Date: 2016-12-16
Type of information: Exercise of an option agreement
Compound: antisense therapeutics against five cancer targets, including IONIS-STAT3Rx and IONIS-KRAS-2.5Rx
Company: Ionis Pharmaceuticals (USA - CA) AstraZeneca (UK)
Therapeutic area: Cancer - Oncology - Cardiovascular diseases - Metabolic diseases
Type agreement: R&D
development
licensing
commercialisation
Action mechanism: 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.
Disease: advanced lymphomas, undisclosed cancers, cardiovascular diseases, metabolic diseases
Details: * On December 11, 2012, Ionis Pharmaceuticals and AstraZeneca have 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 commercialise ISIS-STAT3Rx, a drug Isis is currently evaluating in an early clinical trial in patients with advanced lymphomas.The strategic alliance aims to apply AstraZeneca's experience in developing personalised 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.
Financial terms: 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 program is continuing. In exchange, Isis has granted AstraZeneca an exclusive license to develop and commercialise ISIS-STAT3Rx and a pre-clinical 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 pre-clinical 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.
Latest news: * On December 16, 2016, Ionis Pharmaceuticals announced that it has earned $28 million from AstraZeneca (NYSE:AZN) following AstraZeneca's completion of IND-supporting studies and license of IONIS-KRAS-2.5Rx, or AZD4785. IONIS-KRAS-2.5Rx is a Generation 2.5 antisense drug discovered by Ionis designed to directly target KRAS, one of the most frequently mutated genes in cancer. IONIS-KRAS-2.5Rx will be the first drug to enter clinical development that directly targets KRAS, regardless of mutation type. AstraZeneca will be responsible for further developing and commercializing IONIS-KRAS-2.5Rx. As IONIS-KRAS-2.5Rx advances in development, Ionis is eligible to receive up to $137 million for additional development and regulatory milestone payments. In addition, Ionis is eligible to receive up to low double-digit royalties from sales of the drug. * On November 13, 2014, Isis Pharmaceuticals and AstraZeneca announced a strategic alliance to discover and develop novel delivery methods for antisense oligonucleotides. The new delivery approaches seek to target the desired tissue more effectively. The agreement builds on an existing collaboration between AstraZeneca and Isis Pharmaceuticals and supports AstraZeneca's research and development capabilities in the area of antisense oligonucleotide-based therapeutics and RNA biology. Initial project areas will be oncology and cardiovascular and metabolic diseases. Under the terms of the agreement, each party will fund its own contribution and commit investigators to the collaboration. In line with AstraZeneca's open innovation approach, the companies will work together on an agreed programme and share rights to the results. Isis can apply learnings from this collaboration broadly across its antisense technology platform and AstraZeneca can similarly apply learnings across its broader RNA-based, small molecule and antibody research and development activities. * On November 5, 2014, Isis Pharmaceuticals announced that it has earned a $7.5 million milestone payment, the first of two milestone payments totaling $15 million, from AstraZeneca for the advancement of ISIS-STAT3Rx, also referred to as AZD9150, in patients with advanced cancers. Isis will earn the second $7.5 million milestone payment from AstraZeneca upon initiation of a Phase 2 study. Isis has completed a clinical study of ISIS-STAT3Rx in patients with advanced cancers and plans to present results from this study at an upcoming medical meeting. AstraZeneca is currently evaluating ISIS-STAT3Rx in a Phase 1/2 clinical study in patients with advanced metastatic liver cancer. AstraZeneca plans to initiate additional clinical studies to further evaluate ISIS-STAT3Rx. Under the amended terms of agreement, Isis has earned a $7.5 million milestone payment today. Upon initiation of the Phase 2 study, Isis will earn a second $7.5 million milestone payment and an additional $10 million milestone payment. In total, Isis is eligible to receive up to $70 million in milestone payments as ISIS-STAT3Rx advances through clinical development. In addition, Isis is eligible to earn up to $170 million in regulatory milestone payments plus royalties on the commercial sales of the drug. * On June 10, 2014, Isis Pharmaceuticals announced that AstraZeneca has initiated a Phase 1 clinical study of ISIS-ARRx in patients with prostate cancer. Isis earned a $15 million milestone payment associated with the clinical advancement of ISIS-ARRx. 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. 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. * On June 6, 2013, Isis Pharmaceuticals has announced that it has earned a $6 million payment from AstraZeneca related to continuation of the research collaboration between Isis and AstraZeneca to discover and develop novel antisense therapeutics to treat cancer. In addition to the research collaboration, which includes three cancer targets, Isis and AstraZeneca are developing two antisense drugs, ISIS-ARRx and ISIS-STAT3Rx, discovered by Isis and licensed to AstraZeneca for the treatment of cancer. * On June 3, 2013, Isis Pharmaceuticals has announced that AstraZeneca has added a second development candidate, ISIS-ARRx, to its collaboration with Isis. Isis earned a $10 million milestone payment associated with this decision. ISIS-ARRx, also referred to as AZD5312 and previously referred to as ISIS-AZ1Rx, is an antisense drug designed to treat patients with prostate cancer by inhibiting the production of the androgen receptor. 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. In 2012, Isis entered into a collaboration with AstraZeneca 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 selection of ISIS-ARRx, Isis has earned $35 million in upfront and milestone payments from AstraZeneca and is eligible to earn additional milestone payments as the drug progresses in development as well as royalties on sales if ISIS-ARRx is successfully commercialized. * On May 6, 2013, Isis Pharmaceuticals has announced the initiation of a Phase 1b/2a clinical study of ISIS-STAT3Rx in patients with advanced metastatic hepatocellular carcinoma (HCC).
