DRRX Durect Corporation 2006 Annual Report Clinical Advancements Six programs in product development Manufacturing Scale-up Preparing for late-stage trials and launch Collaborations/Partnerships Providing financial, developmental and commer- cialization resources Clinical Advancements Accomplishments in 2006 Manufacturing Scale-Up Accomplishments in 2006 Remoxy™ completes Special Protocol Assess- ment with the FDA and commences pivotal Phase III study U.S. IND accepted for POSIDUR™, which enters extensive Phase II pro- gram covering soft tissue and orthopedic surgeries 2nd abuse resistant Opioid pain medicine to be commercialized by King Pharmaceuticals – announced positive Phase I studies TRANSDUR™–Bupivacaine completes Phase I studies and starts Phase II Technology transfer to Endo’s contract manufacturer (3M) for TRANSDUR™–Sufentanil Agreement with Hospira to manufacture POSIDUR™ Agreement with Corium to manufacture TRANSDUR–Bupivacaine Collaborations /Partnerships Accomplishments in 2006 Entered agreement with Nycomed to develop and commercialize POSIDUR™ in Europe and other select countries Nycomed, based in Europe, is now the 25th largest pharmaceutical company in the world Progress with existing programs with Endo Pharmaceuticals and King Pharmaceuticals/ Pain Therapeutics – Key Terms: – $202 million in fees and milestones – Blended royalties on net sales of 15-40% – Equally responsible for US/Europe R&D expenses – Retained all commercial rights to the US, Canada, and Asia 2007 Goals Objectives listed by product candidate REMOXY POSIDUR TRANSDUR-Sufentanil TRANSDUR-Bupivacaine – Complete pivotal – Present additional – Initiate additional Phase – Present Phase II Phase II data II clinical studies clinical data Phase III clinical trial for Remoxy – Initiate Phase III – Potential commercializa- tion deal for outside US – Potential commercializa- tion partner – File NDA approximately clinical trials 3 quarters later – Potential commercializa- tion deal for Japan/Asia We are focused on moving our lead products forward in the clinic and supporting our partners in the regulatory process and in manufacturing. Currently we have six product candidates derived from our pharmaceutical systems in development, a number of which should report results from clinical trials during the year. In addition, our business development team continues to pursue additional development and commercialization collaborations in order to fully exploit the potential of our products on a worldwide basis. PG 4 Clinical Pipeline and Delivery Technologies Clinical Phase I Clinical Phase II 2ND ORADUR–Opioid POSIDUR™ Indication: Pain Drug: Undisclosed Partner: King Pharmaceuticals and Pain Therapeutics Technology: ORADUR Indication: Post-Operative Pain Drug: Bupivacaine Partner: Nycomed (Europe, CIS, and selected other countries) Technology: SABER TRANSDUR™–Bupivacaine Indication: Post-Herpetic Neuralgia Drug: Bupivacaine Partner: None Technology: TRANSDUR TRANSDUR™–Sufentanil Indication: Chronic Pain Drug: Sufentanil Clinical Phase III RemOxy™ Indication: Chronic Pain Drug: Oxycodone Partner: Endo Pharmaceuticals (US and Canada) Partner: King Pharmaceuticals and Pain Therapeutics Technology: TRANSDUR Technology: ORADUR memryte™ Indication: Alzheimer’s Disease Drug: Leuprolide Acetate Partner: Voyager Pharmaceuticals Technology: DURIN ORADUR™ Oral Gel-Cap SABeR™ Delivery System TRANSDUR™ Transdermal Patch An oral, sustained release technology with several potential abuse deterrent properties. A patented and versatile depot injectable useful for proteins, peptides and small molecule delivery. Medicated adhesive patch that is placed on the skin to deliver a time released dose topically or systemically. TRANSDUR™ Transdermal Patch TRANSDUR patches are formulated to allow small sizes to deliver therapeutic doses for up to 7 days. ORADUR™ Oral Gel-Cap ORADUR gel-caps provide controlled-release for up to 12 hours DURIN™ Biodegradable Implant Drug-loaded implant system that can deliver active agents from a few weeks to several months, and where the release profile can be tailored for continuous or delayed release. PG 5 PG 6 Letter to Shareholders DURECT made significant progress in 2006 on a number of fronts: • Corporate Partnering, with the establishment of our landmark collaboration with Nycomed covering POSIDUR™, which provides half the funding for product develop- ment worldwide, upfront and milestone payments of $202 million and royalties of 15-40%, with Durect retaining marketing rights in the US, Canada and Asia; • Clinical Development, with two new programs successfully completing Phase I and our most advanced product (Remoxy™) commencing a pivotal Phase III trial under a Special Protocol Assessment with the FDA; • Manufacturing Scale-up in preparation for late stage clinical trials and launch, with the establishment of scale-up/supply agreements with Hospira, 3M and Corium; • Management, with the strengthening of our clinical/regulatory capabilities through the addition of Dr. Peter Langecker as our Chief Medical Officer as well as several other key hires in that group, and our financial team with the addition of Matt Hogan as our Chief Financial Officer; and • Financial, where we burned less than $10 million for the second year in a row while reducing our convertible debt by $20 million and ended the year with $81.6 million in cash and investments. We enter 2007 with our advanced drug delivery technologies having generated a rich pipeline of five programs in Phase II or III clinical trials and a sixth program through Phase I. Each of our product candidates address large market opportunities and strive to confer significant patient benefits over existing products on the market. While we have a number of programs licensed on attractive terms to commercialization partners such as Nycomed, Endo Pharmaceuticals and King Pharmaceuticals, we have also retained US (and Asian) rights to POSIDUR, worldwide rights to the Bupivacaine patch and certain US co-promotion rights to the Sufentanil patch. These rights provide us the pathway to becoming a specialty pharmaceutical company by marketing selected products in the US, thereby capturing more of the value we create through our technology and scientists. Our objectives for 2007 are clear and revolve principally around clinical development for our lead programs. At least four programs should complete significant clinical trials during the year and report results. These programs include Remoxy (completing a pivotal Phase III trial), Memryte (completing a truncated Phase III trial), as well as POSIDUR and the Bupivacaine patch (reporting on Phase II studies). In addition, Endo Pharmaceuticals has stated that they intend to commence Phase II trials in the first half of 2007 for our Sufentanil patch with supplies from 3M, with whom Endo has contracted to perform commercial scale-up development. Finally, we will remain active on the business development front where we will continue to pursue collaborations to fully exploit our technologies and to commercialize our products on a worldwide basis. On behalf of everyone at DURECT, we thank you for your continued support and look forward to reporting on our continued progress in 2007. Pictured from left James E. Brown, D.V.M., President and Chief Executive Officer Felix Theeuwes, D.Sc., Chairman and Chief Scientific Officer PG 7 PG 8 Corporate Directory Corporate Profile DURECT Corporation is an emerging specialty pharmaceutical company developing pharmaceutical systems based on its proprietary drug delivery platform technologies. The Company currently has a number of late-stage pharmaceutical products in development addressing large markets in pain management, with a number of research programs underway targeting chronic disease and other therapeutic areas. For more information, please visit www.durect.com. Forward Looking Statement The statements in this annual report regarding DURECT’s and its collaborative partners’ products in development, anticipated product benefits, anticipated product markets, and clinical trial results and plans, and DURECT’s future business plans and projected financial results are forward-looking statements involving risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to, DURECT’s (and that of its third-party collaborators’, where applicable) abilities to successfully enroll and complete clinical trials, complete the design, development, and manufacturing process development of the product candidates, obtain product and manufacturing approvals from regulatory agencies and manufacture and commercialize the product candidates and marketplace acceptance of the product candidates, as well as DURECT’s ability to fund its growth and operations. Further information regarding these and other risks is included in DURECT’s most recent Quarterly Report on Form 10-Q filed with the SEC under the heading “Risk Factors.” Corporate Officers Board of Directors Annual Meeting SEC Form 10-K A copy of the Company’s annual report to the United States Securities and Exchange Commission on Form 10-K is available without charge upon written request to: DURECT Corporation Attn: Investor Relations 2 Results Way Cupertino, CA 95014 Trademarks POSIDUR™, SABER™, ORADUR™, DURIN™, TRANSDUR™, CHRONOGESIC®, MICRODUR™, ALZET® and LACTEL® are trademarks of DURECT Corporation. Other referenced trademarks belong to their respective owners. The company’s annual meeting of stockholders will be held at 10:00 A.M. local time June 26, 2007 at Company Headquarters Independent Auditors Ernst & Young LLP 1001 Page Mill Road Palo Alto, CA 94304 Phone 650.496.1600 Fax 650.496.4660 Corporate Counsel Heller, Ehrman, White & McAuliffe, LLP 275 Middlefield Road Menlo Park, CA 94025 Phone 650.324.7000 Transfer Agent Computershare 250 Royall Street Canton, MA 02021 Tel: 781.575.3400 Felix Theeuwes, D.Sc. Chairman and Chief Scientific Officer James E. Brown, D.V.M. President and Chief Executive Officer Matthew Hogan Chief Financial Officer Peter J. Langecker, MD, PhD. Chief Medical Officer Paula Mendenhall, Pharm D. Executive Vice President of Operations and Administration Su IL Yum, Ph.D. Executive Vice President, Pharmaceutical Systems R&D Jean I Liu Senior Vice President, General Counsel and Corporate Secretary Nacer E. Dean Abrouk, Ph.D. Vice President Biostatistics Harry Guy Vice President, Engineering and Safety Jian Li Vice President, Finance and Corporate Controller Thomas P. McCracken Vice President and Chief Patent Counsel Andrew R. Miksztal, Ph.D Vice President, Pharmaceutical Research and Development Felix Theeuwes, D.Sc. Chairman and Chief Scientific Officer James E. Brown, D.V.M. President and Chief Executive Officer Dr. Terrence F. Blaschke Director Simon X. Benito Director Michael D. Casey Director David R. Hoffmann Director Armand P. Neukermans, Ph.D. Director Jon S. Saxe Director Corporate Secretary Jean I Liu Senior Vice President and General Counsel For more information, please contact: Matthew Hogan Chief Financial Officer Tel: 408.777.4936 Fax: 408.777.3577 Mailing Address: 2 Results Way Cupertino, CA 95014 PG 9 ) m o c . s o i d u t s l x . w w w ( o i d u t s n g i s e d a , e g r a l a r t x e : n g i s e D d n a t p e c n o C DURECT CORPORATION 2 Results Way Cupertino, CA 95014 Tel: 408.777.1417 Fax: 408.777.3577 www.durect.com NASDAQ: DRRX