Novartis invests in next generation therapies to r

• Novartis enters into an exclusive option agreement with Ionis and Akcea to license two investigational treatments expected to significantly reduce cardiovascular risk in patients living with elevated levels of lipoprotein Lp(a) or ApoCIII, which is a potent regulator of triglycerides
• Investment in biomarker-based therapies bolsters Novartis' cardiovascular specialty pipeline and commitment to address unmet medical need of high-risk atherosclerosis/dyslipidemia patients
• Atherosclerosis, commonly called the "silent killer", is a major cause of death globally and no options exist today to effectively treat patients whose disease is driven by Lp(a) and ApoCIII

Basel, January 06, 2017 - Novartis announced today a collaboration and option agreement with Ionis Pharmaceuticals, Inc. and its affiliate Akcea Therapeutics, Inc., to license two novel treatments with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of lipoproteins known as Lp(a) and ApoCIII. The two investigational antisense therapies developed by Ionis-called AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx -have the potential to lower both lipoproteins up to 90% and significantly reduce cardiovascular risk in high-risk patient populations. In addition Novartis entered into a stock purchase agreement with Ionis.

"Novartis is building a robust cardiovascular portfolio of targeted therapies to address unmet medical need of high-risk patients," said Vasant Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. "Lp(a) and ApoCIII are potent, genetically validated cardiovascular risk reduction targets. The importance of predictive biomarkers in achieving successful cardiovascular outcomes will also be essential in the future payer environment. We look forward to working with Ionis and Akcea to develop both treatments."

Novartis will be able to exercise its options to license and commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx following the achievement of specified development milestones and prior to the initiation of Phase 3 studies for each program. Upon in-licensing Novartis will be responsible for worldwide development and commercialization of both assets.

Ionis' antisense technology is currently the most effective way to inhibit synthesis of both lipoproteins in the liver, according to data published in the Lancet[1]. The GalNAc3-conjugated antisense oligonucleotide technology is 30 times more potent than the parent antisense oligonucleotide, leading to a lower dose and the potential for highly effective therapeutic targeting and much improved tolerability.

The deal is subject to customary closing conditions and regulatory approvals.

About Atherosclerosis Atherosclerosis is a disease in which plaque builds up inside the arteries leading to gradual narrowing and hardening of the arteries and increased risk of blood clots, heart attack and stroke. Atherosclerosis that affects the arteries of the heart is commonly known as coronary heart disease.

About Dyslipidemia Dyslipidemia is the elevation of plasma cholesterol, triglycerides, or both, or a low high-density lipoprotein level that contributes to the development of atherosclerosis.

About Lipoprotein(a) ( Lp(a)) Lp(a) is a lipoprotein that travels through the blood. Elevated levels of Lp(a) collect in the arteries, gradually narrowing the arteries and limiting blood supply to the heart, brain, kidneys and legs. This leads to increased risk of coronary heart disease, atherosclerosis, thrombosis and stroke. Additional information is available through Lipoprotein (a) Foundation at www.lipoproteinafoundation.org

About Apolipoprotein-CIII (ApoCIII) ApoCIII is a protein produced in the liver that plays a central role in the regulation of triglycerides, a type of fat found in the blood. People with elevated levels of ApoCIII have high triglycerides which are associated with multiple metabolic abnormalities such as insulin resistance and/or metabolic syndrome. People who do not produce ApoCIII have lower levels of triglycerides and lower instances of cardiovascular disease.

Disclaimer The foregoing release contains forward-looking statements that can be identified by words such as "invests," "next generation," "option," "investigational," "expected," "pipeline," "commitment," "potential," "building," "portfolio," "will," "look forward," "options," or similar terms, or by express or implied discussions regarding potential marketing approvals for AKCEA-APO(a)-L _Rx, AKCEA-APOCIII-L _Rx and the other products in the Novartis cardiovascular portfolio, or regarding potential future revenues from AKCEA-APO(a)-L _Rx , AKCEA-APOCIII-L _Rx and the other products in the Novartis cardiovascular portfolio, or regarding the possible exercise of the options to license and commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx , or regarding the intended goals and objectives of the transaction with Ionis and Akcea and the license to commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx . You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the necessary government approvals for the transaction or option exercises will be obtained in any particular time frame, or at all. Neither can there be any guarantee that any other closing conditions for the transaction or option exercises will be met in any particular time frame, or at all. Nor can there be any guarantee that the options to license and commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx will be exercised within the expected time frame, or at all. Neither can there be any guarantee that the transaction with Ionis and Akcea and license to commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx will achieve any of their intended goals and objectives, or in any particular time frame. Nor can there be any guarantee that AKCEA-APO(a)-L _Rx , AKCEA-APOCIII-L _Rx or the other products in the Novartis cardiovascular portfolio will be submitted or approved for sale in any market, or at any particular time. Neither can there be any guarantee that AKCEA-APO(a)-L _Rx , AKCEA-APOCIII-L _Rx or the other products in the Novartis cardiovascular portfolio will be commercially successful in the future. In particular, management's expectations regarding AKCEA-APO(a)-L _Rx , AKCEA-APOCIII-L _Rx and the other products in the Novartis cardiovascular portfolio, the transaction with Ionis and Akcea, and the options to license and commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx could be affected by, among other things, the potential that the intended goals and objectives of the transaction with Ionis and Akcea and the license to commercialize AKCEA-APO(a)-L _Rx and AKCEA-APOCIII-L _Rx may not be achieved or may take longer to achieve than expected; the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally, including an unexpected failure to obtain necessary government approvals for the transaction or option exercises, or unexpected delays in obtaining such approvals; the potential that any other closing conditions for the transaction or option exercises may not be met; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com .

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References [1] Lancet 2016; 388: 2239-53 Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials

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