Novartis announces clinical collaboration with Bristol-Myers Squibb to evaluate potential treatments in metastatic colorectal cancer

• Phase I/II study to evaluate Mekinist^® (trametinib) in combination with Opdivo^® (nivolumab) and Opdivo + Yervoy^® (ipilimumab)
   
• Collaboration expands upon existing clinical investigation of Opdivo combination with Novartis investigational and marketed therapies

Basel, June 5, 2017 - Novartis today announced it has entered into a clinical research collaboration in which Bristol-Myers Squibb will investigate the safety, tolerability, and efficacy of Mekinist (trametinib) in combination with Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen as a potential treatment option for metastatic colorectal cancer in patients with microsatellite stable tumors where the tumors are proficient in mismatch repair (MSS mCRC pMMR).

Under the terms of the agreement, the study will be conducted by Bristol Myers-Squibb and is expected to establish recommended dose regimens and the preliminary anti-tumor activity of the combination therapies. Both Bristol Myers-Squibb and Novartis will evaluate the results to determine optimal approaches and potential clinical development of these combinations.

"Novartis has a longstanding heritage in exploring the combination of medicines to broaden our knowledge of mutational driven cancers and develop innovative treatments," said Vas Narasimhan, MD, Head, Global Drug Development and Chief Medical Officer, Novartis. "Along with our ongoing internal immuno-oncology efforts, the expansion of our collaboration with Bristol-Myers Squibb further advances our collective goals to advance the science and to support patients in need."

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Of these, nearly 750,000 were diagnosed in men, and 614,000 in women[1]. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer[1]. In the U.S. alone, an estimated 135,430 patients will be diagnosed with cancer of the colon or rectum in 2017, and approximately 50,000 are estimated to die of their disease[2]. There is wide variation in 5-year survival rates across disease stages, with 5-year survival rates for patients with metastatic or stage IV colorectal cancer around 11%[3]. The incidence of microsatellite stability (MSS) in colorectal tumors varies by stage, with 80% to 85% of exhibiting MSS[4].  

About Mekinist and Important Safety Information
MEKINIST is a kinase inhibitor indicated, as a single agent or in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. MEKINIST is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy. MEKINIST can cause serious side effects including new primary malignancies (cutaneous and non-cutaneous), hemorrhage, inflammation of the colon and perforation of the intestines, blood clots in the legs, cardiomyopathy, eye toxicity, interstitial lung disease, serious fevers, serious skin toxicity, hyperglycemia, and harm to a fetus. Some of these side effects can be fatal in rare cases. The most common side effects when MEKINIST is used as a single-agent are rash, diarrhea, and lymphedema.   

About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, Bristol-Myers Squibb's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

About Yervoy
Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of Yervoy effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. This includes Phase 3 trials in prostate and lung cancers.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "potential," "to evaluate," "will," "investigation," "investigational," "expected," "ongoing," "efforts," "goals," "may," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Mekinist, potential new indications or labeling for other products in the Novartis Oncology portfolio, or regarding potential future revenues from Mekinist and such other products, and potential future revenues arising from the clinical research collaboration with Bristol-Myers Squibb. 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 Mekinist or other products of Novartis and Bristol-Myers Squibb subject to the clinical research collaboration will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that the clinical research collaboration with Bristol-Myers Squibb will achieve any or all of its intended goals and objectives, or be successful. Nor can there be any guarantee that any other product in the Novartis Oncology portfolio will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that Mekinist, any of the other products subject to the clinical research collaboration with Bristol-Myers Squibb, or any other product in the Novartis Oncology portfolio will be commercially successful in the future. In particular, management's expectations regarding such products, and the clinical research collaboration with Bristol-Myers Squibb, could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; 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 and reimbursement pressures; safety, quality or 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.

Opdivo^® and Yervoy^® are registered trademarks of Bristol Myers-Squibb.

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, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

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References
[1] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65: 87-108.
[2] Colorectal Cancer Facts & Figures. American Cancer Society. Available at: https://www.cancer.org/research/cancer-facts-statistics/colorectal-cancer-facts-figures.html. Accessed June 4, 2017.
[3] Colorectal Cancer: Early Detection, Diagnosis, and Staging. American Cancer Society. Available at: https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.html. Updated March 2, 2017. Accessed June 4, 2017.
[4] Chapelle A, Hampel H. Clinical Relevance of Microsatellite Instability in Colorectal Cancer. Journal of Clinical Oncology. 2010; 28 (20): 3380-3387. Available at: http://dx.doi.org/10.1200/JCO.2009.27.0652.

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