MB-105 / Baylor College of Medicine, March Bio - LARVOL DELTA

A phase 2 study to confirm safety and efficacy of MB-105, an autologous CD5-directed CAR T-cell therapy, in relapsed/refractory T-cell lymphoma (R/R TCL). (ASCO 2025) - P2 | "Patients are encouraged to participate in a separate long-term follow-up study. Recruitment is ongoing."

CAR T-Cell Therapy • Clinical • IO biomarker • P2 data • Cutaneous T-cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CD5 • CTCs

ScaleReady Announces March Biosciences as Recipient of G-Rex Grant to Advance Manufacturing of Novel CAR-T Cell Therapy (PRNewswire) - "ScaleReady...announced that March Biosciences has been awarded a $200,000 G-Rex Grant. March Biosciences' G-Rex Grant will be used to advance the manufacturing of their lead asset, MB-105, a novel investigational autologous CAR-T cell therapy targeting CD5 for patients with T-cell lymphomas....As part of the G-Rex Grant, March Biosciences will continue development of a G-Rex-centric fully integrated CAR-T cell manufacturing process to further streamline the scalable cGMP production of MB-105 and other CAR-T products in the research pipeline."

Financing • Lymphoma

March Biosciences Announces First Patient Dosed in Phase 2 Clinical Trial of MB-105, First-in-Class CD5 CAR-T Cell Therapy for T-Cell Lymphoma (GlobeNewswire) - "March Biosciences...today announced that the first patient has been dosed in its Phase 2 clinical trial evaluating MB-105, a first-in-class CD5-targeted CAR-T cell therapy for patients with relapsed or refractory CD5-positive T-cell lymphoma....The trial will be conducted at leading cancer centers across the United States, with the first patient dosed at The University of Texas MD Anderson Cancer Center."

Trial status • Lymphoma

March Biosciences Receives FDA Orphan Drug Designation for MB-105, a First-in-Class CD5 CAR-T Cell Therapy, for T-Cell Lymphoma (GlobeNewswire) - "March Biosciences...announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to MB-105, the company's first-in-class CD5-targeted CAR-T cell therapy, for the treatment of relapsed / refractory CD5-positive T-cell lymphoma....'The MB-105 Phase 1 trial has shown promising safety and efficacy signals in relapsed / refractory T-cell lymphoma patients. This designation further validates our development strategy as we prepare to initiate our Phase 2 clinical trial in early 2025.'"

Orphan drug • Trial status • T Cell Non-Hodgkin Lymphoma

MB-105 in Patients With CD5 Positive T-cell Lymphoma (clinicaltrials.gov) - P2 | N=46 | Recruiting | Sponsor: March Biosciences Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Confirmatory Efficacy and Safety Evaluation of MB-105, a CD5.CAR T Therapy: Multicenter Phase 2 Study in Patients with Relapsed/Refractory T Cell Lymphoma (R/R TCL) (ASH 2024) - P2 | "Once MB-105 arrives at the site, patients undergo 3 days' standard fludarabine/cyclophosphamide conditioning followed by 2 days' rest, rituximab prophylaxis (based on EBV serostatus) and CAR-T infusion on Day 0 as an outpatient with standard supportive measures. Post-MB-105 monitoring includes CAR-T persistence, immune cell populations, viral PCRs, anti-CAR antibodies, cytokines and replication-competent retrovirus.Patients will be asked to participate in long term safety and efficacy follow-up under a separate protocol (MB-105-202). The IND for both MB-105 studies is open, with the first patient visit pending."

Clinical • IO biomarker • P2 data • Bone Marrow Transplantation • Cutaneous T-cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CD5 • CTCs

March Biosciences Closes Oversubscribed $28.4 Million Series A Financing (GlobeNewswire) - "March Biosciences...announced the close of a $28.4 million oversubscribed Series A financing. Mission BioCapital and 4BIO Capital led the financing, with participation from KdT Ventures, Alexandria Venture Investments, Volnay Therapeutics, Modi Ventures, and Mansueto Investments. Existing investors TMC Venture Fund, Cancer Focus Fund, and Small Ventures also participated in the round. March Bio has raised over $51 million to date inclusive of all dilutive and non-dilutive funding....MB-105 has demonstrated a favorable safety profile and durable remissions in relapsed T-cell lymphoma patients in a Phase 1 clinical trial at Baylor College of Medicine, with plans to begin a Phase 2 clinical trial in early 2025. Proceeds from the financing will support the Phase 2 clinical development of MB-105 to expand on this data with optimized manufacturing processes."

Financing • Lymphoma

MB-105 in Patients With CD5 Positive T-cell Lymphoma (clinicaltrials.gov) - P2 | N=46 | Not yet recruiting | Sponsor: March Biosciences Inc

New P2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

MAGENTA: Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Baylor College of Medicine | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • CD5

MAGENTA: Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Baylor College of Medicine | Trial completion date: Sep 2039 ➔ Sep 2040 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • CD5

Anti-tumor Efficacy and Safety of Unedited Autologous CD5.CAR T cells in Relapsed/Refractory Mature T-cell Lymphomas. (PubMed, Blood) - "More patients and longer follow-up are needed for validation. NCT0308190."

CAR T-Cell Therapy • Journal • Bone Marrow Transplantation • CNS Disorders • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation • CD5

March Biosciences Awarded $13.4 Million by CPRIT to Advance Its CD5 CAR-T Therapy for T-cell Lymphoma in Phase 2 Trials (PRNewswire) - "March Biosciences...today announced that it has received a notice of award for a major competitive grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to help support continued clinical development of its innovative chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of relapsed and refractory CD5 positive T-cell cancers. The approximately $13.4 million product development award is intended to support March Bio's upcoming Phase 2 clinical trial of MB-105 for the treatment of relapsed and refractory T-cell lymphomas....March Bio is currently preparing for its Phase 2 trials of MB-105 with a development collaboration with recent CPRIT awardee, CTMC, a joint venture between MD Anderson Cancer Center and National Resilience."

Financing • Oncology

March Biosciences and Cancer Focus Fund Announce $4.8 Million Investment to Support a Phase 2 Clinical Trial of Novel CAR-T Therapy for T-Cell Lymphoma (PRNewswire) - "March Biosciences...and Cancer Focus Fund, LP...today announced that Cancer Focus Fund is investing $4.8 million in funding and providing clinical support for March Bio's upcoming Phase 2 clinical trial of MB-105 for the treatment of relapsed T-cell leukemias and lymphomas....The Phase 2, open label, multi-center trial will assess MB-105 in patients with CD5-positive relapsed/refractory T-cell lymphoma. Patients will receive one dose of MB-105 and will be followed for a minimum of 12 months."

Financing • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Development of CAR T-Cells for T-ALL and LBL (SOHO 2023) - P1 | "In the ongoing clinical trial at Baylor College of Medicine (MAGENTA, NCT03081910) autologous CD5 CAR T-cells produced transient expansion in peripheral blood of patients with refractory or relapsed (r/r) T-ALL/T-LBL producing a short-lived remission in one patient out of eight (13%) across three dose levels ranging from 10e7 to 10e8 CAR T-cells per m2 body surface area. Our preclinical studies showed blocking tonic CAR signaling with tyrosine kinase inhibitors (TKI) ibrutinib and dasatinib during ex vivo expansion of CD5 CAR T-cells minimized the extent of CAR-induced T-cell differentiation and preserved minimally differentiated T-cells co-expressing CD62L and CCR7...Close EBV monitoring and prophylactic B-cell ablation with rituximab has been implemented to reduce the incidence of EBV reactivation post CD5 CAR-T infusion...Systemic ablation of T- and NK-cells was limited due to the repopulation with CD7-negative lymphocyte subsets mirroring the mechanism observed..."

CAR T-Cell Therapy • IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CCR7 • CD5 • CD7 • SELL

CD5 CAR T-cells Promote Selection of Fratricide-Resistant Circulating T-cells Thus Avoiding Global T-cell Aplasia (ASGCT 2023) - P1 | "Despite both normal and malignant T-cells having similar kinetics of CD5 trans-downmodulation upon coculture with CD5 CAR T-cells, healthy peripheral blood T-cells were more resistant to CD5-directed cytotoxicity as a subset of normal T-cells survived a 36-hour coculture with autologous CD5 CAR T-cells while tumor cells were eliminated...These subsets were rapidly replaced with conventional CD5+ T-cells following contraction of CD5 CAR T-cells.Taken together, these results indicate CD5 CAR induces temporary internalization and degradation of CD5 antigen on target cells, but this mechanism provides only short-term protection for normal and malignant T-cells from cytotoxicity. Long-term resistance of normal T-cells in patients having received CD5 CAR T-cell therapy was associated with the emergence of CD5-negative T-cell subsets."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • CD4 • CD5 • CD8 • KLRB1 • NKG7 • TCF7

Early Signals of Anti-Tumor Efficacy and Safety with Autologous CD5.CAR T-Cells in Patients with Refractory/Relapsed T-Cell Lymphoma (ASH 2021) - P1 | "Seven patients received a single dose of CD5.CAR T-cells following lymphodepleting chemotherapy (LDC) with cyclophosphamide and fludarabine, and two patients received an additional dose following initial disease evaluation. Shortened manufacturing resulted in an enrichment of minimally differentiated CCR7+ CD62L+ T-cells (27-fold mean increase in CD4+, 13-fold increase in CD8+; p=0.01) and a 3.5-fold increase in CD27+ CD8+ T-cells (p=0.04) suggesting minimizing duration of ex vivo expansion increases anti-tumor function of CD5.CAR T-cells. Overall, these results show that even in patients with multiply relapsed/resistant TCL, CD5.CAR T-cells can produce anti-tumor responses that are sufficiently durable to enable them to proceed with alloHSCT without inducing clinically significant T-cell aplasia."

CAR T-Cell Therapy • Clinical • Adult T-Cell Leukemia-Lymphoma • Bone Marrow Transplantation • Cutaneous T-cell Lymphoma • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Transplantation • CCR7 • CD27 • CD28 • CD4 • CD5 • CD8

MAGENTA: Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Baylor College of Medicine | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • CD5

Mechanisms Regulating the Resistance of Normal T-cells to CD5 CAR-Mediated Cytotoxicity (ASGCT 2022) - P1 | "To investigate this possibility, we replicated clinical findings by co-culturing T-cells with autologous CD5 CAR T-cells...Tumor cells may employ a similar mechanism to resist CAR T-cell activity. Understanding how normal and malignant T-cells evade CAR-mediated cytotoxicity will inform the design of next-generation cell therapies for patients with T-cell malignancies."

Oncology • CD5

MAGENTA: Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen (clinicaltrials.gov) - P1; N=42; Active, not recruiting; Sponsor: Baylor College of Medicine; Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • CD5