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1 INDICATIONS AND USAGE Mitosol ® is an antimetabolite indicated for use as an adjunct to ab externo glaucoma surgery. Mitosol ® is an antimetabolite indicated as an adjunct to ab externo glaucoma surgery. ( 1 )

2 DOSAGE AND ADMINISTRATION Mitosol ® is intended for topical application to the surgical site of glaucoma filtration surgery. It is not intended for intraocular administration. ( 2 ) • Each vial of Mitosol ® contains 0.2 mg of mitomycin and mannitol in a 1:2 concentration ratio. To reconstitute, add 1 mL of Sterile Water for Injection, then shake to dissolve. If product does not dissolve immediately, allow to stand at room temperature until the product has dissolved into solution. ( 2.2 ) • Fully saturate sponges provided within the Mitosol ® Kit utilizing the entire reconstituted contents of the vial in the manner prescribed in the Instructions for Use. ( 2.3 ) • Apply fully saturated sponges equally to the treatment area, in a single layer, with the use of a surgical forceps. Keep the sponges on the treatment area for two (2) minutes, then remove and return to the Mitosol ® Tray for defined disposal. ( 2.3 ) 2.1 Important Administration Instructions Mitosol ® is intended for topical application to the surgical site of glaucoma filtration surgery. Mitosol ® is a cytotoxic drug. It is not intended for intraocular administration. If intraocular administration occurs, cell death leading to corneal infarction, retinal infarction, and ciliary body atrophy may result. Verify pregnancy status in females of reproductive potential prior to using Mitosol ® . 2.2 Method of Reconstitution Each vial of Mitosol ® contains 0.2 mg of mitomycin and mannitol in a 1:2 concentration ratio. To reconstitute, add 1 mL of Sterile Water for Injection, then shake to dissolve. If product does not dissolve immediately, allow to stand at room temperature until the product dissolves into solution. 2.3 Method of Use Sponges provided within the Mitosol ® Kit should be fully saturated with the entire reconstituted contents in the manner prescribed in the Instructions for Use. A treatment area approximating 10mm x 6mm +/- 2mm should be treated with the Mitosol ® . Apply fully saturated sponges equally to the treatment area, in a single layer, with the use of a surgical forceps. Keep the sponges on the treatment area for two (2) minutes, then remove and return to the Mitosol ® Tray for defined disposal in the Chemotherapy Waste Bag provided. 2.4 Stability Lyophilized Mitosol ® stored at 20°C to 25°C (68°F to 77°F) is stable for the shelf life indicated on the package. Avoid excessive heat. Protect from light. Reconstituted with 1 mL of Sterile Water for Injection at a concentration of 0.2 mg/mL, mitomycin is stable for one (1) hour at room temperature.

3 DOSAGE FORMS AND STRENGTHS Mitosol ® is a sterile lyophilized mixture of mitomycin and mannitol, which, when reconstituted with Sterile Water for Injection, provides a solution for application in glaucoma filtration surgery. Mitosol ® is supplied in vials containing 0.2 mg of mitomycin. Each vial also contains mannitol 0.4 mg, at a 1:2 ratio of mitomycin to mannitol. Each mL of reconstituted solution contains 0.2 mg mitomycin and has a pH between 5.0 and 8.0. Each vial contains a sterile lyophilized mixture of 0.2 mg mitomycin and 0.4 mg mannitol; when reconstituted with Sterile Water for Injection, the solution contains 0.2 mg/mL mitomycin. ( 3 )

5 WARNINGS AND PRECAUTIONS • Cell Death : Mitomycin is cytotoxic. Use of mitomycin in concentrations higher than 0.2 mg/mL or use for longer than 2 minutes may lead to unintended corneal and/or scleral damage including thinning or perforation. Direct contact with the corneal endothelium will result in cell death. ( 5.1 ) • Hypotony : The use of mitomycin has been associated with an increased incidence of post-operative hypotony. ( 5.2 ) • Cataract Development : Use in phakic patients has been correlated to a higher incidence of lenticular change and cataract formation. ( 5.3 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise of potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to use. ( 5.4 , 8.1 , 8.3 ) 5.1 Cell Death Mitomycin is cytotoxic. Use of mitomycin in concentrations higher than 0.2 mg/mL or use for longer than 2 minutes may lead to unintended corneal and/or scleral damage including thinning or perforation. Direct contact with the corneal endothelium will result in cell death. 5.2 Hypotony The use of mitomycin has been associated with an increased incidence of post-operative hypotony. 5.3 Cataract Formation Use in phakic patients has been correlated to a higher incidence of lenticular change and cataract formation. 5.4 Embryo-Fetal Toxicity Based on findings in animals and mechanism of action, Mitosol ® can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Cell Death [see Warnings and Precautions ( 5.1 )] • Hypotony [see Warnings and Precautions ( 5.2 )] • Cataract Formation [see Warnings and Precautions ( 5.3 )] The most frequent adverse reactions to Mitosol ® occur locally and include hypotony, hypotony maculopathy, blebitis, endophthalmitis, vascular reactions, corneal reactions, and cataract. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mobius Therapeutics LLC at 1-877-393-6486 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Ophthalmic Adverse Reactions 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 most frequent adverse reactions to Mitosol ® occur locally, as an extension of the pharmacological activity of the drug. These reactions include: Blebitis: bleb ulceration, chronic bleb leak, encapsulated/cystic bleb, bleb-related infection, wound dehiscence, conjunctival necrosis, thin-walled bleb Cornea: corneal endothelial damage, epithelial defect, anterior synechiae, superficial punctuate keratitis, Descemet's detachment, induced astigmatism Endophthalmitis Hypotony: choroidal reactions (choroidal detachment, choroidal effusion, serous choroidal detachment, suprachoroidal hemorrhage, hypotony maculopathy, presence of supraciliochoroidal fluid, hypoechogenic suprachoroidal effusion) Inflammation: iritis, fibrin reaction Lens: cataract development, cataract progression, capsule opacification, capsular constriction and/or capsulotomy rupture, posterior synechiae Retina: retinal pigment epithelial tear, retinal detachment (serous and rhegatogenous) Scleritis: wound dehiscence Vascular: hyphema, central retinal vein occlusion, hemiretinal vein occlusion, retinal hemorrhage, vitreal hemorrhage and blood clot, subconjunctival hemorrhage, disk hemorrhage Additional Reactions: macular edema, sclera thinning or ulceration, intraocular lens capture, disk swelling, malignant glaucoma, lacrimal drainage system obstruction, ciliary block, corneal vascularization, visual acuity decrease, cystic conjunctival degeneration, upper eyelid retraction, dislocated implants, severe loss of vision.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Based on findings in animals and mechanism of action [see Clinical Pharmacology ( 12.1 )] , Mitosol ® can cause fetal harm when administered to a pregnant woman. There are no available data on Mitosol ® use in pregnant women to inform the drug-associated risk. In animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity ( see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data Parenteral administration of mitomycin in animal reproduction studies produced fetal malformations and embryofetal lethality. 8.2 Lactation Risk Summary There are no data on the presence of mitomycin in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during and for 1 week following administration of Mitosol ® . 8.3 Females and Males of Reproductive Potential Mitosol ® can cause fetal harm when administered to pregnant women [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to using Mitosol ® . 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger patients.

8.1 Pregnancy Risk Summary Based on findings in animals and mechanism of action [see Clinical Pharmacology ( 12.1 )] , Mitosol ® can cause fetal harm when administered to a pregnant woman. There are no available data on Mitosol ® use in pregnant women to inform the drug-associated risk. In animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity ( see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data Parenteral administration of mitomycin in animal reproduction studies produced fetal malformations and embryofetal lethality.

Risk Summary Based on findings in animals and mechanism of action [see Clinical Pharmacology ( 12.1 )] , Mitosol ® can cause fetal harm when administered to a pregnant woman. There are no available data on Mitosol ® use in pregnant women to inform the drug-associated risk. In animal reproduction studies, parenteral administration of mitomycin resulted in teratogenicity ( see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Risk Summary There are no data on the presence of mitomycin in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during and for 1 week following administration of Mitosol ® .

11 DESCRIPTION Mitomycin is an antibiotic isolated from the broth of Streptomyces verticillus Yingtanensis which has been shown to have antimetabolic activity. Mitomycin is a blue-violet crystalline powder with the molecular formula of C 15 H 18 N 4 O 5 and a molecular weight of 334.33. Its chemical name is 7-amino-9α-methoxymitosane and it has the following structural formula: Mitosol ® is a sterile lyophilized mixture of mitomycin and mannitol, which, when reconstituted with Sterile Water for Injection, provides a solution for application in glaucoma filtration surgery. Mitosol ® is supplied in vials containing 0.2 mg of mitomycin. Each vial also contains mannitol 0.4 mg, at a 1:2 ratio of mitomycin to mannitol. Each mL of reconstituted solution contains 0.2 mg mitomycin and has a pH between 5.0 and 8.0. Structural Formula

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mitosol ® inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. Cellular RNA and protein synthesis may also be suppressed. 12.3 Pharmacokinetics Absorption The systemic exposure of mitomycin following ocular administration of Mitosol ® in humans is unknown. Based on a comparison of the proposed dose of up to 0.2 mg to intravenous (IV) doses of mitomycin used clinically for treatment of oncologic indications (up to 20 mg/m 2 ), systemic concentrations in humans upon ocular administration are expected to be multiple orders of magnitude lower than those achieved by IV administration. Elimination Metabolism In humans, mitomycin is cleared from ophthalmic tissue after intraoperative topical application and irrigation, as metabolism occurs in other affected tissues. Systemic clearance is affected primarily by metabolism in the liver. The rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways. Excretion Approximately 10% of an injectable dose of mitomycin is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases.

12.1 Mechanism of Action Mitosol ® inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. Cellular RNA and protein synthesis may also be suppressed.

12.3 Pharmacokinetics Absorption The systemic exposure of mitomycin following ocular administration of Mitosol ® in humans is unknown. Based on a comparison of the proposed dose of up to 0.2 mg to intravenous (IV) doses of mitomycin used clinically for treatment of oncologic indications (up to 20 mg/m 2 ), systemic concentrations in humans upon ocular administration are expected to be multiple orders of magnitude lower than those achieved by IV administration. Elimination Metabolism In humans, mitomycin is cleared from ophthalmic tissue after intraoperative topical application and irrigation, as metabolism occurs in other affected tissues. Systemic clearance is affected primarily by metabolism in the liver. The rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways. Excretion Approximately 10% of an injectable dose of mitomycin is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with Mitosol ® . Intravenous administration of mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical injectable dose in humans, mitomycin produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice. The effect of Mitosol ® on fertility is unknown.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with Mitosol ® . Intravenous administration of mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical injectable dose in humans, mitomycin produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice. The effect of Mitosol ® on fertility is unknown.

14 CLINICAL STUDIES In placebo-controlled studies reported in the medical literature, mitomycin reduced intraocular pressure (IOP) by 3 mmHg in patients with open-angle glaucoma when used as an adjunct to ab externo glaucoma surgery by Month 12. In studies with a historical control reported in the medical literature, mitomycin reduced intraocular pressure (IOP) by 5 mmHg in patients with open-angle glaucoma when used as an adjunct to ab externo glaucoma surgery by Month 12.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Mitosol ® (mitomycin for solution) is available in a kit containing: One Vial containing 0.2 mg mitomycin One 1 mL syringe (Sterile Water For Injection) with Safety Connector One Plunger Rod One Vial Adapter with Spike One 1 mL TB Syringe, Luer Lock One Sponge Container Six 3 mm Absorbent Sponges Six 6 mm Absorbent Sponges Six Half Moon Sponges One Instrument Wedge Sponge One Protective Foam Pouch One Chemotherapy Waste Bag One Label, MMC (mitomycin) Three kits are supplied in each carton (NDC 49771-002-03). 16.2 Storage and Handling Storage Store kits at 20°C to 25°C (68°F to 77°F). Avoid excessive heat. Protect from light. Handling Procedures Mitosol ® is a cytotoxic drug. Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed. Appropriate containment and disposal devices are included within the Mitosol ® (mitomycin for solution) Kit for Ophthalmic Use.

16.2 Storage and Handling Storage Store kits at 20°C to 25°C (68°F to 77°F). Avoid excessive heat. Protect from light. Handling Procedures Mitosol ® is a cytotoxic drug. Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed. Appropriate containment and disposal devices are included within the Mitosol ® (mitomycin for solution) Kit for Ophthalmic Use.

17 PATIENT COUNSELING INFORMATION • Instruct patients to discuss with their physician if they are pregnant or if they might become pregnant [see Use in Specific Populations ( 8.1 )]. • Instruct patients to discuss with their physician if they have demonstrated a hypersensitivity to mitomycin in the past [see Contraindications ( 4.1 )]. • Nursing mothers should be advised that it is not known if Mitosol ® is excreted in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during and for 1 week following administration of Mitosol ® [see Use in Specific Populations ( 8.2 )]. • Patients should be advised of the toxicity of Mitosol ® and potential complications. Manufactured for: Mobius Therapeutics, LLC 1000 Executive Parkway Suite 224 St. Louis, MO 63141

Mitosol ® (mitomycin for solution) 0.2 mg/vial Kit for Ophthalmic Use Read INSTRUCTIONS FOR USE Before Proceeding Instructions for Use A. Outer Pack (Figure A) One Sterile Chemotherapy Waste Bag One Instructions for Use One Package Insert One Inner Tray Two Patient Chart Labels The Outer Pack is to be handled, opened, and its STERILE contents dispensed by the non-sterile circulating nurse. B. STERILE Inner Tray (Figure B) One Vial Containing 0.2 mg mitomycin (inside protective foam pouch) One 1 mL Syringe (Sterile Water for Injection) with Safety Connector One Plunger Rod One Vial Adaptor with Spike (inside protective foam pouch) One 1 mL TB Syringe, Luer Lock One Sponge Container Containing: • Six 3 mm Absorbent Sponges • Six 6 mm Absorbent Sponges • Six Half Moon Sponges • One Instrument Wedge Sponge One Label, MMC (mitomycin) The Sterile Inner Tray is to be handled, opened, and its contents assembled and dispensed by the sterile scrub technician. This tray and its contents are STERILE. 1. Getting Started Non-Sterile Circulating Nurse: Open outer pack. Affect sterile transfer of ALL contents to the sterile field. Sterile Surgical Technician: Open sterile inner tray. 2. Reconstituting Mitosol ® a. Remove vial and vial adapter from blue foam pouch. b. Screw white plunger rod to rubber plunger of pre‑filled syringe. (Fig. 1) c. Press firmly and screw the blue end of the vial adapter into the blue end of the syringe connector. (Fig. 2) NOTE: Do not force plunger. Syringe will not operate if vial adapter and syringe connector are not properly connected. Forcing plunger may result in syringe leakage and Mitosol ® exposure. d. Stand vial upright on a sturdy, flat surface and push on the vial lid until seated and secure. (Fig. 3) e. Inject entire contents of sterile water (1 ml) into vial. (Fig. 4) Do not force syringe plunger. See note at step 2. f. IMPORTANT : INVERT VIAL REPEATEDLY to saturate ALL drug product, including that adhering to stopper, then shake until complete reconstitution of Mitosol ® . If product does not dissolve immediately, allow to stand at room temperature until the product has dissolved into solution. 3. Preparing sponges a. Invert vial and syringe and draw full volume of medication into syringe. (Fig. 5) b. Remove all sponges from sponge tray. c. Return to sponge tray only those sponges to be saturated with Mitosol ® . d. Unscrew the syringe with safety connector from vial and vial adapter. (Fig. 6) Note: DO NOT remove safety connector from syringe. e. Place vial and vial adaptor in chemotherapy waste disposal bag (yellow bag), and set bag aside, within sterile field, for additional use. f. Take sponge container from sterile inner tray. g. Screw both syringes into sponge container; the TB syringe to one end, the syringe with reconstituted Mitosol ® to the other. h. Mitosol ® must be used within 1 hour of reconstitution: • Inject medication into sponge container, saturating sponges. Reconstituted Mitosol ® should remain undisturbed in sponge container for 60 seconds . (Fig. 7) Do not force syringe plunger. See note at step 2. • If any excess fluid remains, withdraw plunger of TB syringe, drawing excess fluid/air into syringe. 4. Using Mitosol ® a. With both syringes connected, the TB syringe to one end, the pre-filled syringe to the other, open sponge container, offering contents to surgeon for placement on surgical site. (Fig. 8) b. Apply saturated sponges to surgical site for two minutes.

TB syringe, drawing excess fluid/air into syringe. 4. Using Mitosol ® a. With both syringes connected, the TB syringe to one end, the pre-filled syringe to the other, open sponge container, offering contents to surgeon for placement on surgical site. (Fig. 8) b. Apply saturated sponges to surgical site for two minutes. Remove sponges from eye and copiously irrigate surgical site. c. As used sponges are removed from surgical site, accept used sponges back into sponge container for disposal. Close container lid. d. With syringes still connected to sponge container, remove entire assembly from surgical field in chemotherapy waste disposal bag. DISPOSE OF CHEMOTHERAPY WASTE BAG AND ITS CONTENTS AS CHEMOTHERAPY WASTE US Patents #7,806,265, #8,186,511, #D685,962, #D685,963, #9,205,075, #9,539,241 and #9,649,428; other international patents issued and pending. A4807998-2 Rev. 07/20 Figure A: Outer Pack Figure B: Sterile Inner Tray Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8

<table cellpadding="7.2pt" width="100%"><col width="47%"/><col width="53%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>A. <content styleCode="bold">Outer Pack</content> (Figure A) </paragraph><paragraph> One Sterile Chemotherapy Waste Bag</paragraph><paragraph> One Instructions for Use</paragraph><paragraph> One Package Insert</paragraph><paragraph> One Inner Tray</paragraph><paragraph> Two Patient Chart Labels</paragraph><paragraph> <content styleCode="italics">The Outer Pack is to be handled, opened, and its </content><content styleCode="bold">STERILE </content><content styleCode="italics">contents dispensed by the non-sterile circulating nurse.</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><renderMultiMedia ID="id41642182" referencedObject="ID_1add348d-38af-425b-8e8b-d935413a023d"/></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>B. <content styleCode="bold">STERILE Inner Tray </content> (Figure B) </paragraph><paragraph> One Vial Containing 0.2 mg mitomycin (inside protective foam pouch)</paragraph><paragraph> One 1 mL Syringe (Sterile Water for Injection) with Safety Connector</paragraph><paragraph> One Plunger Rod</paragraph><paragraph> One Vial Adaptor with Spike (inside protective foam pouch)</paragraph><paragraph> One 1 mL TB Syringe, Luer Lock</paragraph><paragraph> One Sponge Container Containing:</paragraph><paragraph> &#x2022; Six 3 mm Absorbent Sponges</paragraph><paragraph> &#x2022; Six 6 mm Absorbent Sponges</paragraph><paragraph> &#x2022; Six Half Moon Sponges</paragraph><paragraph> &#x2022; One Instrument Wedge Sponge</paragraph><paragraph> One Label, MMC (mitomycin)</paragraph><paragraph> <content styleCode="italics">The Sterile Inner Tray is to be handled, opened, and its contents assembled and dispensed by the sterile scrub technician.</content></paragraph><paragraph><content styleCode="bold"><content styleCode="italics">This tray and its contents are STERILE.</content></content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><renderMultiMedia ID="id-66269582" referencedObject="ID_4995e21d-79cf-4fe6-a697-6dec4e8a56e8"/></td></tr><tr><td styleCode="Botrule " valign="top"/><td styleCode="Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">1. Getting Started </content></paragraph><paragraph><content styleCode="bold"><content styleCode="underline">Non-Sterile Circulating Nurse:</content></content></paragraph><paragraph>Open outer pack. Affect sterile transfer of <content styleCode="bold">ALL </content>contents to the sterile field. </paragraph><paragraph><content styleCode="bold"><content styleCode="underline">Sterile Surgical Technician:</content></content></paragraph><paragraph>Open sterile inner tray.</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><renderMultiMedia ID="id1437801377" referencedObject="ID_72f68b20-106d-43cb-9f0d-f1667278aee4"/></td></tr><tr><td styleCode="Rrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">2. Reconstituting Mitosol^&#xAE; </content> </paragraph><paragraph>a. Remove vial and vial adapter from blue foam pouch. </paragraph><paragraph>b.

7" referencedObject="ID_72f68b20-106d-43cb-9f0d-f1667278aee4"/></td></tr><tr><td styleCode="Rrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">2. Reconstituting Mitosol^&#xAE; </content> </paragraph><paragraph>a. Remove vial and vial adapter from blue foam pouch. </paragraph><paragraph>b. <content styleCode="bold"><content styleCode="underline">Screw</content></content> white plunger rod to rubber plunger of pre&#x2011;filled syringe. <content styleCode="bold">(Fig. 1) </content></paragraph><paragraph>c. <content styleCode="bold"><content styleCode="underline">Press firmly</content></content> and screw the <content styleCode="bold"><content styleCode="underline">blue end</content></content> of the vial adapter into the <content styleCode="bold"><content styleCode="underline">blue end</content></content> of the syringe connector. <content styleCode="bold">(Fig. 2)</content> </paragraph><paragraph><content styleCode="bold">NOTE: Do not force plunger. Syringe will not operate if vial adapter and syringe connector are not properly connected. Forcing plunger may result in syringe leakage and Mitosol^&#xAE; exposure.</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule " valign="top"><renderMultiMedia ID="id-279266892" referencedObject="D34A5041-4E3D-45C9-86CA-CB7DCF9D0F7F"/></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>d. Stand vial upright on a sturdy, flat surface and push on the vial lid until seated and secure. <content styleCode="bold">(Fig. 3)</content> </paragraph><paragraph>e. Inject entire contents of sterile water (1 ml) into vial. <content styleCode="bold">(Fig. 4) </content>Do not force syringe plunger. See note at step 2. </paragraph><paragraph>f. <content styleCode="bold"><content styleCode="underline">IMPORTANT</content>: </content>INVERT VIAL REPEATEDLY to saturate <content styleCode="bold">ALL </content>drug product, including that adhering to stopper, then shake until complete reconstitution of Mitosol^&#xAE;. If product does not dissolve immediately, allow to stand at room temperature until the product has dissolved into solution.</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><renderMultiMedia ID="id-1633088545" referencedObject="EAF27631-CAAC-43FA-BA2E-9F5DA4A72020"/><renderMultiMedia ID="id-392825239" referencedObject="D2943AE4-F9D7-4F6F-9623-2577B124AAF9"/></td></tr><tr><td styleCode="Rrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">3. Preparing sponges </content></paragraph><paragraph>a. <content styleCode="bold"><content styleCode="italics">Invert vial and syringe</content></content> and draw full volume of medication into syringe. <content styleCode="bold">(Fig. 5) </content></paragraph><paragraph>b. Remove all sponges from sponge tray. </paragraph><paragraph>c. Return to sponge tray only those sponges to be saturated with Mitosol^&#xAE;. </paragraph><paragraph>d. Unscrew the syringe with safety connector from vial and vial adapter. <content styleCode="bold">(Fig. 6)</content> Note: <content styleCode="bold">DO NOT</content> remove safety connector from syringe.<content styleCode="bold"> </content></paragraph><paragraph>e. Place vial and vial adaptor in chemotherapy waste disposal bag (yellow bag), and set bag aside, within sterile field, for additional use. </paragraph><paragraph>f. Take sponge container from sterile inner tray. </paragraph><paragraph>g.

nnector from syringe.<content styleCode="bold"> </content></paragraph><paragraph>e. Place vial and vial adaptor in chemotherapy waste disposal bag (yellow bag), and set bag aside, within sterile field, for additional use. </paragraph><paragraph>f. Take sponge container from sterile inner tray. </paragraph><paragraph>g. Screw both syringes into sponge container; the TB syringe to one end, the syringe with reconstituted Mitosol^&#xAE; to the other.</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule " valign="top"><renderMultiMedia ID="id-342558533" referencedObject="E2064CA8-ADC4-44FA-86B0-41C1BAA84D34"/><renderMultiMedia ID="id1978640171" referencedObject="ID_3914815d-5f05-41ac-afb2-ab091e9001ad"/></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>h. <content styleCode="bold"><content styleCode="italics">Mitosol^&#xAE; must be used within 1 hour of reconstitution: </content></content></paragraph><paragraph>&#x2022; Inject medication into sponge container, saturating sponges. Reconstituted Mitosol^&#xAE; should remain undisturbed in sponge container for <content styleCode="bold"><content styleCode="underline">60 seconds</content></content>. <content styleCode="bold">(Fig. 7)</content> Do not force syringe plunger. See note at step 2. </paragraph><paragraph>&#x2022; If any excess fluid remains, withdraw plunger of TB syringe, drawing excess fluid/air into syringe.</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><renderMultiMedia ID="id126750795" referencedObject="ID_2d33a170-1f6a-4699-9c23-24ae5163b233"/></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">4. Using Mitosol^&#xAE; </content></paragraph><paragraph>a. With both syringes connected, the TB syringe to one end, the pre-filled syringe to the other, open sponge container, offering contents to surgeon for placement on surgical site. <content styleCode="bold">(Fig. 8) </content></paragraph><paragraph>b. Apply saturated sponges to surgical site for two minutes. Remove sponges from eye and copiously irrigate surgical site. </paragraph><paragraph>c. As used sponges are removed from surgical site, accept used sponges back into sponge container for disposal. Close container lid. </paragraph><paragraph>d. With syringes still connected to sponge container, remove entire assembly from surgical field in chemotherapy waste disposal bag.</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><renderMultiMedia ID="id1731190523" referencedObject="ID_19912e11-f7d1-4d2d-9774-3a748a452c5b"/></td></tr></tbody></table>

Rx only WARNING Mitomycin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. Bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of mitomycin (see WARNINGS and ADVERSE REACTIONS sections). Hemolytic Uremic Syndrome (HUS) a serious complication of chemotherapy, consisting primarily of microangiopathic hemolytic anemia, thrombocytopenia, and irreversible renal failure has been reported in patients receiving systemic mitomycin. The syndrome may occur at any time during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs, however, most cases occur at doses ≥60 mg of mitomycin. Blood product transfusion may exacerbate the symptoms associated with this syndrome. The incidence of the syndrome has not been defined. Distributed by Archis Pharma LLC Piscataway, NJ 08854 NOVAPLUS is a registered trademarks of of Vizient, Inc. 1033045

WARNING Mitomycin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. Bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of mitomycin (see WARNINGS and ADVERSE REACTIONS sections). Hemolytic Uremic Syndrome (HUS) a serious complication of chemotherapy, consisting primarily of microangiopathic hemolytic anemia, thrombocytopenia, and irreversible renal failure has been reported in patients receiving systemic mitomycin. The syndrome may occur at any time during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs, however, most cases occur at doses ≥60 mg of mitomycin. Blood product transfusion may exacerbate the symptoms associated with this syndrome. The incidence of the syndrome has not been defined.

DESCRIPTION Mitomycin, USP (also known as Mitomycin and/or Mitomycin-C) is an antibiotic isolated from the broth of Streptomyces caespitosus which has been shown to have antitumor activity. The compound is heat stable, has a high melting point, and is freely soluble in organic solvents. Mitomycin for Injection, USP is a sterile dry mixture of mitomycin, USP and mannitol, which when reconstituted with Sterile Water for Injection provides a solution for intravenous administration. Each vial contains either mitomycin, USP 5 mg and mannitol 10 mg, or mitomycin, USP 20 mg and mannitol 40 mg, or mitomycin, USP 40 mg and mannitol 80 mg. Each mL of reconstituted solution will contain 0.5 mg mitomycin, USP and have a pH between 6.0 and 8.0. Mitomycin, USP is a blue-violet crystalline powder with the molecular formula of C 15 H 18 N 4 O 5 , and a molecular weight of 334.33. Its chemical name is 7-amino-9α-methoxymitosane and it has the following structural formula;

CLINICAL PHARMACOLOGY Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. In humans, mitomycin is rapidly cleared from the serum after intravenous administration. Time required to reduce the serum concentration by 50% after a 30 mg bolus injection is 17 minutes. After injection of 30 mg, 20 mg, or 10 mg Intravenous., the maximal serum concentrations were 2.4 mcg/mL, 1.7 mcg/mL, and 0.52 mcg/mL, respectively. Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other tissues as well. The rate of clearance is inversely proportional to the maximal serum concentration because, it is thought, of saturation of the degradative pathways. Approximately 10% of a dose of mitomycin is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases with increasing dose. In children, excretion of intravenously administered mitomycin is similar. Animal Toxicology Mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical dose in man, it produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice.

Animal Toxicology Mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical dose in man, it produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice.

INDICATIONS AND USAGE Mitomycin for Injection, USP is not recommended as single-agent, primary therapy. It has been shown to be useful in the therapy of disseminated adenocarcinoma of the stomach or pancreas in proven combinations with other approved chemotherapeutic agents and as palliative treatment when other modalities have failed. Mitomycin is not recommended to replace appropriate surgery and/or radiotherapy.

CONTRAINDICATIONS Mitomycin is contraindicated in patients who have demonstrated a hypersensitive or idiosyncratic reaction to it in the past. Mitomycin is contraindicated in patients with thrombocytopenia, coagulation disorder, or an increase in bleeding tendency due to other causes.

WARNINGS Patients being treated with mitomycin must be observed carefully and frequently during and after therapy. The use of mitomycin results in a high incidence of bone marrow suppression, particularly thrombocytopenia and leukopenia. Therefore, the following studies should be obtained repeatedly during therapy and for at least eight weeks following therapy: platelet count, white blood cell count, differential, and hemoglobin. The occurrence of a platelet count below 100,000/mm 3 or a WBC below 4,000/mm 3 or a progressive decline in either is an indication to withhold further therapy until blood counts have recovered above these levels. Patients should be advised of the potential toxicity of this drug, particularly bone marrow suppression. Deaths have been reported due to septicemia as a result of leukopenia due to the drug. Patients receiving mitomycin should be observed for evidence of renal toxicity. Mitomycin should not be given to patients with a serum creatinine greater than 1.7 mg percent. Usage in Pregnancy Safe use of mitomycin in pregnant women has not been established. Teratological changes have been noted in animal studies. The effect of mitomycin on fertility is unknown.

PRECAUTIONS Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of this acute respiratory distress occurred within minutes to hours after the vinca alkaloid injection. The total number of doses for each drug has varied considerably. Bronchodilators, steroids and/or oxygen have produced symptomatic relief. A few cases of adult respiratory distress syndrome have been reported in patients receiving mitomycin in combination with other chemotherapy and maintained at FlO 2 concentrations greater than 50% perioperatively. Therefore, caution should be exercised using only enough oxygen to provide adequate arterial saturation since oxygen itself is toxic to the lungs. Careful attention should be paid to fluid balance and overhydration should be avoided. Bladder fibrosis/contraction has been reported with intravesical administration (not an approved route of administration), which in rare cases has required cystectomy. Nursing Mothers It is not known if mitomycin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from mitomycin, it is recommended that nursing be discontinued when receiving mitomycin therapy. Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Nursing Mothers It is not known if mitomycin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from mitomycin, it is recommended that nursing be discontinued when receiving mitomycin therapy.

Geriatric Use Insufficient data from clinical studies of mitomycin are available for patients 65 years of age and older to determine whether they respond differently than younger patients. Postmarketing surveillance suggests that elderly patients may be more susceptible than younger patients to injection site reactions (see ADVERSE REACTIONS : Integument and Mucous Membrane Toxicity ) and hypersensitivity reactions. In general, caution should be exercised when prescribing to elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS Bone Marrow Toxicity This was the most common and most serious toxicity, occurring in 605 of 937 patients (64.4%). Thrombocytopenia and/or leukopenia may occur anytime within 8 weeks after onset of therapy with an average time of 4 weeks. Recovery after cessation of therapy was within 10 weeks. About 25% of the leukopenic or thrombocytopenic episodes did not recover. Mitomycin produces cumulative myelosuppression. Integument and Mucous Membrane Toxicity This has occurred in approximately 4% of patients treated with mitomycin. Cellulitis at the injection site has been reported and is occasionally severe. Stomatitis and alopecia also occur frequently. Rashes are rarely reported. The most important dermatological problem with this drug, however, is the necrosis and consequent sloughing of tissue which results if the drug is extravasated during injection. Extravasation may occur with or without an accompanying stinging or burning sensation and even if there is adequate blood return when the injection needle is aspirated. There have been reports of delayed erythema and/or ulceration occurring either at or distant from the injection site, weeks to months after mitomycin, even when no obvious evidence of extravasation was observed during administration. Skin grafting has been required in some of the cases. Elderly patients may be more susceptible than younger patients to injection site reactions (see PRECAUTIONS: Geriatric Use ). Renal Toxicity 2% of 1,281 patients demonstrated a statistically significant rise in creatinine. There appeared to be no correlation between total dose administered or duration of therapy and the degree of renal impairment. Pulmonary Toxicity This has occurred infrequently but can be severe and may be life-threatening. Dyspnea with a nonproductive cough and radiographic evidence of pulmonary infiltrates may be indicative of mitomycin-induced pulmonary toxicity. If other etiologies are eliminated, mitomycin therapy should be discontinued. Steroids have been employed as treatment of this toxicity, but the therapeutic value has not been determined. A few cases of adult respiratory distress syndrome have been reported in patients receiving mitomycin in combination with other chemotherapy and maintained at FlO 2 concentrations greater than 50% perioperatively. Hemolytic Uremic Syndrome (HUS) This serious complication of chemotherapy, consisting primarily of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (≤100,000/mm 3 ), and irreversible renal failure (serum creatinine ≥1.6 mg/dL) has been reported in patients receiving systemic mitomycin. Microangiopathic hemolysis with fragmented red blood cells on peripheral blood smears has occurred in 98% of patients with the syndrome. Other less frequent complications of the syndrome may include pulmonary edema (65%), neurologic abnormalities (16%), and hypertension. Exacerbation of the symptoms associated with HUS has been reported in some patients receiving blood product transfusions. A high mortality rate (52%) has been associated with this syndrome. The syndrome may occur at any time during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs. Less frequently, HUS has also been reported in patients receiving combinations of cytotoxic drugs not including mitomycin. Of 83 patients studied, 72 developed the syndrome at total doses exceeding 60 mg of mitomycin.

during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs. Less frequently, HUS has also been reported in patients receiving combinations of cytotoxic drugs not including mitomycin. Of 83 patients studied, 72 developed the syndrome at total doses exceeding 60 mg of mitomycin. Consequently, patients receiving ≥60 mg of mitomycin should be monitored closely for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function. The incidence of the syndrome has not been defined. Therapy for the syndrome is investigational. Cardiac Toxicity Congestive heart failure, often treated effectively with diuretics and cardiac glycosides, has rarely been reported. Almost all patients who experienced this side effect had received prior doxorubicin therapy. Acute Side Effects Due to Mitomycin were fever, anorexia, nausea, and vomiting. They occurred in about 14% of 1,281 patients. Other Headache, blurring of vision, confusion, drowsiness, syncope, fatigue, edema, thrombophlebitis, hematemesis, diarrhea, and pain. These did not appear to be dose related and were not unequivocally drug related. They may have been due to the primary or metastatic disease processes. Malaise and asthenia have been reported as part of postmarketing surveillance. Bladder fibrosis/contraction has been reported with intravesical administration (see PRECAUTIONS ). To report SUSPECTED ADVERSE REACTIONS, contact RK Pharma Inc. at 1-844-757-4276 (1-844-4-RKPHARM). or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DOSAGE AND ADMINISTRATION Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Mitomycin should be given intravenously only, using care to avoid extravasation of the compound. If extravasation occurs, cellulitis, ulceration, and slough may result. Each vial contains mitomycin, USP 5 mg and mannitol 10 mg. To administer, add Sterile Water for Injection, 10 mL. Shake to dissolve. If product does not dissolve immediately, allow to stand at room temperature until solution is obtained. After full hematological recovery (see guide to dosage adjustment) from any previous chemotherapy, the following dosage schedule may be used at 6 to 8 week intervals: 20 mg/m 2 intravenously as a single dose via a functioning intravenous catheter. Because of cumulative myelosuppression, patients should be fully reevaluated after each course of mitomycin, and the dose reduced if the patient has experienced any toxicities. Doses greater than 20 mg/m 2 have not been shown to be more effective, and are more toxic than lower doses. The following schedule is suggested as a guide to dosage adjustment: Nadir After Prior Dose Leukocytes/mm 3 Platelets/mm 3 Percentage of Prior Dose To Be Given >4000 >100,000 100% 3000-3999 75,000-99,999 100% 2000-2999 25,000-74,999 70% <2000 <25,000 50% No repeat dosage should be given until leukocyte count has returned to 4000/mm 3 and a platelet count to 100,000/mm 3 . When mitomycin is used in combination with other myelosuppressive agents, the doses should be adjusted accordingly. If the disease continues to progress after two courses of mitomycin, the drug should be stopped since chances of response are minimal. STABILITY Unreconstituted mitomycin stored at room temperature is stable for the lot life indicated on the package. Avoid excessive heat (over 40°C, 104°F). Reconstituted with Sterile Water for Injection to a concentration of 0.5 mg per mL, mitomycin is stable for 14 days refrigerated or 7 days at room temperature. Diluted in various intravenous fluids at room temperature, to a concentration of 20 to 40 micrograms per mL: Intravenous Fluid Stability 0.9% Sodium Chloride Injection 12 hours Sodium Lactate Injection 24 hours The combination of mitomycin (5 mg to 15 mg) and heparin (1,000 units to 10,000 units) in 30 mL of 0.9% Sodium Chloride Injection is stable for 48 hours at room temperature. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED Mitomycin for injection, USP NDC: 71335-2927-1: 5 mg; individually-boxed amber vial Storage: Store dry powder at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature.], protected from light. Avoid excessive heat, over 40°C (104°F). Protect reconstituted solution from light. Store solution under refrigeration 2° to 8°C (36° to 46°F), discard after 14 days. If unrefrigerated, discard after 7 days. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

References ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice Pittsburgh, PA: Oncology Nursing Society; 1999:32-41. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, National Institutes of Health; 1983. US Dept of Health and Human Services, Public Health Service publication NIH 83-2621. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1591. National Study Commission on Cytotoxic Exposure. – Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia. 1983;1:426-428. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clin. 1983;33:258-263. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines.). Am J Health SystPharm. 1996;53:1669-1685. DECEMBER 2021 PI-152-00-NP

SAGENT ® Rx only STABILITY Unreconstituted mitomycin stored at room temperature is stable for the lot life indicated on the package. Avoid excessive heat (over 40°C, 104°F). Reconstituted with Sterile Water for Injection to a concentration of 0.5 mg per mL, mitomycin is stable for 14 days refrigerated or 7 days at room temperature. Diluted in various I.V. fluids at room temperature, to a concentration of 20 to 40 micrograms per mL: I.V. Fluid Stability 0.9 % Sodium Chloride Injection 12 hours Sodium Lactate Injection 24 hours The combination of mitomycin (5 mg to 15 mg) and heparin (1,000 units to 10,000 units) in 30 mL of 0.9% Sodium Chloride Injection is stable for 48 hours at room temperature. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

DESCRIPTION Mitomycin (also known as mitomycin and/or mitomycin-C) is an antibiotic isolated from the broth of Streptomyces caespitosus which has been shown to have antitumor activity. The compound is heat stable, has a high melting point, and is freely soluble in organic solvents. Mitomycin for Injection, USP is a sterile dry mixture of mitomycin and mannitol, which when reconstituted with Sterile Water for Injection provides a solution for intravenous administration. Each Single-Dose vial contains mitomycin 40 mg and mannitol 80 mg. Each mL of reconstituted solution will contain 0.5 mg mitomycin and have a pH between 6.0 and 8.0. Mitomycin is a blue-violet crystalline powder with the molecular formula of C 15 H 18 N 4 O 5 , and a molecular weight of 334.33. Its chemical name is 7-amino-9α-methoxymitosane and it has the following structural formula; Structural Formula

CLINICAL PHARMACOLOGY Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. In humans, mitomycin is rapidly cleared from the serum after intravenous administration. Time required to reduce the serum concentration by 50% after a 30 mg bolus injection is 17 minutes. After injection of 30 mg, 20 mg, or 10 mg I.V., the maximal serum concentrations were 2.4 mcg/mL, 1.7 mcg/mL, and 0.52 mcg/mL, respectively. Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other tissues as well. The rate of clearance is inversely proportional to the maximal serum concentration because, it is thought, of saturation of the degradative pathways. Approximately 10% of a dose of mitomycin is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases with increasing dose. In children, excretion of intravenously administered mitomycin is similar. Animal Toxicology Mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical dose in man, it produces a greater than 100 percent increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50 percent increase in tumor incidence in female Swiss mice.

INDICATIONS AND USAGE Mitomycin for Injection is not recommended as single-agent, primary therapy. It has been shown to be useful in the therapy of disseminated adenocarcinoma of the stomach or pancreas in proven combinations with other approved chemotherapeutic agents and as palliative treatment when other modalities have failed. Mitomycin is not recommended to replace appropriate surgery and/or radiotherapy.

PRECAUTIONS Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of this acute respiratory distress occurred within minutes to hours after the vinca alkaloid injection. The total number of doses for each drug has varied considerably. Bronchodilators, steroids and/or oxygen have produced symptomatic relief. A few cases of adult respiratory distress syndrome have been reported in patients receiving mitomycin in combination with other chemotherapy and maintained at FIO 2 concentrations greater than 50% perioperatively. Therefore, caution should be exercised using only enough oxygen to provide adequate arterial saturation since oxygen itself is toxic to the lungs. Careful attention should be paid to fluid balance and overhydration should be avoided. Bladder fibrosis/contraction has been reported with intravesical administration (not an approved route of administration), which in rare cases has required cystectomy. Nursing Mothers It is not known if mitomycin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from mitomycin, it is recommended that nursing be discontinued when receiving mitomycin therapy. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Insufficient data from clinical studies of mitomycin are available for patients 65 years of age and older to determine whether they respond differently than younger patients. Post-marketing surveillance suggests that elderly patients may be more susceptible than younger patients to injection site reactions (see ADVERSE REACTIONS: Integument and Mucous Membrane Toxicity ) and hypersensitivity reactions. In general, caution should be exercised when prescribing to elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Geriatric Use Insufficient data from clinical studies of mitomycin are available for patients 65 years of age and older to determine whether they respond differently than younger patients. Post-marketing surveillance suggests that elderly patients may be more susceptible than younger patients to injection site reactions (see ADVERSE REACTIONS: Integument and Mucous Membrane Toxicity ) and hypersensitivity reactions. In general, caution should be exercised when prescribing to elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS Bone Marrow Toxicity This was the most common and most serious toxicity, occurring in 605 of 937 patients (64.4%). Thrombocytopenia and/or leukopenia may occur anytime within 8 weeks after onset of therapy with an average time of 4 weeks. Recovery after cessation of therapy was within 10 weeks. About 25% of the leukopenic or thrombocytopenic episodes did not recover. Mitomycin produces cumulative myelosuppression. Integument and Mucous Membrane Toxicity This has occurred in approximately 4% of patients treated with mitomycin. Cellulitis at the injection site has been reported and is occasionally severe. Stomatitis and alopecia also occur frequently. Rashes are rarely reported. The most important dermatological problem with this drug, however, is the necrosis and consequent sloughing of tissue which results if the drug is extravasated during injection. Extravasation may occur with or without an accompanying stinging or burning sensation and even if there is adequate blood return when the injection needle is aspirated. There have been reports of delayed erythema and/or ulceration occurring either at or distant from the injection site, weeks to months after mitomycin, even when no obvious evidence of extravasation was observed during administration. Skin grafting has been required in some of the cases. Elderly patients may be more susceptible than younger patients to injection site reactions (see PRECAUTIONS: Geriatric Use ). Renal Toxicity 2% of 1,281 patients demonstrated a statistically significant rise in creatinine. There appeared to be no correlation between total dose administered or duration of therapy and the degree of renal impairment. Pulmonary Toxicity This has occurred infrequently but can be severe and may be life-threatening. Dyspnea with a non-productive cough and radiographic evidence of pulmonary infiltrates may be indicative of mitomycin-induced pulmonary toxicity. If other etiologies are eliminated, mitomycin therapy should be discontinued. Steroids have been employed as treatment of this toxicity, but the therapeutic value has not been determined. A few cases of adult respiratory distress syndrome have been reported in patients receiving mitomycin in combination with other chemotherapy and maintained at FIO 2 concentrations greater than 50% perioperatively. Hemolytic Uremic Syndrome (HUS) This serious complication of chemotherapy, consisting primarily of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (≤100,000/mm 3 ), and irreversible renal failure (serum creatinine ≥1.6 mg/dL) has been reported in patients receiving systemic mitomycin. Microangiopathic hemolysis with fragmented red blood cells on peripheral blood smears has occurred in 98% of patients with the syndrome. Other less frequent complications of the syndrome may include pulmonary edema (65%), neurologic abnormalities (16%), and hypertension. Exacerbation of the symptoms associated with HUS has been reported in some patients receiving blood product transfusions. A high mortality rate (52%) has been associated with this syndrome. The syndrome may occur at any time during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs. Less frequently, HUS has also been reported in patients receiving combinations of cytotoxic drugs not including mitomycin. Of 83 patients studied, 72 developed the syndrome at total doses exceeding 60 mg of mitomycin.

during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs. Less frequently, HUS has also been reported in patients receiving combinations of cytotoxic drugs not including mitomycin. Of 83 patients studied, 72 developed the syndrome at total doses exceeding 60 mg of mitomycin. Consequently, patients receiving ≥60 mg of mitomycin should be monitored closely for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function. The incidence of the syndrome has not been defined. Therapy for the syndrome is investigational. Cardiac Toxicity Congestive heart failure, often treated effectively with diuretics and cardiac glycosides, has rarely been reported. Almost all patients who experienced this side effect had received prior doxorubicin therapy. Acute Side Effects Due to Mitomycin were fever, anorexia, nausea, and vomiting. They occurred in about 14% of 1,281 patients. Other Headache, blurring of vision, confusion, drowsiness, syncope, fatigue, edema, thrombophlebitis, hematemesis, diarrhea, and pain. These did not appear to be dose related and were not unequivocally drug related. They may have been due to the primary or metastatic disease processes. Malaise and asthenia have been reported as part of post-marketing surveillance. Bladder fibrosis/contraction has been reported with intravesical administration (see PRECAUTIONS ). To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

DOSAGE AND ADMINISTRATION Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Mitomycin should be given intravenously only, using care to avoid extravasation of the compound. If extravasation occurs, cellulitis, ulceration, and slough may result. Each Single-Dose vial contains mitomycin 40 mg and mannitol 80 mg. To administer, add Sterile Water for Injection, 80 mL. Shake to dissolve. If product does not dissolve immediately, allow to stand at room temperature until solution is obtained. After full hematological recovery (see guide to dosage adjustment) from any previous chemotherapy, the following dosage schedule may be used at 6 to 8 week intervals: 20 mg/m 2 intravenously as a single dose via a functioning intravenous catheter. Because of cumulative myelosuppression, patients should be fully re-evaluated after each course of mitomycin, and the dose reduced if the patient has experienced any toxicities. Doses greater than 20 mg/m 2 have not been shown to be more effective, and are more toxic than lower doses. The following schedule is suggested as a guide to dosage adjustment: Nadir After Prior Dose Leukocytes /mm 3 Platelets / mm 3 Percentage of Prior Dose to be given >4000 >100,000 100% 3000 - 3999 75,000 - 99,999 100% 2000 - 2999 25,000 - 74,999 70% <2000 <25,000 50% No repeat dosage should be given until leukocyte count has returned to 4000/mm 3 and a platelet count to 100,000/mm 3 . When mitomycin is used in combination with other myelosuppressive agents, the doses should be adjusted accordingly. If the disease continues to progress after two courses of mitomycin, the drug should be stopped since chances of response are minimal.

<table width="100%"><col width="62.350%" align="left"/><col width="37.650%" align="left"/><tbody><tr><td align="center" valign="top" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">I.V. Fluid</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Stability</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule">0.9 % Sodium Chloride Injection </td><td align="center" valign="top" styleCode="Botrule Rrule">12 hours </td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule">Sodium Lactate Injection </td><td align="center" valign="top" styleCode="Botrule Rrule">24 hours </td></tr></tbody></table>

HOW SUPPLIED Mitomycin for Injection, USP is supplied in amber vials as follows: NDC Mitomycin for Injection, USP Package Factor 25021-252-51 40 mg Single-Dose Vial 1 vial per carton Storage Store dry powder at 25°C (77°F); excursions permitted between 15° and 30°C (59° and 86°F). Protect from light. Avoid excessive heat, over 40°C (104°F). Protect reconstituted solution from light. Store solution under refrigeration 2° to 8°C (36° to 46°F), discard after 14 days. If unrefrigerated, discard after 7 days. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.

<table width="100%" styleCode="Noautorules"><col width="28.100%" align="left"/><col width="40.367%" align="left"/><col width="31.533%" align="left"/><tbody><tr><td align="left" valign="top"><content styleCode="bold">NDC</content></td><td align="left" valign="top"><content styleCode="bold">Mitomycin for Injection, USP</content></td><td align="left" valign="top"><content styleCode="bold">Package Factor</content></td></tr><tr><td align="left" valign="top">25021-252-51 </td><td align="left" valign="top">40 mg Single-Dose Vial </td><td align="left" valign="top">1 vial per carton </td></tr></tbody></table>

Storage Store dry powder at 25°C (77°F); excursions permitted between 15° and 30°C (59° and 86°F). Protect from light. Avoid excessive heat, over 40°C (104°F). Protect reconstituted solution from light. Store solution under refrigeration 2° to 8°C (36° to 46°F), discard after 14 days. If unrefrigerated, discard after 7 days. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.

References ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice Pittsburgh, PA: Oncology Nursing Society; 1999:32-41. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, National Institutes of Health; 1983. US Dept of Health and Human Services, Public Health Service publication NIH 83-2621. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1591. National Study Commission on Cytotoxic Exposure. – Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia. 1983;1:426-428. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clin. 1983;33:258-263. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines.). Am J Health SystPharm. 1996;53:1669-1685. SAGENT ® Mfd. for SAGENT Pharmaceuticals Schaumburg, IL 60195 (USA) Made in India ©2023 Sagent Pharmaceuticals May 2023 SAGENT Pharmaceuticals ®

1 INDICATIONS AND USAGE JELMYTO ® is indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC). JELMYTO is an alkylating drug indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC). ( 1 )

2 DOSAGE AND ADMINISTRATION JELMYTO is for pyelocalyceal use only and not for intravenous use, topical use, or oral administration. ( 2.1 ) Administer 1.3 g of sodium bicarbonate orally the evening prior to, the morning of, and 30 minutes prior to instillation procedure (total of 3.9 g). ( 2.1 ) The dose of JELMYTO to be instilled is 4 mg per mL via ureteral catheter or nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography, not to exceed 15 mL (60 mg of mitomycin). ( 2.2 ) Instill JELMYTO once weekly for six weeks. For patients with a complete response 3 months after JELMYTO initiation, JELMYTO instillations may be administered once a month for a maximum of 11 additional instillations. ( 2.2 ) 2.1 Important Administration Instructions See the Instructions for Administration provided separately. JELMYTO is for pyelocalyceal use only. JELMYTO is not for intravenous use, topical use, or oral administration. Prior to every instillation, instruct the patient to take 1.3 g of sodium bicarbonate orally the evening prior to, the morning of, and 30 minutes prior to the instillation procedure (total of 3.9 g). General anesthesia, local anesthesia, sedation, prophylactic antibiotics and/or antihistamines may be used at the discretion of the treating urologist. If the patient is to be anesthetized, advise the patient not to take sodium bicarbonate within 30 minutes prior to the treatment. Consider withholding diuretics one day prior to instillation until 4 hours post-instillation. When instilling JELMYTO, the entire syringe must be emptied within one minute. Advise patients that JELMYTO may discolor urine to a violet to blue color following the instillation procedure. Advise patients to avoid contact with urine for at least six hours post-instillation, to void urine sitting on a toilet, and to flush the toilet several times after use. 2.2 Recommended Dosage The dose of JELMYTO to be instilled is 4 mg per mL via ureteral catheter or a nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography, not to exceed 15 mL (60 mg of mitomycin). Instill JELMYTO once weekly for six weeks. For patients with a complete response 3 months after JELMYTO initiation, JELMYTO instillations may be administered once a month for a maximum of 11 additional instillations. 2.3 Preparation and Handling See the Instructions for Pharmacy for preparation provided separately. JELMYTO is a hazardous drug. Follow applicable special handling and disposal procedures. 1 JELMYTO must be prepared under chilled conditions. Once reconstituted , the admixture will have a concentration of 4 mg of mitomycin per mL and will appear as a viscous liquid for instillation. Reconstituted JELMYTO has reverse thermal properties with a gelation point of approximately 19°C (66°F). Reconstituted JELMYTO should be instilled as soon as possible after reconstitution. Store reconstituted JELMYTO at 20°C to 25°C (68°F to 77°F) for up to 96 hours (4 days). JELMYTO will appear as a semisolid gel when stored under these conditions. Protect reconstituted JELMYTO from light. JELMYTO must be instilled as a chilled solution using a Uroject12 Lever, a Luer Lock syringe, and a ureteral catheter with molded Luer Lock connector. Once chilled at -3°C to 5°C (27°F to 41°F), JELMYTO will convert to a viscous liquid for instillation and is stable for up to 1 additional hour.

uted JELMYTO from light. JELMYTO must be instilled as a chilled solution using a Uroject12 Lever, a Luer Lock syringe, and a ureteral catheter with molded Luer Lock connector. Once chilled at -3°C to 5°C (27°F to 41°F), JELMYTO will convert to a viscous liquid for instillation and is stable for up to 1 additional hour. Reconstituted JELMYTO must be instilled within 1 hour after it is converted to a viscous liquid.

3 DOSAGE FORMS AND STRENGTHS For pyelocalyceal solution: A kit containing the following: Two 40 mg (each) single-dose vials of sterile, lyophilized, grey to greyish-purple, cake or powder of mitomycin for pyelocalyceal solution One single-dose vial of 20 mL of sterile, clear, colorless gel with or without bubbles at room temperature or clear, colorless liquid at 2°C to 8°C (36°F to 46°F), to be used as a vehicle for reconstitution For pyelocalyceal solution: A kit containing the following: Two 40 mg (each) single-dose vials of mitomycin for pyelocalyceal solution ( 3 ) One vial of 20 mL sterile hydrogel for reconstitution ( 3 )

5 WARNINGS AND PRECAUTIONS Ureteric Obstruction: Ureteric obstruction may occur. Monitor patients for signs and symptoms of ureteric obstruction. Transient or long-term ureteral stents or alternative procedures may be required. Withhold or permanently discontinue JELMYTO based on the severity of the ureteric obstruction. ( 5.1 ) Bone Marrow Suppression: Thrombocytopenia and neutropenia may occur. Monitor blood counts. Withhold or permanently discontinue JELMYTO based on the severity. ( 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Ureteric Obstruction Ureteric obstruction, including ureteral stenosis and hydronephrosis, occurred in patients receiving JELMYTO. In the Olympus study, ureteric obstruction was reported in 58% (n=41) of patients receiving JELMYTO, including 17% (n=12) of patients who experienced Grade 3 obstruction. The median time to first onset was 72 days (range: 15-462). Interventions in the 41 patients experiencing ureteric obstruction included ureteral stent placement (88%), balloon dilatation (29%), and nephroureterectomy (4.9%). In the 36 patients who required ureteral stent placement, the median duration of indwelling stents was 52 days (range: 1-292). Ureteric obstruction did not resolve or resolved with sequelae in 44% (n=18) of these patients. Of the 41 patients who experienced ureteric obstruction, 17% (n=7) experienced Grades 1-2 increase in serum creatinine. In the 42 patients who only received JELMYTO during the treatment phase (no maintenance therapy), ureteric obstruction was reported in 40% (n=17). Monitor patients for signs and symptoms of ureteric obstruction, including flank pain, and fever, and for changes in renal function. Patients who experience obstruction may require transient or long-term ureteral stents or alternative procedures. Withhold or permanently discontinue JELMYTO based on the severity of ureteric obstruction. 5.2 Bone Marrow Suppression The use of JELMYTO can result in bone marrow suppression, particularly thrombocytopenia and neutropenia. In the Olympus study, Grade 3 thrombocytopenia occurred in three patients, Grade 3 anemia in one patient, and Grade 3 neutropenia in one patient. Gross extravasation of JELMYTO via urinary tract perforation or impaired mucosa was not observed in these patients. The following tests should be obtained prior to each treatment: Platelet count, white blood cell count differential and hemoglobin. Withhold JELMYTO for Grade 2 thrombocytopenia or neutropenia. Permanently discontinue for Grade 3 or greater thrombocytopenia or neutropenia. 5.3 Embryo-Fetal Toxicity Based on findings in animals and mechanism of action, JELMYTO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of mitomycin resulted in teratogenicity. Advise females of reproductive potential to use effective contraception during treatment with JELMYTO and for 6 months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JELMYTO and for 3 months following the last dose [see Use in Specific Populations (8.1 , 8.3) and Clinical Pharmacology (12.1) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Ureteric Obstruction [see Warnings and Precautions (5.1) ] Bone Marrow Suppression [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 20%) are ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, nausea, abdominal pain, fatigue, dysuria, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UroGen Pharma at 1-855-987-6436 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 clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. The safety of JELMYTO was evaluated in Olympus, an open-label, single-arm study in 71 patients with LG-UTUC [see Clinical Studies (14) ] . For the 71 patients treated with JELMYTO during the treatment period, the median number of instillations was 6 (range: 3-6). Following initial treatment, 29 patients were treated with up to 11 doses of maintenance instillations, with a median of 6 instillations (range: 1-11). Serious adverse reactions occurred in 39% of patients who received JELMYTO. Serious adverse reactions in > 3% of patients included ureteric obstruction (including ureteric stenosis and hydronephrosis), flank pain, and urosepsis. Two deaths occurred due to cerebrovascular accident and failure to thrive. JELMYTO was permanently discontinued due to an adverse reaction in 17 (24%) patients, including 11 patients who discontinued during the treatment phase and 6 who discontinued during the maintenance phase. Adverse reactions resulting in study drug discontinuation of JELMYTO in > 3% of patients who received JELMYTO included ureteric obstruction. Dosage interruptions due to an adverse reaction occurred in 37% of patients who received JELMYTO. Adverse reactions requiring dosage interruption in > 3% of patients who received JELMYTO included renal dysfunction, ureteric obstruction, urinary tract infection, and flank pain. The most common adverse reactions (≥ 20%) reported were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, nausea, abdominal pain, fatigue, dysuria, and vomiting. Table 1 summarizes the adverse reactions in Olympus. Table 1: Adverse Reactions (≥ 10% All Grades) in Patients Who Received JELMYTO in Olympus JELMYTO Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5) (n=71) Adverse Reaction All Grades (%) Grade 3-4 (%) Renal and urinary disorders Ureteric Obstruction Includes hydronephrosis, obstructive uropathy, pelvi-ureteric obstruction, ureteric obstruction, ureteric stenosis, and urinary tract obstruction. 58 17 Ureteric stenosis 44 9 Hydronephrosis 18 6 Urinary tract obstruction 7 1.4 Pelvi-ureteric obstruction 6 1.4 Ureteric obstruction 2.8 1.4 Obstructive uropathy 1.4 0 Flank pain Includes flank pain and back pain. 41 2.8 Hematuria Includes hematuria and hemorrhage urinary tract. 34 2.8 Urinary tract infection Includes urinary tract infection, pyelonephritis, and urinary tract infection fungal. 34 4.2 Renal dysfunction Includes renal impairment, acute kidney injury, and renal failure.

Flank pain Includes flank pain and back pain. 41 2.8 Hematuria Includes hematuria and hemorrhage urinary tract. 34 2.8 Urinary tract infection Includes urinary tract infection, pyelonephritis, and urinary tract infection fungal. 34 4.2 Renal dysfunction Includes renal impairment, acute kidney injury, and renal failure. 25 2.8 Dysuria 23 0 Pollakiuria 14 0 Gastrointestinal disorders Nausea 25 1.4 Abdominal pain Includes abdominal pain and abdominal pain lower. 24 1.4 Vomiting 20 4.2 General disorders and administration site conditions Fatigue Includes asthenia, fatigue, and malaise. 24 1.4 Pyrexia 13 1.4 Chills 11 0 Blood and lymphatic system disorders Anemia 14 1.4 Skin and subcutaneous tissue disorders Rash Includes rash, dermatitis allergic, rash generalized, genital rash, eczema, rash maculo-papular, and skin exfoliation. 14 0 Pruritus 13 0 Metabolism and nutrition disorders Decreased appetite 10 0 Vascular disorders Hypertension 10 4.2 Selected clinically relevant adverse reactions in < 10% and ≥ 2% of patients who received JELMYTO in Olympus include urinary tract inflammation, bladder spasm, urosepsis, hypersensitivity, and instillation site pain. Table 2 summarizes the laboratory abnormalities in Olympus. Table 2: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients Who Received JELMYTO in Olympus Laboratory Abnormality Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5). Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available. JELMYTO All Grades (%) Grade ≥ 3 (%) Hematology Anemia 38 0 Lymphopenia 21 2.9 Thrombocytopenia 21 2.8 Chemistry Estimated Glomerular Filtration Rate (eGFR) eGFR calculated per MDRD (Modification of Diet in Renal Disease) equation 38 11 Creatinine increased 34 0 Hypoalbuminemia 28 2.8 Hypocalcemia 16 0 Hyperuricemia 16 16 Hyperkalemia 13 1.4 Hypernatremia 11 0

<table width="80%"><caption>Table 1: Adverse Reactions (&#x2265; 10% All Grades) in Patients Who Received JELMYTO in Olympus</caption><col width="60%" align="left" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule Botrule" align="center" colspan="2">JELMYTO<footnote>Graded per National Cancer Institute Common Terminology Criteria for Adverse Events.

"left" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="20%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule Botrule" align="center" colspan="2">JELMYTO<footnote>Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5)</footnote> (n=71)</th></tr><tr><th styleCode="Lrule Rrule" align="center" valign="top">Adverse Reaction</th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade 3-4 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Renal and urinary disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Ureteric Obstruction<footnote>Includes hydronephrosis, obstructive uropathy, pelvi-ureteric obstruction, ureteric obstruction, ureteric stenosis, and urinary tract obstruction.</footnote></td><td styleCode="Rrule">58</td><td styleCode="Rrule">17</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Ureteric stenosis</td><td styleCode="Rrule">44</td><td styleCode="Rrule">9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hydronephrosis</td><td styleCode="Rrule">18</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urinary tract obstruction</td><td styleCode="Rrule">7</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pelvi-ureteric obstruction</td><td styleCode="Rrule">6</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Ureteric obstruction</td><td styleCode="Rrule">2.8</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Obstructive uropathy</td><td styleCode="Rrule">1.4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Flank pain<footnote>Includes flank pain and back pain.</footnote></td><td styleCode="Rrule">41</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hematuria<footnote>Includes hematuria and hemorrhage urinary tract.</footnote></td><td styleCode="Rrule">34</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urinary tract infection<footnote>Includes urinary tract infection, pyelonephritis, and urinary tract infection fungal.</footnote></td><td styleCode="Rrule">34</td><td styleCode="Rrule">4.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Renal dysfunction<footnote>Includes renal impairment, acute kidney injury, and renal failure.</footnote></td><td styleCode="Rrule">25</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dysuria</td><td styleCode="Rrule">23</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pollakiuria</td><td styleCode="Rrule">14</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Gastrointestinal disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">25</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Abdominal pain<footnote>Includes abdominal pain and abdominal pain lower.</footnote></td><td styleCode="Rrule">24</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">20</td><td styleCode="Rrule">4.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">General disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rru

Code="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">20</td><td styleCode="Rrule">4.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">General disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rru le"> Fatigue<footnote>Includes asthenia, fatigue, and malaise.</footnote></td><td styleCode="Rrule">24</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">13</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Chills</td><td styleCode="Rrule">11</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Blood and lymphatic system disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">14</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rash<footnote>Includes rash, dermatitis allergic, rash generalized, genital rash, eczema, rash maculo-papular, and skin exfoliation.</footnote></td><td styleCode="Rrule">14</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pruritus</td><td styleCode="Rrule">13</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Metabolism and nutrition disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Decreased appetite</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Vascular disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypertension</td><td styleCode="Rrule">10</td><td styleCode="Rrule">4.2</td></tr></tbody></table>

styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" align="left"><content styleCode="bold">Vascular disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypertension</td><td styleCode="Rrule">10</td><td styleCode="Rrule">4.2</td></tr></tbody></table> <table width="80%"><caption>Table 2: Select Laboratory Abnormalities (&#x2265; 10%) Worsening from Baseline in Patients Who Received JELMYTO in Olympus</caption><col width="50%" align="left" valign="middle"/><col width="20%" align="center" valign="middle"/><col width="30%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule" rowspan="2">Laboratory Abnormality<footnote>Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 5.0 (NCI CTCAE v5). Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available.</footnote></th><th styleCode="Rrule Botrule" colspan="2">JELMYTO</th></tr><tr><th styleCode="Rrule" align="center">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Hematology</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">38</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lymphopenia</td><td styleCode="Rrule">21</td><td styleCode="Rrule">2.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Thrombocytopenia</td><td styleCode="Rrule">21</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Chemistry</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Estimated Glomerular Filtration Rate (eGFR) <footnote>eGFR calculated per MDRD (Modification of Diet in Renal Disease) equation</footnote></td><td styleCode="Rrule">38</td><td styleCode="Rrule">11</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Creatinine increased</td><td styleCode="Rrule">34</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoalbuminemia</td><td styleCode="Rrule">28</td><td styleCode="Rrule">2.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypocalcemia</td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyperuricemia</td><td styleCode="Rrule">16</td><td styleCode="Rrule">16</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyperkalemia </td><td styleCode="Rrule">13</td><td styleCode="Rrule">1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypernatremia</td><td styleCode="Rrule">11</td><td styleCode="Rrule">0</td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animals and mechanism of action, JELMYTO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on JELMYTO use in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of mitomycin resulted in teratogenicity (see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data Teratological changes have been noted with mitomycin in animal studies. 8.2 Lactation Risk Summary There are no data on the presence of mitomycin in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with JELMYTO and for 1 week following the last dose. 8.3 Females and Males of Reproductive Potential JELMYTO can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating JELMYTO. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with JELMYTO and for 6 months following the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JELMYTO and for 3 months following the last dose. 8.4 Pediatric Use Safety and efficacy in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of patients in the Olympus trial, 75% (53 patients) were 65 years of age and over and 37% (26 patients) were 75 years of age and over. Clinical studies of JELMYTO did not include sufficient numbers of younger patients less than 65 years old to determine whether they respond differently from older patients. 8.6 Renal Impairment No data are available in patients with severe renal impairment. Avoid use of JELMYTO in patients with a Glomerular Filtration Rate of < 30 mL/min.

8.1 Pregnancy Risk Summary Based on findings in animals and mechanism of action, JELMYTO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on JELMYTO use in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of mitomycin resulted in teratogenicity (see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data Teratological changes have been noted with mitomycin in animal studies.

8.5 Geriatric Use Of the total number of patients in the Olympus trial, 75% (53 patients) were 65 years of age and over and 37% (26 patients) were 75 years of age and over. Clinical studies of JELMYTO did not include sufficient numbers of younger patients less than 65 years old to determine whether they respond differently from older patients.

11 DESCRIPTION Mitomycin (also known as mitomycin-C) is an alkylating drug isolated from the broth of Streptomyces . Mitomycin is a blue-violet crystalline powder with a molecular formula of C 15 H 18 N 4 O 5 , and a molecular weight of 334.33. Its chemical name is 7-amino-9α-methoxymitosane, and it has the following structural formula: Mitomycin is heat stable, has a high melting point, and is freely soluble in organic solvents. JELMYTO is supplied in a kit containing two vials of sterile lyophilized mitomycin for pyelocalyceal solution, 40 mg each, and one vial of 20 mL of sterile hydrogel, to be used as a vehicle for reconstitution. Mitomycin for pyelocalyceal solution is a sterile, lyophilized, grey to greyish-purple, cake or powder that contains mitomycin 40 mg and mannitol 80 mg in each vial. Sterile hydrogel is a sterile, clear, colorless gel with or without bubbles at room temperature or clear, colorless liquid at 2°C to 8°C (36°F to 46°F), which contains 0.04 g hydroxypropyl methylcellulose, 5.67 g poloxamer, 0.21 g polyethylene glycol, and water for injection in each vial. Once reconstituted, JELMYTO is a clear, purple, viscous liquid at 2°C to 8°C (36°F to 46°F) or semisolid gel at room temperature with a concentration of 4 mg per mL of mitomycin, which may contain a few visible particles and have a pH between 6.0 and 8.0. Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mitomycin inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. 12.2 Pharmacodynamics There is insufficient data to characterize an exposure-response relationship or time course of pharmacodynamic response for mitomycin. 12.3 Pharmacokinetics Absorption The systemic exposure of mitomycin following instillation of up to 60 mg of mitomycin as JELMYTO into the pyelocalyceal system was evaluated pre-instillation and hourly for up to six hours post-instillation in six patients. The concentrations of mitomycin in plasma were variable and ranged from 2.43 to 12.80 ng/mL over the course of treatment; the mean C max was 6.24 ng/mL, which is estimated to be less than 1% of the expected C max after intravenous administration. Elimination Following instillation into the pyelocalyceal system, JELMYTO forms a semisolid gel which dissolves from normal kidney urine flow releasing mitomycin for up to 4 to 6 hours. Mitomycin is eliminated unchanged in the urine. Systemically absorbed mitomycin is rapidly cleared from the serum and approximately 10% is excreted unchanged in the urine. Metabolism Mitomycin is metabolized primarily in the liver, but metabolism occurs in other tissues as well. It is believed that the rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways.

12.1 Mechanism of Action Mitomycin inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.

12.3 Pharmacokinetics Absorption The systemic exposure of mitomycin following instillation of up to 60 mg of mitomycin as JELMYTO into the pyelocalyceal system was evaluated pre-instillation and hourly for up to six hours post-instillation in six patients. The concentrations of mitomycin in plasma were variable and ranged from 2.43 to 12.80 ng/mL over the course of treatment; the mean C max was 6.24 ng/mL, which is estimated to be less than 1% of the expected C max after intravenous administration. Elimination Following instillation into the pyelocalyceal system, JELMYTO forms a semisolid gel which dissolves from normal kidney urine flow releasing mitomycin for up to 4 to 6 hours. Mitomycin is eliminated unchanged in the urine. Systemically absorbed mitomycin is rapidly cleared from the serum and approximately 10% is excreted unchanged in the urine. Metabolism Mitomycin is metabolized primarily in the liver, but metabolism occurs in other tissues as well. It is believed that the rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate long-term studies in animals to evaluate carcinogenic potential from instillation of mitomycin into the pyelocalyceal system have not been conducted. Mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended intravenous clinical dose in humans, mitomycin produced a greater than 100% increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50% increase in tumor incidence in female Swiss mice. The effect of JELMYTO on fertility is unknown.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate long-term studies in animals to evaluate carcinogenic potential from instillation of mitomycin into the pyelocalyceal system have not been conducted. Mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended intravenous clinical dose in humans, mitomycin produced a greater than 100% increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50% increase in tumor incidence in female Swiss mice. The effect of JELMYTO on fertility is unknown.

14 CLINICAL STUDIES The efficacy of JELMYTO is based on the results of the Olympus study (NCT02793128), an open-label, single-arm, multicenter trial that enrolled 71 patients with treatment-naïve or recurrent non-invasive low-grade upper tract urothelial cancer (LG-UTUC) with at least one measurable papillary tumor 5 to ≤ 15 mm located above the ureteropelvic junction; patients who had larger tumors could have had tumor debulking prior to treatment, in order to meet the criteria. Patients were excluded from the trial for a history of carcinoma in situ (CIS) in the urinary tract, invasive urothelial carcinoma within 5 years, high grade papillary urothelial carcinoma within 2 years; or for BCG treatment within 6 months of JELMYTO treatment. Following biopsy and prior to treatment, patients were required to have at least one remaining visible tumor with a diameter of at least 5 mm. Patients received JELMYTO 4 mg per mL via ureteral catheter or nephrostomy tube with total instillation volume based on individualized volumetric measurements using pyelography with the intent to fill the renal pelvis. Patients were treated with 6 instillations once a week. Patients who maintained a complete response (CR) after the initial treatment period were allowed to proceed to the follow-up period. During the initial treatment period, 71 patients were treated with JELMYTO, of whom 41 were subsequently continued in the follow-up period. During the follow-up period, 29 patients received at least one dose of maintenance therapy. The baseline demographic and disease characteristics for the trial population were: median age 71 years (range: 42-87 years); 68% male; 87% White; 90% Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 and 10% ECOG PS 2. The median number of papillary lesions subsequent to debulking and/or biopsy and prior to treatment was 1 lesion (range: 1, 5), the median diameter of the largest lesion was 8.0 mm (range: 5.0, 15.0), and the median total visible tumor burden was 10.0 mm (range: 5.0, 25.0). Twenty-six (37%) patients underwent tumor debulking during the six weeks preceding enrollment. Of 71 enrolled patients, 48% had tumors located in regions not amenable to endoscopic resection. General anesthesia was used in 37% of patients for at least one instillation during the treatment period and for 83% of patients for at least one instillation during the follow-up period. The major efficacy outcome measures were CR and durability of CR at 12 months after determination of CR based on ureteroscopic and local pathology assessment. CR was defined as complete absence of tumor lesions in the ipsilateral pyelocalyceal system at 3 months after initiation of JELMYTO by urine cytology and ureteroscopy. Biopsy was performed if warranted. Durability of response in patients with a CR was evaluated at 3, 6, 9 and 12 months following the initial assessment. Assessment of durability of CR subsequent to these evaluations was performed per local standards of care. Forty-one patients (58%) achieved CR in the study (95% CI: 45%, 69%). Of the 41 patients who achieved CR, 23 (56%) of the patients remained at CR at the 12-month time point for assessment of durability, 8 (20%) experienced recurrence of disease, and 10 (24%) were unable to be evaluated (died, discontinued from the study, or were indeterminate for ongoing response). The median duration of response was not reached (range: 0, 18.8 months and ongoing).

emained at CR at the 12-month time point for assessment of durability, 8 (20%) experienced recurrence of disease, and 10 (24%) were unable to be evaluated (died, discontinued from the study, or were indeterminate for ongoing response). The median duration of response was not reached (range: 0, 18.8 months and ongoing). One patient, who achieved 6 months of durable CR, was diagnosed with metastatic urothelial carcinoma approximately 4.5 months after the last dose of study medication and died from the disease.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied JELMYTO kit – NDC 72493-103-03 JELMYTO is available in a kit containing the following: Two 40 mg (each) single-dose vials of mitomycin for pyelocalyceal solution supplied as a sterile, lyophilized, grey to greyish-purple, cake or powder. (NDC 72493-101-40) One 20 mL single-dose vial of sterile hydrogel supplied as a sterile, clear, colorless gel with or without bubbles at room temperature or clear, colorless liquid at 2°C to 8°C (36°F to 46°F), to be used as a vehicle for reconstitution. (NDC 72493-102-20) 16.2 Storage and Handling Store the JELMYTO kit at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Avoid excessive heat over 40°C (104°F). Protect from light. JELMYTO is a hazardous drug. Follow applicable special handling and disposal procedures . 1

16.2 Storage and Handling Store the JELMYTO kit at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Avoid excessive heat over 40°C (104°F). Protect from light. JELMYTO is a hazardous drug. Follow applicable special handling and disposal procedures . 1

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Ureteric Obstruction Inform patients that ureteric obstruction may occur, and ureteral stents or alternative procedures may be required during treatment with JELMYTO. Advise patients to contact their healthcare provider immediately if signs and symptoms of ureteric obstruction, including flank pain and/or fever, occur [see Warnings and Precautions (5.1) ]. Bone Marrow Suppression Inform patients that JELMYTO may decrease blood counts such as white blood cells and platelets. Thus, it is important that periodic assessment of their blood counts be performed to detect the development of neutropenia and thrombocytopenia [see Warnings and Precautions (5.2) ]. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare providers of a known or suspected pregnancy [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with JELMYTO and for 6 months following the last dose [see Use in Specific Populations (8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with JELMYTO and for 3 months following the last dose [see Use in Specific Populations (8.3) ]. Lactation Advise women not to breastfeed during treatment with JELMYTO and for 1 week following the last dose [see Use in Specific Populations (8.2) ]. Important Post-Treatment Instructions [see Dosage and Administration (2.1) ] Advise patients that JELMYTO contains mitomycin which is a violet to blue color and may discolor urine following the instillation procedure. Advise patients to avoid contact with urine for at least six hours post-instillation. Advise patients to void sitting on a toilet, flush the toilet several times after use, and to wash hands, perineum or glans with soap and water after each instillation procedure. Advise patients to wash clothing soiled with urine promptly and separately from other clothing.

Distributed by: UroGen Pharma, Inc. Princeton, NJ 08540 JELMYTO ® and UroGen ® are registered trademarks of UroGen Pharma, Ltd. U.S. Patent Nos. 9,040,074 and 9,950,069 Copyright© 2025 UroGen Pharma, Inc. All rights reserved. JEL-PI-005

Patient Information JELMYTO ® (jel-MYE-toe) (mitomycin) for pyelocalyceal solution This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 09/2022 What is JELMYTO? JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC). It is not known if JELMYTO is safe and effective for use in children. Who should not receive JELMYTO? Do not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract. Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you: are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. Females who are able to become pregnant: Your healthcare provider will check to see if you are pregnant before starting treatment with JELMYTO. You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. Talk to your healthcare provider if you have questions about birth control options that are right for you. Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose. are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. Especially tell your healthcare provider if you take water pills (diuretic). How will I receive JELMYTO? Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment. Your healthcare provider will provide instructions about how and when to take sodium bicarbonate. JELMYTO will be given to you by your healthcare provider. You will receive JELMYTO 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider's instructions. Your healthcare provider may recommend up to an additional 11 monthly doses. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. JELMYTO is given to your kidney through a tube called a catheter. During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines. Ask your healthcare provider if you have any questions. After receiving JELMYTO: JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours. To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.

color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours. To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water. Clothing that comes in contact with urine should be washed right away and washed separately from other clothing. What are the possible side effects of JELMYTO? JELMYTO may cause serious side effects, including: Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO. Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO. The most common side effects of JELMYTO include: urinary tract infection blood in your urine side pain nausea trouble with urination kidney problems vomiting tiredness stomach (abdomen) pain Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You can also report side effects to UroGen Pharma at 1-855-987-6436. General information about JELMYTO. Medicines are sometimes prescribed for purposes other than those listed in this Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about JELMYTO that is written for healthcare professionals. What are the ingredients of JELMYTO? Active ingredient: mitomycin Inactive ingredients: hydroxypropyl methylcellulose, mannitol, poloxamer, polyethylene glycol, and water for injection Distributed by: UroGen Pharma, Inc. Princeton, NJ 08540 JELMYTO ® and UroGen ® are registered trademarks of UroGen Pharma, Ltd. U.S. Patent Nos. 9,040,074 and 9,950,069 Copyright© 2022 UroGen Pharma, Inc. All rights reserved. JEL-PPI-003 For more information go to www.JELMYTO.com or call 1-855-987-6436.

<table width="90%"><col width="40%" align="left" valign="top"/><col width="40%" align="left" valign="top"/><col width="20%" align="right" valign="top"/><thead><tr><th styleCode="Lrule Rrule" align="center" colspan="3">Patient Information JELMYTO^&#xAE; (jel-MYE-toe) (mitomycin) for pyelocalyceal solution</th></tr></thead><tfoot><tr><td colspan="2" align="left" valign="top"> This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="right" valign="top">Revised: 09/2022 </td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">What is JELMYTO?</content> JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC). It is not known if JELMYTO is safe and effective for use in children.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Who should not receive JELMYTO? Do not receive JELMYTO if you</content> have a hole or tear (perforation) of your bladder or upper urinary tract.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:</content><list><item>are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. <content styleCode="bold">Females who are able to become pregnant:</content><list listType="unordered" styleCode="circle"><item>Your healthcare provider will check to see if you are pregnant before starting treatment with JELMYTO.</item><item>You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. </item><item>Talk to your healthcare provider if you have questions about birth control options that are right for you. </item></list><content styleCode="bold">Males being treated with JELMYTO:</content><list listType="unordered" styleCode="circle"><item>If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose. </item></list></item><item>are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose. </item></list><content styleCode="bold">Tell your healthcare provider about all the medicines you take</content>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. <content styleCode="bold">Especially tell your healthcare provider if you take water pills (diuretic).</content></td></tr><tr><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">How will I receive JELMYTO?</content><list listType="unordered" styleCode="disc"><item>Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.

take water pills (diuretic).</content></td></tr><tr><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">How will I receive JELMYTO?</content><list listType="unordered" styleCode="disc"><item>Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment. Your healthcare provider will provide instructions about how and when to take sodium bicarbonate.</item><item>JELMYTO will be given to you by your healthcare provider.</item><item>You will receive JELMYTO 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider&apos;s instructions. Your healthcare provider may recommend up to an additional 11 monthly doses.</item><item>If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.</item><item>JELMYTO is given to your kidney through a tube called a catheter.</item><item>During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines. Ask your healthcare provider if you have any questions.</item></list></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">After receiving JELMYTO:</content><list listType="unordered" styleCode="disc"><item>JELMYTO may cause your urine color to change to a violet to blue color.</item><item>Avoid contact between your skin and urine for at least 6 hours.</item><item>To urinate, <content styleCode="bold">males and females should sit</content> on a toilet and flush the toilet several times after you use it.</item><item>After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.</item><item>Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.</item></list></td></tr><tr><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">What are the possible side effects of JELMYTO? JELMYTO may cause serious side effects, including:</content><list listType="unordered" styleCode="disc"><item><content styleCode="bold">Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction).</content> If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.</item><item><content styleCode="bold">Bone marrow problems.</content> JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.</item></list></td></tr><tr><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">The most common side effects of JELMYTO include:</content></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="disc"><item>urinary tract infection</item><item>blood in your urine</item><item>side pain</item><item>nausea</item><item>trouble with urination</item></list></td><td styleCode="Rrule" colspan="2"><list listType="unordered" styleCode="disc"><item>kidney problems</item><item>vomiting</item><item>tiredness</item><item>stomach (abdomen) pain</item></list></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3">Call your doctor for medical advice about side effects.

<td styleCode="Rrule" colspan="2"><list listType="unordered" styleCode="disc"><item>kidney problems</item><item>vomiting</item><item>tiredness</item><item>stomach (abdomen) pain</item></list></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You can also report side effects to UroGen Pharma at 1-855-987-6436.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">General information about JELMYTO.</content> Medicines are sometimes prescribed for purposes other than those listed in this Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about JELMYTO that is written for healthcare professionals.</td></tr><tr><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">What are the ingredients of JELMYTO? Active ingredient:</content> mitomycin <content styleCode="bold">Inactive ingredients:</content> hydroxypropyl methylcellulose, mannitol, poloxamer, polyethylene glycol, and water for injection</td></tr><tr><td styleCode="Lrule Rrule" colspan="3"> Distributed by: <content styleCode="bold">UroGen Pharma, Inc.</content> Princeton, NJ 08540</td></tr><tr><td styleCode="Lrule Rrule" colspan="3">JELMYTO^&#xAE; and UroGen^&#xAE; are registered trademarks of UroGen Pharma, Ltd. U.S. Patent Nos. 9,040,074 and 9,950,069 Copyright&#xA9; 2022 UroGen Pharma, Inc. All rights reserved.</td></tr><tr><td styleCode="Lrule Rrule" colspan="3">JEL-PPI-003 For more information go to www.JELMYTO.com or call 1-855-987-6436.</td></tr></tbody></table>

INSTRUCTIONS FOR PHARMACY (IFP) JELMYTO ® (jel-MYE-toe) (mitomycin) for pyelocalyceal solution Purpose of this Instructions for Pharmacy This Instructions for Pharmacy contains information on how to prepare JELMYTO using pharmacy supplies and a Chilling Block. Intended Use of JELMYTO JELMYTO (mitomycin) for pyelocalyceal solution is indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC). Important Information You Need to Know Before Reconstituting JELMYTO Once reconstituted with sterile hydrogel, JELMYTO will appear as a semisolid gel. Once chilled, JELMYTO will convert to a viscous liquid. Reconstituted JELMYTO must be prepared under chilled conditions. A Chilling Block can be used for this purpose. JELMYTO cannot be prepared without the Chilling Block or other means of chilling. Preparation of JELMYTO must be performed under aseptic conditions. Storage Conditions and Handling Instill the JELMYTO solution as soon as possible after reconstitution. Store reconstituted JELMYTO at 20°C to 25°C (68°F to 77°F) for up to 96 hours (4 days). Protect from light. JELMYTO is a cytotoxic anti-cancer drug. Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed. Supplies Needed: JELMYTO Kit containing: 2 Vials of Mitomycin for Pyelocalyceal Solution, 40 mg/vial 1 Vial Sterile Hydrogel, 20 mL/vial 1 JELMYTO Admixture Label JELMYTO Full Prescribing Information (PI) JELMYTO Instructions for Pharmacy (IFP) JELMYTO Instructions for Administration (IFA) Pharmacy Supplies (Provided by Your Facility) Do not substitute any of these components . 3 × TEVADAPTOR ® or OnGuard ® 2 CSTD Vial Adaptors 3 × TEVADAPTOR ® or OnGuard ® 2 CSTD Syringe Adaptors 1 × Luer Lock connector 2 × 10 mL Luer Lock syringes 1 × 20 mL Luer Lock syringe 1 × 20-25G needle (for drawing up sterile water) 2 mL sterile water 70% Isopropyl alcohol or equivalent 1 × Light protective bag 1 × Chilling Block (device design may vary) Note: The day before your preparation, put the Chilling Block in the freezer at -20°C to -12°C (-4°F to 10.4°F) overnight. Please refer to the Chilling Block Instructions for Use for more information. Steps to Prepare JELMYTO Admixture A. Freeze Chilling Block The day before preparation, put the Chilling Block in the freezer at -20°C to -12°C (-4°F to 10.4°F) overnight. Note: Please refer to the Chilling Block Instructions for Use for additional information. B. Prepare Supplies Remove the Chilling Block from the freezer. Disinfect the Chilling Block with 70% Isopropyl alcohol or equivalent, as per your pharmacy's policy. Allow it to air dry, and then place it upright inside the hood or isolator. Wait 20 minutes before continuing. Connect vial adaptors to all three vials. Connect a syringe adaptor to one of the 10 mL syringes. Connect a syringe adaptor to the 20 mL syringe. Place the three vials, the 10 mL syringe, and the 20 mL syringe into the Chilling Block for at least 10 minutes. While the vials and syringes are in the Chilling Block, withdraw 2 mL of sterile water into the other 10 mL syringe and set aside for later use. C. Create Pre-Wetting Solution (PWS) Slowly fill the chilled 20 mL syringe with 14 mL of sterile hydrogel. Recap the chilled 20 mL syringe and place it in the Chilling Block. Slowly fill the chilled 10 mL syringe with 4 mL of sterile hydrogel. Discard the unused portion of sterile hydrogel. Replace the needle on 2 mL sterile water syringe with the Luer Lock connector.

he chilled 20 mL syringe with 14 mL of sterile hydrogel. Recap the chilled 20 mL syringe and place it in the Chilling Block. Slowly fill the chilled 10 mL syringe with 4 mL of sterile hydrogel. Discard the unused portion of sterile hydrogel. Replace the needle on 2 mL sterile water syringe with the Luer Lock connector. Remove the syringe adaptor from the 4 mL sterile hydrogel syringe. Connect the 4 mL sterile hydrogel syringe to the other side of the Luer Lock connector on the 2 mL sterile water syringe. Gently mix the sterile water with the sterile hydrogel by pushing the plungers back and forth at least 25 times to create the "pre-wetting solution" (PWS). Transfer the 6 mL PWS into one of the syringes. Replace the Luer Lock connector on the 6 mL PWS syringe with a new syringe adaptor. Place the 6 mL PWS syringe in the Chilling Block. D. Mix the Admixture Remove both JELMYTO vials from the Chilling Block. Gently tap the bottom of each vial on the table to ensure all the mitomycin powder is at the bottom of the vials. Remove the chilled 6 mL PWS syringe from the Chilling Block. Inject 3 mL of PWS into each JELMYTO vial. Note: To ensure accurate dosing, the contents of each vial must be the same. Discard the empty PWS syringe. Gently swirl each JELMYTO vial upright at least 15 times, ensuring all powder and admixture is contained at the bottom of the vial. Note: Do not invert or shake the vials. Immediately remove the chilled 14 mL sterile hydrogel syringe from the Chilling Block. Immediately inject 7 mL of sterile hydrogel into each JELMYTO vial. Note: To ensure accurate dosing, the contents of each vial must be the same. Gently swirl each JELMYTO vial upright at least 15 times, ensuring all admixture is contained at the bottom of the vial. Note: Do not invert or shake the vials. Recap and place the 20 mL syringe in the Chilling Block. Mix the JELMYTO admixture vials: Recap and place both JELMYTO vials in the Chilling Block for five minutes . Remove both vials and vigorously swirl them upright at least 15 times, ensuring all admixture is contained at the bottom of the vials. Place both vials back in the Chilling Block. Repeat these steps every five minutes for a total of 30 minutes. Note: Do not invert or shake the vials. E. Prepare Admixture Vial Remove one JELMYTO vial from the Chilling Block. Vigorously swirl the vial upright at least 15 times. Note: Do not invert or shake the vial. Using the chilled 20 mL syringe, slowly withdraw 7 mL of admixture from the vial. Note: If you are having difficulty withdrawing the admixture, place the components back in the Chilling Block until the admixture liquifies again. Discard the empty JELMYTO vial. Remove the remaining JELMYTO vial from the Chilling Block. Inject the contents of the 20 mL syringe into that vial. Now all the admixture is contained in one vial. Recap the vial adaptor. Vigorously swirl the vial upright at least 15 times. Note: Do not invert or shake the vial. Your JELMYTO admixture vial is now complete, with a resultant concentration of 4 mg of mitomycin per mL following reconstitution. F. Dispense Admixture Vial Write the "Discard after" date and time on the supplied admixture label and apply to the prepared JELMYTO admixture vial. You may also substitute your pharmacy's label for dispensing the admixture. Note: The "Discard after" date and time is 96 hours (4 days) from the completion of the preparation at room temperature. Place the JELMYTO admixture vial in a light-protective bag. Transport to the treatment facility along with the JELMYTO Instructions for Administration. Important to Remember All components must be kept cold during the preparation process by placing them in the Chilling Block when they are not in use.

room temperature. Place the JELMYTO admixture vial in a light-protective bag. Transport to the treatment facility along with the JELMYTO Instructions for Administration. Important to Remember All components must be kept cold during the preparation process by placing them in the Chilling Block when they are not in use. If you have difficulty pushing the solution or withdrawing the solution at any time, put the components back in the Chilling Block until the product liquifies. Frequently Asked Questions: How do I connect the vial adaptor? Place the vial adaptor over the vial and press down firmly. You will hear a snap which confirms successful attachment. How do I connect the syringe adaptor? Screw the Luer Lock end of the syringe adaptor onto the syringe hub until it is finger tight. How do I connect the syringe adaptor to the vial adaptor? Place the syringe adaptor over the vial adaptor and align the tabs, then press down firmly. You will hear a snap which confirms successful attachment. How do I disconnect the syringe adaptor from the vial adaptor? Pinch the tabs on the syringe adaptor to separate it from the vial adaptor. Do I need to put the caps on the syringes and vials before placing them back into the chilling block? YES, the chilling block inserts are not sterile. It is important to maintain aseptic technique. Do I have to keep the vials upright when mixing? If so, why? YES, the vials should be upright during all mixing to ensure the contents are fully mixed at the bottom of the vial. I am having difficulty working with the drug product. It seems to be solidifying. If you are having difficulty pushing the solution or withdrawing the solution, place the components back into the Chilling Block until the product liquifies. This "Instructions for Pharmacy" has been approved by the U.S. Food and Drug Administration. Distributed by: UroGen Pharma, Inc. Princeton, NJ 08540 www.JELMYTO.com JELMYTO ® and UroGen ® are registered trademarks of UroGen Pharma, Ltd. TEVADAPTOR ® is a registered trademark of Simplivia Healthcare Ltd. OnGuard ® is a registered trademark of B. Braun Medical Inc. Copyright© 2022 UroGen Pharma, Inc. All rights reserved. JEL-IFP-003 IFP-0002025/Ver. 4 Image Image Image Image Image Image Image Image Image Image

egistered trademarks of UroGen Pharma, Ltd. TEVADAPTOR ® is a registered trademark of Simplivia Healthcare Ltd. OnGuard ® is a registered trademark of B. Braun Medical Inc. Copyright© 2022 UroGen Pharma, Inc. All rights reserved. JEL-IFP-003 IFP-0002025/Ver. 4 Image Image Image Image Image Image Image Image Image Image INSTRUCTIONS FOR ADMINISTRATION (IFA) JELMYTO ® (jel-MYE-toe) (mitomycin) for pyelocalyceal solution For Pyelocalyceal Instillation Only Read and follow this Instructions for Administration prior to each JELMYTO instillation. Purpose of this Instructions for Administration This Instructions for Administration contains information on how to instill JELMYTO using the reconstituted JELMYTO vial which you received from the pharmacy and the devices listed under Supplies Needed , obtained by your facility. Intended Use of JELMYTO JELMYTO (mitomycin) for pyelocalyceal solution is indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC). Important Information You Need to Know Before Instilling JELMYTO JELMYTO must be reconstituted by a healthcare professional prior to instillation. Reconstituted JELMYTO will appear as a semisolid gel. Once chilled, JELMYTO will convert to a viscous liquid for instillation. Once instilled into the patient's pyelocalyceal system, JELMYTO will fill and conform to the cavity and become a gel, thereby exposing the tissue to mitomycin over a prolonged period of time. JELMYTO is viscous, even when it is a liquid in a chilled state. Therefore, you will need a Uroject12 Syringe Lever to instill JELMYTO into the patient. You cannot instill JELMYTO without the Uroject12 device. Reconstituted JELMYTO should be instilled as soon as possible after reconstitution. Store reconstituted JELMYTO at 20°C to 25°C (68°F to 77°F) for up to 96 hours (4 days). Protect from light. When ready to instill, chill JELMYTO to 27°F to 41°F (-3°C to 5°C) for at least 10 minutes, but no longer than one hour, to revert it to a liquid form . See the Steps A through E for complete administration instructions. JELMYTO is a cytotoxic anti-cancer drug. Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed. Supplies Needed: One vial of reconstituted JELMYTO, with a resultant concentration of 4 mg of mitomycin per mL following reconstitution. (prepared and provided by the pharmacy) JELMYTO vial Ancillary Supplies: (to be provided by your facility) Do not substitute any of these components . TEVADAPTOR ® Syringe Adaptor or OnGuard ® 2 CSTD Syringe Adaptor MEDALLION ® COP or MEDALLION ® Luer Lock syringe, 20 mL Ureteral Catheter with molded Luer lock port (5 Fr or 7 Fr) Uroject12 Syringe Lever Note: The Uroject12 Syringe Lever is a multi-use device and must be sterilized or disinfected before use. Please follow the sterilization or disinfection instructions detailed in the Uroject12 Syringe Lever Instructions for Use. An ice bath to chill the vial of JELMYTO prior to instillation. TEVADAPTOR ® or OnGuard ® 2 CSTD Syringe Adaptor MEDALLION ® COP or MEDALLION ® Luer Lock syringe, 20 mL Ureteral Catheter with molded Luer lock port Uroject12 Syringe Lever Ice Bath Instillation Instructions A. Measure the Kidney Volume The Instillation Volume will be equal to the patient's kidney volume. If the kidney volume is already known, proceed to Section B. If the kidney volume is NOT known, or needs to be reassessed, use the following steps: Perform a retrograde pyelogram using diluted contrast (50%) so that the entire renal pelvis and calyces are observed and contrast starts to flow below the ureteropelvic junction (UPJ). Record the volume of contrast injected at this point. Allow the contrast to drain from the kidney. This may take about five minutes.

s: Perform a retrograde pyelogram using diluted contrast (50%) so that the entire renal pelvis and calyces are observed and contrast starts to flow below the ureteropelvic junction (UPJ). Record the volume of contrast injected at this point. Allow the contrast to drain from the kidney. This may take about five minutes. Note: Do not withdraw contrast back into the syringe. Repeat Steps 1 through 3 two more times, for a total of three measurements to improve accuracy. Average the three volume measurements and round to the nearest whole number. This is the patient's kidney volume. B. Select the Instillation Volume Select the kidney volume OR 15 mL, whichever is lower , as the Instillation Volume. Note: Maximum Instillation Volume is 15 mL. Record this volume for future instillations. C. Chill the JELMYTO Place the JELMYTO vial in the ice bath for at least 10 minutes, but no longer than one hour. After at least 10 minutes , advance the ureteral catheter over the guidewire towards the target anatomy in the pyelocalyceal system. D. Prepare the Administration Syringe Once the vial is removed from the ice bath, you have 4 minutes to draw JELMYTO into the administration syringe before it solidifies. After 4 minutes, recap and place the components back in the ice bath for no more than 15 minutes to liquify the JELMYTO. Remove the JELMYTO vial from the ice bath and dry it off. Swirl the vial upright to ensure that JELMYTO is uniformly mixed. Connect the syringe adaptor to the 20 mL Luer Lock syringe. This will be the administration syringe. Slowly withdraw the calculated Instillation Volume of JELMYTO into the administration syringe. Press the "Clutch" button on the Uroject12 and pull the knob out. Insert the administration syringe into the Uroject12 Syringe Lever and rotate it clockwise until it locks in place. While pressing the "Clutch" button, advance the lever to just above the administration syringe's plunger. Immediately proceed with the instillation steps in Section E to avoid JELMYTO solidification. E. Instill JELMYTO Remove the syringe adaptor from the administration syringe. Note: If JELMYTO gets on to the syringe tip or the catheter's Luer Lock port, wipe it off immediately with sterile gauze so it does not solidify and prevent a secure connection. (Refer to Frequently Asked Questions for further details.) Connect the administration syringe to the ureteral catheter's Luer Lock port, by rotating the syringe only. Using fluoroscopy, ensure the ureteral catheter is in the desired anatomical position. Gradually instill the JELMYTO into the patient by turning the knob at a rate of 1-2 seconds per stroke. The entire syringe must be emptied within one minute. Remove the ureteral catheter from the urinary tract. Remove the administration syringe from the Uroject12 by rotating the syringe barrel counter-clockwise. Discard the administration ancillaries according to your facility's disposal procedures. Send the Uroject12 to be reprocessed according to your facility's procedures and the Uroject12 Syringe Lever Instructions for Use. Frequently Asked Questions: How do I connect the syringe adaptor? Screw the Luer Lock end of the syringe adaptor onto the syringe hub until it is finger tight. How do I connect the syringe adaptor to the vial adaptor? Place the syringe adaptor over the vial adaptor and align the tabs; then press down firmly. You will hear a snap which confirms successful attachment. How do I disconnect the syringe adaptor from the vial adaptor? Pinch the tabs on the syringe adaptor to separate it from the vial adaptor. I am having a hard time working with reconstituted JELMYTO. It seems to be solidifying. If you are having difficulty pushing or withdrawing JELMYTO, recap and place the components back into the ice bath until JELMYTO liquifies.

he vial adaptor? Pinch the tabs on the syringe adaptor to separate it from the vial adaptor. I am having a hard time working with reconstituted JELMYTO. It seems to be solidifying. If you are having difficulty pushing or withdrawing JELMYTO, recap and place the components back into the ice bath until JELMYTO liquifies. What should I do if there is JELMYTO spillage from the syringe tip? You will need to clean JELMYTO off the syringe tip and the Luer Lock port of the catheter to ensure the two components can connect securely. To clean the syringe tip, fold a sterile gauze pad in half twice, and push it into the inside of the Luer Lock port to wipe any JELMYTO off the threads. To clean the Luer Lock port on the catheter, use a sterile gauze pad to wipe off any JELMYTO. Verify that the connectors are clean to ensure a secure connection between the syringe and the catheter. This "Instructions for Administration" has been approved by the U.S. Food and Drug Administration. Distributed by: UroGen Pharma, Inc. Princeton, NJ 08540 www.JELMYTO.com JELMYTO ® and UroGen ® are registered trademarks of UroGen Pharma, Ltd. TEVADAPTOR ® is a registered trademark of Simplivia Healthcare Ltd. OnGuard ® is a registered trademark of B. Braun Medical Inc. MEDALLION ® is a registered trademark of Merit Medical Systems, Inc. Copyright© 2022 UroGen Pharma, Inc. All rights reserved. JEL-IFU-003 IFU-Phy-0006722/Ver. 5 Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image

<table width="80%"><col width="78%" align="left" valign="top"/><col width="14%" align="center" valign="top"/><col width="8%" align="center" valign="top"/><tbody><tr><td styleCode="Lrule Rrule Botrule" rowspan="2"><content styleCode="bold">JELMYTO Kit containing:</content><list><item>2 Vials of Mitomycin for Pyelocalyceal Solution, 40 mg/vial</item><item>1 Vial Sterile Hydrogel, 20 mL/vial</item><item>1 JELMYTO Admixture Label</item><item>JELMYTO Full Prescribing Information (PI)</item><item>JELMYTO Instructions for Pharmacy (IFP)</item><item>JELMYTO Instructions for Administration (IFA)</item></list></td><td styleCode="Rrule" colspan="2"><renderMultiMedia referencedObject="MM2"/></td></tr><tr><td styleCode="Botrule" align="center"><renderMultiMedia referencedObject="MM3"/></td><td styleCode="Rrule Botrule"><renderMultiMedia referencedObject="MM4"/></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">Pharmacy Supplies</content> (Provided by Your Facility) <content styleCode="bold">Do not substitute any of these components</content>.<list><item>3 &#xD7; TEVADAPTOR^&#xAE; or OnGuard^&#xAE;2 CSTD Vial Adaptors</item><item>3 &#xD7; TEVADAPTOR^&#xAE; or OnGuard^&#xAE;2 CSTD Syringe Adaptors</item><item>1 &#xD7; Luer Lock connector</item><item>2 &#xD7; 10 mL Luer Lock syringes</item><item>1 &#xD7; 20 mL Luer Lock syringe</item><item>1 &#xD7; 20-25G needle (for drawing up sterile water) </item><item>2 mL sterile water</item><item>70% Isopropyl alcohol or equivalent</item><item>1 &#xD7; Light protective bag</item><item>1 &#xD7; Chilling Block (device design may vary)</item></list><content styleCode="bold">Note:</content> The day before your preparation, put the Chilling Block in the freezer at -20&#xB0;C to -12&#xB0;C (-4&#xB0;F to 10.4&#xB0;F) overnight. Please refer to the Chilling Block Instructions for Use for more information.</td><td styleCode="Rrule" colspan="2"><renderMultiMedia referencedObject="MM5"/></td></tr></tbody></table>

he day before your preparation, put the Chilling Block in the freezer at -20&#xB0;C to -12&#xB0;C (-4&#xB0;F to 10.4&#xB0;F) overnight. Please refer to the Chilling Block Instructions for Use for more information.</td><td styleCode="Rrule" colspan="2"><renderMultiMedia referencedObject="MM5"/></td></tr></tbody></table> <table width="80%"><col width="70%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I connect the vial adaptor?</content> Place the vial adaptor over the vial and press down firmly. You will hear a snap which confirms successful attachment.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM7"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I connect the syringe adaptor?</content> Screw the Luer Lock end of the syringe adaptor onto the syringe hub until it is finger tight.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM8"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I connect the syringe adaptor to the vial adaptor?</content> Place the syringe adaptor over the vial adaptor and align the tabs, then press down firmly. You will hear a snap which confirms successful attachment.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM9"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I disconnect the syringe adaptor from the vial adaptor?</content> Pinch the tabs on the syringe adaptor to separate it from the vial adaptor.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM10"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2"><content styleCode="bold">Do I need to put the caps on the syringes and vials before placing them back into the chilling block?</content> YES, the chilling block inserts are not sterile. It is important to maintain aseptic technique.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Do I have to keep the vials upright when mixing? If so, why?</content> YES, the vials should be upright during all mixing to ensure the contents are fully mixed at the bottom of the vial.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM11"/></td></tr><tr><td styleCode="Lrule Rrule" colspan="2"><content styleCode="bold">I am having difficulty working with the drug product. It seems to be solidifying.</content> If you are having difficulty pushing the solution or withdrawing the solution, place the components back into the Chilling Block until the product liquifies.</td></tr></tbody></table>

Rrule" colspan="2"><content styleCode="bold">I am having difficulty working with the drug product. It seems to be solidifying.</content> If you are having difficulty pushing the solution or withdrawing the solution, place the components back into the Chilling Block until the product liquifies.</td></tr></tbody></table> <table width="65%" styleCode="Noautorules"><col width="5%" align="center" valign="middle"/><col width="95%" align="left" valign="middle"/><tbody><tr><td styleCode="Lrule Toprule Botrule"><renderMultiMedia referencedObject="MM12"/></td><td styleCode="Rrule Toprule Botrule"><content styleCode="bold">Read and follow this Instructions for Administration prior to each JELMYTO instillation.</content></td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="10%" align="center" valign="top"/><col width="90%" align="center" valign="top"/><tbody><tr><td styleCode="Lrule Toprule Rrule Botrule"><renderMultiMedia referencedObject="MM13"/></td><td/></tr><tr><td><content styleCode="bold">JELMYTO vial</content></td><td/></tr></tbody></table> <table width="45%" styleCode="Noautorules"><col width="5%" align="center" valign="middle"/><col width="95%" align="left" valign="middle"/><tbody><tr><td styleCode="Lrule Toprule Botrule"><renderMultiMedia referencedObject="MM14"/></td><td styleCode="Rrule Toprule Botrule"><content styleCode="bold">Do not substitute any of these components</content>. </td></tr></tbody></table>

align="center" valign="middle"/><col width="95%" align="left" valign="middle"/><tbody><tr><td styleCode="Lrule Toprule Botrule"><renderMultiMedia referencedObject="MM14"/></td><td styleCode="Rrule Toprule Botrule"><content styleCode="bold">Do not substitute any of these components</content>. </td></tr></tbody></table> <table width="90%" styleCode="Noautorules"><col width="33%" align="center" valign="middle"/><col width="33%" align="center" valign="middle"/><col width="34%" align="center" valign="middle"/><tbody><tr><td><renderMultiMedia referencedObject="MM15"/></td><td><renderMultiMedia referencedObject="MM16"/></td><td><renderMultiMedia referencedObject="MM17"/></td></tr><tr><td><content styleCode="bold">TEVADAPTOR^&#xAE; or OnGuard^&#xAE;2 CSTD Syringe Adaptor</content></td><td><content styleCode="bold">MEDALLION^&#xAE; COP or MEDALLION^&#xAE; Luer Lock syringe, 20 mL</content></td><td><content styleCode="bold">Ureteral Catheter with molded Luer lock port</content></td></tr><tr><td><renderMultiMedia referencedObject="MM18"/></td><td><renderMultiMedia referencedObject="MM19"/></td><td/></tr><tr><td><content styleCode="bold">Uroject12 Syringe Lever</content></td><td><content styleCode="bold">Ice Bath</content></td><td/></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="80%" align="left" valign="top"/><col width="20%" align="left" valign="top"/><tbody><tr><td><list listType="ordered" styleCode="Arabic"><item>Place the JELMYTO vial <content styleCode="bold">in the ice bath for at least 10 minutes, but no longer than one hour.</content></item><item><content styleCode="bold">After at least 10 minutes</content>, advance the ureteral catheter over the guidewire towards the target anatomy in the pyelocalyceal system.</item></list></td><td><paragraph><renderMultiMedia referencedObject="MM20"/></paragraph></td></tr></tbody></table>

than one hour.</content></item><item><content styleCode="bold">After at least 10 minutes</content>, advance the ureteral catheter over the guidewire towards the target anatomy in the pyelocalyceal system.</item></list></td><td><paragraph><renderMultiMedia referencedObject="MM20"/></paragraph></td></tr></tbody></table> <table width="100%" styleCode="Noautorules"><col width="80%" align="left" valign="top"/><col width="20%" align="left" valign="top"/><tbody><tr><td>Once the vial is removed from the ice bath, <content styleCode="bold">you have 4 minutes to draw JELMYTO into the administration syringe</content> before it solidifies. After 4 minutes, recap and place the components back in the ice bath for no more than 15 minutes to liquify the JELMYTO.</td><td><paragraph><renderMultiMedia referencedObject="MM21"/></paragraph></td></tr></tbody></table>

you have 4 minutes to draw JELMYTO into the administration syringe</content> before it solidifies. After 4 minutes, recap and place the components back in the ice bath for no more than 15 minutes to liquify the JELMYTO.</td><td><paragraph><renderMultiMedia referencedObject="MM21"/></paragraph></td></tr></tbody></table> <table width="80%"><col width="70%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I connect the syringe adaptor?</content> Screw the Luer Lock end of the syringe adaptor onto the syringe hub until it is finger tight.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM26"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I connect the syringe adaptor to the vial adaptor?</content> Place the syringe adaptor over the vial adaptor and align the tabs; then press down firmly. You will hear a snap which confirms successful attachment.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM27"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">How do I disconnect the syringe adaptor from the vial adaptor?</content> Pinch the tabs on the syringe adaptor to separate it from the vial adaptor.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM28"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">I am having a hard time working with reconstituted JELMYTO. It seems to be solidifying.</content> If you are having difficulty pushing or withdrawing JELMYTO, recap and place the components back into the ice bath until JELMYTO liquifies.</td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM29"/></td></tr><tr><td styleCode="Lrule Rrule"><content styleCode="bold">What should I do if there is JELMYTO spillage from the syringe tip?</content> You will need to clean JELMYTO off the syringe tip and the Luer Lock port of the catheter to ensure the two components can connect securely.<list><item>To clean the syringe tip, fold a sterile gauze pad in half twice, and push it into the inside of the Luer Lock port to wipe any JELMYTO off the threads.</item><item>To clean the Luer Lock port on the catheter, use a sterile gauze pad to wipe off any JELMYTO.</item></list> Verify that the connectors are clean to ensure a secure connection between the syringe and the catheter. </td><td styleCode="Rrule"><renderMultiMedia referencedObject="MM30"/></td></tr></tbody></table>