Exhibit 10.8

November 4, 2005

Howard Foyt, M.D., Ph.D.

1205 Sierra Linda Drive

Escondido, CA 92025

Dear Howard:

The purpose of this letter is to provide you with an addendum to the terms set
forth in your offer letter dated September 15, 2005. In addition to the offer of
employment with the same benefits and policy guidelines set forth in your
original offer letter, the following terms will be added. Subject to the
approval of the Board of Directors, you will be granted options to purchase an
additional 8,196 shares of Metabasis Therapeutics, Inc. common stock which will
have an exercise price of the fair market value of the Company’s common stock on
the date of the grant. The option will be granted pursuant to the terms of a
separate stock option agreement and the terms of the Metabasis Therapeutics,
Inc. employee stock plan. This will bring your total stock options to 62,806.

In addition to your base salary, as an Officer of the Company, you will be
eligible to earn an annual discretionary performance bonus (the “Bonus”). Your
target Bonus will be up to 25% of your annual base salary, guaranteed for the
first year of employment. Thereafter, your target Bonus will be up to 25% of
your annual base salary, assuming 100% attainment of individual and company
goals. You must be employed on the date the Bonus is awarded to earn any portion
of the Bonus. The determinations of the Company’s Board of Directors with
respect to your Bonus will be final and binding. The Bonus program is subject to
change or suspension at the discretion of the Company’s Board of Directors.

You will be expected to execute and deliver a Severance Agreement with Metabasis
consistent with the employment agreements that have been executed with the other
officers. The agreement will include accelerated vesting, severance pay and
benefits upon termination without cause or a significant change in
role/responsibilities following a merger or acquisition that results in a change
in control. In addition, if you are terminated without cause in the absence of a
change in control, you will receive a severance package that will include
severance pay and accelerated vesting equal to one year of your then current
option grant, if any. This agreement is attached to this letter and is
incorporated by reference herein.

To formally record your acknowledgement of this addendum, please sign below and
return one original of this letter to me as soon as possible.

Sincerely,

 

/s/ MARK ERION       Mark Erion, Ph.D.       Executive Vice President, Research
and Development       /s/ HOWARD FOYT     November 7, 2005 Howard Foyt, M.D.,
Ph.D.