Exhibit 10.21  AMENDMENT
NO. 6  Dated February 22, 2008  TO that certain Loan and Security
Agreement No. 452 dated as of March 28, 2005,
as amended (Agreement), by and between LIGHTHOUSE
CAPITAL PARTNERS V, L.P. (Lender)
and ARYX
THERAPEUTICS, INC. (Borrower).  (All capitalized terms not otherwise defined herein shall have the
meanings given to such terms in the Agreement.)  Without limiting or amending any other provisions of the Agreement,
Lender and Borrower agree to the following:  I.Section 4.5 of the Agreement shall be deleted in its
entirety and replaced with the following:  4.5Certain Equipment Collateral.  Except as provided in clause (c) below,
the Collateral shall not include the Financed Equipment (the Third Party Financed Equipment) securing the Indebtedness
incurred by Borrower in favor of any Third Party Lender (Third Party
Lender) in connection with any Finance Agreement between a Third
Party Lender and Borrower (Third Party Indebtedness)
in an amount not to exceed $3,000,000; provided, that (a) the Third
Party Indebtedness shall be included in, and shall not exceed, the maximum
amount for equipment financing set forth in clause (v) of the definition
of Permitted Liens, (b) such exception to the Collateral is only to the
extent that Third Party Lender has a security interest in such Financed
Equipment, and (c) such Financed Equipment shall automatically become a
part of the Collateral concurrent with the release by Third Party Lender of its
security interest in the Third Party Financed Equipment.  To the extent that Lender shall have had a
security interest in Third Party Financed Equipment, Lenders security interest
in such Financed Equipment shall be automatically released, but only under the
terms and to the extent set forth in clause (v) of the definition of Permitted
Liens and this Section 4.5.  II.Section 7.10
of the Agreement shall be deleted in its entirety and replaced with the
following:  7.10Deposit and Securities Accounts.  Maintain any deposit accounts or accounts
holding securities owned by Borrower except accounts in which Lender has
obtained a perfected first priority security interest.  Notwithstanding the foregoing, Lenders
security interest shall be subordinate to that of Comerica (i) in that
certain deposit account #385107379682 held with Comerica Bank as security for a
line of credit related to corporate purchasing credit cards; provided, such
account shall not exceed $150,000 and (ii) in Borrowers account #18927-65692
at Comerica supporting letter of credit #596267-43 issued to Biomed Realty
Trust, Inc. in conjunction with Borrowers real property lease; provided, such
letter of credit shall not exceed $703,200 and letter of credit #633778-41
issued to ADP TotalSource, Inc. in conjunction with Borrowers payroll;
provided, such letter of credit shall not exceed $500,000 and such account
subordination shall not exceed $1,203,200.  Except as amended hereby, the Agreement remains unmodified and
unchanged.  BORROWER:
  LENDER:ARYX THERAPEUTICS, INC.
  LIGHTHOUSE CAPITAL PARTNERS V, L.P.By:
  /s/ John Varian
  
  By:
  LIGHTHOUSE MANAGEMENTPARTNERS V, L.L.C.,
  its general partnerName:
  JOHN VARIANBy:
  /s/
  Thomas ConneelyTitle:
  COOName:
  Thomas ConneelyTitle:
  Vice
  President