MGTA-145 / Dianthus Therap - LARVOL DELTA

Single Dose of Tgroβ (EN-145)/Plerixafor Safely and Effectively Mobilizes Primitive HSCs in Mouse Models for In Vivo Gene Therapy of Sickle Cell Disease (ASH 2024) - "The goal of this work is to evaluate the safety and efficacy of Ensoma's tGROβ : EN-145, formerly MGTA-145, in combination with P in our relevant SCD mouse models. In conclusion, our comprehensive mouse studies further validate the in vivo safety and efficacy of single-dose EN-145+P as a robust alternative to G-CSF for primitive HSC mobilization in SCD. These data support the major therapeutic value of EN-145+P for ex vivo and Ensoma's in vivo VLP-based gene therapies in SCD."

Gene therapy • Preclinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • CD46 • CD48 • CXCR2 • PTPRC • SCD • THY1

GroβT rapidly and reliably mobilizes primitive hematopoietic stem and progenitor cells in nonhuman primates. (PubMed, Mol Ther Methods Clin Dev) - "Here, we evaluated a combination of plerixafor (AMD3100, a CXCR4 antagonist) with GroβT (MGTA-145/GroβT, a CXCR2 agonist) against the current gold-standard G-CSF for HSC gene therapy in nonhuman primates (NHPs) for HSC mobilization, leukapheresis, ex vivo gene editing to reactivate fetal hemoglobin, and transplantation. Rapid recovery and robust multilineage long-term engraftment of gene-modified HSCs was achieved in the bone marrow and blood of animals. In summary, AMD3100/GroβT allows highly efficient and reliable mobilization of HSCs, providing a G-CSF-free regimen specifically for SCD but also any other hematological disease or disorder treatable with HSC gene therapy."

Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34 • CXCR2 • THY1

Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma. (PubMed, Blood Cancer J) - P2 | "MGTA-145 or GROβT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers...Lenalidomide and anti-CD38 antibody were part of induction therapy in 92% (n = 23) and 24% (n = 6) of patients, respectively...74% (17 of 23) of grafts with this regimen were minimal residual disease negative by next generation flow cytometry. Graft composition for HSCs and immune cells were similar to a contemporaneous cohort mobilized with G-CSF and plerixafor."

Journal • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Transplantation • CD34 • CXCR2

G-CSF-Free HSC Mobilization with WU-106/AMD3100 Allows for Safe and Efficient In Vivo HSC Transduction and In Vivo Prime Editing of the Sickle Cell Disease Mutation in a Mouse Model (ASGCT 2023) - "Recently, we developed a simpler, rapid, and more HSC-selective mobilization regimen using truncated GRO-β (MGTA-145), a CXCR2 agonist, and plerixafor/AMD3100...Among the alternative G-CSF-free mobilization protocols is also plerixafor plus small molecule VLA4 antagonists, such as BIO5192 or its improved derivatives (e.g. WU-106)...Analysis of the percentage of βS versus βA globin in erythrocytes and phenotypic correction in primary mice (spleen size, histology, blood smears) will be reported. These first data indicate that HSC in vivo gene therapy using the new mobilization approach is safer than GSCF/AMD3100, can be done on one day, and can achieve therapeutically relevant correction levels of the SCD mutation in a relevant mouse model."

Preclinical • Beta-Thalassemia • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD46 • CXCR2 • CXCR4 • IFNG • IL6 • KIT

Mgta-145 + Plerixafor Provides GCSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study (TCT-ASTCT-CIBMTR 2022) - P2 | "At last follow-up, 18 patients have completed transplant with MGTA-145 graft, with melphalan 200 mg/m 2 in 15 patients. This is the first study to evaluate the novel G-CSF-free regimen of MGTA-145 + plerixafor for HSC cell mobilization in hematologic cancers. 88% patients met the primary endpoint. The regimen was well tolerated."

Clinical • P2 data • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain • Oncology • Pain • Transplantation • CD34 • CSF3 • CXCR2 • THY1

A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of Mgta-145 in Combination with Plerixafor for the Mobilization of Hematopoietic Stem Cells in Patients with Sickle Cell Anemia (ASH 2022) - P2 | "Participants must have a documented diagnosis of SCA, have a hydroxyurea washout period, and have adequate white blood cell counts and cardiopulmonary, renal, and liver function. Core exploratory endpoints include characterization of the phenotype and function of cells collected by apheresis and assessment of the gene-modifying potential of mobilized CD34+ cells. The results of this trial will establish if MGTA-145 with plerixafor will rapidly and safely mobilize robust numbers of high-quality SCs for HSCT in SCA."

Clinical • Combination therapy • P2 data • Anemia • Bone Marrow Transplantation • Cardiovascular • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Sickle Cell Disease • Transplantation • CD34 • CXCR2

Study of MGTA-145 and Plerixafor in Patients With Sickle Cell Disease (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Magenta Therapeutics, Inc. | N=14 ➔ 1 | Trial completion date: Dec 2023 ➔ Feb 2023 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Dec 2022; This study was voluntarily terminated due to a business decision not to proceed, and not due to any safety issue.

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

Phase 1 Clinical Study of Mgta-145 in Combination with Plerixafor Shows Rapid Single-Day Mobilization and Collection of CD34+ HSCs without G-CSF (TCT-ASTCT-CIBMTR 2020) - "These data suggest that the combination can enable the collection of sufficient HSCs for transplant in a single day. Further clinical development as a first line mobilization product is warranted in hematologic malignancies, autoimmune diseases, and gene therapy."

Clinical • Combination therapy • P1 data • CD34 • CSF3 • CXCR2

Mgta-145 + Plerixafor Provides GCSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study (ASH 2021) - P2 | "Induction therapy was VRD in 68% (17), daratumumab VRD in 24% (6), CyBorD in 8% (2) patients. Median duration of induction was 4 months (3-6) and median lenalidomide exposure was 5 cycles (1-8), with > VGPR in 88% of patients...At last follow-up, 18 patients have completed transplant with MGTA-145 mobilized graft, with melphalan 200 mg/m 2 in 15 (83%) patients... This is the first study to evaluate the novel G-CSF-free regimen of MGTA-145 + plerixafor for HSC cell mobilization & collection for hematologic malignancies. The study cohort was representative of transplant eligible patients with MM, with 88% patients meeting the primary endpoint. The regimen was well tolerated."

Clinical • P2 data • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Oncology • Pain • Transplantation • CD34 • CSF3 • CXCR2 • THY1

IRB-57056: MGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Surbhi Sidana, MD | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Study of MGTA-145 and Plerixafor in Patients With Sickle Cell Disease (clinicaltrials.gov) - P2 | N=14 | Recruiting | Sponsor: Magenta Therapeutics, Inc.

Combination therapy • New P2 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

[VIRTUAL] Phase 2 study of MGTA-145 + plerixafor for rapid and reliable hematopoietic stem cell (HSC) mobilization for autologous transplant in multiple myeloma. (ASCO 2021) - P2 | "Induction therapy was VRD in 7 and daratumumab + VRD in 3 patients; median induction duration: 4 months (3-6) & median lenalidomide exposure: 6 cycles (4-6), with > VGPR in 70%...All 6 patients in the safety cohort have completed transplant with melphalan 200 mg/m2... This is the first study to evaluate the novel regimen of MGTA-145 + plerixafor for same day stem cell mobilization & collection in myeloma/hematologic malignancies, with 100% efficacy in interim analysis and the first to demonstrate successful engraftment in patients with cells collected with this GCSF free regimen."

P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Oncology • Pain • Transplantation • CD34 • CXCR2 • HIP1

MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: Magenta Therapeutics, Inc. | N=56 ➔ 7 | Active, not recruiting ➔ Terminated; This study was voluntarily terminated due to a business decision not to proceed and not due to any safety issue

Combination therapy • Enrollment change • Trial termination • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD34 • HLA-DRB1

"$MGTA to focus on MGTA-117 development and is pausing certain MGTA-145 investments, including MGTA-145 dosing and administration optimization clinical trial in healthy subjects. Workforce reduction of 14%" (@BioStocks)

Clinical

MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies (clinicaltrials.gov) - P2 | N=56 | Active, not recruiting | Sponsor: Magenta Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Apr 2022 | Trial primary completion date: Aug 2022 ➔ Sep 2021

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD34 • HLA-DRB1

Update on Phase II study of MGTA-145 + plerixafor for stem cell mobilization in multiple myeloma (YouTube) - "Surbhi Sidana, MD...gives an overview of the design and preliminary results of a Phase II study assessing the efficacy of MGTA-145, a novel CXCR2 agonist, in combination with plerixafor in mobilizing hematopoietic stem cells (HSCs) in transplant-eligible patients with multiple myeloma (NCT04552743)."

Interview • P2 data • Video

[VIRTUAL] PHASE 2 STUDY OF MGTA-145 + PLERIXAFOR FOR RAPID AND RELIABLE HEMATOPOIETIC STEM CELL (HSC) MOBILIZATION FOR AUTOLOGOUS STEM CELL TRANSPLANT IN MULTIPLE MYELOMA (EHA 2021) - P2 | "Induction therapy was VRD in 7 and daratumumab + VRD in 3 patients; median induction duration: 4 months (3-6) & median lenalidomide exposure: 6 cycles (4-6), with > VGPR in 70%...All 6 patients in the safety cohort have completed transplant with melphalan 200 mg/m2...67% of grafts were minimal residual disease negative with next generation flow cytometry. Conclusion This is the first study to evaluate the novel regimen of MGTA-145 + plerixafor for same day stem cell mobilization & collection in myeloma/hematologic malignancies, with 100% efficacy in interim analysis and the first to demonstrate successful engraftment in patients with cells collected with this GCSF free regimen."

P2 data • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Oncology • Pain • Transplantation • CD34 • CXCR2 • HIP1

Magenta Therapeutics Reports Third Quarter Financial Results and Program Highlights (Businesswire) - P2, N=56; NCT04762875; Sponsor: Magenta Therapeutics, Inc; "88% of patients (22/25) treated with MGTA-145 plus plerixafor met the primary endpoint of mobilization and collection of 2 million CD34+ stem cells per kg in up to two days of same-day mobilization and apheresis. 68% of patients (17/25) achieved the primary endpoint in a single day of dosing and collection. Three patients who did not meet the primary endpoint successfully collected hematopoietic stem cells (HSCs) with subsequent G-CSF plus plerixafor dosing and 2-3 apheresis sessions...The regimen of MGTA-145 and plerixafor was well tolerated....the company intends to explore further development of MGTA-145 in a Phase 2b clinical setting."

P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Magenta Therapeutics Reports Second Quarter Financial Results and Recent Program Highlights (Businesswire) - "Initiation of a Phase 2 clinical trial in sickle cell disease in collaboration with bluebird bio is planned for Q4 2021 to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in patients with sickle cell disease where mobilization and collection is difficult and there is a clear unmet medical need."

New P2 trial • Hematological Disorders • Sickle Cell Disease

MGTA-145 + Plerixafor in the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma (clinicaltrials.gov) - P2; N=25; Active, not recruiting; Sponsor: Stanford University; Recruiting ➔ Active, not recruiting; Trial primary completion date: Mar 2022 ➔ Jul 2021

Clinical • Combination therapy • Enrollment closed • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

Magenta Therapeutics Reports Second Quarter Financial Results And Recent Program Highlights (Magenta Therapeutics Press Release) - "Magenta Therapeutics...today reported financial results for the second quarter ended June 30, 2021, and recent program highlights...Enrollment is complete for Phase 2 clinical trial in multiple myeloma. This 25-patient, investigator-initiated, Phase 2 open-label clinical trial, led by Surbhi Sidana, M.D...is designed to evaluate the ability of MGTA-145, in combination with plerixafor, to mobilize and collect stem cells for autologous stem cell transplant in patients with multiple myeloma."

MGTA-145 and plerixafor for HSC mobilization in myeloma (YouTube) - "Surbhi Sidana, MD...shares an update on a Phase II study (NCT04552743) of MGTA-145, a CXCR2 agonist, plus plerixafor for rapid and reliable hematopoietic stem cell (HSC) mobilization for autologous stem cell transplant (auto-SCT) in patients with multiple myeloma."

Interview • Video

Surbhi Sidana, MD, Discusses MGTA-145 Plus Plerixafor for Same-Day HSC Mobilization in MM (Oncology Learning Network) - "Surbhi Sidana, MD...discusses a phase 2 study of the combination regimen MGTA-145 plus plerixafor for same-day hematopoietic stem cell (HSC) mobilization for autologous transplant in patients with multiple myeloma (MM); these data were presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting."

Video

Magenta Therapeutics Announces Additional Preliminary Positive Results from Ongoing Phase 2 Clinical Trial of MGTA-145 and Plerixafor in Patients with Multiple Myeloma at the American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - P2, N=25; NCT04552743; "The investigator-initiated, 25-patient Phase 2 clinical trial is designed to evaluate the ability of MGTA-145, in combination with plerixafor, to mobilize and collect hematopoietic stem cells for autologous stem cell transplant in patients with multiple myeloma. This study is led by Surbhi Sidana...All patients (15/15) have met the primary endpoint of mobilization and collection of 2 million CD34+ stem cells per kg in up to two days. Twelve of 15 patients achieved the primary endpoint in a single day of dosing and collection; All transplanted patients to date (12/12) successfully engrafted, with median recovery of neutrophils after 12.5 days and platelets after 18 days, which are within transplant expectations in multiple myeloma....Final clinical data from this trial are anticipated by the end of 2021."

P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

"Stay tuned for new additional Phase 2 data for MGTA-145 coming out tomorrow morning! #ASCO21" (@DanBudwick)

New P2 trial • P2 data