VICAL INCORPORATED 10390 Pacific Center Court

Exhibit 10.49

VICAL INCORPORATED

10390 Pacific Center Court

San Diego, CA 92121-4340

May 19, 2006

Dr. David Kaslow

Vical Incorporated

10390 Pacific Center Court

San Diego, CA 92121-4340

Dear David:

This Amendment (the “Amendment”) to your Letter Agreement with Vical Incorporated (the “Company”) dated September 13, 2001, as amended by the Letter Agreement dated October 4, 2001 and the Letter Agreement dated April 15, 2005 (collectively, the “Agreement”) amends the terms and conditions of the Agreement to the extent provided herein. Except as specifically amended by this Amendment, the terms and conditions of the Agreement shall remain in full force and effect.

Paragraph 8(c) of the Agreement is hereby deleted in its entirety and replaced with the following:

“(c) Salary Continuation”. Subject to subsection (d) below, the Company will continue to pay your Base Compensation (at the annual rate then in effect) for up to twelve months following the termination of your employment if, prior to the expiration of your rights to salary continuation as provided below:

The payments under this subsection (c) will cease in the event of your death. In order to receive your salary continuation, you will be required to sign a release in a form acceptable to the Company, of any and all claims that you may have against the Company. The salary continuation rights described in this paragraph 8(c) shall expire on October 8, 2006; provided, however, that such rights shall automatically renew for successive 1 year periods unless the Company provides written notice to you at least 90 days prior to the next scheduled expiration date that such rights will not be renewed.”

This Amendment may be executed in two or more counterparts, each of which shall be deemed an original and all of which together shall constitute one and the same instrument. This Amendment shall be governed by and construed in accordance with the laws of the State of California, without regard to conflicts of law principles.

Please sign this Amendment and return it to the Company at your earliest convenience.