Delving into the Latest Updates on MB-CART2019.1 with Synapse

Overview

Basic Info

Drug Type

Autologous CAR-T

Synonyms

Anti-CD20-anti-CD19 CAR T cells, CD20-CD19-targeting CAR T Cells, DALY II USA

+ [1]

Target

CD19 x CD20

Mechanism

CD19 inhibitors(B-lymphocyte antigen CD19 inhibitors), CD20 inhibitors(B-lymphocyte antigen CD20 inhibitors), T lymphocyte replacements

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

B-Cell LymphomaDiffuse Large B-Cell LymphomaChronic Lymphocytic Leukemia+ [3]

Inactive Indication-

Originator Organization

Miltenyi Biotec, Inc.

Active Organization

Miltenyi Biomedicine GmbHStartup

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationPRIME (EU)

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This is a single-arm, multi-center, open-label Phase II study to determine the safety and efficacy of MB-CART2019.1 in pediatric and adolescent subjects (aged between 6 months and <18 years, ≥6 kg body weight [BW]) with mature B-cell neoplasms and aggressive lymphomas that relapsed after or are refractory to one or more prior therapies, including subjects with primary refractory disease.

Start Date01 Apr 2025

Sponsor / Collaborator

Miltenyi Biomedicine GmbHStartup

NCT06508775 / RecruitingNot Applicable

Long-Term Follow-up of Patients Treated With Miltenyi Cell and Gene Therapies

The goal of this Long-Term Follow-Up Trial is to assess long-term safety and efficacy of Miltenyi CAR T treatment.

Start Date05 May 2024

Sponsor / Collaborator

Miltenyi Biomedicine GmbHStartup

NCT04844866 / Active, not recruitingPhase 2

A Pivotal Phase II Randomised, Multi-centre, Open-label Study to Evaluate the Efficacy and Safety of MB-CART2019.1 Compared to SoC Therapy in Participants With r/r DLBCL, Who Are Not Eligible for HDC and ASCT

This is a pivotal Phase II randomised, multi-centre, open-label study to evaluate the efficacy and safety of MB-CART2019.1 compared to standard of care therapy in participants with relapsed/refractory diffuse large B-cell lymphoma, who are not eligible for high-dose chemotherapy and autologous stem cell transplantation.

Start Date18 Aug 2021

Sponsor / Collaborator

Miltenyi Biomedicine GmbHStartup

[+1]

100 Clinical Results associated with MB-CART2019.1

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100 Translational Medicine associated with MB-CART2019.1

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100 Patents (Medical) associated with MB-CART2019.1

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11

Literatures (Medical) associated with MB-CART2019.1

01 Nov 2024·The Lancet Rheumatology

CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series

Article

Author: Auth, Janina ; Fuchs, Florian ; Bergmann, Christina ; Krickau, Tobias ; Hagen, Melanie ; Harrer, Thomas ; Kretschmann, Sascha ; Mackensen, Andreas ; Uder, Michael ; Aigner, Michael ; Bozec, Aline ; Rothe, Tobias ; Horch, Raymund E ; Tur, Carlo ; Tascilar, Koray ; Liphardt, Anna-Maria ; Grieshaber-Bouyer, Ricardo ; Spörl, Silvia ; Müller, Fabian ; Schett, Georg ; Völkl, Simon ; Kuwert, Torsten ; Györfi, Andrea-Hermina ; Chenguiti Fakhouri, Sara ; Taubmann, Jule ; Bäuerle, Tobias ; Coppers, Birte ; Wirsching, Andreas ; Distler, Jörg H W ; Raimondo, Maria G ; Bayerl, Nadine ; Eckstein, Markus ; Berking, Carola ; Atzinger, Armin ; Dees, Clara ; Kharboutli, Soraya

BACKGROUNDCD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis.METHODSSix patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 10⁶ CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months.FINDINGSBetween April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36-53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342-585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100-100) at 6 months. Median mRSS decreased by 31% (IQR 29-38), corresponding to a median of 8 points (IQR 7-13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3-4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18-275) at the latest observational timepoint.INTERPRETATIONWe provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis.FUNDINGDeutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung.

27 Jun 2023·JAMA

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome.

Article

Author: Faul, Christoph ; Lengerke, Claudia ; Bornemann, Antje ; Braun, Christiane ; Schmidt, Marina ; Horger, Marius ; Schneider, Janine ; Bethge, Wolfgang ; Stanger, Anna ; Pecher, Ann-Christin ; Atar, Daniel ; Seitz, Christian ; Hensen, Luca ; Klein, Reinhild ; Henes, Joerg ; Lutz, Katrin ; Schairer, Rebekka

ImportanceAutoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome.ObjectiveTo test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement.Design, Setting, and ParticipantsThis case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity.ExposurePrior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion.Main Outcomes and MeasuresThe patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes.ResultsRapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%).Conclusions and RelevanceCD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

01 Jan 2023·Therapeutic Advances in Neurological Disorders

Repurposing MS immunotherapies for CIDP and other autoimmune neuropathies: unfulfilled promise or efficient strategy?

Review

Author: Lehmann, Helmar C. ; Dalakas, Marinos C. ; Kohle, Felix

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number of studies that explored the efficacy of DMTs in animal models of AN but also in some CIDP patients. We here review the available preclinical and clinical data of approved MS therapeutics in terms of their applicability to AN, especially CIDP. Promising therapeutic approaches appear to be B cell–directed and complement-targeting strategies, such as anti-CD20/anti-CD19 agents, Bruton’s tyrosine kinase inhibitors and anti-C5 agents, as they exert their effects in the periphery. This is a major advantage because, in contrast to MS, their action in the periphery is sufficient to exert significant immunomodulation.

100 Deals associated with MB-CART2019.1

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	Phase 2	NL	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	ES	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	SE	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	LT	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	HU	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	FR	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	PL	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Diffuse Large B-Cell Lymphoma	Phase 2	IT	Miltenyi Biomedicine GmbHStartup	18 Aug 2021
Chronic Lymphocytic Leukemia	Phase 2	DE	Miltenyi Biomedicine GmbHStartup	25 Feb 2019
Small Lymphocytic Lymphoma	Phase 2	DE	Miltenyi Biomedicine GmbHStartup	25 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03870945 (EHA2022)	Phase 1	B-cell lymphoma recurrent	12	MB-CART2019.1	(bcuyhuerhs) = fnolkyiaaq ltinkusqmj (shsmqyppfg )	-	12 May 2022
NCT03870945 (ASH2020) Manual	Phase 1	B-Cell Lymphoma CD19 Positive \| CD20 Positive	12	MB-CART2019.1	(ogddqtkyop) = CRS grade 1 occurred in 3/6 patients on DL1 and DL2 each, and CRS grade 2 in 2 patients on DL2. rrmlchwddl (khcdjekbnz ) View more	Positive	05 Nov 2020
NCT03870945 (ASH2020) Manual	Phase 1	B-Cell Lymphoma CD19 Positive \| CD20 Positive	12	MB-CART2019.1		Positive	05 Nov 2020