Delving into the Latest Updates on Solitumomab with Synapse

Overview

Basic Info

Drug Type

Bispecific T-cell Engager (BiTE)

Synonyms

Anti-CD3 anti-EpCAM bispecific antibody, MT110 monoclonal antibody, Solitomab

+ [3]

Target

CD3 x EpCAM

Action

stimulants, modulators

Mechanism

CD3 stimulants(T cell surface glycoprotein CD3 stimulants), EpCAM modulators(Epithelial cell adhesion molecule modulators)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [3]

Active Indication-

Inactive Indication

Adenocarcinoma of LungBreast CancerCastration-Resistant Prostatic Cancer+ [4]

Originator Organization

Micromet AG

Active Organization-

Inactive Organization

Amgen Research (Munich) GmbH

License Organization-

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 315601010

Source: *****

An Open-label, Multi-center Dose Escalation Phase I Study to Investigate the Safety and Tolerability of a Continuous Infusion of the Bispecific T-cell Engager (BiTE) MT110 in Locally Advanced, Recurrent or Metastatic Solid Tumors Which Commonly Express EpCAM and Are Not Amenable to Curative Treatment

This phase I dose escalation study is intended to define the safety, tolerability and maximal tolerable dose (MTD) of MT110 in patients with advanced solid tumors.

Start Date01 Mar 2008

Sponsor / Collaborator

Amgen Research (Munich) GmbH

100 Clinical Results associated with Solitumomab

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100 Translational Medicine associated with Solitumomab

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100 Patents (Medical) associated with Solitumomab

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27

Literatures (Medical) associated with Solitumomab

01 Feb 2024·Preparative biochemistry & biotechnology

Studies on a new antimicrobial peptide from Vibrio proteolyticus MT110

Article

Author: Sahoo, Debendra K ; Verma, Himanshu ; Nandal, Jitender ; Mihooliya, Kanti N

The marine environment is known for its vast diversity of the microbial population; however, less explored for bioactive compounds. In this study, an AMP produced by a new marine isolate, Vibrio proteolyticus MT110, showed broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. The AMP was purified to homogeneity using ethyl acetate extraction followed by RP-HPLC, and LC-MS analysis showed its molecular weight as 980 Da. The MIC of AMP (peptide-MT110) was obtained in the 7.81-31.25 µg/mL range against different indicator strains. Peptide-MT110 showed stability of its antimicrobial activity at 15-121 °C and pH 4-10 and in the presence of various hydrolytic enzymes. The peaks at 1536 cm^-1 and 1712 cm^-1 wavenumbers in FTIR spectra confirmed the peptidic nature of AMP, and its amino acid analysis confirmed the presence of tyrosine and isoleucine. The antibacterial activity of peptide-MT110 is confirmed by PI assay and TEM. The optimization of peptide-MT110 production using statistical methods resulted in a 2.64-fold higher production. The physicochemical properties and stability in wide pH and temperature ranges showed the potential of peptide-MT110 for its development as a drug candidate. This is believed to be the first report on an AMP from Vibrio proteolyticus.

31 Dec 2023·Oncoimmunology

Novel Fab-peptide-HLA-I fusion proteins for redirecting pre-existing anti-CMV T cell immunity to selectively eliminate carcinoma cells

Article

Author: Samplonius, Douwe F. ; Helfrich, Wijnand ; Britsch, Isabel ; Ploeg, Emily M. ; van Wijngaarden, Anne P. ; Ke, Xiurong ; Hendriks, Mark. A.J.M.

Typically, anticancer CD8^pos T cells occur at low frequencies and become increasingly impaired in the tumor micro environment. In contrast, antiviral CD8^pos T cells display a much higher polyclonality, frequency, and functionality. In particular, cytomegalovirus (CMV) infection induces high numbers of 'inflationary' CD8^pos T cells that remain lifelong abundantly present in CMV-seropositive subjects. Importantly, these so-called inflationary anti-CMV T cells increase with age, maintain a ready-to-go state, populate tumors, and do not become exhausted or senescent. Given these favorable attributes, we devised a novel series of recombinant Fab-peptide-HLA-I fusion proteins and coined them 'ReTARGs'. A ReTARG fusion protein consists of a high-affinity Fab antibody fragment directed to carcinoma-associated cell surface antigen EpCAM (or EGFR), fused in tandem with soluble HLA-I molecule/β2-microglobulin, genetically equipped with an immunodominant peptide derived from CMV proteins pp65 (or IE-1). Decoration with EpCAM-ReTARG^pp65 rendered EpCAM-expressing primary patient-derived carcinoma cells highly sensitive to selective elimination by cognate anti-CMV CD8^pos T cells. Importantly, this treatment did not induce excessive levels of proinflammatory T cell-secreted IFNγ. In contrast, analogous treatment with equimolar amounts of EpCAM/CD3-directed bispecific T-cell engager solitomab resulted in a massive release of IFNγ, a feature commonly associated with adverse cytokine-release syndrome. Combinatorial treatment with EpCAM-ReTARG^pp65 and EGFR-ReTARG^IE-1 strongly potentiated selective cancer cell elimination owing to the concerted action of the corresponding cognate anti-CMV CD8^pos T cell clones. In conclusion, ReTARG fusion proteins may be useful as an alternative or complementary form of targeted cancer immunotherapy for 'cold' solid cancers.

13 Apr 2023·Cells

A Novel Hydrogel-Based 3D In Vitro Tumor Panel of 30 PDX Models Incorporates Tumor, Stromal and Immune Cell Compartments of the TME for the Screening of Oncology and Immuno-Therapies.

Article

Author: Lashuk, Kanstantsin ; Harrod, Christopher M. ; Hribar, Kolin C. ; Xue, Bin ; Bomya, Zoji ; Schuler, Julia

Human-relevant systems that mimic the 3D tumor microenvironment (TME), particularly the complex mechanisms of immuno-modulation in the tumor stroma, in a reproducible and scalable format are of high interest for the drug discovery industry. Here, we describe a novel 3D in vitro tumor panel comprising 30 distinct PDX models covering a range of histotypes and molecular subtypes and cocultured with fibroblasts and PBMCs in planar (flat) extracellular matrix hydrogels to reflect the three compartments of the TME-tumor, stroma, and immune cells. The panel was constructed in a 96-well plate format and assayed tumor size, tumor killing, and T-cell infiltration using high-content image analysis after 4 days of treatment. We screened the panel first against the chemotherapy drug Cisplatin to demonstrate feasibility and robustness, and subsequently assayed immuno-oncology agents Solitomab (CD3/EpCAM bispecific T-cell engager) and the immune checkpoint inhibitors (ICIs) Atezolizumab (anti-PDL1), Nivolumab (anti-PD1) and Ipilimumab (anti-CTLA4). Solitomab displayed a strong response across many PDX models in terms of tumor reduction and killing, allowing for its subsequent use as a positive control for ICIs. Interestingly, Atezolizumab and Nivolumab demonstrated a mild response compared to Ipilimumab in a subset of models from the panel. We later determined that PBMC spatial proximity in the assay setup was important for the PD1 inhibitor, hypothesizing that both duration and concentration of antigen exposure may be critical. The described 30-model panel represents a significant advancement toward screening in vitro models of the tumor microenvironment that include tumor, fibroblast, and immune cell populations in an extracellular matrix hydrogel, with robust and standardized high content image analysis in a planar hydrogel. The platform is aimed at rapidly screening various combinations and novel agents and forming a critical conduit to the clinic, thus accelerating drug discovery for the next generation of therapeutics.

1

News (Medical) associated with Solitumomab

16 Mar 2023

·www.prnewswire.com

Myosin Therapeutics Closes Seed Round to Continue Development of Innovative Therapies for Glioblastoma and Stimulant Use Disorder

Myosin Therapeutics Inc., a biotechnology company leveraging its innovative platform technology to identify new molecular entities capable of selectively targeting nanomotor proteins, announced today that it supplemented its National Institutes of Health (NIH) funding with a seed funding round to advance the company's lead programs on glioblastoma and stimulant use disorder. Myosin Therapeutics, Inc. (the "Company") is developing its lead compound, MT-125, to treat glioblastoma, which is a highly aggressive form of brain cancer with a 95% fatality rate and limited treatment options available. In early models, MT-125 has shown that it can simultaneously arrest cancer cell division and migration, and therefore could be a first-in-class therapy. The Company believes that this funding should allow it to reach IND filing for MT-125. Stimulant use disorder, which includes dependence on drugs such as methamphetamine and cocaine, affects millions of people worldwide, is associated with significant morbidity and mortality, and has no FDA-approved treatments. The Company believes that this capital infusion along with existing funding from the National Institute of Health should provide the funding needed to advance Myosin Therapeutics' other lead compound, MT-110, for stimulant use disorders through Phase 1 clinical trials. "We are excited to receive this funding, which will allow us to rapidly advance our first-in-class treatments for glioblastoma and stimulant use disorder, two devastating conditions that lack effective treatments," said Dr. Courtney Miller, co-founder of Myosin Therapeutics. "Our platform for targeting the largely untapped families of nanomotor proteins represents a unique and promising strategy for oncology, in particular." The seed funding round was led by Mint12 Pharma, LLC, with participation from the University of Florida Ventures, DeepWork Capital, and the Florida Opportunity Fund. Mint12 Pharma's Managing Partner, Dave Adams, said, "We are thrilled to partner with Myosin Therapeutics to develop innovative therapies for these two conditions that currently lack effective treatment. Myosin's nanomotor platform has tremendous potential and we look forward to seeing the company's progress in the coming years." About Myosin Therapeutics. Myosin Therapeutics is a Jupiter, FL-based biotechnology company spun out of The Herbert Wertheim UF Scripps Institute (formerly Scripps Research, Florida) focused on develop therapies for central nervous system and oncology indications with a platform for targeting molecular nanomotor proteins. The company's lead programs for glioblastoma and stimulant use disorder target myosin motor proteins, which play a critical role in a wide range of cellular processes. Myosin Therapeutics was founded in 2020 by Drs. Courtney Miller, Patrick Griffin, and Theodore Kamenecka. To learn more about the company, please visit www.myosintherapeutics.com. Mint12 Pharma invests in new patented core pharmaceutical and biotech technologies that have the potential to address fast growing and underserved markets with no current FDA approved therapies by providing financing, placing new executive management to support existing scientific leadership, and governance oversight. Mint12 Pharma provides Seed and Series A financing to companies and is led by an experienced team of Pharma/Biotech operators and investing professionals. SOURCE Myosin Therapeutics Inc.

100 Deals associated with Solitumomab

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of Lung	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008
Breast Cancer	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008
Castration-Resistant Prostatic Cancer	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008
Colorectal Cancer	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008
Gastroesophageal junction adenocarcinoma	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008
Ovarian Cancer	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008
Small Cell Lung Cancer	Phase 1	Germany	Amgen Research (Munich) GmbH	01 Mar 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00635596 (Pubmed \| Oncoimmunology) Manual	Phase 1	Solid tumor	65	solitomab	coykwebrtl(kakztircqx) = Fifteen patients had dose-limiting toxicities (DLTs): eight had transient abnormal liver parameters shortly; one had supraventricular tachycardia (grade 3); Six patients had a DLT of diarrhea ebcvczwaie (oxkrfjueyu ) View more	Negative	18 Apr 2018
AACR2012	Not Applicable	germ cell cancers	-	EpCAM/CD3-bispecific BiTE antibody (T regulatory cells)	qtxdajvbjv(ejczetotat) = blwoajkhqf mkudgnzawx (ktdvbsqlio )	-	15 Apr 2012

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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