KRESLADI

5 WARNINGS AND PRECAUTIONS Serious Infections: Monitor patients for signs and symptoms of infection before and after KRESLADI infusion and treat appropriately. Administer prophylactic antimicrobials according to institutional guidelines. ( 5.1 ) Veno-Occlusive Disease: Monitor patients for signs and symptoms of veno-occlusive disease including assessment of liver function tests during the first month following KRESLADI infusion. ( 5.2 ) Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after KRESLADI infusion. If neutrophil engraftment does not occur administer rescue cells. ( 5.3 ) Delayed Platelet Engraftment: Monitor patients for thrombocytopenia and bleeding until platelet engraftment and count recovery. ( 5.4 ) LVV-mediated Insertional Oncogenesis: Monitor patients at least annually for hematologic malignancies for at least 15 years after KRESLADI infusion. ( 5.5 ) Hypersensitivity Reactions: Monitor for hypersensitivity reactions during the infusion. ( 5.6 ) 5.1 Serious Infections Serious infections have occurred with KRESLADI administration [see Adverse Reactions (6.1) ]. Increased susceptibility to infections may occur due to administration of myeloablative conditioning prior to KRESLADI infusion. Monitor patients for signs and symptoms of infection before and after KRESLADI infusion and treat appropriately. Administer prophylactic antimicrobials according to institutional guidelines. Avoid administration of KRESLADI in patients with active bloodstream infections or other serious, untreated infections. Any blood products required after KRESLADI infusion should be irradiated. 5.2 Veno-Occlusive Disease Veno-occlusive disease has occurred with KRESLADI treatment [see Adverse Reactions (6.1) ]. Increased susceptibility to veno-occlusive disease may occur due to administration of myeloablative conditioning prior to KRESLADI infusion. Monitor patients for signs and symptoms of veno-occlusive disease including assessment of liver function tests during the first month following KRESLADI infusion. 5.3 Neutrophil Engraftment Failure Neutrophil engraftment failure may occur after treatment with KRESLADI. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of KRESLADI. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with KRESLADI, provide rescue treatment with the back-up collection of CD34+ cells [see Preparation Before KRESLADI Infusion (2.2) ] . 5.4 Delayed Platelet Engraftment Delayed platelet engraftment may occur after treatment with KRESLADI. Monitor platelet counts and bleeding until platelet engraftment and platelet recovery are achieved. 5.5 LVV-Mediated Insertional Oncogenesis Lentiviral vector (LVV)-mediated insertional oncogenesis may occur after treatment with KRESLADI. Hematologic malignancy is a lifelong risk and patients treated with KRESLADI may develop hematologic malignancy at any time following treatment. Monitor for hematologic malignancies clinically, and with a complete blood count (with differential) at least annually and integration site analysis as warranted for at least 15 years after treatment with KRESLADI and as clinically indicated. If malignancy is detected in any patient who received KRESLADI, contact Rocket Pharmaceuticals, Inc. at 1-800-982-2410 for reporting and to obtain instructions on collection of samples for testing. 5.6 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis may occur with the infusion of KRESLADI. The dimethyl sulfoxide (DMSO) in KRESLADI may cause hypersensitivity reactions which may occur in patients with and without prior exposure to DMSO. Monitor patients for signs and symptoms of hypersensitivity reactions during and after KRESLADI infusion. If a hypersensitivity reaction occurs, pause infusion if ongoing and manage according to clinical practice. 5.7 Anti-retroviral Use Anti-retroviral medications may interfere with manufacturing of KRESLADI [see Drug Interactions (7.2) ] . If a patient requires anti-retrovirals for HIV prophylaxis, mobilization and apheresis of CD34+ cells for KRESLADI manufacturing should be delayed until HIV infection is adequately ruled out. Patients should not take anti-retroviral medications for at least one month prior to mobilization, or for the expected duration required for the elimination of the anti-retroviral medications, and until all cycles of apheresis are completed. 5.8 Interference with Serology Testing Patients who have received KRESLADI are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to LVV provirus insertion resulting in a false-positive test for HIV. Therefore, patients who have received KRESLADI should not be screened for HIV infection using a PCR-based assay. 5.9 Blood, organ, tissue and cell donation Patients treated with KRESLADI should not donate blood, organs, tissues, or cells for transplantation at any time in the future.

6 ADVERSE REACTIONS The most common non-laboratory adverse reactions (≥ 30%): mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection. ( 6.1 ) The most common laboratory adverse reactions (≥ 30%): hemoglobin decreased, platelet count decreased, neutrophil count decreased, leukocyte count decreased, aspartate aminotransferase increased, and alanine aminotransferase increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rocket Pharmaceuticals at 1-800-982-2410 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to KRESLADI in one clinical study (Study RP-L201-0318). A total of 9 pediatric patients with severe LAD-I received a single dose of intravenous KRESLADI with a median dose of 4.3 × 10 6 CD34+ cells/kg (range: 2.8 to 10 CD34+ cells/kg) [see Clinical Studies (14) ]. The median duration of follow up after KRESLADI administration was 4.2 years (range: 3.6 to 5.7 years). Serious adverse reactions were reported in 4 patients (44%) including serious infections (n=4), pulmonary arterial hypertension (n=1), sensorineural deafness (n=1), and veno-occlusive disease (n=1). Table 1 presents the most common adverse reactions reported in Study RP-L201-0318. Table 1: Non-Laboratory Adverse Reactions Reported in ≥ 20% of Patients in Study RP-L201-0318 (N=9) Adverse Reaction All Grades (%) Grade ≥3 (%) Gastrointestinal disorders Note: Adverse reactions are defined as adverse events that occurred from myeloablative conditioning administration through year 2 following KRESLADI administration. Nausea/Vomiting Includes multiple related terms 4 (44%) 0 Constipation 2 (22%) 0 General disorders and administration site conditions Mucositis 8 (89%) 5 (56%) Febrile neutropenia 6 (67%) 6 (67%) Pyrexia 3 (33%) 0 Infections and infestations Upper respiratory tract infection 8 (89%) 5 (56%) Viral infection 7 (78%) 1 (11%) Skin infection 3 (33%) 0 Device-related infection Device-related infection includes vascular device infection, device related bacteremia, and bacteremia that occurred with a central line in place 3 (33%) 2 (22%) Lower respiratory tract infection 2 (22%) 1 (11%) Gastroenteritis 2 (22%) 1 (11%) Skin candidiasis 2 (22%) 0 Urinary tract infection 2 (22%) 0 Skin and subcutaneous tissue disorders Skin lesion Skin lesion includes pyoderma gangrenosum, skin lesion, aseptic pustule, lip erythema, hand erythema, skin erythema at port site, and skin hyperpigmentation 6 (67%) 1 (11%) Rash Rash includes rash, eczema, atopic dermatitis and diaper dermatitis 4 (44%) 0 Alopecia 2 (22%) 0 Table 2 presents laboratory abnormalities that worsened from baseline in ≥20% of patients in Study RP-L201-0318. Table 2: Laboratory Abnormalities that Worsened from Baseline Reported in ≥ 20% of Patients in Study RP-L201-0318 (N=9) Baseline laboratory values were assessed prior to myeloablative conditioning Laboratory Abnormality All events occurred within 30 days post-infusion except for liver enzymes increased, which occurred in 3 patients within 30 days and in one patient after 90 days post-infusion All Grades (%) Grade ≥ 3 (%) Hemoglobin decreased 9 (100%) 9 (100%) Platelet count decreased 9 (100%) 9 (100%) Neutrophil count decreased 9 (100%) 9 (100%) Leukocyte count decreased 5 (56%) 5 (56%) Aspartate aminotransferase increased 4 (44%) 0 Alanine aminotransferase increased 3 (33%) 0

<table width="80%"><caption>Table 1: Non-Laboratory Adverse Reactions Reported in &#x2265; 20% of Patients in Study RP-L201-0318 (N=9)</caption><col width="45%" align="left" valign="middle"/><col width="25%" align="center" valign="middle"/><col width="30%" align="center" valign="middle"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule" align="center">Adverse Reaction</th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265;3 (%)</th></tr><tr><th styleCode="Lrule Rrule" colspan="3">Gastrointestinal disorders</th></tr></thead><tfoot><tr><td colspan="3">Note: Adverse reactions are defined as adverse events that occurred from myeloablative conditioning administration through year 2 following KRESLADI administration.</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea/Vomiting<footnote ID="fnt1a">Includes multiple related terms</footnote></td><td styleCode="Rrule">4 (44%)</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Constipation</td><td styleCode="Rrule">2 (22%)</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">General disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Mucositis<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">8 (89%)</td><td styleCode="Rrule">5 (56%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Febrile neutropenia</td><td styleCode="Rrule">6 (67%)</td><td styleCode="Rrule">6 (67%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">3 (33%)</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Infections and infestations</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Upper respiratory tract infection<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">8 (89%)</td><td styleCode="Rrule">5 (56%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Viral infection<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">7 (78%)</td><td styleCode="Rrule">1 (11%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Skin infection<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">3 (33%)</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Device-related infection<footnote>Device-related infection includes vascular device infection, device related bacteremia, and bacteremia that occurred with a central line in place</footnote></td><td styleCode="Rrule">3 (33%)</td><td styleCode="Rrule">2 (22%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lower respiratory tract infection<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">2 (22%)</td><td styleCode="Rrule">1 (11%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Gastroenteritis</td><td styleCode="Rrule">2 (22%)</td><td styleCode="Rrule">1 (11%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Skin candidiasis<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">2 (22%)</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urinary tract infection<footnoteRef IDREF="fnt1a"/></td><td styleCode="Rrule">2 (22%)</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Skin lesion<footnote>Skin lesion includes pyoderma gangrenosum, skin lesion, aseptic pustule, lip erythema, hand erythema, skin erythema at port site, and skin hyperpigmentation</footnote></td><td styleCode="Rrule">6 (67%)</td><td styleCode="Rrule">1 (11%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rash<footnote>Rash includes rash, eczema, atopic dermatitis and diaper dermatitis</footnote></td><td styleCode="Rrule">4 (44%)</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule"> Alopecia</td><td styleCode="Rrule">2 (22%)</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="80%"><caption>Table 2: Laboratory Abnormalities that Worsened from Baseline Reported in &#x2265; 20% of Patients in Study RP-L201-0318 (N=9)<footnote>Baseline laboratory values were assessed prior to myeloablative conditioning</footnote></caption><col width="50%" align="left" valign="middle"/><col width="25%" align="center" valign="middle"/><col width="25%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule">Laboratory Abnormality<footnote>All events occurred within 30 days post-infusion except for liver enzymes increased, which occurred in 3 patients within 30 days and in one patient after 90 days post-infusion</footnote></th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hemoglobin decreased</td><td styleCode="Rrule">9 (100%)</td><td styleCode="Rrule">9 (100%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Platelet count decreased</td><td styleCode="Rrule">9 (100%)</td><td styleCode="Rrule">9 (100%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Neutrophil count decreased</td><td styleCode="Rrule">9 (100%)</td><td styleCode="Rrule">9 (100%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Leukocyte count decreased</td><td styleCode="Rrule">5 (56%)</td><td styleCode="Rrule">5 (56%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Aspartate aminotransferase increased</td><td styleCode="Rrule">4 (44%)</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule">Alanine aminotransferase increased</td><td styleCode="Rrule">3 (33%)</td><td styleCode="Rrule">0</td></tr></tbody></table>