LYFGENIA

1 INDICATIONS AND USAGE LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events. LYFGENIA is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events. ( 1 ) Limitations of Use Following treatment with LYFGENIA, patients with α-thalassemia trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions. LYFGENIA has not been studied in patients with more than two α-globin gene deletions. ( 1 ) Limitations of Use Following treatment with LYFGENIA, patients with α-thalassemia trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions [see Adverse Reactions (6.1) ] . LYFGENIA has not been studied in patients with more than two α-globin gene deletions.

2 DOSAGE AND ADMINISTRATION For autologous use only. For one-time single-dose intravenous use only. For autologous use only. For intravenous use only. Patients are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for LYFGENIA manufacturing. ( 2.2 ) Dosing of LYFGENIA is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. ( 2.1 ) The minimum recommended dose is 3 × 10 6 CD34+ cells/kg. ( 2.1 ) Myeloablative conditioning must be administered before infusion of LYFGENIA. ( 2.2 ) Following myeloablative conditioning, allow a minimum of 48 hours of washout before LYFGENIA infusion. ( 2.2 ) Verify that the patient's identity matches the unique patient identification information on the LYFGENIA infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, irradiate, or refreeze LYFGENIA. ( 2.2 ) Do not use an in-line blood filter or an infusion pump. ( 2.3 ) Administer LYFGENIA within 4 hours after thawing. ( 2.3 ) Administer each infusion bag of LYFGENIA via intravenous infusion over a period of less than 30 minutes. ( 2.3 ) 2.1 Dose LYFGENIA is provided as a single dose for infusion containing a suspension of CD34+ cells in one to four infusion bags. The minimum recommended dose of LYFGENIA is 3 × 10 6 CD34+ cells/kg. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose. 2.2 Preparation Before LYFGENIA Infusion Confirm that autologous hematopoietic stem cell (HSC) transplantation is appropriate for the patient before mobilization and apheresis and before myeloablative conditioning are initiated. Perform screening for infectious diseases, specifically human immunodeficiency virus 1 & 2 (HIV-1/HIV-2), in accordance with clinical guidelines before collection of cells for manufacturing. There are no data on use of LYFGENIA in HIV-positive patients. Prepare for Mobilization and Apheresis Prepare patients for mobilization with at least 2 cycles of scheduled transfusions (one each month) with erythrocytapheresis being preferred. For at least 60 days prior to mobilization and through myeloablative conditioning, patients should undergo a transfusion regimen to reach a target Hb of 8-10 g/dL, not to exceed 12 g/dL, and HbS of less than 30% to reduce the risk of SCD-related complications. Perform erythrocytapheresis within a recommended 4 days preceding mobilization to reach the target of less than 30% HbS. Manage other concomitant medications (as applicable) as described below: Hydroxyurea: Discontinue at least 2 months prior to mobilization. Patients should not resume hydroxyurea until all cycles of apheresis are completed. Disease-modifying agents (e.g., L-glutamine, voxelotor and crizanlizumab): Discontinue at least 2 months prior to mobilization as the interaction between disease modifying agents and mobilization agents is unknown. Erythropoietin: Discontinue at least 2 months prior to mobilization. Iron chelation: Discontinue at least 7 days prior to mobilization. Granulocyte-colony stimulating factor (G-CSF): Do not administer G-CSF prior to or with mobilization agents. Anti-retrovirals: Discontinue prophylactic HIV anti-retroviral medications at least one month prior to mobilization and do not resume until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. Mobilization and Apheresis Perform HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing. Administer plerixafor to mobilize stem cells prior to the apheresis procedure at a dose of 0.24 mg/kg/day. 1 Begin apheresis approximately 4 to 6 hours after plerixafor administration. If more than one apheresis day is required, confirm platelet counts to be ≥ 75 × 10 9 /L within 24 hours of subsequent apheresis sessions, prior to administration of plerixafor on that day. If platelet counts do not meet these criteria, defer mobilization and apheresis until the platelet counts recover to ≥ 75 × 10 9 /L. For patients undergoing more than 1 mobilization cycle, separate each cycle by at least 14 days. Administer daily plerixafor 4 to 6 hours prior to each apheresis collection. If a sufficient number of cells are collected after the first mobilization cycle, no further mobilization/apheresis is required. In clinical studies, the minimum number of CD34+ cells to manufacture LYFGENIA was collected in most patients with 1 or 2 cycles of mobilization and apheresis which typically required 2 consecutive collection days per cycle. Maximize CD34+ cell collection to obtain as many CD34+ stem cells as possible for product manufacturing during each mobilization and apheresis cycle. Target a minimum collection of 16.5 × 10 6 CD34+ cells/kg for manufacturing and back-up. If, after manufacturing, the minimum dose of 3 × 10 6 CD34+ cells/kg is not achieved, the patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, to obtain more cells for additional manufacture. Multiple drug product lots may be administered to comprise the final dose. Retain ≥ 1.5 × 10 6 CD34+ cells/kg from the collection for back-up. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning. The back-up collection may be needed for rescue treatment if there is: 1) compromise of hematopoietic stem cells or LYFGENIA before infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with LYFGENIA. Manage concomitant medications (as applicable) between apheresis and conditioning as described below: Transfusions: Scheduled transfusions can be continued between apheresis and conditioning. Patients should maintain total hemoglobin (Hb) levels of 8 to 10 g/dL. Hb levels should not exceed 12 g/dL. A scheduled transfusion should be performed within 2 days prior to conditioning. Hydroxyurea: If administered after apheresis, discontinue hydroxyurea at least 2 days prior to myeloablative conditioning. Disease-modifying agents (e.g., L-glutamine, voxelotor and crizanlizumab): Discontinue disease modifying agents at least 2 months prior to conditioning as the interaction between disease modifying agents and conditioning agents are unknown. Iron chelation: If administered after apheresis, discontinue iron chelation at least 7 days prior to myeloablative conditioning. G-CSF: Do not administer G-CSF between mobilization and conditioning. Anti-retrovirals and erythropoietin: There are no data regarding use of anti-retrovirals or erythropoietin between apheresis and conditioning. Myeloablative Conditioning Do not begin myeloablative conditioning until the complete set of infusion bag(s) constituting the dose of LYFGENIA has been received and stored at the treatment center and the availability of the back-up collection is confirmed. Myeloablative conditioning with busulfan must be administered before infusion of LYFGENIA. Busulfan should be administered via a central venous line. For patients weighing less than 35 kg, administer every 6 hours; for patients weighing 35 kg or more, busulfan can be administered either once daily or every 6 hours. Calculate the dose on the basis of the lower of the ideal versus actual body weight. The recommended initial dose of busulfan is 3.2 mg/kg/day for 4 consecutive days as a 3-hour infusion for a total of 4 doses. 2 To achieve myeloablation, the busulfan target AUC is 5000 (range 4400 to 5400) μM*min for a once daily dosing regimen. For divided dosing, initial dose of busulfan is 0.8 mg/kg/dose every 6 hours as a 2-hour infusion for 16 consecutive doses. Target AUC is 1250 (range 1100 to 1350) μM*min for a q6h dosing regimen. Perform pharmacokinetic (PK) monitoring after the first dose and adjust dose to achieve the target AUC. Adjust sample collection based on whether a 2-hour or 3-hour infusion is used. If feasible, daily busulfan PK measurement is recommended. Administer seizure prophylaxis with agents other than phenytoin at least 12 hours prior to initiating busulfan. Do not use phenytoin because of its induction of cytochrome P450 and resultant increased clearance of busulfan. Consider prophylaxis for hepatic veno-occlusive disease (VOD)/hepatic sinusoidal obstruction syndrome with ursodeoxycholic acid or defibrotide. After completion of the myeloablative conditioning, allow a minimum of 48 hours of washout before LYFGENIA infusion. Receipt and Storage of LYFGENIA LYFGENIA is shipped in the vapor phase of liquid nitrogen shipper. Confirm patient identifiers on the product label(s) and Lot Information Sheet within the shipper. If there are any concerns about the product or packaging upon receipt, contact Genetix Biotherapeutics at 1-833-999-6378. Keep the infusion bag(s) in the metal cassette(s) and transfer LYFGENIA from the vapor phase of liquid nitrogen shipper to the treatment center vapor phase of liquid nitrogen storage at ≤ -140°C (-220°F). Store in the vapor phase of liquid nitrogen at ≤ -140°C (-220°F) until ready for thaw and administration. Preparation of LYFGENIA for Infusion Coordinate the timing of LYFGENIA thaw and infusion. Confirm the infusion time in advance and adjust the start time of LYFGENIA thaw such that it will be available for infusion when the patient and healthcare providers are ready. Note that each infusion bag must be completely administered within 4 hours after thawing. Remove each metal cassette from liquid nitrogen storage and remove each infusion bag from the metal cassette. Confirm that LYFGENIA is printed on the infusion bag(s). Confirm that patient identity matches the unique patient identifiers located on the LYFGENIA infusion bag(s). Do not infuse LYFGENIA if the information on the patient-specific label on the infusion bag does not match the intended patient and contact Genetix Biotherapeutics at 1-833-999-6378. Ensure the correct number of infusion bags are present. Use the accompanying Lot Information Sheet to confirm that each infusion bag is within the expiration date. Inspect each infusion bag for any breaches of integrity before and after thawing and before infusion. If an infusion bag is compromised, follow the local guidelines and contact Genetix Biotherapeutics immediately at 1-833-999-6378. If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag. Maintain any additional infusion bag(s), if applicable, at less than or equal to -140°C (-220°F) until time to thaw. Thaw LYFGENIA at 37°C (98.6°F) in a water bath or dry bath. Thawing of each infusion bag takes approximately 2 to 4 minutes. Do not leave LYFGENIA unattended. Do not submerge the infusion ports in a water bath. After thaw, mix the contents gently by massaging the infusion bag to disperse clumps of cellular material until all of the contents are uniform. If visible cell clumps remain, continue to gently mix the contents of the bag. Most small clumps of cellular material should disperse with gentle manual mixing. Do not filter, wash, spin down and/or resuspend LYFGENIA in new media prior to infusion. Do not sample, alter, irradiate or refreeze LYFGENIA. 2.3 Administration LYFGENIA is for autologous use only. The patient's identity must match the patient identifiers on the LYFGENIA cassette(s) and infusion bag(s). Do not infuse LYFGENIA if the information on the patient-specific label does not match the intended patient. Administer LYFGENIA within 4 hours after thawing. Do not use an in-line blood filter or an infusion pump. Before infusion, confirm that the patient's identity matches the unique patient identifiers on the LYFGENIA infusion bag(s). Use the Lot Information Sheet to confirm the total number of infusion bags to be administered. Expose the sterile port on the infusion bag by tearing off the protective wrap covering the port. Infuse LYFGENIA as soon as possible after thawing and complete the infusion within 4 hours. Administer each infusion bag of LYFGENIA via intravenous infusion over a period of less than 30 minutes. If more than one infusion bag is provided, administer the contents of each infusion bag completely before proceeding to thaw and infuse the contents of the next infusion bag. Administer the entire contents of each infusion bag to ensure that as many cells as possible are infused into the patient. After administration of each drug product, the infusion bag and any associated tubing are flushed with at least 50 mL of 0.9% sodium chloride solution to ensure as many cells as possible are infused into the patient. After LYFGENIA Administration Standard procedures for patient management after HSC transplantation should be followed after LYFGENIA infusion. Irradiate any blood products required for at least the first 3 months after LYFGENIA infusion and per transplant physician's recommendation. There is no experience regarding the use of hydroxyurea, anti-retrovirals, erythropoietin or disease-modifying agents, such as voxelotor or crizanlizumab, after LYFGENIA infusion. Avoid use of myelosuppressive iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation when appropriate. G-CSF is not recommended for 21 days after LYFGENIA infusion. Patients should not donate blood, organs, tissues, or cells at any time in the future. LYFGENIA contains human blood stem cells that are genetically modified with a replication-incompetent, self-inactivating lentiviral vector (LVV). Follow universal precautions and local biosafety guidelines (Biosafety Level 2) for handling and disposal of LYFGENIA to avoid potential transmission of infectious diseases.

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS Delayed Platelet Engraftment : Monitor patients frequently for thrombocytopenia and bleeding until platelet engraftment and platelet recovery are achieved. ( 5.2 ) Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after LYFGENIA infusion. If neutrophil engraftment does not occur, administer rescue cells. ( 5.3 ) Insertional Oncogenesis : There is a potential risk of insertional oncogenesis after treatment with LYFGENIA. ( 5.4 ) Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. ( 5.5 ) 5.1 Hematologic Malignancy Hematologic malignancy has occurred in patients treated with LYFGENIA (Study 1, Group A). At the time of initial product approval, two patients treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A) developed acute myeloid leukemia (AML). One patient with α-thalassemia trait (Study 1, Group C) has been diagnosed with myelodysplastic syndrome (MDS) [see Adverse Reactions (6.1) ] . The additional hematopoietic stress associated with mobilization, conditioning, and infusion of LYFGENIA, including the need to regenerate the hematopoietic system, may increase the risk of a hematologic malignancy. Patients with sickle cell disease have an increased risk of hematologic malignancy as compared to the general population. 3, 4 Patients treated with LYFGENIA may develop hematologic malignancies and should have lifelong monitoring. Monitor for hematologic malignancies with a complete blood count (with differential) at least every 6 months for at least 15 years after treatment with LYFGENIA, and integration site analysis at Months 6, 12, and as warranted. In the event that a malignancy occurs, contact Genetix Biotherapeutics at 1-833-999-6378 for reporting and to obtain instructions on collection of samples for testing. Post-Marketing Long Term Follow-Up Study Patients who intend to receive treatment with LYFGENIA are encouraged to enroll in the study, as available, to assess the long-term safety of LYFGENIA and the risk of malignancies occurring after treatment with LYFGENIA by calling Genetix Biotherapeutics at 1-833-999-6378. The study includes monitoring (at pre-specified intervals) for clonal expansion. 5.2 Delayed Platelet Engraftment Delayed platelet engraftment has been observed with LYFGENIA. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia. Two patients (4%) required more than 100 days post treatment with LYFGENIA to achieve platelet engraftment [see Adverse Reactions (6.1) ] . Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. 5.3 Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with LYFGENIA. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 0.5 × 10 9 cells/L obtained on different days by Day 43 after infusion of LYFGENIA. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with LYFGENIA, provide rescue treatment with the back-up collection of CD34+ cells [see Adverse Reactions (6.1) ] . 5.4 Insertional Oncogenesis There is a potential risk of lentiviral vector-mediated insertional oncogenesis after treatment with LYFGENIA. 5.5 Hypersensitivity Reactions Allergic reactions may occur with the infusion of LYFGENIA. The dimethyl sulfoxide (DMSO) or dextran 40 in LYFGENIA may cause hypersensitivity reactions, including anaphylaxis. 5.6 Anti-retroviral Use Patients should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization and until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication [see Dosing and Administration (2.2) and Drug Interactions (7.2) ] . If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells. 5.7 Hydroxyurea Use Patients should not take hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed. If hydroxyurea is administered between mobilization and conditioning, discontinue 2 days prior to initiation of conditioning [see Dosing and Administration (2.2) and Drug Interactions (7.3) ] . 5.8 Iron Chelation Do not administer myelosuppressive iron chelators for 6 months post-treatment with LYFGENIA [see Dosing and Administration (2.2) and Drug Interactions (7.4) ] . 5.9 Interference with PCR-based Testing Patients who have received LYFGENIA are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a possible false-positive PCR assay test result for HIV. Therefore, patients who have received LYFGENIA should not be screened for HIV infection using a PCR-based assay.

7 DRUG INTERACTIONS No formal drug interaction studies have been performed. LYFGENIA is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Anti-retrovirals : Discontinue anti-retroviral medications at least one month prior to mobilization and until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. ( 7.2 ) Hydroxyurea : Discontinue 2 months prior to mobilization and 2 days prior to conditioning. ( 7.3 ) Iron chelation : Discontinue at least 7 days prior to mobilization and conditioning. ( 7.4 ) 7.1 Live Vaccines Follow institutional guidelines for vaccine administration. The safety of immunization with live viral vaccines during or following LYFGENIA treatment has not been studied. Recommendations for vaccination schedules should be followed as per guidelines post-autologous hematopoietic stem cell transplant and functional asplenia. 7.2 Anti-retrovirals Patients should not take anti-retroviral medications for at least one month prior to mobilization for required and until all cycles of apheresis are completed [see Warnings and Precautions (5.6) ] . There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. Anti-retroviral medications may interfere with manufacturing of LYFGENIA. 7.3 Hydroxyurea Patients should not take hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed and should discontinue 2 days prior to initiation of conditioning [see Warnings and Precautions (5.7) ]. 7.4 Iron Chelation Drug-drug interactions between iron chelators and the mobilization process and myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of mobilization or conditioning. Myelosuppressive iron chelators (e.g., deferiprone) should be restarted no sooner than 6 months after LYFGENIA infusion [see Warnings and Precautions (5.8) ] . Non-myelosuppressive iron chelation should be restarted no sooner than 3 months after LYFGENIA infusion. Phlebotomy can be used in lieu of iron chelation, when appropriate.

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Hematologic Malignancy [see Warnings and Precautions (5.1) ] Delayed Platelet Engraftment [see Warnings and Precautions (5.2) ] Neutrophil Engraftment Failure [see Warnings and Precautions (5.3) ] Insertional Oncogenesis [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genetix Biotherapeutics at 1-833-999-6378 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Safety was based on patients with sickle cell disease in one open-label, single-arm clinical trial and one long-term follow-up study. Of the 54 patients who initiated stem cell collection, the median (min, max) age across the studies was 25 (12, 43) years, 63% were males, 89% were Black or African American, 2% were Asian, 2% White/Caucasian and 4% were not reported. The median (min, max) duration of follow-up was 42 (12, 87) months. Mobilization and apheresis triggered SAEs of sickle cell crisis in 6 (14%, 6/44) patients who initiated mobilization in the intent-to-treat population. All patients who initiated conditioning (100%, 45/45) experienced at least one adverse event attributed to conditioning. The majority of conditioning-attributed events were non-serious and were consistent with the known effects of alkylating agents. Thirty-three (73%, 33/45) patients who received LYFGENIA experienced at least one serious adverse event (SAE). Most SAEs were related to conditioning or underlying disease. Table 1 presents the adverse drug reactions following treatment with LYFGENIA (Day 1) to Month 24. Table 1: Adverse Reactions ≥ Grade 3 (> 5%) Following Treatment with LYFGENIA from Day 1 to Month 24 (N = 45) Includes adverse events associated with busulfan myeloablative conditioning and underlying sickle cell disease. Adverse Reaction Grade 3 or Higher n (%) Blood and lymphatic system disorders -- Thrombocytopenia 31 (69) Neutropenia 27 (60) Febrile neutropenia 20 (44) Anemia Includes a patient with α-thalassemia trait who was diagnosed with myelodysplastic syndrome after Month 24. 15 (33) Leukopenia 15 (33) Sickle cell anemia with crisis Includes events prior to Month 6 and non-adjudicated occurrences. 7 (16) Gastrointestinal disorders -- Stomatitis 32 (71) Nausea 4 (9) General disorders and administration site conditions -- Pyrexia 3 (7) Infections and infestations -- Bacteremia 3 (7) Investigations -- Aspartate aminotransferase increased 8 (18) Alanine aminotransferase increased 6 (13) Gamma-glutamyl transferase increased 6 (13) Blood bilirubin increased 3 (7) Metabolism and nutrition disorders -- Decreased appetite 5 (11) Respiratory, thoracic, and mediastinal disorders -- Pharyngeal inflammation 5 (11) Three patients died during LYFGENIA clinical trials; one from sudden cardiac death due to underlying disease and two from acute myeloid leukemia who were treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A). Anemia Two patients developed anemia following LYFGENIA treatment; one patient continues to require monthly packed red blood cell (pRBC) transfusions. The other patient has been diagnosed with MDS. Both subjects had α-thalassemia trait (-α3.7 /-α3.7) [see Limitations of Use (1) ]. Infusion-related reactions to LYFGENIA Pre-medication for infusion reactions was managed at physician discretion. Infusion-related reactions to LYFGENIA were observed in 2 patients on the day of LYFGENIA infusion. Both infusion-related reactions resolved and were Grade 1. Events included hot flush and decreased diastolic blood pressure. Platelet engraftment delay Platelet engraftment, defined as having 3 consecutive platelet values ≥ 50 × 10 9 /L obtained on different days after the initial post-transplant nadir without receiving any platelet transfusions for 7 days immediately preceding and during the evaluation period, was achieved in all patients (median [min, max] Day 37 [19, 235]) after LYFGENIA infusion. Two patients treated with LYFGENIA achieved platelet engraftment after Day 100; one of these patients was administered eltrombopag until Day 234 [see Warnings and Precautions (5.2) ]. Neutrophil engraftment All patients achieved neutrophil engraftment. Neutrophil engraftment, defined as having 3 consecutive ANC laboratory values ≥ 0.5 × 10 9 cells/L obtained on 3 different days by Day 43, was reported on median (min, max) Day 20 (12, 35) after LYFGENIA infusion.

8.1 Pregnancy Risk Summary There are no available data on LYFGENIA administration in pregnant women. Consider the risks associated with myeloablative conditioning agents on pregnancy and fertility. No reproductive and developmental toxicity studies in animals have been conducted with LYFGENIA to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether LYFGENIA has the potential to be transferred to the fetus. Therefore, LYFGENIA should not be administered to women who are pregnant, and pregnancy after LYFGENIA infusion should be discussed with the treating physician. 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.