TREGZI

TREGZI is an FDA-registered drug product whose active ingredient is ALLOGENEIC REGULATORY T CELL IMMUNOTHERAPY WITH HSPC AND T CELLS-VLDQ. It is labelled by Orca Biosystems Inc. and marketed as a cellular therapy product. Identifiers on file: NDC 85866-223, application BLA125868, label effective 20260630. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing ALLOGENEIC REGULATORY T CELL IMMUNOTHERAPY WITH HSPC AND T CELLS-VLDQ are most often described in connection with: hematopoietic stem, matched donor, cell transplantation, myeloablative preparative, immunologic reconstitution, improve chronic, treatment adults, hematological malignancies. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies. TREGZI™ is an allogeneic regulatory T cell-based immunotherapy with hematopoietic stem and progenitor cells and T cells indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease (cGVHD)-free survival, in the treatment of adults with hematological malignancies. ( 1 )

2 DOSAGE AND ADMINISTRATION For intravenous use only . ( 2.1 ) Verify patient's identity prior to infusion. ( 2.2 ) TREGZI is provided as 4 separate infusion bags (HSPCs, Tregs, Tcons, and Tcon diluent). ( 2.1 ) Administer an appropriate myeloablative preparative regimen before infusion of TREGZI. ( 2.2 ) DO NOT use a leukodepleting filter. ( 2.2 ) See Full Prescribing Information for instructions on receipt, preparation, and administration of TREGZI ( 2.2 , 16 ) 2.1 Dose For intravenous use only. A single dose of TREGZI consists of hematopoetic stem and progenitor cells (HSPCs), regulatory T cells (Tregs), conventional T cells (Tcons), and Tcon diluent provided in 4 separate infusion bags labeled for the specific patient. Each patient-specific infusion bag of TREGZI contains a batch-dependent concentration of allogeneic cells (see Table 1 ). Patient-specific dose information can be found within the Certificate of Analysis (COA). Table 1 TREGZI Route of Administration, Dose Regimen, and Target Dose Range Component Dose Regimen Target Viable Cell Dose Range (Cells per Patient kg) Abbreviations: HSPCs, hematopoietic stem and progenitor cells; Tregs, regulatory T cells; Tcons, conventional T cells. HSPCs Intravenous, once, on day 0 ≥1.0 × 10 6 Tregs Intravenous, once, on day 0 immediately after administration of HSPCs 1.3 × 10 6 to 3.5 × 10 6 Tcons Intravenous, once, on day +2 to +3 (after the start of HSPC infusion on day 0) 1.3 × 10 6 to 6.9 × 10 6 Tcon diluent Intravenous, once, administered with Tcons drug product on day +2 to +3 (after HSPC infusion on day 0) 30 mL 2.2 Preparation and Administration Preparing Patient for TREGZI Infusion Pretreatment Administer an appropriate myeloablative preparative regimen before infusion of TREGZI. Receipt of TREGZI Do not irradiate. TREGZI is shipped directly to the treatment center in two transport containers [See How Supplied/Storage and Handling (16) ] : A refrigerated cardboard shipping container at 2°C to 8°C (36°F to 46°F), containing the HSPC infusion bag and Treg infusion bag in a single protective carton. A cardboard box containing: 1) A liquid nitrogen dry vapor shipper at below -125°C (below -193°F), containing the cryopreserved Tcon infusion bag in a protective metal cassette. 2) A protective carton containing the Tcon diluent infusion bag stored at ambient temperature (20°C to 25°C, 68°F to 77°F). Upon receipt of the refrigerated cardboard shipping container containing the HSPC and Treg carton and infusion bags: Match the identity of the patient with the patient identifiers on the carton and infusion bags containing the HSPCs and Tregs. If the information on the patient-specific label does not match the intended patient, do NOT infuse TREGZI and contact Orca Bio at 1-877-411-6722. Inspect the HSPC and Treg infusion bags for any breaches of bag integrity such as breaks, leaking by the port line seal, or cracks. If an infusion bag is compromised, follow the institutional procedures for handling, storage and disposal and contact Orca Bio at 1-877-411-6722. Upon receipt of the cardboard box containing the (1) Tcon metal cassette and infusion bag and (2) Tcon diluent carton and infusion bag: Do NOT open the Tcon metal cassette upon receipt. Only open the metal cassette to verify the patient identifiers and inspect the Tcon infusion bag immediately prior to thawing. Match the identity of the patient with the patient identifiers on the (1) metal cassette containing the Tcon infusion bag and (2) carton and infusion bags containing the Tcon diluent. If the information on the patient-specific label does not match the intended patient, do NOT infuse TREGZI and contact Orca Bio at 1-877-411-6722. Inspect the Tcon diluent infusion bag for any breaches of bag integrity such as breaks, leaking by the port line seal, or cracks. If an infusion bag is compromised, follow the institutional procedures for handling, storage and disposal and contact Orca Bio at 1-877-411-6722. Premedication Administer diphenhydramine and/or acetaminophen approximately 30 minutes before TREGZI HSPC and Tcon infusions per institutional guidance. The use of corticosteroids as premedication is strongly discouraged. Day 0: Preparation and Administration of TREGZI HSPCs and Tregs Confirm the patient's identity matches the patient identifiers on each of the HSPC and Treg infusion bags. Do NOT infuse the HSPCs and Tregs if the information on the patient-specific label does not match the intended patient. Central venous catheter access is recommended for TREGZI infusion. Infuse HSPCs (Step 1 of Administration) and Tregs (Step 2 of Administration) promptly after receipt and verification of the expiry date and time listed on the bag label, carton label or Certificate of Analysis (COA). Infuse HSPCs and Tregs immediately after removal from refrigeration. Do not warm infusion bags prior to infusion. Day 0: Preparation of HSPCs and Tregs for Infusion Remove the HSPC and Treg infusion bags from refrigerated storage immediately prior to infusion. Agitate each infusion bag by inverting or gently massaging to prevent cell clumping. If visible cell clumping remains, continue to disperse clumps per institutional guidance prior to infusion. Day 0: Administration of HSPCs and Tregs Do NOT use a leukodepleting filter. 3. Prime the tubing with 0.9% sodium chloride. 4. Infuse the entire contents of HSPC infusion bag (Step 1 of Administration) by either gravity or a peristaltic pump at a rate of up to 5 mL/min. 5. After infusion of the entire contents of the HSPC infusion bag, add approximately 10 mL of 0.9% sodium chloride to the empty infusion bag and administer to the patient at the same infusion rate per institutional guidance. Repeat this process to achieve a total of two rinses. 6. Immediately after infusion of the HSPCs and two rinses on day 0, infuse the entire contents of the Treg infusion bag by either gravity or a peristaltic pump at a rate of up to 5 mL/min. 7. After infusion of the entire contents of the Treg infusion bag, add approximately 10 mL of 0.9% sodium chloride to the empty infusion bag and administer to the patient at the same infusion rate per institutional guidance. Repeat this process to achieve a total of two rinses. Day +2 to Day +3: Preparation and Administration of TREGZI Tcons Tcons are supplied cryopreserved in an infusion bag that is protected by a corresponding overwrap bag and packed in a metal cassette. Patient identifiers are found on the cassette and infusion bag labels. Do NOT open the metal cassette until immediately before thawing. Confirm the patient's identity matches the patient identifiers on the Tcon and Tcon diluent infusion bags. Do NOT infuse the Tcons if the information on the patient-specific label does not match the intended patient. Central venous catheter access is recommended for TREGZI infusion. Infuse Tcons (Step 3a of Administration) after thaw and dilution using the Tcon diluent (Step 3b of Administration) as soon as possible. If the Tcons can not be administered immediately, the Tcon infusion bag must be stored at 2°C to 8°C and infused within 4 hours. Day +2 to Day +3: Preparation - Thawing of Tcons Preparation of the Tcons for infusion occurs on day +2 to +3 after the start of HSPC infusion on day 0. Refrigerate the Tcon diluent infusion bag at 2°C to 8°C for at least 30 minutes prior to removing the Tcon metal cassette from liquid nitrogen storage. Remove Tcon metal cassette from liquid nitrogen storage. Open the protective cassette and remove the Tcon infusion bag. Remove the Tcon infusion bag from the overwrap bag. Place Tcon infusion bag in a sterile plastic bag and seal the bag tightly. Place the sealed plastic bag in a 37°C water bath for approximately 1 to 1.5 minutes until the cell suspension is slushy in texture. Gently massage the Tcon infusion bag during thawing. Remove the sealed bag from the water bath and remove the Tcon infusion bag. Discard outer plastic bag. Wipe down the Tcon infusion bag with 70% isopropanol. Day +2 to Day +3: Preparation - Dilution of Tcons with Tcon Diluent 9. Remove the Tcon diluent infusion bag from refrigeration. 10. Using a dispensing pin and syringe or transfer set with gravity, over a period of 3 minutes, slowly transfer the contents of the Tcon diluent infusion bag into the Tcon infusion bag. Rock the infusion bag back and forth during transfer to mix. 11. If administering the Tcons immediately, store the Tcon infusion bag at room temperature (18°C to 25°C). If not administering the Tcons immediately, store the Tcon infusion bag at 2°C to 8°C. 12. Immediately prior to infusion, gently agitate each infusion bag by inverting or gently massaging to prevent cell clumping per institutional guidance. If visible cell clumping remain continue to disperse clumps by gentle massaging per institutional guidance prior to infusion. Day +2 to Day +3: Administration of Tcons DO NOT use a leukodepleting filter. 13. Prime the tubing with 0.9% sodium chloride. 14. Infuse the entire contents of the Tcon infusion bag by either gravity or a peristaltic pump at a rate of up to 5 mL/min. 15. After infusion of the entire contents of Tcon infusion bag, add approximately 10 mL of 0.9% sodium chloride to the empty infusion bag and administer to the patient at the same infusion rate per institutional guidance. Repeat this process to achieve a total of two rinses. 16. Treat patients with a single agent calcineurin inhibitor as prophylaxis to decrease the risk of GVHD starting the day after Tcon administration. TREGZI contains human blood cells. Follow universal precautions and local biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.

4 CONTRAINDICATIONS None. None ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥20%) were mucositis, diarrhea, rash, viral infections, infections - pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, aGVHD, edema, and fungal infections. ( 6.1 ) The most common Grade 3-4 laboratory abnormalities (≥ 20%) are lymphocyte count decreased, platelet count decreased, leukocyte count decreased, neutrophil count decreased, and hemoglobin decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Orca Bio at 1-877-290-6722 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. The safety data described in this section reflects exposure to TREGZI in one clinical study (Precision-T Study) which enrolled patients with advanced hematologic malignancies eligible for HLA-matched allogeneic stem cell transplantation following myeloablative preparative regimen. The study treated 88 patients with TREGZI and 94 patients with standard of care (SoC) unmanipulated graft. The patients were followed for a duration of 24 months [see Clinical Studies (14) ]. Serious adverse reactions within the first 100 days occurred in 25 patients (28%) treated with TREGZI including bacterial infections (n=12; 14%), pyrexia (n=4; 5%), venooclusive liver disease (n=3; 3%), and viral infections (n=3; 3%). Fatal adverse reactions occurred in 3 patients (3%). Non-relapse deaths at 12 months occurred in 3/88 (3.4%) patients in the TREGZI group and in 11/94 (11.7%) patients in the SoC control group [see Clinical Studies (14) ]. In the TREGZI treated safety population, the most common (greater than or equal to 10%) Grade 3 or 4 nonlaboratory adverse reactions were mucositis (28%), bacterial infection (18%), infection – pathogen unspecified (18%), and viral infection (14%). Table 3 summarizes the most common nonlaboratory adverse reactions occurring in ≥10% patients treated with TREGZI or unmanipulated allograft control group in Precision-T Study. Table 3 Adverse Reactions occurring in ≥10% of patients treated with TREGZI or unmanipulated allograft control arm in Precision-T Study Adverse Reactions TREGZI (N = 88) SoC Control (N=94 ) All Grades % Grade 3 or Higher % All Grades % Grade 3 or Higher % Infections and infestations Infections and infestations were calculated for the first 2 years after transplantation. Abbreviations: GVHD, Graft-Versus-Host disease. Viral infections 51 14 47 19 Infections - pathogen unspecified 45 18 56 30 Bacterial infections 40 18 38 16 Fungal infections 20 3 18 0 Gastrointestinal disorders Diarrhea includes multiple related terms 69 1 79 6 Abdominal pain 45 0 54 1 Vomiting 44 1 35 0 Nausea 41 1 44 2 Immune system disorders Acute graft-versus-host disease Acute GVHD graded by MAGIC standardization criteria (Harris 2016) as determined by an independent review committee; calculated for the first year after transplantation. 38 6 46 15 General disorders and administration site conditions Mucositis 85 28 88 37 Edema 30 0 38 3 Respiratory, thoracic and mediastinal disorders Pneumonia 5 5 17 15 Skin and Subcutaneous Tissue Disorders Rash 65 0 55 0 Vascular Disorders Hemorrhage 39 6 33 1 Other clinically important adverse reactions that occurred in less than 10% of patients treated with TREGZI include the following: Hepatobiliary disorders: veno-occlusive liver disease 3% in TREGZI group and 2% in control group. Immune system disorders: moderate to severe chronic Graft-versus-host disease (GVHD) 13% in TREGZI group and 41% in control group as per International NIH Chronic GVHD Diagnosis and Staging. Injury, poisoning, and procedural complications: Secondary graft failure 1% in TREGZI group and 0% in control group. Table 4 summarizes the most common Grade 3 or 4 laboratory abnormalities occurring in ≥10% of patients in Precision-T Study. Laboratory Abnormalities Table 4 Grade 3 or 4 Laboratory Abnormalities Occurring in ≥10% of Patients in Precision-T Study Laboratory Abnormality Includes lab abnormalities for the first 100 days , Baseline lab values were assessed prior to conditioning regimen. Denominators ranged from 79 to 87 for TREGZI arm and 90 to 93 for Control arm for lab tests, based on the number of patients with a baseline value and at least one post treatment value for each lab test. TREGZI Grade 3 or 4 % SoC Control Grade 3 or 4 % Lymphocyte count decreased 98 94 Platelet count decreased 93 96 Leukocyte count decreased 89 89 Neutrophil count decreased 77 83 Hemoglobin decreased 71 81 Alanine aminotransferase increased 12 7

What is TREGZI used for?
1 INDICATIONS AND USAGE TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies. TREGZI™ is an allogeneic regulatory T cell-based immunotherapy with …

Who makes TREGZI?
Orca Biosystems Inc. is the labeler of record for TREGZI.

Is TREGZI prescription or over-the-counter?
The FDA label for this product is recorded as cellular therapy. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has TREGZI been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.