**EXHIBIT 10.48A**

**SECOND AMENDMENT TO LICENSE AND SALE AGREEMENT**

             **THIS SECONDAMENDMENT TO LICENSE AND SALE AGREEMENT**(the“Amendment”) is made and entered into as of March 16, 2001 (the “AmendmentEffective Date”), by and between **METABOLEX, INC.**, aDelaware corporation (“Metabolex”), and **SHAMAN PHARMACEUTICALS, INC.,**a Delaware corporation (“Shaman”). Metabolex and Shaman may be referred to herein as a “Party,” or,collectively, as “Parties.”

**RECITALS**

             **A.**         Metabolex and Shaman are parties to the License and SaleAgreement dated as of August 10, 1999, as amended effective December 4, 2000(as amended, the “Agreement”), regarding the grant of licenses to Metabolex byShaman in the diabetes area under intellectual property relating to certaincompounds and extracts and the purchase of certain related materials byMetabolex.

             **B.**         The Parties have entered into that certain Asset SaleAgreement, dated as of February 13, 2001, under which Metabolex has agreed topurchase, and Shaman has agreed to sell to Metabolex, certain additional assetsof Shaman relating to its diabetes program, and in conjunction with, and as acondition to the closing of such asset sale, the Parties are obligated to enterinto this Amendment to amend the terms of the Agreement as provided herein.

 

**NOW, THEREFORE,**the Parties agree as follows:

**1.          AMENDMENT OF THE AGREEMENT**

TheParties hereby agree to amend the terms of the Agreement as providedbelow.  To the extent that the Agreementis explicitly amended by this Amendment, the terms of the Amendment willcontrol where the terms of the Agreement are contrary to or conflict with thefollowing provisions.  Where theAgreement is not explicitly amended, the terms of the Agreement will remain inforce.  Capitalized terms used in thisAmendment shall have the meanings as ascribed below or elsewhere in thisAmendment, or if not so defined herein shall have the same meanings as suchterms are defined in the Agreement.

**             1.1        Amendment Of License Rights UnderSections 2.1, 2.2 And 2.3(a).**  Effectiveimmediately and automatically as of the Amendment Effective Date, all ofMetabolex’s license rights under Sections 2.1, 2.2 and 2.3(a) of the Agreementare and shall be perpetual and irrevocable, and to the extent that such licenserights under the Technology as to particular fields or uses were non-exclusive(as of just prior to the Amendment Effective Date), such license rights are andshall be exclusive, even as to Shaman and any of its successors in interest tothe applicable Intellectual Property Rights.

**             1.2        Amendment Of Section 2.2(c).**  Effectiveimmediately and automatically as of the Amendment Effective Date, Metabolex’slicense rights under Section 2.2(c) of the Agreement include the rights, withfull rights to sublicense, to discover, develop, make, have made, use, import,offer for sale, sell and otherwise commercialize Metabolex Extracts for alluses in all fields, except commercialization rights for Dietary Supplements.

 

**             1.3        Amendment Of Rights Under Sections2.3(b) And (c).**  Effective immediately and automaticallyas of the Amendment Effective Date, (a) Metabolex’s license rights underSections 2.3(b) and (c) of the Agreement shall include the entire NutritionalArea (including areas outside the Metabolic Disease Field) except forcommercialization rights for Dietary Supplements, and (b) each Party’s rightsto grant further licenses (or sublicenses, as applicable) under their rightsunder Section 2.3(b) of the Agreement will not be limited to granting licenseson a product by product basis, but instead each Party may assign such licensesor grant sublicenses thereunder for all or part of its correspondingco-exclusive and exclusive license rights (as applicable).

             **1.4        Amendment of Section 11.1(c).**  Effectiveimmediately and automatically as of the Amendment Effective Date, the licensepreviously granted to Metabolex under Section 11.1(c) of the Agreement shallinclude the full rights to commercialize Dietary Supplements in all countries,including without limitation the United States, Mexico, Central America, SouthAmerica and Africa, and all such license rights shall be irrevocable.

**             1.5        Termination of Certain Sections.**  Effectiveimmediately and automatically as of the Amendment Effective Date, Sections3.6(c), 3.7, 4.1, 4.2, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 11.1(d), 11.2and 11.3 of the Agreement are terminated and of no further force or effect.

**             1.6        Amendment Effective Date.**  The Partiesunderstand and agree that this Amendment is and will be effective only upon theissuance of a proper, final, non-appealable order approving the proposed saleof certain of Shaman’s assets to Metabolex pursuant to the Asset Sale Agreementand this Amendment by the Bankruptcy Court, including, without limitation,entry of an order by the Bankruptcy Court approving the Asset Sale Agreementwith a finding that Metabolex is buying property in good faith in accordancewith 11 U.S.C. § 363(m), which order is not stayed within ten (10) days ofentry thereof, in a form satisfactory to Metabolex (“Approval Order”).

**2.          MISCELLANEOUS**

**             2.1        FullForce and Effect.**  This Amendment amends the termsof the Agreement and is deemed incorporated into, and governed by all otherterms of, the Agreement.  The provisionsof the Agreement, as amended by this Amendment, remain in full force and effectpursuant to the Agreement.

**             2.2        Counterparts.**  ThisAmendment may be executed in two or more counterparts, each of which shall bedeemed an original, but all of which together shall constitute one and the sameinstrument.

             **IN WITNESS WHEREOF,**the Parties have executed this Amendment induplicate originals by their authorized officers as of the date and year firstwritten below.

|   |   | **SHAMAN PHARMACEUTICALS, INC.**           |
|--------|--------|--------------------------------------------|
|   |   |                                       |
|   |   | By:  /s/ Steven R. King               |
|   |   |                                       |
|   |   | Name:  Steven R. King                 |
|   |   |                                       |
|   |   | Title:   Chief Operating Officer |
|   |   |                                       |
|   |   | **METABOLEX, INC.**                        |
|   |   |                                       |
|   |   | By:   /s/ Thomas A. Glaze        |
|   |   |                                       |
|   |   | Name:  Thomas A. Glaze                |
|   |   |                                       |
|   |   | Title:   President and CEO       |