ZEVASKYN

1 INDICATIONS AND USAGE ZEVASKYN is indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB). ZEVASKYN is an autologous cell sheet-based gene therapy indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB). ( 1 )

2 DOSAGE AND ADMINISTRATION For autologous topical application on wounds only The recommended dose of ZEVASKYN is based on the surface area of the wound(s). One sheet of ZEVASKYN covers an area of 41.25 cm 2 . ( 2.1 ) Up to twelve ZEVASKYN sheets may be manufactured from the patient biopsies and supplied for potential use. ( 2.1 ) Verify the patient’s identity prior to ZEVASKYN application. ( 2.2 ) See full prescribing information for ZEVASKYN preparation, and administration instructions. ( 2.2 , 2.3 ) Figure 1 2.1 Recommended Dose For autologous topical application on wounds only. The recommended dose of ZEVASKYN is based on the surface area of the wound(s). One sheet of ZEVASKYN covers an area of 41.25 cm 2 . Up to twelve ZEVASKYN sheets may be manufactured from the patient biopsies and supplied for potential use. 2.2 Receipt and Preparation Receipt of ZEVASKYN ZEVASKYN is shipped directly to the qualified treatment center sealed in transport packaging. If the patient is expected to be ready for same-day application, transport the packaging to the operating room. Hold at room temperature (15-25°C) until preparation to maintain cell viability. If the patient is not expected to be ready for same-day application, store the packaging containing ZEVASKYN in a secure onsite location at room temperature (15-25°C) until preparation to maintain cell viability. Preparation ZEVASKYN is to be prepared by the manufacturer in an appropriate healthcare setting for surgical application by a qualified healthcare provider. Manufacturer will conduct Quality Control (QC) testing to release the product immediately prior to surgery in the operating room. Verify patient’s identity during preparation. Hold ZEVASKYN at room temperature (15-25°C) until application. Apply all selected sheets in a single surgical session. 2.3 Administration Below is the list of standard surgical supplies needed for ZEVASKYN administration and not provided by the manufacturer: scalpel scissors forceps resorbable sutures non-adhesive dressings topical antibiotic ointment 1. Verify patient’s identity prior to ZEVASKYN application. Do not apply ZEVASKYN if the information on the patient-specific label(s) does not match the intended patient. 2. Prepare wound by debridement under general or other appropriate anesthesia to accommodate ZEVASKYN sheet(s). 3. Before surgical application, pick up ZEVASKYN sheet with forceps by grasping the titanium ligating clips (Figure 1). Handle ZEVASKYN sheets only with forceps and only by the titanium ligating clips. Figure 1. ZEVASKYN sheets removed with forceps for application 4. Do not trim ZEVASKYN sheets. 5. Apply unaltered ZEVASKYN sheets onto the wound bed only (nylon suture on the ZEVASKYN sheet facing away from wound) by affixing via resorbable sutures. Do not suture ZEVASKYN onto healthy intact skin. Do not overlap ZEVASKYN sheets on wounds. 6. Apply all selected sheets in a single surgical session. 7. Cover area of application of ZEVASKYN sheets with non-adhesive dressings and topical antibiotic ointment. After ZEVASKYN application 8. Instruct patient to leave the treated area undisturbed for 5-10 days at the discretion of the physician based on individual needs for immobilization of treated areas and post-surgical recovery. 9. Instruct patient to keep dressings dry and not submerge the treated area in water until the gauze of the ZEVASKYN product falls off the treatment site. Gauze backing should fall off within 2-3 weeks of ZEVASKYN surgical application.

4 CONTRAINDICATIONS None. None.

5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions to vancomycin, amikacin, or product excipients may occur with ZEVASKYN application. ( 5.1 ) Retroviral vector (RVV)-mediated insertional oncogenesis may potentially occur after treatment with ZEVASKYN. ( 5.2 ) Transmission of Infectious Agents may occur because ZEVASKYN is manufactured using human- and bovine-derived reagents. ( 5.3 ) 5.1 Hypersensitivity Reactions Severe hypersensitivity reactions to vancomycin, amikacin, or product excipients may occur with ZEVASKYN application. Monitor for signs and symptoms of hypersensitivity reactions such as itching, swelling, hives, difficulty breathing, runny nose, watery eyes, nausea, and in severe cases, anaphylaxis and treat according to standard clinical practice. 5.2 R etroviral Vector (R VV ) -Mediated I nsertional O ncogenesis RVV-mediated insertional oncogenesis may potentially occur after treatment with ZEVASKYN [see N onclinical T oxicology ( 13 ) ] . Monitor patients lifelong after treatment with ZEVASKYN for the development of malignancies. In the event that a malignancy occurs, contact Abeona Therapeutics Inc. at 1-844-888-2236 to obtain instructions on collecting patient samples for testing. 5. 3 Transmission of Infectious Agents Transmission of infectious disease or agents may occur with ZEVASKYN administration because it is manufactured using human and bovine-derived reagents, which are tested for human and animal viruses, bacteria, fungi, and mycoplasma before use. These measures do not eliminate the risk of transmitting these or other infectious diseases or agents.

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥5%) were procedural pain and pruritus. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Abeona Therapeutics Inc at 1-844-888-2236 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to the rates in the clinical trials of another product and may not reflect the rates observed in practice. The safety data described in this section reflects exposure of 11 patients to ZEVASKYN in the VIITAL study [see Clinical Studies ( 14 ) ] . The median number of sheets patients received was 6 (range 3-6), and the total exposure time was 6 months following ZEVASKYN application. The most common adverse reactions occurring in ≥5% of patients were procedural pain (n=3; 27%) and pruritus (n=1; 9%).

8.1 Pregnancy Risk Summary There are no available data with ZEVASKYN use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with ZEVASKYN. 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. Clinical Considerations Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy at the time of treatment with ZEVASKYN.