0001047469-04-013879 Sample Contracts

Shares METABASIS THERAPEUTICS, INC. Common Stock UNDERWRITING AGREEMENT
Underwriting Agreement • April 28th, 2004 • Metabasis Therapeutics Inc • Pharmaceutical preparations • New York

SG COWEN & CO., LLC DEUTSCHE BANK SECURITIES INC. THOMAS WEISEL PARTNERS LLC LEGG MASON WOOD WALKER, INCORPORATED As Representatives of the several Underwriters c/o SG Cowen & Co., LLC 1221 Avenue of the Americas New York, New York 10020

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EXCLUSIVE LICENSE AND RESEARCH COLLABORATION AGREEMENT
Exclusive License and Research Collaboration Agreement • April 28th, 2004 • Metabasis Therapeutics Inc • Pharmaceutical preparations

This Agreement (this "Agreement") is dated as of December 23, 2003 (the "Effective Date"), and is entered into by and between MERCK & CO., INC., a corporation organized and existing under the laws of New Jersey ("Merck"), and METABASIS THERAPEUTICS, INC., a corporation organized and existing under the laws of Delaware ("Metabasis").

AMENDED AND RESTATED COLLABORATIVE RESEARCH AND DEVELOPMENT AND LICENSE AGREEMENT
Collaborative Research and Development and License Agreement • April 28th, 2004 • Metabasis Therapeutics Inc • Pharmaceutical preparations • California

THIS AMENDED AND RESTATED COLLABORATIVE RESEARCH AND DEVELOPMENT AND LICENSE AGREEMENT (this "Agreement"), dated as of June 30, 1999, is between METABASIS THERAPEUTICS, INC., a Delaware corporation having its principal place of business at 9390 Towne Centre Drive, San Diego, California 92121 ("MTI"), and SANKYO CO., LTD., a Japanese corporation having its principal place of business at 5-1 Nihonbashi-Honcho, 3-chome, Chuo-ku, Tokyo 103, Japan ("Sankyo").

EXCLUSIVE OPTION AGREEMENT
Exclusive Option Agreement • April 28th, 2004 • Metabasis Therapeutics Inc • Pharmaceutical preparations • California

THIS EXCLUSIVE OPTION AGREEMENT (the "Agreement") is made as of October 21, 2002 (the "Option Effective Date") by and between METABASIS THERAPEUTICS, INC., a Delaware corporation ("Metabasis"), and SANKYO CO., LTD., a Japanese corporation ("Sankyo").

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