Exhibit 10.104

AMENDMENT TO AMENDED AND RESTATED 2001 INCENTIVE PLAN OF

BIODELIVERY SCIENCES INTERNATIONAL, INC.

WHEREAS, BioDelivery Sciences International, Inc. (the “Company”) maintains the
The BioDelivery Sciences International, Inc. Amended and Restated 2001 Incentive
Plan (the “Plan”);

WHEREAS, the Plan provides for the grant of Options and other equity awards,
including restricted stock unit awards and performance share unit awards;

WHEREAS, the Board of Directors of the Company (the “Board”) has heretofore
delegated its authority to administer the Plan to the Compensation Committee of
the Board (the “Committee”);

WHEREAS, pursuant to resolutions of the Committee, dated July 23, 2008, the
Committee granted authority to the Chairman of the Committee (the “Chairman”) to
investigate and implement an amendment to the Plan to provide for the treatment
of these awards granted under the Plan after July 20, 2001 in the event of a
Change in Control of the Company;

WHEREAS, the Chairman, in consultation with counsel, has reviewed and approved
the amendment to the Plan set forth herein pursuant to the authority granted the
Chairman by the Committee; and

WHEREAS, capitalized terms used but not defined herein shall have the meanings
set forth in the Plan;

NOW, THEREFORE, pursuant to resolutions of the Committee, dated July 23, 2008,
and pursuant to the authority granted to the Chairman thereunder, the Plan shall
be, and it hereby is, amended as follows:

1. Effect of Change in Control. Section 7.1 of the Plan is hereby deleted and
replaced in its entirety with the following amended Section 7.1:

“7.1 EFFECT OF CHANGE IN CONTROL ON OPTIONS.

(a) Upon the occurrence of a Change in Control, each Option which is outstanding
immediately prior to the Change in Control shall immediately become fully Vested
and exercisable.

(b) Upon the occurrence of a Change in Control, the surviving, continuing,
successor, or purchasing corporation or other business entity or parent thereof,
as the case may be (the “ACQUIRING CORPORATION”), may, without the consent of
any Participant, either assume the Company’s rights and obligations under
outstanding Options (as the same may be vested pursuant to Section 7.1(a)
hereof) or substitute for such outstanding Options substantially equivalent
options or rights for, or in relation to, the Acquiring Corporation’s stock, in
each case without amending or modifying any material term of the applicable
Options.”

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3. Protection Period Following Change in Control. The following new Section 7.3
is hereby added to the Plan:

“7.3 PROTECTION PERIOD. Except to the extent required by applicable law, for the
entirety of the period beginning on the date of the Change in Control and ending
on the second anniversary of the date of the Change in Control (the “PROTECTION
PERIOD”), the material terms of the Plan shall not be modified in any manner
that is materially adverse to the Participants (it being understood that this
Section 7.3 shall not require that any specific type or levels of equity awards
be granted to Participants following the Change in Control). During the
Protection Period, the Plan may not be amended or modified to reduce or
eliminate the protections set forth in this Section 7.3 and may not be
terminated.”

4. Application. This Amendment shall apply to Option and other equity awards
granted after July 20, 2001.

 

   

/s/ William S. Poole

Date: November 19, 2008     William S. Poole     Chairman, Compensation
Committee