b'LONSURF + bevacizumab IMPROVED PROGRESSION-FREE SURVIVAL 1,2 Prescribing Information]. Patients received LONSURF 35 mg/m2/doseIndian or Alaska Native, and 9.6% were unknown; and baseline ECOG (n=533) or placebo (n=265) twice daily on Days 1 through 5 and Days 8performance status 0 (46%), 1 (54%), or 2 (0.2%).100 through 12 of each 28-day cycle. In RECOURSE, 12% of patients receivedSerious adverse reactions occurred in 25% of patients. The most frequent LONSURF for more than 6 months and 1% of patients received LONSURFserious adverse reactions (2%) were intestinal obstruction (2.8%), and 9080 5.6 for more than 1 year. COVID-19 (2%). Fatal adverse reactions occurred in 1.2% of patients who months EFFICACY: SECONDARY ENDPOINT The study population characteristics were: median age 63 years; 61% male;received LONSURF in combination with bevacizumab, including rectal fistula Percentage of patients70 (4.5-5.9) 57% White, 35% Asian, and 1% Black.(0.4%), bowel perforation (0.4%) and atrial fibrillation (0.4%).60 Median PFS increasedThe most common adverse reactions or laboratory abnormalities (10% inPermanent treatment discontinuation due to an adverse reaction occurred 50 LONSURF + bevacizumab (n=246) by 3.2 monthsincidence) in patients treated with LONSURF at a rate that exceeds the rate in 13% of patients. The adverse reaction which resulted in permanent 40 LONSURF (n=246) in patients receiving placebo were anemia, neutropenia, asthenia/fatigue,treatment discontinuation in 2% of patients was fatigue.30 HR=0.44 ([95% CI: 0.36-0.54]; P0.001) nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting,Dosage reductions due to an adverse reaction or laboratory abnormality 2.4 abdominal pain, and pyrexia. occurred in 7% of patients. At least one dose reduction in 3.7% of patients 20 months In RECOURSE, 3.6% of patients discontinued LONSURF for an adversewas required for neutropenia.10 (2.1-3.2) reaction and 14% of patients required a dose reduction. The most commonDosage interruptions due to an adverse reaction occurred in 11% of patients 0 adverse reactions or laboratory abnormalities leading to dose reduction werewho received LONSURF in combination with bevacizumab. The adverse 0 1 23 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.reaction that required dosage interruption in 2% of patients was nausea.No. at risk Month Table 3 and Table 4 list the adverse reactions and laboratory abnormalitiesThe most common adverse reactions or laboratory abnormalities (20% LONSURF + bevacizumab 246 242 198 179 153 128 99 89 70 61 52 43 25 18 13 7 4 2 0 (graded using CTCAEv4.03), respectively, observed in RECOURSE.in incidence) in patients treated with LONSURF in combination with LONSURF 246 236 147 109 74 56 36 29 19 12 8 6 2 2 1 1 0 0 0 Table 3bevacizumab were neutropenia, anemia, thrombocytopenia, fatigue, nausea, Adverse Reactions (5%) in Patients Receiving LONSURF and at a Higher Incidence (2%) than in Patients Receiving Placeboincreased aspartate aminotransferase, increased alanine aminotransferase, SELECTED IMPORTANT SAFETY INFORMATION (contd) in RECOURSE increased alkaline phosphatase, decreased sodium, diarrhea, abdominal pain, and decreased appetite. Table 5 and Table 6 list the adverse reactions ADVERSE REACTIONS (contd) Adverse Reactions LONSURF Placebo and laboratory abnormalities, respectively, observed in SUNLIGHT.The most common adverse reactions or laboratory abnormalities (20% in incidence) in patients treated (N=533) (N=265)with LONSURF in combination with bevacizumab vs LONSURF alone were neutropenia (80% vs 68%), anemia (68% AllGradesAllGradesTable 5:Adverse Reactions (5%) in SUNLIGHTGrades 3-4* Grades 3-4* Adverse Reactions LONSURF +LONSURF vs 73%), thrombocytopenia (54% vs 29%), fatigue (45% vs 37%), nausea (37% vs 27%), increased aspartate aminotransferase(%) (%) (%) (%) Bevacizumab(34% vs 28%), increased alanine aminotransferase (33% vs 23%), increased alkaline phosphate (31% vs 36%), decreased General(N=246) (N=246)sodium (25% vs 20%), diarrhea (21% vs 19%), abdominal pain (20% vs 18%), and decreased appetite (20% vs 15%). Asthenia/fatigue 52 7 35 9 (%) (%)AllGrade AllGradePlease see brief summary of Prescribing Information below and on adjacent pages.Pyrexia 19 1.3 14 0.4 Grades3 or 4Grades3 or 4GastrointestinalGastrointestinal disordersReferences: 1. LONSURF. Prescribing Information. Taiho Oncology, Inc; 2023. 2. Prager GW, Taieb J, Fakih M, et al.Nausea 48 1.9 24 1.1 Nausea371.6271.6Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med. 2023;388:1657-1667.Diarrhea 32 3 12 0.4doi:10.1056/NEJMoa2214963 Diarrhea*211.2192.4 Vomiting 28 2.1 14 0.4 Abdominal pain*202.8183.7 TAIHO ONCOLOGY, INC. 2023. All rights reserved. LONSURFis a registered trademark of Taiho Pharmaceutical Co., LtdAbdominal pain 21 2.4 19 3.8used under license by Taiho Oncology, Inc. 11/2023 LON-PM-US-1728 v2 Vomiting*190.8151.6Stomatitis 8 0.4 6 0 Stomatitis*130.44.10Metabolism and nutrition Constipation110110.8Decreased appetite 39 3.6 29 4.9 General disorders and administration site conditionslower than those achieved at the recommended dosage of 35 mg/m2twiceInfections27 7 16 4.9 Fatigue*455378Initial U.S. Approval: 2015 daily. Advise pregnant women of the potential risk to the fetus. AdviseNervous systemPyrexia4.9060.4Brief Summary of Prescribing Informationfemales of reproductivepotential to use an effective method of contraceptionDysgeusia 7 0 2.3 0nsert. during treatment with LONSURF and for at least 6 months after t Infections and3182481INDICATIONS AND USAGE Skin and subcutaneous tissueinfestations* 1.1Metastatic Colorectal Cancer 6ADVERSE REACTIONS Alopecia 7 0 1.1 0 Metabolism and nutrition disordersLONSURF, as a single agent or in combination with bevacizumab, is indicated ibed elsewhere*No Grade 4 definition for nausea, abdominal pain, or fatigue in National Decreased appetite200.8151.2for the treatment of adult patients with metastatic colorectal cancerin the labeling: Cancer Institute Common TerminologySevere Myelosuppression [see Warnings and Precautions (5.1)]Incidence reflects 64 preferred terms in the Infections and Infestations Musculoskeletal and connective tissue disorderschemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an6.1Clinical Trials Experience system organ class.Musculoskeletal pain*181.2112anti-EGFR therapy. Becauseclinical trials are conducted underwidely varyingconditions, adverseTable 4Laboratory Abnormalities in RECOURSE Nervous system disorder4CONTRAINDICATIONS reaction rates observed in the clinical trials of a drug cannot be directlyLaboratory Parameter* LONSURF Placebo Headache803.70None. compared to rates in the clinical trials of another drug and ma Vascular disorders5WARNINGS AND PRECAUTIONS rates observed in practice. AllGradesAllGrades 5.1Severe Myelosuppression The data described in the WARNINGS AND PRECAUTIONS section and belowGrades3-4 Grades3-4 Hypertension*11621.2In the 1114 patients who received LONSURF as a single agent, LONSURFnts with(%) (%) (%) (%) Hemorrhage*101.23.70.8caused severe or life-threatening myelosuppression (Grade 3-4)consistingmetastatic colorectal cancer in RECOURSE, 246 patients with metastaticHematologic Renal and urinary disordersof neutropenia (38%), anemia (17%), thrombocytopenia (4%) and febrilecolorectal cancer treated with LONSURF as monotherapy in SUNLIGHT and Anemia 77 18 33 3 Proteinuria6 0.81.2 0neutropenia (3%). Three patients (0.3%) died due to neutropenicinfection/ 335 patients with metastatic gastric cancer in TAGS. Among the1114 patientsNeutropenia67 38 0.8 0 *Represents a composite of multiple related termssepsis; four other patients (0.5%) died due to septic shock. Atotal of 14% ofwho received LONSURF as a single agent, 12% were exposed for 6 months patients received granulocyte-colony stimulating factors. or longer and 1% were exposed for 12 months or longer. The most commonThrombocytopenia 42 5 8 0.4 Table 6: Select Laboratory Abnormalities (10%) in SUNLIGHTIn the 246 patients whoreceived LONSURF in combination with bevacizumab,adverse reactions or laboratory abnormalities (10%) were neutropenia,* Worst Grade at least one grade higher than baseline, with percentagesLONSURF + LONSURFaLONSURF caused severe or life-threatening myelosuppression (Grade 3-4)anemia, thrombocytopenia, fatigue, nausea, decreased appetite, diarrhea,based on number of patients with post-baseline samples, which may beLaboratory parametersBevacizumaba consisting of neutropenia (52%), anemia (5%), thrombocytopenia (4%)vomiting, abdominal pain, and pyrexia. 533 (LONSURF) or 265 (placebo)and febrile neutropenia (0.4%). One patient (0.4%) died due toabdominalAmong the 246 patients with metastatic colorectal cancer treated with One Grade 4 anemia adverse reaction based on clinical criteria was All Grade All Gradesepsisand two other patients (0.8%) died due to septic shock. A total ofLONSURF in combination with bevacizumab in SUNLIGHT, 39% werereported Grades 3 or 4 Grades 3 or 429% of patients received granulocyte-colony stimulating factors. Obtainexposed for 6 months or longer, and 14% were exposed for 12 months orIn RECOURSE, pulmonary emboli occurred more frequently in LONSURF- (%) (%) (%) (%)complete blood counts prior to and on Day 15 of each cycle of LONSURFlonger. The most common adverse reactions or laboratory abnormalitiestreated patients (2%) compared to no patients on placebo. Hematologyand more frequently as clinicallyindicated. Withhold LONSURF for severe(20%) were neutropenia, anemia, thrombocytopenia, fatigue, nausea,LONSURF in combination with bevacizumab Neutrophils decreased80526839myelosuppression and resume at the next lower dosage[see Dosage andincreased AST, increased ALT, increased alkaline phosphatase, decreasedThe safety of LONSURF in combination with bevacizumab was evaluated in Administration (2.2) in the full Prescribing Information]. sodium, diarrhea, abdominal pain, and decreased appetite. SUNLIGHT, an international, randomized, open label study in patients withHemoglobin decreased68573115.2Embryo-Fetal Toxicity Metastatic Colorectal Cancer previously treated metastatic colorectal cancer [see Clinical Studies (14.1) Platelets decreased544.1290.8Based on animal studies and its mechanism of action, LONSURF can causeLONSURF as a single agent in the full Prescribing Information]. (continued)ipiracilThe safety of LONSURF was evaluated in RECOURSE, a randomized (2:1), The study population characteristics were: median age 63 years (20 tocaused embryo-fetal lethalityand embryo-fetal toxicityin pregnant rats whendouble-blind, placebo-controlled trial in patients with previously treated90 years); 52% male; 88% White, 1.4% Black, 0.2% Asian, 0.2% American orally administered during gestation at dosage levels resulting in exposuresmetastatic colorectal cancer [see Clinical Studies (14.1) in the full Taiho_Directory_USMed_Dec2023_FullAd_NAout_7.875x10.75_L09.indd 3 11/27/23 6:17 PM Taiho_Directory_USMed_Dec2023_FullAd_NAout_7.875x10.75_L09.indd 4 11/27/23 6:17 PM'