Phase I, Open-Label, Multi-Center, Dose Escalation With Expansion Trial of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy in Relapse/Refractory Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies

Open label, nonrandomized, dose-escalation with cohort expansion study of MVT-5873/MVT-1075 in subjects with previously treated, Carbohydrate Antigen 19-9 (CA19-9) positive malignancies (e.g., pancreatic adenocarcinoma).

Start Date01 Jun 2017

Sponsor / Collaborator

BioNTech Research & Development, Inc.

100 Clinical Results associated with MVT-1075

100 Translational Medicine associated with MVT-1075

100 Patents (Medical) associated with MVT-1075

1,039

Literatures (Medical) associated with MVT-1075

01 May 2024·Journal of Anatomy

Postnatal changes in thyroid cartilage shape and cartilage matrix composition are not synchronized in Mus musculus

Article

Author: Riede, Tobias ; Dellafaille, Jolien ; Coyne, Megan

AbstractThe study was conducted to quantify laryngeal cartilage matrix composition and to investigate its relationship with cartilage shape in a mouse model. A sample of 30 mice (CD‐1 mouse, Mus musculus) from five age groups (postnatal Days 2, 21, 90, 365, and 720) were used. Three‐dimensional mouse laryngeal thyroid cartilage reconstructions were generated from contrast‐enhanced micro‐computed tomography (CT) image stacks. Cartilage matrix composition was estimated as Hounsfield units (HU). HU were determined by overlaying 3D reconstructions as masks on micro‐CT image stacks and then measuring the attenuation. Cartilage shape was quantified with landmarks placed on the surface of the thyroid cartilage. Shape differences between the five age groups were analyzed using geometric morphometrics and multiparametric analysis of landmarks. The relationship between HU and shape was investigated with correlational analyses. Among five age groups, HU became higher in older animals. The shape of the thyroid cartilage changes with age throughout the entire life of a mouse. The changes in shape were not synchronized with changes in cartilage matrix composition. The thyroid cartilage of young and old M. musculus larynx showed a homogenous mineralization pattern. High‐resolution contrast‐enhanced micro‐CT imaging makes the mouse larynx accessible for analysis of genetic and environmental factors affecting shape and matrix composition.

01 Apr 2024·American Journal of Hematology

Hydroxyurea is associated with later onset of acute splenic sequestration crisis in sickle cell disease: Lessons from the European Sickle Cell Disease Cohort—Hydroxyurea (ESCORT‐HU) study

Article

Author: Etienne-Julan, Maryse ; Oevermann, Lena ; Loko, Gylna ; Elenga, Narcisse ; de Montalembert, Mariane ; Allali, Slimane ; Castex, Marie-Pierre ; Joseph, Laure ; Cannas, Giovanna ; Galactéros, Frédéric ; Brousse, Valentine ; Benkerrou, Malika

AbstractAcute splenic sequestration crisis (ASSC) is a potentially life‐threatening complication of sickle cell disease (SCD), typically occurring in young patients under 5 years of age, with a median age at first episode of less than 2 years. Because a beneficial effect of hydroxyurea (HU) on spleen perfusion and splenic function has been suspected, we hypothesized that HU treatment might be associated with later onset of ASSC in patients with SCD. To investigate this hypothesis, we analyzed data from the ESCORT‐HU study on a large cohort of patients with SCD receiving HU, enrolled between January 2009 and June 2017 with a follow‐up of 7309 patient‐years of observation. The median age at ASSC of the 14 patients who experienced a first episode of ASSC during the study period was 8.0 [IQR: 5.0–24.1] years. The median age at HU initiation was significantly lower in these 14 patients (4.8 [IQR: 3.3–18.7] years) compared to the 1664 patients without ASSC (19.9 [8.8–33.4] years, p = .0008). These findings suggest that ASSC may occur at an unusually late age in patients receiving HU, possibly reflecting longer preservation of spleen perfusion and function secondary to early initiation of HU. Further studies are needed to better characterize the effects of HU on spleen perfusion/function and on the occurrence of ASSC in patients with SCD (ClinicalTrials.gov identifier: NCT02516579; European registry ENCEPP/SDPP/10565).

06 Mar 2024·G3: Genes, Genomes, Genetics

Functional analysis of chromatin-associated proteins in Sordaria macrospora reveals similar roles for RTT109 and ASF1 in development and DNA damage response

Article

Author: Nowrousian, Minou ; Bollermann, Jonas ; Kramer, Mike ; Breuer, Jan ; Ferreira, David Emanuel Antunes

AbstractWe performed a functional analysis of two potential partners of ASF1, a highly conserved histone chaperone that plays a crucial role in the sexual development and DNA damage resistance in the ascomycete Sordaria macrospora. ASF1 is known to be involved in nucleosome assembly and disassembly, binding histones H3 and H4 during transcription, replication and DNA repair and has direct and indirect roles in histone recycling and modification as well as DNA methylation, acting as a chromatin modifier hub for a large network of chromatin-associated proteins. Here, we functionally characterized two of these proteins, RTT109 and CHK2. RTT109 is a fungal-specific histone acetyltransferase, while CHK2 is an ortholog to PRD-4, a checkpoint kinase of Neurospora crassa that performs similar cell cycle checkpoint functions as yeast RAD53. Through the generation and characterization of deletion mutants, we discovered striking similarities between RTT109 and ASF1 in terms of their contributions to sexual development, histone acetylation, and protection against DNA damage. Phenotypic observations revealed a developmental arrest at the same stage in Δrtt109 and Δasf1 strains, accompanied by a loss of H3K56 acetylation, as detected by western blot analysis. Deletion mutants of rtt109 and asf1 are sensitive to the DNA damaging agent methyl methanesulfonate, but not hydroxyurea. In contrast, chk2 mutants are fertile and resistant to methyl methanesulfonate, but not hydroxyurea. Our findings suggest a close functional association between ASF1 and RTT109 in the context of development, histone modification, and DNA damage response, while indicating a role for CHK2 in separate pathways of the DNA damage response.

100 Deals associated with MVT-1075

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Carcinoma	Phase 2	US	BioNTech Research & Development, Inc.	01 Jun 2017
Colorectal Cancer	Phase 1	-	Memorial Sloan Kettering Cancer Center	-
Colorectal Cancer	Phase 1	-	MabVax Therapeutics, Inc.	-
Lung Cancer	Phase 1	-	Memorial Sloan Kettering Cancer Center	-
Lung Cancer	Phase 1	-	MabVax Therapeutics, Inc.	-
Pancreatic Cancer	Phase 1	-	Memorial Sloan Kettering Cancer Center	-
Pancreatic Cancer	Phase 1	-	MabVax Therapeutics, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2018	Phase 1	Neoplasms \| Pancreatic Cancer	-	MVT-1075/MVT-5873	heukmbqaac(hxbdzbxgno) = ojtepclsrm vsfdwdfqze (lqdqmfxgqa ) View more	-	01 Jul 2018
ASH2011	Phase 1	Refractory acute myeloid leukemia	11	Midostaurin	(grtqsdqywx) = another patient developed grade 4 hyperglycemia jdglapeavc (khuapeqfri ) View more	-	18 Nov 2011
ASH2011	Phase 1	Refractory acute myeloid leukemia	11	Control (Saline)		-	18 Nov 2011

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