AstraZeneca and Isis Pharmaceuticals, Inc., a leading company in antisense drug discovery and development, have formed a strategic alliance for the discovery and development of novel generation anti-sense therapeutics against five cancer targets, which includes a license to develop and commercialise ISIS-STAT3Rx, a drug Isis is currently evaluating in an early clinical trial in patients with advanced lymphomas. Anti-sense 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 personalised medicines to enhance the drug discovery and development process for four research programmes 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’ anti-sense 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’ anti-sense 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 commercialisation of oncology products and Isis’ innovative approach to discovering novel medicines reflect a common goal of bringing new medicines to cancer patients.”

B Lynne Parshall, Chief Operating Officer and Chief Financial Officer at Isis said: “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 pre-clinical animal models to validate targets and develop predictive assays to identify which patients would benefit the most from these new targets.”

“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, Ph.D., Senior Vice President, anti-sense 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 haematologic 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 upfront 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 programme is continuing. In exchange, Isis has granted AstraZeneca an exclusive license to develop and commercialise ISIS-STAT3Rx and a pre-clinical programme as well as an option to license products developed under a separate research programme. Once licensed, AstraZeneca will be responsible for all further development and commercialisation. 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 programme and pre-clinical milestones for the other programmes. Isis is also eligible to receive downstream development and approval milestone payments, license fees for research programme targets as well as royalties on sales from products that are successfully commercialised.

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