Mitosol

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.

4 CONTRAINDICATIONS • Hypersensitivity to mitomycin. ( 4.1 ) 4.1 Hypersensitivity Mitosol ® is contraindicated in patients that have demonstrated a hypersensitivity to mitomycin in the past.

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.

8.1 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.