Adagrasib

1 INDICATIONS AND USAGE KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) Colorectal cancer (CRC)* • In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. ( 1.2 ) *These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of a clinical benefit in confirmatory trials. ( 1.1 , 1.2 ) 1.1 KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer KRAZATI, as a single-agent, is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test [see Dosage and Administration (2.1) ] , who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) [see Clinical Studies (14.1) ]. Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial. 1.2 KRAS G12C-Mutated Locally Advanced or Metastatic Colorectal Cancer KRAZATI in combination with cetuximab is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test [see Dosage and Administration (2.1) ] , who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on ORR and DOR [see Clinical Studies (14.2) ] . Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.

2 DOSAGE AND ADMINISTRATION • Recommended dosage as a single agent for NSCLC and in combination with cetuximab for CRC: 600 mg orally twice daily. ( 2.2 ) • Swallow tablets whole with or without food. ( 2.2 ) 2.1 Patient Selection Non-Small Cell Lung Cancer Select patients for treatment of locally advanced or metastatic NSCLC with KRAZATI based on the presence of KRAS G12C mutation in plasma or tumor specimens [see Clinical Studies (14.1) ] . If no mutation is detected in a plasma specimen, test tumor tissue. Colorectal Cancer Select patients for treatment of locally advanced or metastatic CRC with KRAZATI based on the presence of KRAS G12C mutation in tumor specimens [see Clinical Studies (14.2) ] . Information on FDA-approved tests for the detection of a KRAS G12C mutation is available at: https://www.fda.gov/CompanionDiagnostics 2.2 Recommended Dosage The recommended dosage of KRAZATI as a single agent or in combination with cetuximab is 600 mg orally twice daily until disease progression or unacceptable toxicity. Refer to the cetuximab prescribing information for cetuximab dosage information [see Clinical Studies (14.2) ]. Take KRAZATI at the same time every day with or without food [see Clinical Pharmacology (12.3) ]. Swallow tablets whole. Do not chew, crush or split tablets. If vomiting occurs after taking KRAZATI, do not take an additional dose. Resume dosing at the next scheduled time. If a dose is inadvertently missed, it should be skipped if greater than 4 hours have elapsed from the expected dosing time. Resume dosing at the next scheduled time. 2.3 Dosage Modifications for Adverse Reactions Recommended dose reductions for adverse reactions for use of KRAZATI as a single agent or in combination with cetuximab are outlined in Table 1. If adverse reactions occur, a maximum of two dose reductions are permitted. Permanently discontinue KRAZATI in patients who are unable to tolerate 600 mg once daily. Table 1: Recommended KRAZATI Dosage Reductions for Adverse Reactions Dose Reduction Dosage First dose reduction 400 mg twice daily Second dose reduction 600 mg once daily Refer to the cetuximab prescribing information for dose modifications for adverse reactions associated with cetuximab. When KRAZATI is administered in combination with cetuximab, withhold or permanently discontinue cetuximab when KRAZATI is withheld or permanently discontinued. Treatment with KRAZATI as a single agent may be continued if cetuximab is permanently discontinued. [see Clinical Pharmacology (12.1) , Clinical Studies (14.2) ] . The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2: Recommended KRAZATI Dosage Modifications for Adverse Reactions ALT = alanine aminotransferase; AST = aspartate aminotransferase; ILD = Interstitial Lung Disease; ULN = upper limit of normal Adverse Reaction Severity Grading defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Dosage Modification When KRAZATI is administered in combination with cetuximab, withhold or permanently discontinue treatment with cetuximab when withholding or permanently discontinuing treatment with KRAZATI. Nausea or vomiting despite appropriate supportive care (including anti-emetic therapy) [see Warnings and Precautions (5.1) ] Grade 3 or 4 • Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline. • Resume KRAZATI at the next lower dose level. Diarrhea despite appropriate supportive care (including anti-diarrheal therapy) [see Warnings and Precautions (5.1) ] Grade 3 or 4 • Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline. • Resume KRAZATI at the next lower dose level. QTc Interval Prolongation [see Warnings and Precautions (5.2) ] QTc absolute value greater than 500 ms or Greater than an increase of 60 ms from baseline • Withhold KRAZATI until QTc interval less than 481 ms or return to baseline. • Resume KRAZATI at the next lower dose level. Torsade de pointes, polymorphic ventricular tachycardia or signs or symptoms of serious or life-threatening arrhythmia • Permanently discontinue KRAZATI Hepatotoxicity [see Warnings and Precautions (5.3) ] Grade 2 AST or ALT • Decrease KRAZATI to the next lower dose level. Grade 3 or 4 AST or ALT • Withhold KRAZATI until recovery to ≤ Grade 1 or return to baseline. • Resume KRAZATI at the next lower dose level. AST or ALT > 3 × ULN with total bilirubin > 2 × ULN in the absence of alternative causes • Permanently discontinue KRAZATI Interstitial Lung Disease / Pneumonitis [see Warnings and Precautions (5.4) ] Any Grade • Withhold KRAZATI if ILD/pneumonitis is suspected. • Permanently discontinue KRAZATI if ILD/pneumonitis is confirmed Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 or 4 • Withhold KRAZATI until ≤ Grade 1 or return to baseline. • Resume KRAZATI at the next lower dose level.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.1) ] • QTc Interval Prolongation [see Warnings and Precautions (5.2) ] • Hepatotoxicity [see Warnings and Precautions (5.3) ] • Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.4) ] • Single agent use in NCSLC: The most common adverse reactions (≥ 25%) were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, and decreased appetite. The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, hypokalemia, hyponatremia, increased lipase, decreased leukocytes, decreased neutrophils and increased alkaline phosphatase. ( 6.1 ) • In combination with cetuximab in CRC: The most common adverse reactions (≥ 25%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, and cough. The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased potassium, decreased magnesium, decreased hemoglobin, increased aspartate aminotransferase, increased lipase, decreased albumin, and increased alanine aminotransferase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to adagrasib as a single agent at 600 mg orally twice daily in 366 patients with NSCLC and other solid tumors enrolled in KRYSTAL-1 and KRYSTAL-12 (NCT04685135), respectively. Among 366 patients who received adagrasib, 39% of patients were exposed for 6 months or longer and 12% were exposed for greater than one year. In this pooled safety population, the most common (≥ 25%) adverse reactions were nausea (70%), diarrhea (69%), vomiting (57%), fatigue (55%), musculoskeletal pain (38%), hepatotoxicity (37%), renal impairment (33%), edema (30%), dyspnea (26%), and decreased appetite (29%). In this pooled safety population, the most common Grade 3 or 4 (≥ 2%) laboratory abnormalities were decreased lymphocytes (20%), decreased hemoglobin (7%), increased alanine aminotransferase (4.5%), increased aspartate aminotransferase (4.2%), hypokalemia (3.6%), hyponatremia (3.4%), increased lipase (2.5%), decreased leukocytes (2.5%), decreased neutrophils (2.3%), and increased alkaline phosphatase (2.0%). The data described in WARNINGS AND PRECAUTIONS and below also reflects exposure to adagrasib in combination with cetuximab in 94 patients with KRAS G12C-mutated, locally advanced or metastatic CRC in KRYSTAL-1. Non-Small Cell Lung Cancer The safety of adagrasib was evaluated in patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC in KRYSTAL-1 [see Clinical Studies (14.1) ] . Patients received adagrasib 600 mg orally twice daily (n = 116). Among patients who received adagrasib, 45% were exposed for 6 months or longer and 4% were exposed for greater than one year. The median age of patients who received adagrasib was 64 years (range 25 to 89), 56% female, 84% White, 8% Black or African American, and 4.3% Asian. Serious adverse reactions occurred in 57% of patients who received adagrasib. Serious adverse reactions in ≥ 2% of patients were pneumonia (17%), dyspnea (9%), renal impairment (8%), sepsis (5%), hypoxia (4.3%), pleural effusion (4.3%), respiratory failure (4.3%), anemia (3.4%), cardiac failure (3.4%), hyponatremia (3.4%), hypotension (3.4%), muscular weakness (3.4%), pyrexia (3.4%), dehydration (2.6%), diarrhea (2.6%), mental status changes (2.6%), pulmonary embolism (2.6%), and pulmonary hemorrhage (2.6%). Fatal adverse reactions occurred in 11% of patients who received adagrasib due to pneumonia (3.4%), respiratory failure (1.7%), sudden death (1.7%), cardiac failure (0.9%), cerebrovascular accident (0.9%), mental status change (0.9%), pulmonary embolism (0.9%), and pulmonary hemorrhage (0.9%). Permanent discontinuation of adagrasib due to an adverse reaction occurred in 13% of patients. Adverse reactions which resulted in permanent discontinuation of adagrasib occurring in two patients each (1.7%) were pneumonia and pneumonitis and occurring in one patient each (0.9%) were cerebrovascular accident, dyspnea, decreased ejection fraction, encephalitis, gastrointestinal obstruction, hemorrhage, hepatotoxicity, hypotension, muscular weakness, pulmonary embolism, pyrexia, respiratory failure and sepsis. Dose interruptions of adagrasib due to an adverse reaction occurred in 77% of patients. Adverse reactions requiring dosage interruption in ≥ 2% of patients who received adagrasib included nausea, hepatotoxicity, fatigue, vomiting, pneumonia, renal impairment, diarrhea, QTc interval prolongation, anemia, dyspnea, increased lipase, decreased appetite, dizziness, hyponatremia, muscular weakness, increased amylase, pneumonitis, sepsis and decreased weight. Dose reductions of adagrasib due to an adverse reaction occurred in 28% of patients. Adverse reactions which required dose reductions in ≥ 2% of patients who received adagrasib included hepatotoxicity, fatigue, nausea, diarrhea, vomiting, and renal impairment. The most common adverse reactions (≥ 20%) were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium. Table 3 summarizes the adverse reactions in KRYSTAL-1. Table 3: Adverse Reactions (≥ 20%) in Patients with KRAS G12C-mutated NSCLC Who Received Adagrasib in KRYSTAL-1 Adverse Reaction Adagrasib N = 116 All Grades (%) Grade 3 or 4 (%) Gastrointestinal Disorders Diarrhea Grouped term. 70 0.9 Nausea 69 4.3 Vomiting 56 0.9 Constipation 22 0 Abdominal pain 21 0 General Disorders and Administration Site Conditions Fatigue 59 7 Edema 32 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 41 7 Hepatobiliary Disorders Hepatotoxicity , Hepatotoxicity includes mixed liver injury, blood alkaline phosphatase increased, alanine aminotransferase increased, aspartate aminotransferase increased, liver function test increased, blood bilirubin increased, and bilirubin conjugated increased. 37 10 Renal and Urinary Disorders Renal impairment , Renal impairment includes acute kidney injury and increased blood creatinine. 36 6 Respiratory Dyspnea 35 10 Cough 24 0.9 Metabolism and Nutrition Disorders Decreased appetite 30 4.3 Infections and Infestations Pneumonia 24 17 Nervous System Disorders Dizziness 23 0.9 Cardiac Disorders Electrocardiogram QT prolonged 20 6 Table 4 summarizes the laboratory abnormalities in KRYSTAL-1. Table 4: Select Laboratory Abnormalities Occurring (≥ 25%) That Worsened from Baseline in Patients with KRAS G12C-mutated NSCLC Who Received Adagrasib in KRYSTAL-1 Laboratory Abnormality Adagrasib Denominator used to calculate the rate varied from 106 to 113 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocytes decreased 64 25 Hemoglobin decreased 51 8 Platelets decreased 27 0 Chemistry Aspartate aminotransferase increased 52 6 Sodium decreased 52 8 Creatinine increased 50 0 Albumin decreased 50 0.9 Alanine aminotransferase increased 46 5 Lipase increased 35 1.8 Magnesium decreased 26 0 Potassium decreased 26 3.5 Colorectal Cancer The safety of adagrasib combined with cetuximab was evaluated in 94 patients with KRAS G12C-mutated, locally advanced or metastatic CRC in KRYSTAL-1 [see Clinical Studies (14.2) ] . Patients started treatment with adagrasib 600 mg twice daily in combination with cetuximab weekly (n = 17) or every two weeks (n = 77) . Among patients who received adagrasib in combination with cetuximab, 60% were exposed for greater than 6 months and 12% were exposed for greater than 12 months. Serious adverse reactions occurred in 30% of patients who received adagrasib in combination with cetuximab. The most common serious adverse reactions (≥ 2%) were pneumonia (4.3%), pleural effusion, pyrexia, acute kidney injury, dehydration, and small intestinal obstruction (2.1% each). A fatal adverse reaction of pneumonia occurred in 1 patient who received adagrasib in combination with cetuximab. Adverse reactions leading to discontinuation of adagrasib occurred in 2 patients. Adverse reactions which resulted in permanent discontinuation of adagrasib (1 patient each) included abdominal pain and prolonged QT interval. Adverse reactions leading to dose interruptions of adagrasib occurred in 62% of patients. The most common adverse reactions or laboratory abnormalities leading to dose interruption in ≥ 2% of patients who received adagrasib included diarrhea, nausea, vomiting, abdominal pain, dizziness, headache, pneumonia, alanine aminotransferase increased, aspartate aminotransferase increased, dyspnea, fatigue, pleural effusion, rash, anemia, electrocardiogram QT prolongation, blood bilirubin increased, blood creatinine increased, decreased appetite, dehydration, hemorrhage, hypomagnesemia, lipase increased, muscular weakness, musculoskeletal pain, and pyrexia. Adverse reactions leading to dose reductions of adagrasib occurred in 35% of patients. The most common adverse reactions or laboratory abnormalities leading to dose reductions in ≥ 2% of patients who received adagrasib included fatigue, increased aspartate aminotransferase, increased alanine aminotransferase, nausea, decreased appetite, electrocardiogram QT prolongation, dizziness, acute kidney injury, diarrhea, dysarthria, and vomiting. The most common adverse reactions (≥ 20%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, dizziness, cough, constipation, and peripheral neuropathy. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, increased alanine aminotransferase, decreased magnesium, decreased albumin, increased lipase, decreased potassium, increased aspartate aminotransferase, increased creatinine, decreased sodium, decreased calcium, increased amylase, and increased alkaline phosphatase. Table 5 summarizes the adverse reactions in patients with metastatic CRC in KRYSTAL-1. Table 5: Adverse Reactions (≥ 20 %) in Patients with KRAS G12C-mutated CRC Received Adagrasib in Combination with Cetuximab in KRYSTAL-1 Adverse Reaction Graded per CTCAE version 5.0. Adagrasib in Combination with Cetuximab N = 94 All Grades (%) Grade 3 or 4 (%) Skin and subcutaneous tissue disorders Rash Grouped term; includes multiple related terms. 84 4.3 Dry skin 36 0 Gastrointestinal Disorders Nausea 68 2.1 Diarrhea 65 5 Vomiting 57 0 Abdominal pain 30 4.3 Constipation 23 0 General Disorders and Administration Site Conditions Fatigue 57 3.2 Musculoskeletal pain 47 4.3 Edema 28 0 Hepatobiliary Disorders Hepatotoxicity 38 10 Nervous System Disorders Headache 37 4.3 Dizziness 24 2.1 Peripheral neuropathy 20 1.1 Metabolism and Nutrition Disorders Decreased appetite 30 0 Blood and lymphatic system disorders Anemia 27 7 Respiratory Cough 25 0 Other clinically relevant adverse reactions observed in less than 20% of patients were infusion related reactions (15%). Table 6 summarizes the laboratory abnormalities in patients with metastatic CRC in KRYSTAL-1. Table 6: Selected Laboratory Abnormalities (≥ 25%) in Patients Who Received Adagrasib in Combination with Cetuximab in KRYSTAL-1 Laboratory Abnormality Adagrasib in Combination with Cetuximab The denominator used to calculate the rate varied from 82 to 92 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocytes decreased 63 17 Hemoglobin decreased 48 5 Leukocytes decreased 27 1.1 Chemistry Alanine aminotransferase increased 51 2.2 Magnesium decreased 49 7 Albumin decreased 46 2.2 Lipase increased 41 3.3 Potassium decreased 40 9 Aspartate aminotransferase increased 39 4.3 Creatinine increased 30 1.1 Sodium decreased 30 0 Calcium decreased 29 1.1 Amylase increased 29 0 Alkaline phosphatase increased 29 1.1

12.3 Pharmacokinetics The pharmacokinetics of adagrasib were studied in healthy subjects and in patients with KRAS G12C-mutated NSCLC or CRC. Adagrasib pharmacokinetic data are presented as mean (percent coefficient of variation) unless otherwise specified. Adagrasib AUC and C max increase dose proportionally over the dose range of 400 mg to 600 mg (0.67 to 1 times the approved recommended dose). Adagrasib steady-state was reached within 8 days following administration of the approved recommended dosage and accumulation was approximately 6-fold. Absorption The median (min, max) T max of adagrasib is approximately 6 (6, 12) hours. Effect of Food No clinically significant differences in the pharmacokinetics of adagrasib were observed following administration of a high-fat and high-calorie meal (containing approximately 900 to 1000 calories, 50% from fat). Distribution The apparent volume of distribution of adagrasib is 942 L (57%). Human plasma protein binding of adagrasib is approximately 98% in vitro. Elimination The adagrasib terminal elimination half-life is 23 hours (16%) and the apparent oral clearance (CL/F) is 37 L/h (54%) in patients. Metabolism Adagrasib is metabolized primarily by CYP3A4 following single dose administration. Adagrasib inhibits its own CYP3A4 metabolism following multiple dosing to steady-state which permits CYP2C8, CYP1A2, CYP2B6, CYP2C9, and CYP2D6 to contribute to its metabolism at steady-state. Excretion Following a single oral dose of radiolabeled adagrasib, approximately 75% of the dose was recovered in feces (14% as unchanged) and 4.5% recovered in urine (2% as unchanged). Specific Populations No clinically significant differences in the pharmacokinetics of adagrasib based on age (19 to 89 years), sex, race (White, Black or African American, or Asian), body weight (36 to 146 kg), ECOG PS (0, 1), tumor type (NSCLC or CRC), or tumor burden. No clinically significant differences in the pharmacokinetics of adagrasib are expected in patients with mild to severe renal impairment (CLcr 15 to < 90 mL/min estimated by Cockcroft-Gault equation) or in patients with mild to severe hepatic impairment (Child-Pugh classes A to C). Drug Interaction Studies Clinical Studies and Model-Informed Approaches The following table describes the effect of other drugs on the pharmacokinetics of adagrasib. Table 7: Effect of Other Drugs on Adagrasib C max = maximum plasma concentration; AUC = area under the plasma concentration-time curve Concomitant Drug Adagrasib Dosage Changes in C max or AUC of Adagrasib C max % Decrease AUC % Decrease Rifampin (a strong CYP3A inducer) 600 mg single dose 88% 95% 600 mg multiple doses > 61% Predicted changes in C max or AUC of adagrasib. > 66% Strong CYP3A Inhibitors: Adagrasib C max increased by 2.4-fold and AUC increased by 4-fold following concomitant use of a single dose of 200 mg (0.33 times the approved recommended dose) with itraconazole (a strong CYP3A inhibitor). No clinically significant differences in the pharmacokinetics of adagrasib at steady state were predicted when used concomitantly with itraconazole. No clinically significant differences in the pharmacokinetics of adagrasib were predicted or observed when used concomitantly with efavirenz (a moderate CYP3A inducer), pantoprazole (a proton pump inhibitor), or rosuvastatin (a BCRP/OATP substrate). The following table describes the effect of adagrasib on the pharmacokinetics of other drugs. Table 8: Effect of Adagrasib on Other Drugs C max = maximum plasma concentration; AUC = area under the plasma concentration-time curve Concomitant Drug Adagrasib Dosage Fold Increase of Concomitant Drug C max AUC Midazolam (a sensitive CYP3A substrate) 400 mg 0.66 times the approved recommended dosage. twice daily 4.8-fold 21-fold 600 mg twice daily 3.1-fold Predicted changes in C max or AUC of concomitant drug. 31-fold Warfarin (a sensitive CYP2C9 substrate) 600 mg twice daily 1.1-fold 2.9-fold Dextromethorphan (a sensitive CYP2D6 substrate) 400 mg twice daily 1.9-fold 1.8-fold 600 mg twice daily 1.7-fold 2.4-fold Digoxin (a P-gp substrate) 600 mg twice daily 1.9-fold 1.5-fold In Vitro Studies Cytochrome P450 (CYP) Enzymes: Adagrasib may inhibit CYP2B6. Transporter Systems: Adagrasib may be a substrate of BCRP and may inhibit MATE-1/MATE-2K.