<PAGE>   1

                                                                  Exhibit 10.81


                                 PROMISSORY NOTE



US $2,640,752.50                                               January 16, 2001


        FOR VALUE RECEIVED, the undersigned hereby unconditionally promises to
pay to the order of EPIMMUNE INC. (the "Company"), with its principal place of
business at 5820 Nancy Ridge Drive, San Diego, California 92121, or at such
other place as the holder hereof may designate in writing, in lawful money of
the United States of America and in immediately available funds, the principal
sum of two million six hundred forty thousand seven hundred fifty-two dollars
and fifty cents (US $2,640,752.50) together with interest accrued from the date
hereof on the unpaid principal at the rate of 5.61% per annum, compounded
annually, or the maximum rate permissible by law (which under the laws of the
State of California shall be deemed to be the laws relating to permissible rates
of interest on commercial loans), whichever is less, as follows:

        PRINCIPAL AND INTEREST REPAYMENT. The outstanding principal amount
hereunder, together with accrued and unpaid interest thereon calculated on the
basis of a 360-day year for the actual number of days elapsed, shall be due and
payable in full on January 16, 2005, four (4) years from the date of this
promissory note (the "Note");

provided, however, that in the event that the undersigned's Continuous Service
(as defined in that certain Restricted Stock Purchase Agreement between the
undersigned and the Company of even date herewith) with the Company is
terminated for any reason prior to payment in full of this Note, then this Note
shall be accelerated and all remaining unpaid principal and interest shall
become due and payable immediately after such termination.

        If the undersigned fails to pay any of the principal and accrued
interest when due, the Company, at its sole option, shall have the right to
accelerate this Note, in which event the entire principal balance and all
accrued interest shall become immediately due and payable, and immediately
collectible by the Company pursuant to applicable law and the terms of this
note.

        This Note may be prepaid without penalty. All money paid toward the
satisfaction of this Note shall be applied first to the payment of interest as
required hereunder and then to the retirement of the principal.

        The full amount of this Note is secured by a pledge of shares of the
Company, and is subject to all of the terms and provisions of the Restricted
Stock Purchase Agreement and the Stock Pledge Agreement, each of even date
herewith between the undersigned and the Company. With respect to each
indivisible share of Company stock purchased with the proceeds of this Note, the
undersigned shall be personally liable for repayment of fifty percent (50%) of
the amounts due under this Note, and shall not be personally liable for
repayment of the remaining fifty percent (50%) of the amounts due under this
Note.



                                        1


<PAGE>   2

        The undersigned hereby represents and agrees that the amounts due under
this Note are not consumer debt, and are not incurred primarily for personal,
family or household purposes, but are for business and commercial purposes only.

        The undersigned hereby waives presentment, protest and notice of
protest, demand for payment, notice of dishonor and all other notices or demands
in connection with the delivery, acceptance, performance, default or endorsement
of this Note.

        The holder hereof shall be entitled to recover, and the undersigned
agrees to pay when incurred, all costs and expenses of collection of this Note,
including without limitation, reasonable attorneys' fees.

        This Note shall be governed by, and construed, enforced and interpreted
in accordance with, the laws of the State of California, excluding conflict of
laws principles that would cause the application of laws of any other
jurisdiction.


                                            Signed  /s/ Emile Loria
                                                    ---------------------------
                                                    EMILE LORIA




                                        2