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Turkish SME supported with SME Phase I award is looking for a Biotech company and a University research group for joint Eurostars grant application

Country of Origin: Turkey
Reference Number: RDTR20201207001
Publication Date: 9 December 2020

Summary

A biopharmaceutical SME from Turkey is developing a Eurostars proposal  to profile MEIS oncogene in patient derived tumor organoids and xenografts models and outline the potential of the first-in-class MEIS inhibitors. 
Partners sought: A company and a university research group with expertise in ex vivo cancer PDX models, organoids, in vivo efficacy in animal models and diagnostic development are sought.

Description

Meis1 was first discovered in BXH-2 mouse leukemia model. Studies in the last decade have shown that Meis1 has crucial roles in cellular metabolism, redox state, and tumorigenesis. Meis1 maintains cytoplasmic glycolysis through transactivation of hypoxic tumor markers, namely Hif-1α and Hif-2α. MEIS proteins includes MEIS1, MEIS2 and MEIS3 proteins. MEIS proteins are known as an oncogene and overexpressed in various cancers. Intriguingly, a high level of Meis1 expression was found to be associated with resistance to conventional chemotherapies. 
Turkish SME is a biopharmaceutical company developing innovative and personalized therapeutics for the treatment of patients with MEIS+ cancers. It has developed first-in-class, selective, drug-like small molecule MEIS inhibitors.
Studies demonstrated that blocking the MEIS proteins in tumors could:
• Block cancer cell growth
• Enhance cancer death through induction of apoptosis
• Modulate gene expression in metabolism

This MEISi-Explore project, aims to profile MEIS oncogene in patient derived tumor organoids and PDX models and to outline potential of the first-in-class MEIS inhibitors. Within this proposal, a range of disease profiling and efficacy experiments will be performed to determine highly responsive cancers and their correlation with MEIS content. MEISi-Explore will identify the highly responding cancer (sub)types by ex vivo and in vivo studies and to develop complementary diagnostics. This could allow decisive design of clinical studies and development of a targeted and personalized treatment for patients suffering from cancer with MEIS misregulation. The new candidate drug will be supported by safety and efficacy data packages and be ready for clinical trials within 18 months after completion of the project.

Proposal is being developed for the Eurostars programme which is designed for collaborative international R&D projects working on a marketable product, process or service.

Preliminary work packages of the proposal are:
WP 1: Disease profiling and high throughput analysis of candidate drug sensitivity and combinations in ex vivo cancer PDX models.
WP 2: MEIS+ patient derived tumor organoid development and efficacy analysis
WP 3: In vivo efficacy analysis of MEIS inhibitors in PDX animal models
WP 4: MEIS diagnostic kit development

Partners Sought: A company and a university research group with expertise in ex vivo cancer PDX models, organoids, and in vivo efficacy in animal models.
Moreover a sub-contractor is being sought for in-vitro diagnostic kit development.

Deadline of the Eurostars Call: 4 February 2021.

Deadline for EOIs: 11 January 2021

Advantages and Innovations

MEIS proteins are promising drug targets for cancer, cardiac regeneration, and stem cell function. Turkish SME has used in silico, in vitro and in vivo approaches to develop small-molecule MEIS inhibitors (MEISi). In silico screening of a million druggable small molecules allowed the company to identify putative MEISi. MEIS dependent luciferase reporter assays were used to validate in vitro efficacy of MEIS inhibitors. Small molecules named MEISi-1 and MEISi-2 demonstrated a significant inhibition of MEIS-luciferase activity. In addition, inhibition of MEIS protein resulted in down regulation of MEIS target gene expression. By this approach, the Turkish SME developed several novel anticancer MEISi lead molecules.

Stage Of Development

Proposal under development

Requested partner

Company and university research group with expertise in ex vivo cancer PDX models, organoids, and in vivo efficacy in animal models. 
A sub-contractor is being sought for in-vitro diagnostic kit development.

Partners’ Roles in Details
Partner 1 
Type of partner sought: Academic or SME
Specific area of activity of the partner: (At least one of the areas (1&2) below)
(1) Disease profiling and high throughput analysis of candidate drug sensitivity and combinations in ex vivo cancer PDX models.
(2) Academic research group or industry with outstanding scientific expertise in organoid development.

Task to be performed: (According to the areas above)
(1) Profiling of MEIS1/2/3 expression in patient derived tumor ex vivo fragments and selecting MEIS+ cancer of each cancer type. Phonotypical profiling (i.e. cell viability, cytotoxicity…) of MEIS+ Cancer cell viability post treatment with MEIS inhibitors to determine best responding cancer types. Optional: Analysis of MEIS inhibitors in healthy and corresponding  MEIS- PDX tumor fragments.
(2) Development and characterization of 3D organoid models of tumor samples with MEIS+ and MEIS- phenotype. Analysis of MEIS inhibitors in MEIS+ tumor organoids (i.e.viability, growth, apoptosis, morphology etc) and other required characterizations.

Partner 2
Type of partner sought: SME
Specific area of activity of the partner: In vivo tumor models
Task to be performed: In vivo efficacy analysis of MEIS inhibitors in PDX animal models, and analysis of combinatorial effect with current chemotherapeutics (optional) and other required characterizations, safety and efficacy analysis.

Sub-Contractor
Type of partner sought: SME
Specific area of activity of the partner: Biotech company with proven record of track diagnostic kit development
Task to be performed:  Profiling of MEIS1/2/3 expression in primary tumor samples and to develop MEIS specific diagnostic tools. Preparation of an IVD/CE diagnostic kit to select patients for clinical trials and other required validations, certifications, and regulatory planning.  After the project, the partner could be involved in the commercialization of the project results as well.

Cooperation offer ist closed for requests