Isis Pharmaceuticals Announces $31-Million Strategic Cancer Alliance

Isis Pharmaceuticals, Inc. and AstraZeneca recently announced a strategic alliance for the discovery and development of novel-generation antisense therapeutics against five cancer targets, which includes a license to develop and commercialize ISIS-STAT3Rx, a drug Isis is currently evaluating in an early clinical trial in patients with advanced lymphomas. Antisense therapies target the proteins involved in disease processes by destroying the RNA that is involved in creating these proteins. The Isis discovery platform develops specific therapies that bind to messenger RNA (mRNA) and inhibit the production of disease-causing proteins.

The strategic alliance aims to apply AstraZeneca’s experience in developing personalized medicines to enhance the drug discovery and development process for four research programs in the oncology area and to aid in the development of ISIS-STAT3Rx for patient populations that could benefit the most from inhibition of STAT3, a protein that drives cancer growth. The combination of Isis’ antisense technology and its new Generation 2.5 chemistry, which increases the potency of its therapeutics, provides AstraZeneca the opportunity to develop drugs that could be much more effective in cancers that are difficult to address with conventional small molecules or antibodies.

“Isis’ antisense technology platform allows AstraZeneca to broaden our oncology research efforts beyond traditional drug discovery methods, while at the same time becoming more specific about how we target cancer,” said Susan Galbraith, Head of the AstraZeneca Oncology Innovative Medicines Unit. “AstraZeneca’s expertise in oncology translational science and our global capabilities in development and commercialization of oncology products and Isis’ innovative approach to discovering novel medicines reflect a common goal of bringing new medicines to cancer patients.”

“We are excited to collaborate with AstraZeneca, a global leader in oncology, to apply our technology and drug discovery expertise to developing novel anti-cancer agents. We will benefit from AstraZeneca’s extensive oncology expertise in the use of novel preclinical animal models to validate targets and develop predictive assays to identify which patients would benefit the most from these new targets,” added B. Lynne Parshall, Chief Operating Officer and chief financial officer at Isis.

“ISIS-STAT3Rx is our first cancer drug to incorporate our new technology, and we are encouraged by the early clinical data we have observed,” said Brett Monia, PhD, Senior Vice President, Antisense Drug Discovery at Isis. “While STAT3 is implicated in a number of different cancers, the focus in our ongoing clinical study is to evaluate the effectiveness of our drug in hematologic malignancies, such as lymphoma. We have worked closely with AstraZeneca to design a rapid path to the market for ISIS-STAT3Rx in these patient populations. While working toward this goal, AstraZeneca’s resources, expertise and development capabilities also provide us the opportunity to evaluate ISIS-STAT3Rx as a broad-based anti-tumor agent.”

Under the terms of the agreement, Isis will receive from AstraZeneca $31 million in up-front and near-term payments, comprising a $25-million payment on signing followed by a $6 million payment in the second quarter of 2013 assuming the research program is continuing. In exchange, Isis has granted AstraZeneca an exclusive license to develop and commercialize ISIS-STAT3Rx and a preclinical program as well as an option to license products developed under a separate research program. Once licensed, AstraZeneca will be responsible for all further development and commercialization.

AstraZeneca will be responsible for all development of ISIS-STAT3Rx other than the conduct of the ongoing clinical trial, which Isis will complete. Isis is eligible to receive further milestone payments subject to achieving certain predefined clinical success criteria for the ISIS-STAT3Rx program and preclinical milestones for the other programs. Isis is also eligible to receive downstream development and approval milestone payments, license fees for research program targets, as well as royalties on sales from products that are successfully commercialized.

ISIS-STAT3Rx is the first drug in Isis’ pipeline that incorporates Isis’ Generation 2.5 chemistry, which was developed to increase potency of antisense drugs thereby creating opportunities for drugs like ISIS-STAT3Rx to be more effective in addressing targets in a broader range of tissues, including tumors. ISIS-STAT3Rx is designed to inhibit the production of signal transducer and activator of transcription 3 (STAT3), a protein critical for tumor growth and survival.

Because STAT3 is overexpressed in numerous types of cancers, ISIS-STAT3Rx has the potential to be broadly useful for both solid and hematological tumors. Isis recently reported encouraging data from its ongoing Phase I study showing that ISIS-STAT3Rx had an acceptable safety profile and treatment with ISIS-STAT3Rx resulted in clear responses in a number of patients with advanced cancer who were refractory to multiple prior chemotherapy treatments. The indication of activity so early in development in a Phase I study prompted Isis to initiate a follow up clinical study to evaluate the safety and efficacy of ISIS-STAT3Rx in focused patient populations with lymphomas and other advanced hematologic cancers linked to activation of STAT3 who have failed other treatment options.

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development, and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. For more information, visit www.astrazeneca.com.

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 25 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, and cancer. For more information, visit www.isispharm.com.