Isis Pharmaceuticals Earns $15 Million from AstraZeneca for Initiation of Phase 1 Study of ISIS-AR Rx

Successful collaboration with AstraZeneca includes two novel cancer drugs in clinical development
PR Newswire Isis Pharmaceuticals, Inc.

CARLSBAD, Calif., June 10, 2014 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (ISIS) announced today that AstraZeneca has initiated a Phase 1 clinical study of ISIS-ARRx in patients with cancer.  Isis earned a $15 million milestone payment associated with the clinical advancement of ISIS-ARRx.  ISIS-ARRx is an antisense drug designed to treat patients with prostate cancer by inhibiting the production of the androgen receptor (AR).  AstraZeneca is planning to develop ISIS-ARRx broadly to treat patients under a variety of settings during the course of prostate cancer treatment, including both as a single agent and in combination therapy.

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.Isis Pharmaceuticals, Inc.
"This important milestone takes us another step further to understanding how we can develop ISIS-ARRx to better treat prostate cancer – both as a single agent or in combination with other agents in the AstraZeneca portfolio.  We look forward to building our close collaboration with Isis Pharmaceuticals to complete this study and to evaluate the broader therapeutic potential of the Isis antisense technology," said Susan Galbraith, Vice President, Head of Oncology Innovative Medicines, AstraZeneca.

"AR is a well-validated target in prostate cancer, and as such, has been a target of interest for many years.  Our antisense approach may allow us to avoid the limitations, including the emergence of resistance, characteristic of other AR-targeted therapeutic approaches.  Furthermore, ISIS-ARRx is designed to reduce the production of all known AR variants and, as such, could be effective in patients with prostate cancer regardless of the type of AR they produce," said Brett Monia, Ph.D., senior vice president, antisense drug discovery at Isis.

"AstraZeneca's extensive experience in successfully developing and commercializing drugs to treat hormone-related cancers, like prostate cancer, is a significant advantage for program success.  Together with AstraZeneca, we have expanded our efforts in developing drugs to treat patients with prostate cancer.  We look forward to working closely with AstraZeneca to complete this study and to evaluate the broader therapeutic potential of ISIS-ARRx," said B. Lynne Parshall, chief operating officer at Isis.

The open-label, dose-escalation Phase 1 study will evaluate the safety and efficacy of ISIS-ARRx in patients with advanced solid tumors, such as metastatic castrate resistant prostate, breast, bladder and ovarian cancers, where the androgen receptor pathway is potentially a contributing factor.  The endpoints for the study include measurements of anti-tumor activity and AR and AR-variant levels in tumor biopsies.  The study will also evaluate safety.

ISIS-ARRx, also referred to as AZD5312, is an antisense drug designed to inhibit the production of AR for the treatment of patients with prostate cancer.  Prostate cancer is the second leading cause of cancer deaths in men in the United States.  Prostate cancer growth, proliferation and progression are all androgen-dependent, and AR function is involved in disease progression at all stages of prostate cancer.  For patients diagnosed with metastatic prostate cancer, current treatments largely involve opposing the action of androgens by blocking the androgen receptor or removing circulating androgens.  Although androgen deprivation therapy approaches are initially effective in delaying disease progression in patients with metastatic prostate cancer, over time the course of the disease will progress in many of these patients.  Resistance to current therapies is frequent and can occur through a variety of mechanisms including the activation of AR signaling in tumor cells through the amplification, over expression and mutation of the AR gene.

ISIS-ARRx is designed to reduce the production of all known forms of AR, including variants of the AR gene, and therefore has the potential to be an effective treatment for all stages of prostate cancer, including prostate cancer patients who are resistant to current therapies.  ISIS-ARRx is the second drug to enter clinical development in Isis' pipeline that incorporates Isis' generation 2.5 chemistry.  Isis developed its generation 2.5 chemistry to increase the potency of antisense drugs thereby creating opportunities for drugs like ISIS-STAT3Rx and ISIS-ARRx to be effective in more difficult to treat cancers.

Isis and AstraZeneca are collaborating to discover and develop antisense drugs to treat cancer.  The collaboration combines AstraZeneca's experience and expertise in developing anti-cancer agents with Isis' antisense technology platform to broaden Isis' cancer franchise.  With the initiation of the Phase 1 study for ISIS-ARRx, Isis has earned $57 million in upfront and milestone payments from its relationship with AstraZeneca and is eligible to earn additional milestone payments as the drug progresses in development as well as royalties on sales of ISIS-ARRx if it is commercialized.

Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners.  Isis' broad pipeline consists of 32 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer.  Isis' partner, Genzyme, is commercializing Isis' lead product, KYNAMRO®, in the United States and other countries for the treatment of patients with homozygous FH.  Isis' patents provide strong and extensive protection for its drugs and technology.  Additional information about Isis is available at

This press release includes forward-looking statements regarding Isis' strategic alliance with AstraZeneca and the discovery, development, activity, therapeutic and commercial potential and safety of ISIS-ARRx.  Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement.  Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.  Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements.  Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis.  As a result, you are cautioned not to rely on these forward-looking statements.  These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2013, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to Isis Pharmaceuticals and its subsidiaries.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.  KYNAMRO® is a registered trademark of Genzyme Corporation.