<PAGE>

                                                                    EXHIBIT 10.5
                                 AMENDMENT TO
                             EMPLOYMENT AGREEMENT

     THIS AMENDMENT TO EMPLOYMENT AGREEMENT ("Agreement") is effective as of
this 30/th/ day of April, 2001 (the "Effective Date"), by and between RIBOZYME
PHARMACEUTICALS, INC., a Delaware corporation (the "Company"), and J. Wayne
Cowens  ("Executive").

     WHEREAS, Executive is currently an at-will employee of the Company;

     WHEREAS, the Board of Directors of the Company (the "Board") has determined
that it is in the best interests of the Company and its stockholders to assure
that the Company will have the continued dedication of Executive,
notwithstanding the possibility, threat or occurrence of a Change of Control (as
defined herein);

     WHEREAS, in order to accomplish the objective described in the preceding
recital, the Board desires to cause the Company to enter into this Agreement as
set forth herein.

     NOW, THEREFORE, in consideration of the premises, the mutual covenants and
agreements contained in this Agreement, and other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the
Company and Executive hereby agree as follows:

     1.1  Term. The term of this Agreement ("Term") shall commence on the
          ----
Effective Date and shall continue until the earlier of: (a) ninety days after
Executive's termination of employment with the Company if no Change of Control
shall have then been commenced, publicly announced or occurred; or (b) the
second anniversary of a Change of Control.

     1.2  Accelerated Vesting of Options. If:
          ------------------------------

          (a)  a Change of Control shall have occurred and the Executive's
          employment with the Company is terminated by the Executive for Good
          Reason; or

          (b) during the period from ninety days prior to the commencement or
          public announcement of a Change of Control until two years after a
          Change of Control the Executive's employment with the Company is
          terminated by the Company other than for Cause;

then all unvested options granted to the Executive by the Company or any
successor entity prior to, simultaneously with or in connection with the Change
of Control  shall vest immediately prior to such termination of Employment.

     1.3  Good Reason.
          -----------

     (a)  As used in this Agreement, the term "Good Reason" means:
<PAGE>

          (i)   a material diminution in the nature of Executive's authorities,
          duties, responsibilities or status (including offices, titles,
          reporting requirements and supervisory functions), from those in
          effect immediately prior to the Change of Control.  Notwithstanding
          the foregoing, Executive shall not assert as "Good Reason" the sole
          fact that a portion of Executive's duties and responsibilities
          directly attributable to a change in the ownership of the Company,
          resulting from the Change of Control has been eliminated (the
          "Eliminated Duties and Responsibilities"), unless the performance of
          all or any portion of the Eliminated Duties and Responsibilities
          continue to be required; or

          (ii)  the required relocation of Executive's place of employment to a
          location in excess of thirty-five (35) miles from the Executive's
          place of employment at the time Executive terminates employment,
          except for required travel on Company business to an extent
          substantially equivalent to Executive's business travel obligations
          immediately prior to the Change of Control; or

          (iii)  any reduction by the Company of Executive's base salary, or a
          material reduction in Executive's bonus opportunities, profit sharing
          opportunities, or other incentive opportunities from those in effect
          immediately prior to the Change of Control.

     (b)  If, at any time during the Term of this Agreement, whether before or
     after the occurrence of a Change of Control, Executive receives a written
     description from the Company of the nature of Executive's authorities,
     duties, responsibilities, status, salary, bonus and other employee
     benefits, or job location thereafter, and Executive accepts in writing such
     new authorities, duties, responsibilities, status, salary, bonus and other
     employee benefits, or job location ("New Office") with the Company without
     determining that the New Office causes a Good Reason as set forth in
     Section 1.2(a), then for the remaining Term, the New Office shall be the
     authorities, duties, responsibilities, status, salary, bonus and other
     employee benefits, or job location to be used by Executive in determining
     whether Good Reason occurs thereafter pursuant to Section 1.2(a).

     1.4  Change of Control.  As used herein, the term "Change of Control" shall
          -----------------
mean the occurrence with respect to the Company of any of the following events:

          (a) An acquisition (other than directly from the Company) of any
     voting securities of the Company (the "Voting Securities") by any "Person"
     (as the term Person is used for purposes of Section 13 (d) or 14(d) of the
     Securities Exchange Act of 1934, as amended (the "Exchange Act"))
     immediately after which such Person has "Beneficial Ownership" (within the
     meaning of Rule 13d-3 promulgated under the Exchange Act) of fifty percent
     (50%) or more of the combined voting power of the then outstanding Voting
     Securities; provided, however, that in determining whether a Change of
     Control has occurred, Voting Securities which are acquired in a "Non-
     Control Acquisition" (as hereinafter defined) shall not constitute an
     acquisition which would cause a Change of Control. A "Non-Control
     Acquisition" shall mean an acquisition by (i) an employee

                                       2
<PAGE>

     benefit plan (or a trust forming a part thereof) maintained by (A) the
     Company or (B) any subsidiary or (ii) the Company or any Subsidiary;

          (b) The individuals who, as of the date hereof, are members of the
     Board (the "Incumbent Board"), cease for any reason to constitute at least
     two-thirds of the Board; provided, however, that if the election or
     nomination for election by the Company's stockholders of any new director
     was approved by a vote of at least two-thirds of the Incumbent Board, such
     new director shall, for purposes of this Agreement, be considered as a
     member of the Incumbent Board; provided, further, however, that no
     individual shall be considered a member of the Incumbent Board if (1) such
     individual initially assumed office as a result of either an actual or
     threatened "Election Contest" (as described in Rule 14a-11 promulgated
     under the Exchange Act) or other actual or threatened solicitation of
     proxies or consents by or on behalf of a Person other than the Board (a
     "Proxy Contest") including by reason of any agreement intended to avoid or
     settle any Election Contest or Proxy Contest or (2) such individual was
     designated by a Person who has entered into an agreement with the Company
     to effect a transaction described in clause (i) or (iii) of this paragraph;
     or

          (c) Approval by stockholders of the Company of:

              (i) A merger, consolidation or reorganization involving the
          Company, unless,

                  (A) The stockholders of the Company immediately before such
              merger, consolidation or reorganization, own, directly or
              indirectly, immediately following such merger, consolidation or
              reorganization, at least seventy-five percent (75%) of the
              combined voting power of the outstanding Voting Securities of the
              corporation (the "Surviving Corporation") in substantially the
              same proportion as their ownership of the Voting Securities
              immediately before such merger, consolidation or reorganization;

                  (B) The individuals who were members of the Incumbent Board
              immediately prior to the execution of the agreement providing for
              such merger, consolidation or reorganization constitute at least
              two-thirds of the members of the board of directors of the
              Surviving Corporation; and

                  (C) no Person (other than the Company, any Subsidiary, any
              employee benefit plan (or any trust forming a part thereof)
              maintained by the Company, the Surviving Corporation or any
              Subsidiary, or any Person who, immediately prior to such merger,
              consolidation or reorganization, had Beneficial Ownership of fifty
              percent (50%) or more of the then outstanding Voting Securities)
              has Beneficial Ownership of fifty percent (50%) or more of the
              combined voting power of the Surviving Corporation's then
              outstanding Voting Securities.

                                       3
<PAGE>

               (ii)  A complete liquidation or dissolution of the Company; or

               (iii)  An agreement for the sale or other disposition of all or
          substantially all of the assets of the Company to any Person (other
          than a transfer to a Subsidiary)

          Notwithstanding the foregoing, a Change of Control shall not be deemed
     to occur solely because any Person (the "Subject Person") acquired
     Beneficial Ownership of more than the permitted amount of the outstanding
     Voting Securities as a result of the acquisition of Voting Securities by
     the Company which, by reducing the number of Voting Securities outstanding,
     increased the proportional number of shares Beneficially Owned by the
     Subject Person, provided that if a Change of Control would occur (but for
     the operation of this sentence) as a result of the acquisition of Voting
     Securities by the Company, and after such share acquisition by the Company,
     the Subject Person becomes the Beneficial Owner of any additional Voting
     Securities Beneficially Owned by the Subject Person, then a Change of
     Control shall occur.

     1.5  Cause. The term "Cause" shall mean (a) willful misconduct by Executive
          -----
or gross neglect by Executive of Executive's duties as an employee, officer or
director of the Company which continues for more than thirty (30) days after
Executive's receipt of written notice to Executive specifically identifying the
willful misconduct or gross neglect of Executive and directing Executive to
discontinue the same, (b) the commission by Executive of a crime constituting a
felony, or (c) the commission by Executive of an act, other than an act taken in
good faith within the course and scope of Executive's employment, which is
directly detrimental to the Company and exposes the Company to material
liability.

     1.6  Governing Law.  This Agreement shall be governed by and construed in
          -------------
accordance with the laws of the state of Colorado.

     1.7  Assignability.  This Agreement is personal to Executive and without
          -------------
the prior written consent of the Company shall not be assignable by Executive
other than by will or the laws of descent and distribution.  This Agreement
shall inure to the benefit of and be enforceable by Executive's legal
representatives and heirs.  This Agreement shall inure to the benefit of and be
binding upon the Company and its successors and assigns.  The Company shall
require any corporation, entity, individual or other person who is the successor
(whether direct or indirect, by purchase, merger, consolidation, reorganization,
or otherwise) to all or substantially all of the business and/or assets of the
Company, to expressly assume and agree to perform, by a written agreement in
form and substance satisfactory to Executive, all of the obligations of the
Company under this Agreement, prior to or contemporaneously with a Change of
Control.  As used in this Agreement, the term "Company" shall mean the Company
as hereinbefore defined and any successor to its business and/or assets as
aforesaid which assumes and agrees to perform this Agreement by operation of
law, written agreement, or otherwise.

     1.8  Waiver.  The waiver of any breach of any term or condition of this
          ------
Agreement shall not be deemed to constitute the waiver of any breach of the same
or any other term or condition of this Agreement.

                                       4
<PAGE>

     1.9  Severability.  In the event any provision of this Agreement is found
          ------------
to be unenforceable or invalid, such provision shall be severable from this
Agreement and shall not affect the enforceability or validity of any other
provision of this Agreement.  If any provision of this Agreement is capable to
two constructions, one of which would render the provision void and the other
that would render the provision valid, then the provision shall have the
construction that renders it valid.



                                       5
<PAGE>

     IN WITNESS WHEREOF, the parties have executed this Agreement as of the
Effective Date.

                              RIBOZYME PHARAMCEUTICALS, INC.



                              By:  /s/  Howard W. Robin
                                 --------------------------------------



                              EXECUTIVE



                              /s/ J. Wayne Cowens
                              -----------------------------------------


                                       6