Pafolacianine

1. INDICATIONS AND USAGE CYTALUX is indicated as an adjunct for intraoperative identification of: Malignant lesions in adult patients with ovarian cancer. Malignant and non-malignant pulmonary lesions in adult patients with known or suspected cancer in the lung. CYTALUX is an optical imaging agent indicated as an adjunct for intraoperative identification of: Malignant lesions in adult patients with ovarian cancer. Malignant and non-malignant pulmonary lesions in adult patients with known or suspected cancer in the lung. ( 1 )

2 DOSAGE AND ADMINISTRATION For recommended testing, evaluations, and premedications, see Full Prescribing Information. ( 2.1 ) Recommended intravenous dosage of CYTALUX is: Adult Patients with Ovarian Cancer: 0.025 mg/kg over 60 minutes, 1 hour to 9 hours prior to surgery Adult Patients with Known or Suspected Cancer in the Lung: 0.025 mg/kg over 60 minutes, 1 hour to 24 hours prior to surgery. ( 2.2 ) For preparation, management of infusion-related reactions, and imaging information see Full Prescribing Information. CYTALUX should only be used by trained surgeons using FDA cleared imaging systems. ( 2.3 , 2.4 , 2.5 ) 2.1 Recommended Testing, Evaluations and Premedications Prior to Administration of CYTALUX Obtain a pregnancy test in females of reproductive potential and verify the absence of pregnancy prior to administration of CYTALUX [ see Warnings and Precautions (5.3) and Use in Specific Populations ( 8.1 , 8.3 ) ]. Discontinue folate, folic acid, or folate containing supplements 48 hours before administration of CYTALUX [ see Drug Interactions (7) ]. Consider administering antihistamines and/or anti-nausea medication for prophylaxis against infusion related reactions [ see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage and Administration Adult Patients with Ovarian Cancer The recommended dose of CYTALUX is a single intravenous infusion of 0.025 mg/kg diluted in 250 mL of 5% Dextrose Injection, administered over 60 minutes using a dedicated infusion line, 1 hour to 9 hours prior to surgery. Adult Patients with Known or Suspected Cancer in the Lung The recommended dose of CYTALUX is a single intravenous infusion of 0.025 mg/kg diluted in 250 mL of 5% Dextrose Injection, administered over 60 minutes using a dedicated infusion line, 1 hour to 24 hours prior to surgery. 2.3 Preparation and Storage Instructions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. 1. Use aseptic technique for the preparation of CYTALUX infusion solution. 2. Only use 5% Dextrose Injection for dilution. Do not use other diluents due to incompatibility [see Warnings and Precautions ( 5.4 )] . 3. CYTALUX vials should be stored and thawed in the original carton protected from light. Remove carton containing one single vial of CYTALUX from freezer and record the date, time and thawing condition on the carton. Thaw at room temperature between 20°C to 25°C (68°F to 77°F) for at least 60 minutes or under refrigerated conditions between 2°C to 8°C (36°F to 46°F) for at least 6 hours. When thawed under refrigerated conditions, allow the vial to stand at room temperature for 15 minutes before dilution. Once thawed, an individual CYTALUX vial may be stored at room temperature between 20°C to 25°C (68°F to 77°F) for a maximum single period of 24 hours or under refrigerated conditions between 2°C to 8°C (36°F to 46°F) for a maximum single period of up to 30 days, prior to preparation for infusion. If CYTALUX vial is not used within the maximum single period at either room temperature or under refrigerated conditions, the vial may be refrozen up to three times. If the vial has been thawed after the third refreeze, it must be used. If not used after the third refreeze, do not use and discard the vial. Each vial of CYTALUX may be penetrated only once at the time of preparation of infusion solution. Once penetrated, the vial may not be refrozen. 4. Hand shake or vortex the thawed CYTALUX vial for 60 seconds. 5. Withdraw the calculated volume of CYTALUX for a dose of 0.025 mg/kg. Discard any unused portion in the vial. 6. Add into a 250 mL of 5% Dextrose Injection, USP bag. 7. Gently swirl the bag by hand for 1 minute to mix the solution. 8. Visually inspect the infusion bag. The solution should be light blue/green to clear in color and should not contain any visible particulate matter. 9. Protect the infusion bag from light using a light-blocking cover during infusion and storage. 10. If not immediately used, store the diluted CYTALUX infusion solution in a refrigerator at 2°C to 8°C (36°F to 46°F) for not more than 24 hours. Once the bag is removed from refrigeration, infusion must be completed within 3 hours. 2.4 Management of Infusion-Related Reactions If the patient develops an infusion reaction during administration, interrupt the infusion and treat with antihistamines and/or anti-nausea medication as necessary, based on clinical decision. Complete the infusion within 3 hours of the start of the initial administration [ see Warnings and Precautions (5.1) ]. 2.5 Imaging Clinical data demonstrate that near infrared (NIR) imaging devices that excite at 760 nm to 785 nm and detect emission at 790 nm to 815 nm are suitable for use with CYTALUX. CYTALUX is to be used with an NIR imaging system cleared by the FDA for specific use with pafolacianine. CYTALUX should only be used by surgeons who have completed a training program on t

6 ADVERSE REACTIONS The following clinically significant adverse reaction is described elsewhere in the labeling: • Infusion-Related Reactions [ see Warnings and Precautions ( 5.1 ) ] Most common adverse reactions (incidence ≥1%; ovarian and lung combined) included nausea, vomiting, abdominal pain, flushing, other infusion-related reactions, hypersensitivity, elevation in blood pressure, dyspepsia, and chest discomfort. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact On Target Laboratories at 1-844-434-9333 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 safety of CYTALUX was evaluated in four open label clinical studies, two studies (N = 44 and N = 150) in patients with ovarian cancer and two studies (N = 100 and N = 112) in patients with known or suspected cancer in the lung. A total of 406 patients received 0.025 mg/kg of CYTALUX via intravenous administration. The demographic characteristics of the study population were 82% female (66% female in lung studies), mean age 64 years (range 26 to 89 years), 85% White, 6% Black or African American, 5% Asian, and 4% other race, 5% Hispanic or Latino, 92% Not Hispanic or Latino, and 3% unreported ethnicity. Adverse reactions that occurred in > 1% of patients are presented in Table 1. Table 1. Adverse Reactions from Clinical Studies Reported in ≥ 1% of CYTALUX Treated Patients with Ovarian Cancer or Known or Suspected Cancer in the Lung Adverse Reaction CYTALUX 0.025 mg/kg (N = 406) % Nausea 13 Vomiting 5 Abdominal pain 2 Flushing 2 Other infusion-related reactions 2 Hypersensitivity 2 Elevation in blood pressure 1 Dyspepsia 1 Chest discomfort 1 Adverse reactions occurred during the administration of CYTALUX in 17% of patients. Overall, the safety profile observed in patients treated with CYTALUX 0.025 mg/kg was similar between patients with ovarian cancer and patients with known or suspected cancer in the lung.

7 DRUG INTERACTIONS Use of folate, folic acid, or folate-containing supplements may reduce binding of pafolacianine to folate receptors and could reduce the detection of lesions with CYTALUX. Avoid administration of folate, folic acid, or folate-containing supplements within 48 hours before administration of CYTALUX [see Dosage and Administration (2.1) and Clinical Pharmacology (12.1) ]. Folate Supplements: Avoid folate, folic acid, or folate-containing supplements within 48 hours before administration of CYTALUX. (7) See 17 for PATIENT COUNSELING INFORMATION.