Delving into the Latest Updates on EMI-137 with Synapse

Overview

Basic Info

Drug Type

Peptide drug conjugates, Fluorophore-conjugated therapeutics

Synonyms

Target

c-Met

Mechanism

c-Met modulators(Hepatocyte growth factor receptor modulators)

Therapeutic Areas

Other Diseases

Active Indication

Diagnostic agents

Inactive Indication

Barrett EsophagusBreast CancerColonic Cancer+ [8]

Originator Organization

GE Healthcare, Inc.

Active Organization

GE Healthcare, Inc.

Edinburgh Molecular Imaging Ltd.Startup

Inactive Organization

Netherlands Cancer Insitute

University Medical Center of Utrecht

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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Gene Sequence

Sequence Code 1277664502

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EMI-137 in laparoscopic colonic resections is a single-centre stage IIa developmental study.
Ten adult participants with a diagnosis of colon adenocarcinoma undergoing laparoscopic colonic will be recruited to the trial. Participants will receive a single intravenous dose of the IMP - EMI-137 1 to 3 hours before surgery. The ability of EMI-137 to produce visible intra-operative fluorescence of primary colon cancer and lymph node metastases will be explored and evaluated.

Start Date14 Feb 2018

Sponsor / Collaborator

University of Leeds

[+1]

EUCTR2016-003128-22-GB / Not yet recruitingPhase 2

Intraoperative imaging of colon cancer using a fluorescent peptide (EMI-137) against the c-Met receptor

Start Date19 Oct 2017

Sponsor / Collaborator

University of Leeds

100 Clinical Results associated with EMI-137

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100 Translational Medicine associated with EMI-137

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100 Patents (Medical) associated with EMI-137

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7

Literatures (Medical) associated with EMI-137

01 Aug 2022·European Journal of Nuclear Medicine and Molecular Imaging

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection

Article

Author: van Hemel, Bettien M ; Links, Thera P ; Sondorp, Luc H J ; Coppes, Robert P ; Metman, Madelon J H ; Nguyen, Anh H ; Gill, Anthony J ; van Diest, Paul J ; Jonker, Pascal K C ; Löwik, Clemens W G M ; van Ginhoven, Tessa M ; Jansen, Liesbeth ; Fehrmann, Rudolf S N ; van Dam, Gooitzen M ; Sywak, Mark S ; Robinson, Dominic J ; Kruijff, Schelto

Abstract PurposePatients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively.MethodsWe used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissues (NTT) to identify tumor-specific antigens for a clinically available near-infrared fluorescent tracer. Protein expression of the top prioritized antigen was immunohistochemically validated with a tissue microarray containing primary PTC (n = 741) and NTT (n = 108). Staining intensity was correlated with 10-year locoregional recurrence-free survival (LRFS). A phase 1 study (NCT03470259) with EMI-137, targeting MET, was conducted to evaluate safety, optimal dosage for detecting PTC NM with MFGI, feasibility of NM detection with quantitative fiber-optic spectroscopy, and selective binding of EMI-137 for MET.ResultsMET was selected as the most promising antigen. A worse LRFS was observed in patients with positive versus negative MET staining (81.9% versus 93.2%; p = 0.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13 mg/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (p < 0.0001) and spectroscopy (p < 0.0001). MFGI identified 5/19 levels (26.3%) without NM. EMI-137 binds selectively to MET.ConclusionMET is overexpressed in PTC and associated with increased locoregional recurrence rates. Perioperative administration of EMI-137 is safe and facilitates NM detection using MFGI and spectroscopy, potentially reducing the number of negative PCLNDs with more than 25%.Clinical trial registration.NCT03470259.

01 Mar 2022·Surgical OncologyQ3 · MEDICINE

A novel fluorescent c-met targeted imaging agent for intra-operative colonic tumour mapping: Translation from the laboratory into a clinical trial

Q3 · MEDICINE

Article

Author: Nick P. West ; Gemma R. Armstrong ; David G. Jayne ; Christophe Portal ; Mohammed I. Khot ; Damian J. Tolan ; Thomas A. Hughes ; Sarah L. Perry ; Tom I. Maisey ; Jim P. Tiernan

BACKGROUNDThe c-Met protein is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model.METHODSHT-29 SiRNA transfection confirmed specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in BALB/c mice, EMI-137 was injected and biodistribution analysed through in vivo fluorescent imaging. Nine patients, received a single intravenous EMI-137 bolus (0.13 mg/kg), 1-3 h before laparoscopic-assisted colon cancer surgery (NCT03360461). Tumour and LN fluorescence was assessed intraoperatively and correlated with c-Met expression in eight samples by immunohistochemistry.FINDINGSc-Met expression HT-29 cells was silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed up to 6 h post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants, 4/9 showed increased tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited high c-Met protein expression.INTERPRETATIONEMI-137, binds specifically to the human c-Met protein, is safe, and with further refinement, shows potential for application in fluorescence-guided surgery.

01 Jan 2022·Journal of Nuclear MedicineQ1 · MEDICINE

c-MET Receptor–Targeted Fluorescence on the Road to Image-Guided Surgery in Penile Squamous Cell Carcinoma Patients

Q1 · MEDICINE

Article

Author: Vries, Hielke M de ; Poel, der ; Bekers, Elise ; Karakullukcu, M Baris ; van Oosterom, Matthias N ; Buckle, Tessa ; Brouwer, Oscar R ; van Leeuwen, Fijs W B ; van, Henk G

In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal-epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). Methods: EMI-137 tracer performance was initially assessed ex vivo (n = 10) via incubation of freshly excised pSCC in a solution containing EMI-137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumor visualization was assessed after intravenous administration of EMI-137 to 5 pSCC patients scheduled for surgical resection using a cyanine-5 fluorescence camera. Fluorescence imaging results were related to standard pathologic tumor evaluation and c-MET immunohistochemistry. Three of the 5 in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green- ^99mTc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. Results: No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET-based tumor visualization in all patients. Histopathologic analyses showed that all pSCCs expressed c-MET, with expression levels of at least 70% in 14 of 15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumors, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumor targeting with lymphatic mapping. As such, simultaneous use of cyanine-5 and indocyanine green in the same patient proved to be feasible. Conclusion: Fluorescence imaging of c-MET receptor- expressing pSCC tumors after intravenous injection of EMI-137 was shown to be feasible and can be combined with fluorescence-based lymphatic mapping. This combination is unique and paves the way toward further development of this surgical guidance approach.

100 Deals associated with EMI-137

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diagnostic agents	Phase 2	-	GE Healthcare, Inc.	-
Diagnostic agents	Phase 2	-	Edinburgh Molecular Imaging Ltd.Startup	-
Penile Neoplasms	Discovery	NL	Netherlands Cancer Insitute	12 Oct 2019
Tongue Neoplasms	Discovery	NL	Netherlands Cancer Insitute	11 Oct 2019
Ovarian Cancer	Discovery	GB	Edinburgh Molecular Imaging Ltd.Startup	09 Sep 2019
Colonic Cancer	Discovery	GB	Edinburgh Molecular Imaging Ltd.Startup	14 Feb 2018
Lymphatic Metastasis	Discovery	GB	Edinburgh Molecular Imaging Ltd.Startup	14 Feb 2018
Breast Cancer	Discovery	GB	-	13 Nov 2015
Barrett Esophagus	Discovery	NL	University Medical Center of Utrecht	-
Thyroid Cancer	Discovery	NL	Edinburgh Molecular Imaging Ltd.Startup	-