cedazuridine and decitabine

7 DRUG INTERACTIONS Drugs Metabolized by Cytidine Deaminase : Avoid coadministration with INQOVI. ( 7 ) 7.1 Effects of INQOVI on Other Drugs Drugs Metabolized by Cytidine Deaminase Cedazuridine is an inhibitor of the cytidine deaminase (CDA) enzyme. Coadministration of INQOVI with drugs that are metabolized by CDA may result in increased systemic exposure with potential for increased toxicity of these drugs [see Clinical Pharmacology (12.3) ] . Avoid coadministration of INQOVI with drugs that are metabolized by CDA.

1 INDICATIONS AND USAGE INQOVI is a combination of decitabine, a nucleoside metabolic inhibitor, and cedazuridine, a cytidine deaminase inhibitor, indicated: For treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. ( 1.1 ) In combination with venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. ( 1.2 ) 1.1 Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. 1.2 Acute Myeloid Leukemia INQOVI is indicated in combination with venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

2 DOSAGE AND ADMINISTRATION The recommended dosage of INQOVI is 1 tablet (35 mg decitabine and 100 mg cedazuridine) taken orally once daily on Days 1 through 5 of each 28-day cycle. ( 2.2 ) Take INQOVI on an empty stomach. ( 2.2 ) 2.1 Important Administration Information Do NOT substitute INQOVI for an intravenous decitabine product within a cycle. Consider administering antiemetics prior to each dose to minimize nausea and vomiting [see Adverse Reactions (6.1) ]. Take INQOVI on an empty stomach at least 2 hours before or 2 hours after eating. When INQOVI is given in combination with venetoclax, advise patients to take INQOVI 2 hours before or 2 hours after venetoclax. Refer to the venetoclax Prescribing Information for recommended dosage and administration. 2.2 Recommended Dosage INQOVI Monotherapy for MDS or CMML The recommended dosage of INQOVI is 1 tablet (containing 35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 of each 28-day cycle for a minimum of 4 cycles until disease progression or unacceptable toxicity. A complete or partial response may take longer than 4 cycles. INQOVI in Combination with Venetoclax for AML The recommended dosage of INQOVI in combination with venetoclax is 1 tablet (containing 35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 of each 28-day cycle until disease progression or unacceptable toxicity. Match Day 1 of INQOVI dosing with Day 1 of venetoclax dosing for each 28-day cycle. 2.3 Administration Instruct patients of the following: Take INQOVI at approximately the same time each day. Swallow tablets whole. Do not cut, crush, or chew tablets. Take one tablet a day for 5 days in each cycle. If the patient misses a dose within 12 hours of the time it is usually taken, instruct patients to take the missed dose as soon as possible and then to resume the normal daily dosing schedule. Extend the dosing period by one day for every missed dose to complete 5 daily doses for each cycle. Do not take an additional dose if vomiting occurs after INQOVI administration but continue with the next schedule dose. INQOVI is a hazardous drug. Follow applicable special handling and disposal procedures. 1 2.4 Monitoring and Dosage Modifications for Adverse Reactions INQOVI Monotherapy for MDS or CMML Hematologic Adverse Reactions Obtain complete blood cell counts prior to initiating INQOVI and before each cycle. Delay the next cycle if absolute neutrophil count (ANC) is less than 1,000/µL and platelets are less than 50,000/µL in the absence of active disease. Monitor complete blood cell counts until ANC is 1,000/µL or greater and platelets are 50,000/µL or greater [see Warnings and Precautions (5.1) ] . If hematologic recovery occurs (ANC at least 1,000/µL and platelets at least 50,000/µL) within 2 weeks of achieving remission, continue INQOVI at the same dose. If hematologic recovery does not occur (ANC at least 1,000/µL and platelets at least 50,000/µL) within 2 weeks of achieving remission, Delay INQOVI for up to 2 additional weeks AND Resume at a reduced dose by administering INQOVI on Days 1 through 4. Consider further dose reductions in the order listed in Table 1 if myelosuppression persists after a dose reduction. Maintain or increase dose in subsequent cycles as clinically indicated. Table 1: Recommended INQOVI Dose Reductions for Myelosuppression (Monotherapy for MDS or CMML) Dose Reduction Dosage First 1 tablet orally once daily on Days 1 through 4 Second 1 tablet orally once daily on Days 1 through 3 Third 1 tablet orally once daily on Days 1, 3 and 5 Manage persistent severe neutropenia and febrile neutropenia with supportive treatment [see Warnings and Precautions (5.1) ]. Non-Hematologic Adverse Reactions Delay the next cycle for the following non-hematologic adverse reactions and resume at the same or reduced dose upon resolution: Serum creatinine 2 mg/dL or greater Serum bilirubin 2 times upper limit of normal (ULN) or greater Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 2 times ULN or greater Active or uncontrolled infection INQOVI in Combination with Venetoclax for AML Monitor blood cell counts frequently through resolution of cytopenias. Dose modification and interruptions for cytopenias are dependent on remission status. For Cycle 1, bone marrow assessment for response may be performed as early as Day 22. In the absence of bone marrow remission (bone marrow blasts < 5%), do not delay INQOVI in combination with venetoclax. Hematologic Adverse Reactions Obtain complete blood cell counts prior to initiating INQOVI and before each cycle. Monitor complete blood cell counts until neutrophils and platelet counts have recovered to Grade 1 or 2 [see Warnings and Precautions (5.1) ] . If hematologic recovery occurs (ANC at least 1,000/µL and platelets at least 50,000/µL) within 2 weeks of achieving remission, continue INQOVI at the same dose. If hematologic recovery does not occur (ANC at least 1,000/µL and platelets at least 50,000/µL) within 2 weeks of achieving remission, delay INQOVI for up to 2 additional weeks and consider reducing the number of days of INQOVI per cycle according to Table 2 . Table 2: Recommended INQOVI Dose Reductions for Adverse Reactions (Combination with Venetoclax for AML) Dose Reduction Dosage First 1 tablet orally once daily on Days 1, 2 and 3 Second 1 tablet orally once daily on Days 1, 3 and 5 Third 1 tablet orally once daily on Days 1 and 2 Manage persistent severe neutropenia and febrile neutropenia with supportive treatment [see Warnings and Precautions (5.1) ]. Refer to the venetoclax prescribing information for dosage modifications for hematologic adverse reactions associated with venetoclax. Non-Hematologic Adverse Reactions Dose reductions of INQOVI for non-hematologic adverse reactions are provided in Table 2 . Refer to the venetoclax prescribing information for dosage modifications for non-hematologic adverse reactions associated with venetoclax.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] In MDS or CMML, the most common adverse reactions (incidence ≥ 20%) are fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased. ( 6.1 ) In AML in combination with venetoclax, the most common adverse reactions (incidence ≥ 20%) are neutropenia, febrile neutropenia, thrombocytopenia, hemorrhage, anemia, infection (bacterial/viral), diarrhea, fatigue, mucositis, constipation, arthralgia, dyspnea, decreased appetite, edema, nausea, white blood cell count decreased, sepsis, pneumonia, rash, transaminitis, myalgia, arrhythmia, and abdominal pain. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased, lymphocytes decreased, platelets decreased, and hemoglobin decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Taiho Oncology, Inc. at 1-844-878-2446 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice. INQOVI Monotherapy for MDS or CMML The safety of INQOVI was evaluated in a pooled safety population that includes patients enrolled in Study ASTX727-01-B and Study ASTX727-02 [see Clinical Studies (14.1) ]. Patients were randomized to receive INQOVI (35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 in Cycle 1 and decitabine 20 mg/m 2 intravenously on Days 1 through 5 in Cycle 2, or the reverse sequence, and then INQOVI (35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 of each 28-day cycle in Cycles 3 and beyond. Patients were allowed to have one prior cycle of decitabine or azacitidine and there was no limit for body weight or surface area. Among the patients who received INQOVI, 61% of patients were exposed for 6 months or longer and 24% were exposed to INQOVI for greater than 1 year. Serious adverse reactions occurred in 68% of patients who received INQOVI. Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions occurred in 6% of patients. These included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death. Permanent discontinuation due to an adverse reaction occurred in 5% of patients who received INQOVI. The most frequent adverse reactions resulting in permanent discontinuation were febrile neutropenia (1%) and pneumonia (1%). Dose interruptions due to an adverse reaction occurred in 41% of patients who received INQOVI. Adverse reactions requiring dosage interruptions in > 5% of patients who received INQOVI included neutropenia (18%), febrile neutropenia (8%), thrombocytopenia (6%), and anemia (5%). Dose reductions due to an adverse reaction occurred in 19% of patients who received INQOVI. Adverse reactions requiring dosage reductions in >2% of patients who received INQOVI included neutropenia (12%), anemia (3%), and thrombocytopenia (3%). The most common adverse reactions (≥20%) were fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased. Table 3 summarizes the adverse reactions in the pooled safety population. Table 3: Adverse Reactions (≥10%) in Patients Who Received INQOVI in Pooled Safety Population Adverse Reactions INQOVI Cycle 1 N=107 Intravenous Decitabine Cycle 1 N=106 INQOVI Includes adverse reactions that occurred during all cycles, including during treatment with 1 cycle of intravenous decitabine. All Cycles N=208 All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%) General disorders and administration site conditions Fatigue Includes fatigue, asthenia, and lethargy 29 2 25 0 55 5 Hemorrhage Includes contusion, epistaxis, petechiae, hematuria, conjunctival hemorrhage, mouth hemorrhage, purpura, angina bullosa hemorrhagica, gingival bleeding, hematoma, hemoptysis, eye contusion, hemorrhagic diathesis, increased tendency to bruise, vaginal hemorrhage, abdominal wall hematoma, blood blister, bone contusion, catheter site bruise, ecchymosis, genital hemorrhage, intra-abdominal hematoma, oral mucosa hematoma, periorbital hemorrhage, procedural hemorrhage, pulmonary alveolar hemorrhage, retinal hemorrhage, scleral hemorrhage, thrombotic thrombocytopenic purpura, tongue hemorrhage, and vessel puncture site hemorrhage 24 2 17 0 43 3 Edema Includes edema peripheral, peripheral swelling, swelling face, fluid overload, localized edema, face edema, edema, eye swelling, eyelid edema, fluid retention, periorbital swelling, scrotal edema, scrotal swelling, and swelling 10 0 11 0 30 0.5 Pyrexia 7 0 7 0 19 1 Gastrointestinal disorders Constipation Includes constipation and feces hard 20 0 23 0 44 0 Mucositis Includes oropharyngeal pain, stomatitis, mouth ulceration, proctalgia, oral pain, gingivitis, oral disorder, gingival pain, colitis, glossodynia, mouth swelling, pharyngitis, proctitis, duodenitis, enteritis, gingival discomfort, gingival swelling, lip disorder, lip ulceration, mucosal ulceration, nasal ulcer, noninfective gingivitis, oral mucosal blistering, oral mucosal erythema, pharyngeal erythema, pharyngeal ulceration, tongue ulceration, and vulvitis 18 1 24 2 41 4 Nausea 25 0 16 0 40 0.5 Diarrhea Includes diarrhea and feces soft 16 0 11 0 37 1 Transaminase increased Includes alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, gamma-glutamyltransferase increased, liver function test increased, and transaminases increased 12 1 3 0 21 3 Abdominal pain Includes abdominal pain, abdominal pain upper, abdominal pain lower, epigastric discomfort, and abdominal discomfort 9 0 7 0 19 1 Vomiting 5 0 5 0 15 0 Musculoskeletal and connective tissue disorders Myalgia Includes myalgia, pain in extremity, muscle spasms, pain, musculoskeletal pain, non-cardiac chest pain, muscular weakness, musculoskeletal chest pain, flank pain, musculoskeletal stiffness, muscle strain, and musculoskeletal discomfort 9 2 16 1 42 3 Arthralgia Includes arthralgia, back pain, neck pain, joint stiffness, pain in jaw, joint swelling, bursitis, joint range of motion decreased, and joint injury 9 1 13 1 40 3 Respiratory, thoracic, and mediastinal disorders Dyspnea Includes dyspnea, dyspnea exertional, hypoxia, wheezing, chronic obstructive pulmonary disease, and tachypnoea 17 3 9 3 38 6 Cough Includes cough and productive cough 7 0 8 0 28 0 Blood & lymphatic system disorders Febrile neutropenia 10 10 13 13 33 32 Skin and subcutaneous tissue disorders Rash Includes maculo-papular rash, rash, erythema, skin lesion, folliculitis, dermatitis, dermatitis acneiform, eczema, erythema multiforme, rash erythematous, seborrheic keratosis, skin ulcer, dermatitis allergic, dermatitis contact, eczema nummular, genital erythema, rash papular, rash pruritic, rash pustular, seborrheic dermatitis, skin exfoliation, skin irritation, stasis dermatitis, and ulcerative keratitis 12 1 11 1 33 0.5 Nervous system disorders Dizziness Includes dizziness, vertigo, postural dizziness, and positional vertigo 16 1 11 0 33 2 Headache Includes headache, sinus pain, and sinus headache 22 0 13 0 30 0 Neuropathy Includes hypoesthesia, paresthesia, neuropathy peripheral, gait disturbance, peripheral sensory neuropathy, ataxia, balance disorder, brachial plexopathy, carpal tunnel syndrome, and radicular pain 4 0 8 0 13 0 Metabolism and nutritional disorders Decreased appetite 10 1 6 0 24 2 Infections and infestations Upper respiratory tract infection Includes upper respiratory tract infection, nasopharyngitis, sinusitis, and viral upper respiratory tract infection 6 0 3 0 23 1 Pneumonia Includes pneumonia, pneumonitis, atypical pneumonia, and lung infection 7 7 7 5 21 15 Sepsis Includes sepsis, bacteremia, septic shock, endocarditis, pseudomonal bacteremia, and staphylococcal bacteremia 6 6 2 1 14 11 Cellulitis Includes cellulitis, catheter site cellulitis, and infected bite 4 1 3 2 12 5 Investigations Renal impairment Includes blood creatinine increased, acute kidney injury, blood urea increased, blood creatine increased, and renal failure 9 0 8 1 18 0 Weight decreased 5 0 3 0 10 1 Injury, poisoning, and procedural complications Fall 4 0 1 0 12 1 Psychiatric disorders Insomnia 6 0 2 0 12 0.5 Vascular disorders Hypotension Includes hypotension, blood pressure decreased, and cardiogenic shock 4 0 6 1 11 2 Cardiac Disorders Arrhythmia Includes sinus tachycardia, atrial fibrillation, bradycardia, tachycardia, atrial flutter, sinus bradycardia, and conduction disorder 3 0 2 0 11 1 Clinically relevant adverse reactions in < 10% of patients who received INQOVI included: Acute febrile neutrophilic dermatosis (Sweet’s syndrome) (1%) Tumor lysis syndrome (0.5%) Table 4: Select Laboratory Abnormalities (>20%) Worsening from Baseline in Patients Who Received INQOVI in Pooled Safety Population Lab Abnormality Includes any lab abnormalities that worsened by one or more grades. Grade 3-4 includes any lab abnormalities that worsened to Grade 3 or Grade 4. INQOVI Cycle 1 The denominator used to calculate the rate varied from 103 to 107 for INQOVI Cycle 1, from 102 to 106 for Intravenous Decitabine Cycle and from 203 to 208 for INQOVI All Cycles based on the number of patients with a baseline value and at least one post-treatment value. Intravenous Decitabine Cycle 1 INQOVI All Cycles All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%) Hematology Leukocytes decreased 79 65 77 59 87 81 Platelet count decreased 79 65 77 67 82 76 Neutrophil count decreased 70 65 62 59 73 71 Hemoglobin decreased 58 41 59 36 71 55 Chemistry Glucose increased 19 0 11 0 54 7 Albumin decreased 22 1 20 0 45 2 Alkaline phosphatase increased 22 1 12 0 42 0.5 Glucose decreased 14 0 17 0 40 1 Alanine aminotransferase increased 13 1 7 0 37 2 Sodium decreased 9 2 8 0 30 4 Calcium decreased 16 0 12 0 30 2 Aspartate aminotransferase increased 6 1 2 0 30 2 Creatinine increased 7 0 8 0 29 0.5 INQOVI in Combination with Venetoclax for AML The safety of INQOVI in combination with venetoclax (INQOVI+VEN) in adult patients 75 years of age and older or those who have comorbidities precluding the use of intensive induction chemotherapy was evaluated in Study ASTX727-07 (N=159) [see Clinical Studies (14.2) ]. Patients received INQOVI (35 mg decitabine and 100 mg cedazuridine) orally once daily on Days 1 through 5 of the first 28-day cycle in combination with venetoclax given as a ramp up on Day 1 (100 mg) and Day 2 (200 mg), followed by venetoclax 400 mg daily from Day 3 onward. Among the patients who received INQOVI+VEN, the median duration of exposure was 5.5 months (range 0.2-28 months): 47% of patients were exposed to INQOVI for 6 months or longer and 20% of patients were exposed to INQOVI for greater than 1 year. Serious adverse reactions occurred in 82% of patients who received INQOVI+VEN. Serious adverse reactions in > 5% of patients included febrile neutropenia (31%), sepsis (22%), pneumonia (15%), infection (bacterial/viral) (10%), hemorrhage (9%), and dyspnea (6%). Fatal adverse reactions occurred in 8% of patients who received INQOVI+VEN. These included sepsis (5%), dyspnea (2%), myocardial infarction (1%), hemolytic anemia (1%), and tumor lysis syndrome (1%). Permanent discontinuation of INQOVI due to an adverse reaction occurred in 9% of patients who received INQOVI+VEN. The most frequent adverse reaction resulting in permanent discontinuation in more than 1 patient was hemorrhage (1%). Dosage interruptions of INQOVI due to an adverse reaction occurred in 55% of patients who received INQOVI+VEN. Adverse reactions requiring dosage interruptions in ≥ 5% of patients who received INQOVI+VEN included neutropenia (40%), febrile neutropenia (11%), infection (bacterial/viral) (8%), and thrombocytopenia (8%). Dose reductions of INQOVI due to an adverse reaction occurred in 6% of patients who received INQOVI+VEN. The most common adverse reactions requiring dosage reductions of INQOVI were neutropenia (4%), thrombocytopenia (1%), and infection (1%). The most common adverse reactions (≥ 20%) were neutropenia, febrile neutropenia, thrombocytopenia, hemorrhage, anemia, infection (bacterial/viral), diarrhea, fatigue, mucositis, constipation, arthralgia, dyspnea, decreased appetite, edema, nausea, white blood cell count decreased, sepsis, pneumonia, rash, transaminitis, myalgia, arrhythmia, and abdominal pain. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased hemoglobin. Table 5 summarizes the adverse reactions in ASTX727-07. Table 5: Adverse Reactions (≥ 20% All-Grades or ≥ 5% Grades 3-4) in Patients with AML Who Received INQOVI+VEN in ASTX727-07 Adverse Reactions Phase 2 (N=159) All Grades (%) Grades 3-4 (%) Abbreviations: N=total number of patients; n=number of patients; SOC = System Organ Class Gastrointestinal Disorders Diarrhea 38 4 Mucositis Consists of multiple, related terms , Includes gingivitis, mouth ulceration, stomatitis, oropharyngeal pain, aphthous ulcer, colitis, enterocolitis, gingival discomfort, gingival disorder, gingival injury, glossodynia, lip injury, neutropenic colitis, odynophagia, oesophagitis, oropharyngeal discomfort, pharyngeal inflammation, proctalgia, proctitis, pulpitis dental, tongue ulceration, ulcer, vulvovaginitis, enteritis 36 6 Constipation 36 1 Nausea 31 0 Abdominal Pain 21 3 General Disorders and Administration Site Conditions Fatigue 36 8 Edema 31 2 Metabolism and Nutrition Disorders Decreased Appetite 31 3 Blood System and Lymphatic System Disorders Neutropenia 60 58 Febrile Neutropenia 52 52 Thrombocytopenia 52 50 Anemia 41 36 White Blood Cell Count Decreased 28 28 Hepatobiliary Disorders Transaminitis 24 4 Infections and Infestations Infection (excludes fungal) 40 13 Sepsis 28 18 Pneumonia 25 20 Musculoskeletal and Connective Tissue Disorders Arthralgia , Includes arthralgia, back pain, bone pain, joint effusion, joint injury, joint range of motion decreased, neck pain, pain in extremity, pain in jaw, pelvic pain, polyarthritis, spinal osteoarthritis, spinal pain, periarthritis, osteoarthritis 35 6 Myalgia , Includes muscle spasms, muscular weakness, musculoskeletal chest pain, musculoskeletal stiffness, myalgia, non-cardiac chest pain, flank pain, musculoskeletal pain 23 4 Cardiac Disorders Arrhythmia , Includes arrhythmia, atrial fibrillation, atrial flutter, atrioventricular block, atrioventricular block first degree, extrasystoles, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, tachycardia, ventricular arrhythmia, ventricular tachycardia 21 4 Respiratory, Thoracic, and Mediastinal Disorders Dyspnea , Includes dyspnoea, dyspnoea exertional, hypoxia, wheezing, respiratory failure, acute respiratory failure 30 12 Renal and Urinary Disorders Renal Insufficiency 18 5 Vascular Disorders Hemorrhage 42 9 Hypotension 19 6 Skin and Subcutaneous Tissue Disorders Rash , Includes actinic keratosis, catherter site erythema, catherter site rash, dermatitis, dermatitis acneiform, eczema, erythema, erythema multiforme, papule, rash, rash erythematous, rash macular, rash maculo-papular, rash pruritic, seborrhoeic keratosis, skin disorder, skin exfoliation, skin hyperpigmentation, skin irritation, skin lesion, skin ulcer, and Stevens-Johnson Syndrome. 25 1 Clinically relevant adverse reactions in < 10% of patients who received INQOVI+VEN included: Acute febrile neutrophilic dermatosis (Sweet’s syndrome) (1%) Tumor lysis syndrome (2%) Table 6 summarizes the laboratory abnormalities identified in the combined AML safety population. Table 6: Select Laboratory Abnormalities (> 40% All Grade AEs) in Patients Who Received INQOVI+VEN in ASTX727-07 Lab Abnormality Phase 2 (N=159) All Grades (%) Grades 3-4 (%) Hematology and Coagulation Lymphocytes (10 9 /L) Decreased 97 81 Leukocytes (10 9 /L) Decreased 91 91 Platelets (10 9 /L) Decreased 70 69 Hemoglobin (g/L) Decreased 54 50 Neutrophils (10 9 /L) Decreased 48 48 Chemistry Albumin (g/L) Decreased 60 7 Bilirubin (umol/L) Increased 54 7 Alkaline Phosphatase (u/L) Increased 43 1 Creatinine (umol/L) Increased 41 4 Aspartate Aminotransferase (u/L) Increased 41 3 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of intravenous decitabine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Differentiation syndrome Respiratory, Thoracic and Mediastinal Disorders: Interstitial lung disease Cardiac Disorders: Cardiomyopathy