RELEASE: Taiho Oncology and Servier Announce Phase 3 Data Release for Trifluridine/Tipiracil (LONSURF®) (2)

- Taiho Oncology and Servier announce the publication in the New England Journal of Medicine of core Phase 3 data of trifluridine/tipiracil (LONSURF®) in combination with bevacizumab in patients with refractory metastatic colorectal cancer

PRINCETON, N.J. and PARIS, May 4, 2023 /PRNewswire/ -- Taiho Oncology, Inc. and Servier today announced the publication of results from the pivotal Phase 3 SUNLIGHT* clinical trial of trifluridine/tipiracil (LONSURF®), alone or in combination with Bevacizumab in Refractory Metastatic Colorectal Cancer (mCRC) in the May 4 issue of the New England Journal of Medicine (NEJM).

The results of this multinational trial, led by Professor Josep Tabernero, MD, PhD, Head of Medical Oncology at Vall d'Hebron University Hospital, Barcelona, ​​Spain, showed that treatment with the investigational combination of trifluridine/tipiracil and bevacizumab produced Statistically significant and clinically relevant improvements in overall survival and progression-free survival in patients with refractory mCRC after disease progression or intolerance to two prior chemotherapy regimens, compared with trifluridine/tipiracil alone. In addition, the median time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance status score was significantly delayed in patients receiving the investigational combination of trifluridine/tipiracil and bevacizumab. The safety profile of the investigational combination was consistent with that of each agent.

"People with metastatic colorectal cancer who have progressed after treatment with fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and epidermal growth factor receptor (EGFR) antibodies - if they are RAS wild type - have limited treatment options. There is an increasing need for new approaches that improve survival in this population," explained Marwan Fakih, MD, City of Hope Professor of Medical Oncology and Therapeutics Research, and US Principal Investigator of the SUNLIGHT trial. "The publication of the SUNLIGHT results in the New England Journal of Medicine demonstrates the scientific quality and potential impact of this experimental combination in the treatment of metastatic colorectal cancer."

Professor Tabernero added: "Trifluridine/tipiracil plus bevacizumab may represent a significant new treatment option in mCRC patients who have progressed after two lines of therapy."

Based on the results of the SUNLIGHT trial, Servier and Taiho Oncology respectively submitted a type II variant for approval to the European Medicines Agency (EMA) and a supplemental new drug application (sNDA) to the Food and Drug Administration (FDA). of the United States for the combination of trifluridine/tipiracil and bevacizumab in the treatment of adult patients with mCRC previously treated with chemotherapy based on fluoropyrimidine, oxaliplatin and irinotecan, an anti-VEGF biologic treatment and, in the case of wild-type RAS, a treatment anti-EGFR. Taiho Oncology announced on April 18, 2023 that the FDA has accepted the sNDA for Priority Review and has set a Prescription Drug User Fee Act (PDUFA) early action date of August 13, 2023.

Click here for the original article, "Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer."

Click here for the NEJM "Quick Take" video summarizing the paper's findings.

About colorectal cancerColorectal cancer is the third most common type of cancer worldwide1, with nearly 1.4 million people diagnosed with colorectal cancer (CRC) each year, or 10% of cancer cases worldwide. world1. CRC is the second most common cause of cancer mortality, being responsible for 881,000 deaths worldwide in 20182. The global incidence of colorectal cancer is expected to exceed 3 million cases per year by 20403, and the number is projected to of deaths increases by more than 70% to 1.6 million per year3.

About the SUNLIGHT Trial SUNLIGHT is a multinational, randomized, active-controlled, open-label, two-arm Phase 3 clinical trial to investigate the efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone, in patients with refractory mCRC after two chemotherapy regimens. A total of 492 patients were randomly assigned (in a 1:1 ratio) to receive trifluridine/tipiracil in combination with bevacizumab or trifluridine/tipiracil monotherapy. The primary objective was to evaluate trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil alone, in terms of OS (primary endpoint). Key secondary endpoints were PFS, overall response rate (ORR), disease control rate (TCE), and quality of life (QoL), as well as the safety and tolerability of trifluridine/tipiracil used in combination with bevacizumab compared with trifluridine/tipiracil monotherapy.

The SUNLIGHT trial was conducted by Servier and Taiho Oncology, Inc. For more information about SUNLIGHT, please visit: https://clinicaltrials.gov/ct2/show/NCT0....

About LONSURFLONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co, Ltd. LONSURF consists of a thymidine-based nucleoside analogue, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases the exposure to trifluridine by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, leading to DNA dysfunction and inhibition of cell proliferation.

Indications and use in the United States LONSURF is indicated for the treatment of adult patients with:

IMPORTANT SAFETY INFORMATION, WARNINGS AND PRECAUTIONS

Indications and useLONSURF is indicated for the treatment of adult patients with:

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression: LONSURF caused severe and life-threatening myelosuppression (Grade 3-4) consisting of neutropenia (38%), anemia (18%), thrombocytopenia (5%), and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection. 12% of LONSURF-treated patients received granulocyte colony-stimulating factors. Obtain complete blood counts before and on day 15 of each LONSURF cycle and more frequently as clinically indicated. Discontinue LONSURF in case of febrile neutropenia, absolute neutrophil count less than 500/mm3 or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose as clinically indicated.

Embryo-Fetal Toxicity: LONSURF may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise women of reproductive potential to use effective contraception during treatment and for at least 6 months after the last dose.

USE IN SPECIFIC POPULATIONS

Lactation: It is not known if LONSURF or its metabolites are present in human milk. There are no data to evaluate the effects of LONSURF or its metabolites in the breastfed infant or the effects on milk production. Due to the potential for serious adverse reactions in nursing infants, women are advised not to breast-feed during treatment with LONSURF and for 1 day after the final dose.

Male Contraception: Due to the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use: Patients 65 years of age and older receiving LONSURF had a higher incidence of the following compared with patients less than 65 years of age: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia ( 22% vs. 16%) and grade 3 or 4 thrombocytopenia (7% vs. 4%).

Hepatic Impairment: Do not initiate treatment with LONSURF in patients with baseline moderate or severe hepatic impairment (total bilirubin greater than 1.5 times the ULN value and any AST). Patients with severe hepatic impairment (total bilirubin greater than 3 times the ULN and any AST) were not studied. No adjustment of the starting dose of LONSURF is recommended in patients with mild hepatic impairment.

Renal Impairment: No starting dose adjustment of LONSURF is recommended in patients with mild or moderate renal impairment (CLcr 30 to 89 mL/min). Reduce the starting dose of LONSURF in patients with severe renal impairment (CLcr 15 to 29 mL/min) to a recommended dose of 20 mg/m2.

ADVERSE REACTIONS

Most Common Adverse Drug Reactions in LONSURF-Treated Patients (≥5%): The most common adverse drug reactions in LONSURF-treated patients vs. placebo-treated patients with mCRC, respectively, were asthenia/fatigue (52% vs 35%). %), nausea (48% vs 24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), infections (27% vs to 16%), abdominal pain (21% vs. 18%), pyrexia (19% vs. 14%), stomatitis (8% vs. 6%), dysgeusia (7% vs. 2%), and alopecia (7% versus 1%). In metastatic gastric or gastroesophageal junction (GEJ) cancer, the most frequent adverse reactions were, respectively, nausea (37% vs 32%), decreased appetite (34% vs 31%), vomiting (25% vs to 20%), infections (23% vs. 16%), and diarrhea (23% vs. 14%).

Pulmonary emboli were more common in patients treated with LONSURF than placebo: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

Cases of interstitial lung disease (0.2%), including fatal cases, have been reported in clinical studies and in clinical practice in Asia.

Laboratory Test Abnormalities in LONSURF-Treated Patients: The most common laboratory test abnormalities in LONSURF-treated patients versus placebo-treated patients with mCRC, respectively, were anemia (77% vs 33%), neutropenia ( 67% vs. 1%) and thrombocytopenia (42% vs. 8%). In metastatic gastric cancer or GEJ, test abnormalities were, respectively, neutropenia (66% vs 4%), anemia (63% vs 38%), and thrombocytopenia (34% vs 9%).

See full US Prescribing Information. https://www.taihooncology.com/us/prescribing-information.pdf

About Taiho Oncology, Inc. The mission of Taiho Oncology, Inc. is to improve the lives of cancer patients, their families, and their caregivers. The company specializes in the development of orally administered anticancer agents and markets these drugs for various types of tumors in the United States. Taiho Oncology's growing product portfolio for selectively targeted and antimetabolic anticancer agents is led by a world-class clinical development organization. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd., which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey, and oversees its parent company's European and Canadian operations, located in Zug, Switzerland, and Oakville, Ontario, Canada.

For more information visit the website http://www.taihooncology.com

About Servier Founded to serve healthcare, Servier is a global, foundation-governed group that aspires to make a meaningful social impact, both for patients and for a sustainable world. With its unique governance model, it can fully serve its calling with a long-term vision: being committed to therapeutic progress in service of patients' needs. The group's 21,400 employees are committed to this shared vocation, a source of inspiration every day.

As the world leader in cardiology, Servier's ambition is to become a renowned, focused and innovative player in oncology, focusing on difficult-to-treat cancers. For this reason, the group allocates more than 50% of its R&D budget to the development of specific and innovative therapies in oncology.

Neurosciences and immunoinflammatory diseases are the future drivers of growth. In these areas, Servier focuses on a limited number of diseases where a precise patient profile makes it possible to deliver a targeted therapeutic response through precision medicine.

To promote access for all to quality care at a lower cost, the group also proposes a range of quality generic medicines that cover most pathologies, relying on strong brands in France, Eastern Europe, Brazil and Nigeria.

In all these areas, the group includes the voice of the patient in each phase of the life cycle of a drug.

Headquartered in France, Servier has a strong geographic presence in more than 150 countries and achieved revenues of €4.9 billion in 2022.

More information on the group's website: servier.com

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LONSURF is a registered trademark of Taiho Pharmaceutical Co., Ltd.

*The SUNLIGHT trial is a Phase III study of triflUridine/tipiracil in combination with bevacizumab versus triflUridine/tipiracil as a single agent in patients with refractory metastatic colorectal cancer.

Taiho Oncology Media Contact: Judy Kay MooreTaiho Oncology, Inc.574-526-2369jumoore@taihooncology.com www.taihooncology.com

ServierGrupo press contact: presse@servier.com I Tel. 33 (0)1 55 72 40 21 United States: Julia.Ferreira@servier.com I 1 857.262.3852

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