CD45-ADC / Dianthus Therap - LARVOL DELTA

Broadly-neutralizing antibodies and CCR5 -edited hematopoietic stem cell transplantation synergistically delay virus recrudescence in a nonhuman primate model of HIV (ASGCT 2025) - "Bulk CD34+ HSPCs were collected after G-CSF/Plerixafor mobilization, edited with NHP CCR5-specific CRISPR ribonucleoprotein (RNP) complexes, cryopreserved, and transplanted after conditioning with either myeloablative busulfan or an anti-CD45 antibody-drug conjugate (ADC)...At ART withdrawal, a subset of animals received a single infusion of VRC07.523.LS, a safe and effective bNAb with potency against HIV and SHIV.C.CH505.v2, and is currently in clinical trials in people living with HIV (PWH)...Our ongoing efforts are focused on quantitative comparisons between busulfan- and CD45-ADC conditioning regimens, the latter of which may also directly deplete latently-infected cells. Disease Focus of Abstract:HIV"

Preclinical • Bone Marrow Transplantation • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Transplantation • CD34

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate. (PubMed, Cell Stem Cell) - "HbF levels were further boosted by stress erythropoiesis or hydroxyurea. CD45 antibody-drug conjugate (ADC) conditioning achieved comparable engraftment and HbF reactivation, whereas lentiviral vector tracking showed polyclonal reconstitution with dynamics similar to animals conditioned with total body irradiation (TBI) or busulfan. Joining CD45-ADC conditioning with combined enhancer editing presents an effective strategy for β-hemoglobinopathies, enabling durable HbF reactivation without chemotherapy."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • PTPRC

Nongenotoxic CD45-ADC-Based Conditioning Maintains Potent Suppression of Plasma Viremia in Nonhuman Primate Model of HIV (ASGCT 2024) - "We have advanced our model of HIV-specific HSPC gene therapy in a clinically relevant model and observe long term persistence of CCR5-edited HSPC and progeny in vivo after targeted conditioning. Myeloablative busulfan, CD117-ADC and CD45-ADC conditioning all supported engraftment without impaired resistance to SHIV. In our model of antiretroviral therapy-suppressed HIV infection, hematopoietic recovery and engraftment of edited cells after CD45-ADC conditioning was comparable to busulfan and achieved tissue-specific depletion of CD45+ cells."

Preclinical • Gene Therapies • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Neutropenia • Oncology • Transplantation • CD34 • KIT • PTPRC

Alloengraftment without significant toxicity or GVHD in CD45 antibody-drug conjugate conditioned Fanconi anemia mice. (PubMed, Blood) - "Moreover, single dose anti-human CD45-ADC given to rhesus macaque nonhuman primates on days -6 or -10 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable FA patients."

Journal • Preclinical • Anemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • Transplantation • FANCA • FANCC • FANCG • PTPRC

Clearing and replacing tissue-resident myeloid cells with an anti-CD45-antibody-drug conjugate. (PubMed, Blood Adv) - "Notably, this reduced existent atherosclerotic plaque burden. Overall, these results indicate that anti-CD45-ADC clears both HSC and TRM from their niches enabling cell replacement to achieve disease modification in a resident myeloid cell driven disease."

Journal • Atherosclerosis • Bone Marrow Transplantation • Cardiovascular • Dyslipidemia • Hematological Disorders • Metabolic Disorders • Transplantation • TET2

Transplantation after CD45-ADC corrects Rag1 immunodeficiency in congenic and haploidentical settings. (PubMed, J Allergy Clin Immunol) - "Conditioning with CD45-ADC alone allows full donor chimerism and immune reconstitution in Rag1 hypomorphic mice even following haploidentical transplantation, opening the way for the implementation of similar approaches in humans."

Journal • Graft versus Host Disease • Immunology • Primary Immunodeficiency • Transplantation • PTPRC • RAG1

CONDITIONING USING MGTA-45, AN ANTI-CD45 ANTIBODY-DRUG CONJUGATE, DEPLETES HSCS AND IMMUNE CELLS AND ENABLES TRANSPLANT IN NONHUMAN PRIMATES (EBMT 2023) - "A single dose of 3 mg/kg MGTA-45 resulted in long-term disease-free survival in all animals (median >330 days) while control groups (vehicle, isotype-ADC, or cytarabine standard of care) had median survival of 52-64 days (P < 0.005, n=5-8 mice/group).  Targeting CD45-expressing hematopoietic cells with MGTA-45, a novel anti-CD45-ADC, potently depleted HSCs and immune cells in vitro and in vivo and enabled donor cell engraftment in a nonhuman primate transplant model. MGTA-45 also significantly extended survival in a PDX model of AML refractory to standard of care. Overall, targeted conditioning using MGTA-45 could improve the risk-benefit profile of HSCT, expanding the patient population able to receive these potentially curative therapies."

Immune cell • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infertility • Leukemia • Oncology • Pediatrics • Sexual Disorders • Transplantation • CD34

A Single Dose of Anti-CD45 Antibody-Drug Conjugate Conditioning Enables Transplant in Nonhuman Primates (TCT-ASTCT-CIBMTR 2023) - "Engraftment following a single dose of 0.3 mg/kg anti-CD45-ADC conditioning was comparable to conditioning with four daily doses of toxic myeloablative busulfan chemotherapy...A single dose of 3 mg/kg anti-CD45-ADC resulted in long-term disease-free survival in all animals (median >330 days) while control groups (vehicle, isotype-ADC, or cytarabine standard of care) had a median survival of only 52-64 days ( P < 0.005, n = 5-8 mice/group)... Targeting CD45-expressing hematopoietic cells with a novel anti-CD45-ADC potently depleted HSCs and immune cells in vitro and in vivo and enabled autologous transplant in a clinically relevant nonhuman primate gene-therapy model. Anti-CD45-ADC also significantly extended survival in a PDX model of AML refractory to standard of care. Overall, targeted conditioning using anti-CD45-ADC could improve the risk-benefit profile of HSCT, expanding the patient population able to receive these potentially curative therapies."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gene Therapies • Hematological Disorders • Hematological Malignancies • Infertility • Leukemia • Oncology • Sexual Disorders • Transplantation • CD34

Development of Anti-CD45 Antibody Drug Conjugates As Targeted Conditioning Agents for Transplantation/Gene Therapy with Potent Anti-Leukemic Properties (ASH 2022) - "Following engraftment, mice were conditioned with 1 mg/kg anti-CD45 ADC or controls...Unpaired t-test p-values indicated. B) OCIM1 bearing mice treated with anti-human CD45 ADCs show prolonged survival compared to Isotype ADC or naked antibody."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gene Therapies • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • T Acute Lymphoblastic Leukemia • Transplantation • CD34

Magenta Therapeutics Reports Third Quarter Financial Results and Recent Program Highlights (GlobeNewswire) - "Magenta has completed a dose-ranging toxicology preclinical study successfully with no unexpected findings. The data inform dosing for a Good Laboratory Practices toxicology study intended to support a planned Investigational New Drug (IND) application...Magenta expects to provide a further update on the CD45-ADC program in December 2022...Research and development expenses were $11.2 million in the third quarter of 2022, compared to $10.8 million in the third quarter of 2021. The increase was driven primarily by higher preclinical and manufacturing costs to support our IND-enabling studies for CD45-ADC..."

Commercial • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology

Magenta Therapeutics Reports Second Quarter Financial Results and Recent Program Highlights (GlobeNewswire) - "Magenta has recently completed the in-life portion of a dose-ranging toxicology study and will use the resulting data to inform dosing for its planned GLP toxicology study. Other IND-enabling activities and plans are ongoing. Magenta expects to provide a further update on the CD45 program in Q4 2022."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Magenta Therapeutics Highlights Recent Pipeline Progress and Milestone Expectations for 2022 (Businesswire) - "MGTA-117 Phase 1/2 clinical trial is open for enrollment for patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes; clinical data expected in 2022; CD45 antibody drug conjugate is Magenta’s second conditioning program; dose range toxicology results expected in second half of 2022."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

CD45-targeted antibody-drug-conjugate successfully conditions for allogeneic hematopoietic stem cell transplantation. (PubMed, Blood) - "When CD45-ADC was combined with pre-transplant TBI (50cGy) and post-transplant Rapamycin, Cytoxan or a JAK inhibitor, 90-100% of recipients achieved stable chimerism (mean: 77%, 59%, 78%, respectively). At a higher dose (5mg/kg), CD45-ADC as a single agent was sufficient for rapid, high level multi-lineage chimerism sustained through the 22 weeks observation period. Therefore, CD45-ADC has potential utility to confer the benefit of fully myeloablative conditioning but with substantially reduced toxicity when given as a single agent or at lower doses in conjunction with reduced intensity conditioning."

Journal • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Immune Modulation • Immunology • Inflammation • Transplantation • CD40LG • PTPRC

Magenta Therapeutics to Present Additional Data from Phase 1 MGTA-145 Stem Cell Mobilization Program and Preclinical Updates on Targeting Conditioning Program at Transplantation and Cellular Therapy (TCT) 2021 Annual Meeting (Businesswire) - "Magenta Therapeutic...announced data presentations across its stem cell mobilization and targeted conditioning programs at the Transplantation and Cellular Therapy (TCT) Annual Meeting...Oral Presentation Showcasing Preclinical Study of MGTA-117 Targeted ADC Conditioning Program; Poster Presentation Highlighting Preclinical Data of CD45-ADC Targeted Conditioning Program; Oral Presentation of MGTA-456 Stem Cell Therapy Expansion Program in Patients with Blood Cancer..."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

[VIRTUAL] Targeted CD45 Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model As a Single Agent (TCT-ASTCT-CIBMTR 2021) - "Methods The anti-murine CD45-ADC was engineered for rapid clearance (t1/2=1.7hr) to enable HSCT after conditioning...This targeted, readily translatable approach for safer conditioning could improve the risk-benefit profile for allogenic and haploidentical HSCT and may extend the curative potential of HSCT to more patients suffering from malignant and non-malignant blood disorders that would benefit from HSCT. Figure"

Preclinical • Hematological Disorders • Transplantation • PTPRC

[VIRTUAL] Targeted CD45 Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model As a Single Agent (TCT-ASTCT-CIBMTR 2021) - "Methods The anti-murine CD45-ADC was engineered for rapid clearance (t1/2=1.7hr) to enable HSCT after conditioning...This targeted, readily translatable approach for safer conditioning could improve the risk-benefit profile for allogenic and haploidentical HSCT and may extend the curative potential of HSCT to more patients suffering from malignant and non-malignant blood disorders that would benefit from HSCT. Figure"

Preclinical • Hematological Disorders • Transplantation • PTPRC

[VIRTUAL] Targeted CD45 Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model As a Single Agent (TCT-ASTCT-CIBMTR 2021) - "Methods The anti-murine CD45-ADC was engineered for rapid clearance (t1/2=1.7hr) to enable HSCT after conditioning...This targeted, readily translatable approach for safer conditioning could improve the risk-benefit profile for allogenic and haploidentical HSCT and may extend the curative potential of HSCT to more patients suffering from malignant and non-malignant blood disorders that would benefit from HSCT. Figure"

Preclinical • Hematological Disorders • Transplantation • PTPRC

[VIRTUAL] Targeted CD45 Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model As a Single Agent (TCT-ASTCT-CIBMTR 2021) - "Methods The anti-murine CD45-ADC was engineered for rapid clearance (t1/2=1.7hr) to enable HSCT after conditioning...This targeted, readily translatable approach for safer conditioning could improve the risk-benefit profile for allogenic and haploidentical HSCT and may extend the curative potential of HSCT to more patients suffering from malignant and non-malignant blood disorders that would benefit from HSCT. Figure"

Preclinical • Hematological Disorders • Transplantation • PTPRC

[VIRTUAL] Targeted CD45 Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model As a Single Agent (TCT-ASTCT-CIBMTR 2021) - "Methods The anti-murine CD45-ADC was engineered for rapid clearance (t1/2=1.7hr) to enable HSCT after conditioning...This targeted, readily translatable approach for safer conditioning could improve the risk-benefit profile for allogenic and haploidentical HSCT and may extend the curative potential of HSCT to more patients suffering from malignant and non-malignant blood disorders that would benefit from HSCT. Figure"

Preclinical • Hematological Disorders • Transplantation • PTPRC

[VIRTUAL] Single Agent CD45-Targeted Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model (ASH 2020) - "Conclusion Conditioning with CD45-ADC was well-tolerated, fully myeloablative, and enabled complete chimerism in a full mismatch allo-HSCT model as a single agent. This targeted, readily translatable approach for safer conditioning could improve the risk-benefit profile for allogenic and haploidentical HSCT and may extend the curative potential of HSCT to more patients suffering from blood cancers and other diseases that may benefit from HSCT."

Preclinical • Hematological Disorders • Hematological Malignancies • Infertility • Oncology • Sexual Disorders • Transplantation • PTPRC

[VIRTUAL] Reversing Clonal Hematopoiesis and Associated Atherosclerotic Disease By Targeted Antibody-Drug-Conjugate (ADC) Conditioning and Transplant (ASH 2020) - "In conclusion, these data demonstrate that CD45-ADC and HSCT efficiently replaces the disease driving myeloid cells in the atherosclerosis plaques leading to an overall reduction in disease burden. CD45-ADC and transplantation may thus offer a novel therapy for CH and its associated morbidities."

Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Hypertension • Transplantation • PTPRC • TET2

".@MagentaTx $MGTA will report updates across its product portfolio, including MGTA-145, MGTA-117 & CD45 ADC, at #ASH20." (@DanBudwick)

PTPRC

[VIRTUAL] A NOVEL TARGETED APPROACH TO ACHIEVE IMMUNE SYSTEM RESET: CD45-TARGETED ANTIBODY DRUG CONJUGATES AMELIORATE DISEASE IN PRECLINICAL AUTOIMMUNE DISEASE MODELS AND ENABLE AUTOHSCT (EBMT 2020) - "These results suggest that targeted immune depletion with a single dose of CD45-ADC may be sufficient to enable auto-HSCT and immune reset in multiple AID indications without toxic side effects. Targeted conditioning with CD45-ADC may represent a better tolerated approach for removing disease-causing cells as part of immune reset through autoHSCT and may significantly reduce the morbidity and mortality associated with current conditioning."

Preclinical • CNS Disorders • Diabetes • Fibrosis • Graft versus Host Disease • Immunology • Metabolic Disorders • Multiple Sclerosis • Rheumatology • Scleroderma • Systemic Sclerosis • Transplantation • CD34

[VIRTUAL] A NOVEL TARGETED APPROACH TO ACHIEVE IMMUNE SYSTEM RESET: CD45-TARGETED ANTIBODY DRUG CONJUGATES AMELIORATE DISEASE IN PRECLINICAL AUTOIMMUNE DISEASE MODELS AND ENABLE AUTOHSCT (EBMT 2020) - "These results suggest that targeted immune depletion with a single dose of CD45-ADC may be sufficient to enable auto-HSCT and immune reset in multiple AID indications without toxic side effects. Targeted conditioning with CD45-ADC may represent a better tolerated approach for removing disease-causing cells as part of immune reset through autoHSCT and may significantly reduce the morbidity and mortality associated with current conditioning."

Preclinical • CNS Disorders • Diabetes • Fibrosis • Graft versus Host Disease • Immunology • Metabolic Disorders • Multiple Sclerosis • Rheumatology • Scleroderma • Systemic Sclerosis • Transplantation • CD34

[VIRTUAL] A NOVEL TARGETED APPROACH TO ACHIEVE IMMUNE SYSTEM RESET: CD45-TARGETED ANTIBODY DRUG CONJUGATES AMELIORATE DISEASE IN PRECLINICAL AUTOIMMUNE DISEASE MODELS AND ENABLE AUTOHSCT (EBMT 2020) - "These results suggest that targeted immune depletion with a single dose of CD45-ADC may be sufficient to enable auto-HSCT and immune reset in multiple AID indications without toxic side effects. Targeted conditioning with CD45-ADC may represent a better tolerated approach for removing disease-causing cells as part of immune reset through autoHSCT and may significantly reduce the morbidity and mortality associated with current conditioning."

Preclinical • CNS Disorders • Diabetes • Fibrosis • Graft versus Host Disease • Immunology • Metabolic Disorders • Multiple Sclerosis • Rheumatology • Scleroderma • Systemic Sclerosis • Transplantation • CD34