Ionis and Akcea to Collaborate with Novartis to Develop and AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx

Ionis Pharmaceuticals and Akcea Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals, Inc., have closed on their exclusive, worldwide option and collaboration agreement with Novartis to develop and commercialize AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRxfollowing clearance under the Hart-Scott-Rodino Antitrust Improvements Act.  Following this approval and closing of the transaction, Novartis will pay Ionis and Akcea a $75 million up-front payment and make a $100 million equity investment in Ionis, which equates to 1,631,435 shares at $61.30 per share.  Novartis has an obligation to make a further equity investment of $50 million in the next 18 months in either Ionis at the same premium as the initial investment or in Akcea.  Ionis and Akcea are also eligible to receive a license fee as well as development, regulatory and commercial milestone payments for each drug as it advances.  In addition, Ionis and Akcea are eligible to receive tiered royalties in the mid-teens to low twenty percent range on net sales of each drug.

ABOUT Lp(a)
Lp(a) is considered a key driver for cardiovascular disease due to its association with an increased risk of coronary heart disease.  Lp(a) is a lipoprotein particle that is assembled in the liver and consists of the apolipoprotein(a) protein covalently linked to LDL-cholesterol.  Diet and lifestyle changes have little impact on Lp(a) levels and current therapies are not able to adequately reduce elevated levels of Lp(a) to acceptable levels in patients who have severely elevated Lp(a).  Additional information is available through Lipoprotein (a) Foundation at www.lipoproteinafoundation.org.

In a Phase 1/2a study in healthy volunteers with elevated Lipoprotein(a), AKCEA-APO(a)-LRx produced significant and sustained reductions in Lp(a) of up to 97% with mean reduction of 79% after only a single, small volume dose and with multiple doses, observed reductions of Lp(a) of up to 99% with a mean reduction of 92%.

ABOUT APOCIII AND TRIGLYCERIDES
ApoC-III is a protein produced in the liver that plays a central role in the regulation of serum triglycerides.  Humans who do not produce ApoC-III have lower levels of triglycerides and lower instances of cardiovascular disease.  Humans with elevated levels of ApoC-III have high triglycerides associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome.  In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.

AKCEA-APOCIII-LRx is currently being evaluated in a Phase 1/2a study in healthy volunteers with elevated triglycerides.