Genetix Presents Recent Patient Experience Data from U.S. Commercial Gene Therapy Implementation at the 67th American Society of Hematology (ASH) Annual Meeting

• Operational real-world data analyzed from patients prescribed ZYNTEGLO™ and LYFGENIA™
• Data demonstrates the value proposition of one-time, durable gene therapy for the treatment of sickle cell disease and beta-thalassemia
• Lessons learned from ZYNTEGLO launch accelerated access for LYFGENIA
• 392 patients enrolled and 115 patients treated highlights substantial growth in commercial demand since launch
• Genetix is actively investing in revamping the commercial strategy and expanding manufacturing capacity to meet growing demand

SOMERVILLE, Mass.--(BUSINESS WIRE)--Genetix Biotherapeutics Inc. today announced real-world data from the commercial implementation of ZYNTEGLO™ and LYFGENIA™, first-in-class ex vivo gene addition therapies for the treatment of beta-thalassemia and sickle cell disease. With over 250 patients treated with these therapies, inclusive of clinical trials and commercial treatments, and long-term follow-up data beyond 10 years, Genetix has the most robust long-term dataset in ex vivo gene therapy for hemoglobinopathies.

The analysis of commercial implementation, presented at the American Society of Hematology’s (ASH) Annual Meeting, continues to demonstrate the value of these one-time durable gene therapies. With over 390 patients enrolled for treatment and 115 treated patients, the analysis demonstrates substantial growth in commercial demand for ZYNTEGLO and LYFGENIA and highlights opportunities to further enhance the treatment journey for patients and providers.

“These data demonstrate significant progress in commercial gene therapy adoption for hemoglobinopathies,” said Anju Chawla, MD, VP of Clinical Science. “Lessons learned from the ZYNTEGLO launch have enabled accelerated access to LYFGENIA for sickle cell patients. Our results show the growing demand and scalability of our one-time, durable gene therapies and Genetix continues to be deeply committed to continuing to enhance the treatment journey for the thousands of U.S. patients who still need treatment.”

New real-world data presented from ZYNTEGLO & LYFGENIA commercial launch
Since FDA approval of ZYNTEGLO (August, 2022) and LYFGENIA (December, 2023) through mid-November 2025:

• 392 patients enrolled for treatment
• 216 patients have initiated cell collection
• 115 patients have completed treatment

Lessons learned from the ZYNTEGLO launch accelerated access to LYFGENIA
In comparison to the ZYNTEGLO launch, LYFGENIA commercial launch metrics demonstrated:

• 2x faster lead time from FDA approval to first patient enrollment
• 167% faster enrollment rates in the first quarter post approval
• 6x more treatment center activations in the first quarter post approval

Opportunities to Enhance the Patient Journey
This recent real-world data highlights clear opportunities to further enhance the treatment journey for patients and providers. The time between patient enrollment and scheduling of cell collection can be impacted by manufacturing capacity. Additionally, while the majority of the 115 patients treated needed only a single cell collection, patients that require additional cell collection cycles experience extended treatment timelines.

Genetix remains committed to further optimizing the patient treatment journey and is actively investing in the following strategic priorities:

• Expanding manufacturing capacity to shorten scheduling lead times and meet the growing commercial demand
• Broadening the Qualified Treatment Center (QTC) network and strengthening collaboration to improve cell collection success rates
• Enhancing manufacturing capabilities, such as enabling the ability to cryopreserve patient stem cells, to significantly improve the treatment experience
• Continuing to execute HGB-210, the fully-enrolled lovo-cel (lovotibeglogene autotemcel) Phase 3 study, an open-label, multi-site, single-dose trial in adults and pediatric patients (2-17 years of age) with sickle cell disease

About LYFGENIA™ (lovotibeglogene autotemcel)
LYFGENIA is a one-time ex-vivo lentiviral vector (LVV) gene addition therapy approved for eligible patients with sickle cell disease, in which a functional β-globin gene is added to patients’ own hematopoietic (blood) stem and progenitor cells (HSPCs). This addition results in the production of adult hemoglobin with anti-sickling properties (HbA^T87Q) which has a similar oxygen-binding affinity to wild-type HbA. LYFGENIA has been shown to limit sickling of red blood cells and reduce or eliminate vaso-occlusive events (VOEs).

LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of VOEs.

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.

IMPORTANT SAFETY INFORMATION FOR LYFGENIA (lovotibeglogene autotemcel)

Boxed WARNING: HEMATOLOGIC MALIGNANCY

Hematologic malignancy has occurred in patients treated with LYFGENIA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through integration site analysis at Months 6, 12, and as warranted.

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).

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.

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.

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.

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.

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 × 109 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.

Insertional Oncogenesis

There is a potential risk of lentiviral vector-mediated insertional oncogenesis after treatment with LYFGENIA.

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.

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. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.

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.

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. Do not administer myelosuppressive iron chelators (e.g., deferiprone) for 6 months post-treatment with LYFGENIA. 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.

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.

Adverse Reactions

The most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia.

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).

Pregnancy/Lactation

Advise patients of the risks associated with myeloablative conditioning agents, including on pregnancy and fertility.

LYFGENIA should not be administered to women who are pregnant, and pregnancy after LYFGENIA infusion should be discussed with the treating physician.

LYFGENIA is not recommended for women who are breastfeeding, and breastfeeding after LYFGENIA infusion should be discussed with the treating physician.

Females and Males of Reproductive Potential

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before LYFGENIA administration.

Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra-uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of LYFGENIA.

Advise patients of the options for fertility preservation.

Please see full Prescribing Information, including Boxed WARNING and Medication Guide for LYFGENIA.

About ZYNTEGLO™ (betibeglogene autotemcel)
ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene addition therapy approved for eligible patients with transfusion-dependent beta-thalassemia who require regular red blood cell (RBC) transfusions, in which functional copies of a modified form of the beta-globin gene (β^A-T87Q-globin gene) is added into a patient’s own HSPCs. This addition results in the production of adult hemoglobin (HbA^T87Q) enabling total hemoglobin to reach normal or near normal levels. ZYNTEGLO has been shown to eliminate the need for regular RBC transfusions.

ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular RBC transfusions.

IMPORTANT SAFETY INFORMATION FOR ZYNTEGLO (betibeglogene autotemcel)

Delayed Platelet Engraftment

Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100.

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.

Risk of Neutrophil Engraftment Failure

There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. 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 ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells.

Risk of Insertional Oncogenesis

There is a potential risk of lentiviral vector (LVV)-mediated insertional oncogenesis after treatment with ZYNTEGLO.

Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, 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.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis.

Anti-retroviral and Hydroxyurea Use

Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.

Interference with Serology Testing

Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR-based assay.

Adverse Reactions

The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

Drug Interactions

Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates.

Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these 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.

Pregnancy/Lactation

Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility.

ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician.

ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician.

Females and Males of Reproductive Potential

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration.

Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO.

Advise patients of the option to cryopreserve semen or ova before treatment if appropriate.

Please see full Prescribing Information and Patient Information for ZYNTEGLO.

About Genetix Biotherapeutics
Genetix Biotherapeutics Inc. is a privately-held, commercial-stage biotechnology company dedicated to delivering genetic therapies for patients with severe rare diseases. Backed by more than 30 years of pioneering genetic therapy innovation, the company has FDA-approved treatments for sickle cell disease, β-thalassemia, and cerebral adrenoleukodystrophy that directly treat the underlying cause of disease. Genetix is committed to commercial execution, scaling patient access, and improving the treatment experience for patients and providers. Genetix is headquartered in Somerville, Massachusetts.