SERVIER

Servier and Taiho Oncology, Inc. a subsidiary of Taiho Pharmaceutical Co., Ltd. (Japan), today presented LONSURF^® (trifluridine/tipiracil, TAS-102) clinical data in metastatic gastric cancer (mGC), metastatic gastroesophageal junction adenocarcinoma (mGEJC) and metastatic colorectal cancer (mCRC) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Patients over the age of 65 make up 60% of those with gastric cancer, with the average age of diagnosis being 68 years old.¹ Therefore it is important to demonstrate the effectiveness of LONSURF for the treatment of gastric cancer for this population. To determine the efficacy and tolerability of LONSURF a subgroup analysis from the global Phase III trial TAGS was conducted. This study demonstrated that the safety and efficacy of LONSURF in patients 65 years and older who have a higher incidence of moderate renal impairment versus the placebo was comparable to the overall population included in TAGS. Additionally there were no reported treatment-related deaths among this sub-population, dose modification was more common but this did not lead to an increase in discontinuation compared to the overall population.²

“We are pleased to present further data from the global Phase III trial TAGS, the subgroup analyses reinforces the clinical benefit and safety profile of LONSURF for those aged over 65 years old with mGC and for patients with mGEJC,” said Patrick Therasse, Head of Servier Research and Development Oncology. “Patients with mGC/mGEJC have no standard of care in the EU, and the data supports LONSURF as an effective and tolerable treatment option for those patients with advanced disease.”

The abstracts presented at ASCO were:

• A subgroup analysis from the Phase III TAGS trial in previously treated mGC and mGEJC patients demonstrates safety and efficacy of LONSURF in patients 65 and older who have a higher incidence of moderate renal impairment vs the overall population. (abstract #4037 )
• A subgroup analysis from the Phase III TAGS trial demonstrates a manageable safety profile and consistent efficacy in patients with previously treated mGEJC. (abstract #4038 )
• Health-related quality of life (HRQoL) data from the Phase III TAGS trial in previously treated mGC and mGEJC patients shows that treatment with LONSURF is associated with a trend toward a lower risk of QoL deterioration than placebo consistent across all symptoms and functional scales. (abstract #4043 )
• A pooled safety analysis of patients receiving at least one dose of LONSURF in the two Phase III trials, TAGS and RECOURSE studies demonstrates a consistent safety profile across patients with mGC/mGEJC or mCRC compared with placebo. (abstract #4039 )

LONSURF is indicated in the European Union for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan- based chemotherapies, anti-VEGF agents, and anti-EGFR agents. Applications for an additional indication in mGC including mGEJC for LONSURF are currently under review by health authorities in Australia, the European Union, Japan and Switzerland.

In February 2019, the U.S. Food and Drug Administration (FDA) approved LONSURF for the treatment of adult patients with metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

#ENDS#

About TAGS

TAGS (TA S-102 G astric S tudy) is a Taiho-sponsored, global, randomized, double-blind, placebo controlled, Phase III study evaluating the efficacy and safety of LONSURF in 507 adult patients with previously treated mGC or mGEJC. The primary endpoint was overall survival (OS), and the key secondary endpoints included progression-free survival (PFS), safety and tolerability, as well as quality of life. LONSURF demonstrated statistically significant improvement in OS and PFS compared with placebo. The median OS improved from 3.6 months with placebo to 5.7 months with LONSURF, HR 0.69 (95% confidence interval [CI], 0·56-0·85; P=0.00058).

For more information on TAGS, please visit www.ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02500043 ). The ClinicalTrials.gov Identifier is NCT02500043.

About RECOURSE

The RECOURSE trial is a global, randomized, double-blind, placebo-controlled Phase III trial evaluating the efficacy and safety of LONSURF in patients with previously treated mCRC. The trial enrolled 800 patients in North America, Japan, Europe and Australia. Patients were randomized (2:1) to receive LONSURF (35 mg/m2) or placebo, plus BSC, twice daily. The study met its primary and secondary endpoints of OS and PFS versus placebo. The median OS improved from 5.3 months with placebo to 7.1 months with LONSURF, HR 0.68 (95% CI, 0.58 to 0.81; P<0.001).

About Metastatic Gastric Cancer

Gastric cancer, also known as stomach cancer, is a disease in which malignant cells form in the lining of the stomach. It is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and colorectal cancer), with an estimated 780,000 deaths annually.³

When cancer spreads it is called advanced cancer. Locally advanced cancer is when the cancer has grown outside the organ it started in but hasn’t spread to other parts of the body. When the cancer spreads to other parts of the body, this is called metastatic cancer. In the last two decades, the proportion of patients with gastric cancer who present with metastases has risen to over 40%.⁴

Standard chemotherapy regimens for advanced gastric cancer include fluoropyrimidines, platinum derivatives, and taxanes (with ramucirumab), or irinotecan. The addition of trastuzumab to chemotherapy is standard of care for patients with HER2/neu-positive advanced gastric cancer. However, after failure of first- and second-line therapies, there are neither approved nor standard third-line treatments in the EU.

About Metastatic Colorectal Cancer

Colorectal cancer is the third most common cancer worldwide with approximately 1.8 million new diagnoses in 2018. Each year there are over 880,000 deaths making it the second biggest cancer killer worldwide (after lung cancer).⁵

Those with metastatic disease (where the cancer has spread from the primary site) the average five-year survival is approximately 11%.⁶ Standard chemotherapy regimens for advanced mCRC include fluoropyrimidines, oxaliplatin, irinotecan or targeted treatments, such as those that target vascular endothelial growth factors (VEGF) or endothelial growth factor receptors (EGFR).

Over the last decade, clinical outcomes for patients with mCRC have improved considerably due to the advent of novel treatment agents, predictive biomarkers, and a more strategic approach to the delivery of systemic therapies. Currently, the median overall survival for patients with mCRC being treated both in phase III trials and in large observational series or registries is 30 months – more than double that of 20 years ago.^7,8,9

About LONSURF ¹⁰

LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation.

In the EU, LONSURF is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.

As of May 2019, LONSURF has been approved as a treatment for advanced mCRC in 67 countries and regions. In February 2019, LONSURF has been approved as a treatment for mGC/mGEJC in the United States.

LONSURF was discovered and developed by Taiho Pharmaceutical. In June 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico and Asia.

About Servier

Servier is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes). With a strong international presence in 149 countries and a turnover of 4.2 billion euros in 2018, Servier employs 22,000 people worldwide. Entirely independent, the Group reinvests 25% of its turnover (excluding generics) in research and development and uses all its profits for development. Corporate growth is driven by Servier’s constant search for innovation in five areas of excellence: cardiovascular, immune-inflammatory and neurodegenerative diseases, cancer and diabetes, as well as by its activities in high-quality generic drugs. Servier also offers eHealth solutions beyond drug development.

Becoming a key player in oncology is part of Servier’s long-term strategy. Currently, there are twelve molecular entities in clinical development in this area, targeting gastro-intestinal and lung cancers and other solid tumors, as well as different types of leukemia and lymphomas. This portfolio of innovative cancer treatments is being developed with partners worldwide, and covers different cancer hallmarks and modalities, including cytotoxics, proapoptotics, immune targeted therapies, to deliver life-changing medicines to patients.

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About Taiho Pharmaceutical Co., Ltd. (Japan)

Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd., is an R&D-driven specialty pharma focusing on the three fields of oncology, allergy and immunology, and urology. Its corporate philosophy takes the form of a pledge: “We strive to improve human health and contribute to a society enriched by smiles.” In the field of oncology in particular, Taiho Pharmaceutical is known as a leading company in Japan for developing innovative medicines for the treatment of cancer, a reputation that is rapidly expanding through their extensive global R&D efforts. In areas other than oncology, as well, the company creates and markets quality products that effectively treat medical conditions and can help improve people's quality of life. Always putting customers first, Taiho Pharmaceutical also aims to offer consumer healthcare products that support people's efforts to lead fulfilling and rewarding lives.

For more information about Taiho Pharmaceutical, please visit: https://www.taiho.co.jp/en/ .

¹ American Cancer Society. Key Statistics About Stomach Cancer. Available at: https://www.cancer.org/cancer/stomach-cancer/about/key-statistics.html . Last accessed May 2019

² American Society of Clinical Oncology (ASCO). Abstract 4037. Available at: http://abstracts.asco.org/239/AbstView_239_255071.html . Last accessed May 2019

³ World Health Organisation. Globocan (2018), gastric cancer. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf . Last accessed May 2019

⁴ Bernards N, Creemers GJ, Nieuwenhuijzen GA, et al. No improvement in median survival for patients with metastatic gastric cancer despite increased use of chemotherapy. Ann Oncol. 2013;24:3056–60.

⁵ World Health Organisation. Globocan (2018), colorectal cancer. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/10_8_9-Colorectum-fact-sheet.pdf Last accessed May 2019.

⁶ American Cancer Society. Survival Rates for Colorectal Cancer, by Stage. Available at: https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.html Last accessed May 2019.

⁷ Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet (London, England). 2014;383(9927):1490-1502.

⁸ Price TJ, Segelov E, Burge M, et al. Current opinion on optimal systemic treatment for metastatic colorectal cancer: outcome of the ACTG/AGITG expert meeting ECCO 2013. Expert review of anticancer therapy. 2014;14(12):1477-1493.

⁹ Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Annals of Oncology: official journal of the European Society for Medical Oncology. 2016;27(8):1386-1422.

¹⁰ European Medicines Agency. LONSURF summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/lonsurf-epar-product-information_en.pdf Last accessed May 2019

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