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Isis' Partners Present Clinical Data on Antisense Drugs at the American Society of Clinical Oncology

Monday, June 2, 2008 General News
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CHICAGO and CARLSBAD, Calif., June 2 IsisPharmaceuticals, Inc. (Nasdaq: ISIS) announced today that two of the Company'spartnered oncology drugs were highlighted during the American Society ofClinical Oncology (ASCO) meeting. Data from both drugs highlighted positiveactivity that supports the continuation of clinical development, and bothdrugs were well tolerated up to very high doses. Results from Eli Lilly'sPhase 1 clinical trial evaluating LY2181308 in patients with cancer andupdated data from OncoGenex's Phase 2 trial evaluating OGX-011 in patientswith hormone refractory prostate cancer (HRPC) were presented yesterday, June1, at the annual ASCO meeting in Chicago. Both Lilly and OncoGenex aredeveloping additional anticancer drugs discovered by Isis.
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In both presentations, antisense drugs being developed by Isis' partnersOncoGenex and Lilly continue to demonstrate the potential of antisensetechnology to treat multiple cancers. OncoGenex presented Phase 2 data onOGX-011 demonstrating better than expected survival results in combinationwith chemotherapy, reduction in levels of clusterin (the target of OGX-011),durable reductions in pain, and a decline in PSA, a protein that is oftenelevated in patients with prostate cancer. Encouraging data from this trialsupport initiation of registration trials required for product approval.OGX-011 was jointly discovered and is being co-developed by Isis andOncoGenex. Lilly presented first-in-human data from LY2181308 that showed thedrug distributed to tumor cells with evidence of reduced survivin proteinlevels in tumor cells, LY2181308's target and one of the most commonlyelevated proteins in cancer. Lilly has selected a dose of 750 mg/week ofLY2181308 for Phase 2 studies where LY2181308 will be evaluated in combinationwith other oncology agents.
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"The progress our partners are making with our antisense drugs demonstratethe potential of antisense technology to provide new, first-in-class treatmentoptions to treat a variety of cancers. Antisense drugs are highly selectivefor their targets which minimizes the off target interactions that areresponsible for so many toxicities observed with traditional drugs in oncologystudies," said Brett Monia, Ph.D., Vice President of Drug Discovery Researchat Isis Pharmaceuticals. "The encouraging safety profiles observed in bothLilly's and OncoGenex's studies support further clinical evaluation of bothdrugs."

OGX-011 and LY2181308 are part of Isis' cancer portfolio of first-in-classdrugs, which act upon biological targets associated with cancer progressionand/or treatment resistance. The distribution of antisense drugs to tumorcells and the high degree of specificity of these drugs to their target makethem attractive new treatment options for a broad range of cancers.

ABOUT ISIS PHARMACEUTICALS, INC.

Isis is exploiting its expertise in RNA to discover and develop noveldrugs for its product pipeline and for its partners. The Company hassuccessfully commercialized the world's first antisense drug and has 18 drugsin development. Isis' drug development programs are focused on treatingcardiovascular and metabolic diseases. Isis' partners are developingantisense drugs invented by Isis to treat a wide variety of diseases. IbisBiosciences, Inc., Isis' majority-owned subsidiary, is developing andcommercializing the Ibis T5000(TM) Biosensor System, a revolutionary system toidentify infectious organisms. Isis is a joint owner of Regulus TherapeuticsLLC, a joint venture focused on the discovery, development andcommercialization of microRNA therapeutics. As an innovator in RNA-based drugdiscovery and development, Isis is the owner or exclusive licensee of over1,500 issued patents worldwide. Additional information about Isis isavailable at http://www.isispharm.com.

This press release includes forward-looking statements regarding Isis'business,
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