation and regulation as to the disclosure of price sensitiveinformation. Consequently you should avoid making any statements that mightrisk a breach of these requirements without prior clearance from the Board orCompany Secretary.

**Insurance**

The Company has directors’ and officers’ liabilityinsurance and it is intended to maintain such cover for the full term of yourappointment. The current indemnity limit is £15 million.

**Independentprofessional advice**

Occasions may arise when you consider that you needprofessional advice in the furtherance of your duties as a director.Circumstances may occur when it will be appropriate for you to seek advice fromindependent advisors at the Company’s expense. The Company will reimburse thefull cost of expenditure incurred in accordance with the schedule of MattersReserved for the Main Board.

Please indicate your acceptance of these terms bysigning and returning the enclosed copy of the letter.
| Yours sincerely |   | Approved by |
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