FDA label 02969043-bbcd-aead-e063-6294a90a3a24

5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.1 , 8.1 , 8.3 ) 5.1 Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period organogenesis caused adverse developmental outcomes including embryo-fetal mortality and malformations at maternal exposures (AUC) less than those in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose [see Use in Specific Populations (8.1 , 8.3) , Nonclinical Toxicology (13.1) ] .

6 ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kadmon Pharmaceuticals, LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely variable conditions, adverse reaction 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. Chronic Graft versus Host Disease In two clinical trials (Study KD025-213 and Study KD025-208), 83 adult patients with chronic GVHD were treated with REZUROCK 200 mg once daily [see Clinical Studies (14.1) ] . The median duration of treatment was 9.2 months (range 0.5 to 44.7 months). Fatal adverse reaction was reported in one patient with severe nausea, vomiting, diarrhea and multi-organ failure. Permanent discontinuation of REZUROCK due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of REZUROCK in >3% of patients included nausea (4%). Adverse reactions leading to dose interruption occurred in 29% of patients. The adverse reactions leading to dose interruption in ≥2% were infections (11%), diarrhea (4%), and asthenia, dyspnea, hemorrhage, hypotension, liver function test abnormal, nausea, pyrexia, edema, and renal failure with (2% each). The most common (≥20%) adverse reactions, including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension. Table 2 summarizes the nonlaboratory adverse reactions. Table 2: Nonlaboratory Adverse Reactions in ≥10% Patients with Chronic GVHD Treated with REZUROCK Adverse Reaction REZUROCK 200 mg once daily (N=83) All Grades (%) Grades 3–4 (%) Infections and infestations Infection (pathogen not specified) infection with an unspecified pathogen includes acute sinusitis, device related infection, ear infection, folliculitis, gastroenteritis, gastrointestinal infection, hordeolum, infectious colitis, lung infection, skin infection, tooth infection, urinary tract infection, wound infection, upper respiratory tract infection, pneumonia, conjunctivitis, sinusitis, respiratory tract infection, bronchitis, sepsis, septic shock. 53 16 Viral infection includes influenza, rhinovirus infection, gastroenteritis viral, viral upper respiratory tract infection, bronchitis viral, Epstein-Barr viremia, Epstein-Barr virus infection, parainfluenzae virus infection, Varicella zoster virus infection, viral infection. 19 4 Bacterial infection includes cellulitis, Helicobacter infection, Staphylococcal bacteremia, catheter site cellulitis, Clostridium difficile colitis, Escherichia urinary tract infection, gastroenteritis Escherichia coli, Pseudomonas infection, urinary tract infection bacterial. 16 4 General disorders and administration site conditions Asthenia includes fatigue, asthenia, malaise. 46 4 Edema includes edema peripheral, generalized edema, face edema, localized edema, edema. 27 1 Pyrexia 18 1 Gastrointestinal Nausea includes nausea, vomiting. 42 4 Diarrhea 35 5 Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower. 22 1 Dysphagia 16 0 Respiratory, thoracic and mediastinal Dyspnea includes dyspnea, dyspnea exertional, apnea, orthopnea, sleep apnea syndrome. 33 5 Cough includes cough, productive cough. 30 0 Nasal congestion 12 0 Vascular Hemorrhage includes contusion, hematoma, epistaxis, increased tendency to bruise, conjunctival hemorrhage, hematochezia, mouth hemorrhage, catheter site hemorrhage, hematuria, hemothorax, purpura. 23 5 Hypertension 21 7 Musculoskeletal and connective tissue Musculoskeletal pain includes pain in extremity, back pain, flank pain, limb discomfort, musculoskeletal chest pain, neck pain, musculoskeletal pain. 22 4 Muscle spasm 17 0 Arthralgia 15 2 Nervous system Headache includes headache, migraine. 21 0 Metabolism and nutrition Decreased appetite 17 1 Skin and subcutaneous Rash includes rash, rash maculo-papular, rash erythematous, rash generalized, dermatitis exfoliative. 12 0 Pruritus includes pruritus, pruritus generalized. 11 0 Table 3 summarizes the laboratory abnormalities in REZUROCK. Table 3: Selected Laboratory Abnormalities in Patients with Chronic GVHD Treated with REZUROCK REZUROCK 200 mg once daily Grade 0–1 Baseline Grade 2–4 Max Post Grade 3–4 Max Post Parameter (N) (%) (%) Chemistry Phosphate decreased 76 28 7 Gamma Glutamyl Transferase increased 47 21 11 Calcium decreased 82 12 1 Alkaline Phosphatase increased 80 9 0 Potassium increased 82 7 1 Alanine Aminotransferase increased 83 7 2 Creatinine increased 83 4 0 Hematology Lymphocytes decreased 62 29 13 Hemoglobin decreased 79 11 1 Platelets decreased 82 10 5 Neutrophil Count decreased 83 8 4

<table width="80%" ID="TABLE2"><caption>Table 2: Nonlaboratory Adverse Reactions in &#x2265;10% Patients with Chronic GVHD Treated with REZUROCK</caption><col width="34%" align="left" valign="top"/><col width="33%" align="center" valign="top"/><col width="33%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th rowspan="2" styleCode="Lrule Rrule" valign="bottom">Adverse Reaction</th><th colspan="2" styleCode="Rrule">REZUROCK 200 mg once daily (N=83) </th></tr><tr><th align="center" styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grades 3&#x2013;4 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Infections and infestations</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Infection (pathogen not specified) <footnote ID="K990">infection with an unspecified pathogen includes acute sinusitis, device related infection, ear infection, folliculitis, gastroenteritis, gastrointestinal infection, hordeolum, infectious colitis, lung infection, skin infection, tooth infection, urinary tract infection, wound infection, upper respiratory tract infection, pneumonia, conjunctivitis, sinusitis, respiratory tract infection, bronchitis, sepsis, septic shock.</footnote></td><td styleCode="Rrule">53</td><td styleCode="Rrule">16</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Viral infection <footnote ID="K1003">includes influenza, rhinovirus infection, gastroenteritis viral, viral upper respiratory tract infection, bronchitis viral, Epstein-Barr viremia, Epstein-Barr virus infection, parainfluenzae virus infection, Varicella zoster virus infection, viral infection.</footnote></td><td styleCode="Rrule">19</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Bacterial infection <footnote ID="K1016">includes cellulitis, Helicobacter infection, Staphylococcal bacteremia, catheter site cellulitis, Clostridium difficile colitis, Escherichia urinary tract infection, gastroenteritis Escherichia coli, Pseudomonas infection, urinary tract infection bacterial.</footnote></td><td styleCode="Rrule">16</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">General disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Asthenia <footnote ID="K1037">includes fatigue, asthenia, malaise.</footnote></td><td styleCode="Rrule">46</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Edema <footnote ID="K1050">includes edema peripheral, generalized edema, face edema, localized edema, edema.</footnote></td><td styleCode="Rrule">27</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Pyrexia</td><td styleCode="Rrule">18</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nausea <footnote ID="K1082">includes nausea, vomiting.</footnote></td><td styleCode="Rrule">42</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Rrule">35</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Abdominal pain <footnote ID="K1106">includes abdominal pain, abdominal pain upper, abdominal pain lower.</footnote></td><td styleCode="Rrule">22</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Dysphagia</td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Respiratory, thoracic and mediastinal</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Dyspnea <footnote ID="K1138">includes dyspnea, dyspnea exertional, apnea, orthopnea, sleep apnea syndrome.</footnote></td><td styleCode="Rrule">33</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Cough <footnote ID="K1151">includes cough, productive cough.</footnote></td><td styleCode="Rrule">30</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nasal congestion</td><td styleCode="Rrule">12</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Vascular</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hemorrhage <footnote ID="K1183">includes contusion, hematoma, epistaxis, increased tendency to bruise, conjunctival hemorrhage, hematochezia, mouth hemorrhage, catheter site hemorrhage, hematuria, hemothorax, purpura.</footnote></td><td styleCode="Rrule">23</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hypertension</td><td styleCode="Rrule">21</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Musculoskeletal and connective tissue</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Musculoskeletal pain <footnote ID="K1215">includes pain in extremity, back pain, flank pain, limb discomfort, musculoskeletal chest pain, neck pain, musculoskeletal pain.</footnote></td><td styleCode="Rrule">22</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Muscle spasm</td><td styleCode="Rrule">17</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Arthralgia</td><td styleCode="Rrule">15</td><td styleCode="Rrule">2</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Nervous system</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache <footnote ID="K1258">includes headache, migraine.</footnote></td><td styleCode="Rrule">21</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Metabolism and nutrition</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased appetite</td><td styleCode="Rrule">17</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Skin and subcutaneous</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Rash <footnote ID="K1298">includes rash, rash maculo-papular, rash erythematous, rash generalized, dermatitis exfoliative.</footnote></td><td styleCode="Rrule">12</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule">Pruritus <footnote ID="K1310">includes pruritus, pruritus generalized.</footnote></td><td styleCode="Rrule">11</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="90%" ID="TABLE3"><caption>Table 3: Selected Laboratory Abnormalities in Patients with Chronic GVHD Treated with REZUROCK</caption><col width="40%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th rowspan="2" styleCode="Lrule Rrule"/><th colspan="3" styleCode="Rrule">REZUROCK 200 mg once daily </th></tr><tr styleCode="Botrule"><th align="center" styleCode="Rrule">Grade 0&#x2013;1 Baseline </th><th styleCode="Rrule">Grade 2&#x2013;4 Max Post </th><th styleCode="Rrule">Grade 3&#x2013;4 Max Post </th></tr><tr><th styleCode="Lrule Rrule">Parameter</th><th styleCode="Rrule">(N)</th><th styleCode="Rrule">(%)</th><th styleCode="Rrule">(%)</th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="4" styleCode="Lrule Rrule"><content styleCode="bold">Chemistry</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Phosphate decreased</td><td styleCode="Rrule">76</td><td styleCode="Rrule">28</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Gamma Glutamyl Transferase increased</td><td styleCode="Rrule">47</td><td styleCode="Rrule">21</td><td styleCode="Rrule">11</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Calcium decreased</td><td styleCode="Rrule">82</td><td styleCode="Rrule">12</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Alkaline Phosphatase increased</td><td styleCode="Rrule">80</td><td styleCode="Rrule">9</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Potassium increased</td><td styleCode="Rrule">82</td><td styleCode="Rrule">7</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Alanine Aminotransferase increased</td><td styleCode="Rrule">83</td><td styleCode="Rrule">7</td><td styleCode="Rrule">2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Creatinine increased</td><td styleCode="Rrule">83</td><td styleCode="Rrule">4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td colspan="4" styleCode="Lrule Rrule"><content styleCode="bold">Hematology</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Lymphocytes decreased</td><td styleCode="Rrule">62</td><td styleCode="Rrule">29</td><td styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hemoglobin decreased</td><td styleCode="Rrule">79</td><td styleCode="Rrule">11</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Platelets decreased</td><td styleCode="Rrule">82</td><td styleCode="Rrule">10</td><td styleCode="Rrule">5</td></tr><tr><td styleCode="Lrule Rrule">Neutrophil Count decreased</td><td styleCode="Rrule">83</td><td styleCode="Rrule">8</td><td styleCode="Rrule">4</td></tr></tbody></table>