Druggable Small Molecule Inhibitor of MEIS Proteins

Project Information

MEISi

Grant agreement ID: 888430

DOI

10.3030/888430

Project closed

EC signature date 29 November 2019

Start date 1 December 2019

End date 31 May 2020

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

€ 71 429,00

EU contribution

€ 50 000,00

Coordinated by

MEINOX ILAC TEKNOLOJILERI AS
Türkiye

Periodic Reporting for period 1 - MEISi (Druggable Small Molecule Inhibitor of MEIS Proteins)

Reporting period: 2019-12-01 to 2020-05-31

Summary of the context and overall objectives of the project

MEIS proteins are implicated in various cellular processes including regeneration, stem cell/progenitor function, cellular metabolism, cell proliferation, redox state, apoptosis. The benefit presents to the targeted drug discovery market is to provide tools to modulate molecular mechanisms of the noncommunicable diseases (NCDs) including cancer, cardiovascular disorders, diabetes and obesity.

Noncommunicable diseases (NCDs) including cardiovascular disorders (CVDs), obesity, diabetes and cancer present difficult challenges as the subject of basic research activities towards understanding their progression and biology. In order to improve the treatment procedures with targeted approaches, the pharmaceutical industry needs new molecular agents that can exploit the genetic and molecular dependencies of the NCDs.

Small molecules are increasingly being used as tools to modulate signalling pathways and understand the molecular basis of diseases. Whether to regulate stem cell biology by affecting reprogramming or to better understand the mechanism of cancers by targeting tumorigenic signalling nodes, the right small molecule can transform a research finding to the development of therapeutics.

Drug discovery of small molecules from target selection through to clinical evaluation is a very complex, challenging but rewarding area of investment. There are many obstacles along the journey from initial hit-finding activities, through optimization of compounds and eventually to delivery of robust candidate drugs for clinical evaluation.

The aim of the project is to investigate the feasibility of the business opportunities based on the drug-like substance “MEISi”, which specifically targets the deadliest noncommunicable diseases; cardiovascular disorders, obesity, diabetes and cancer. Divided into two main categories as Research-use-Only Molecules and Pharmaceutical Drugs, potential strengths and weaknesses of all product alternatives are separately assessed in terms of both technical and business aspects.

The technical studies cover detailed descriptions of the projected products, corresponding development and industrialization plans, an overview of international standards and current regulations in the targeted markets as well as risk management studies.

An in-depth market analysis conducted based on several market segments such as drug discovery processes, medical application fields and regional differences. The recent sectoral trends, potential customer/user analysis, competition analysis based on SMEs with similar focus and a detailed overview of market opportunities and barriers were also reviewed in the feasibility study.

The feasibility report concludes with the reflections based on the major outcomes of the study and offers relevant recommendations. Results show that both Research-use-Only and Drug applications for MEISi show great economic potential, offering viable and sustainable business ventures. Hence the effective roadmap is currently drawn in such a way that, the necessary activities for both options will be performed simultaneously, enabling the company to pursue a variety of opportunities at the same time.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The aim of the feasibility study is to assess the feasibility of using the drug-like small molecule MEISi for the development of research-use-only and pharmaceutical products. The study concentrates on various aspects involved in the small molecule drug discovery market, classified under the process, application field and region segments.
Although the pharmaceutical industry operates under very strictly regulated conditions which makes things even harder for smaller companies, undermet needs of an increasing patient population comes to the fore as an opportunity for smaller firms which are quicker to internalize novel technologies and to respond to ever changing needs of the society, hence more innovative than larger incumbent firms. The hardship resulting from regulatory issues can be handled more easily by the support of a consulting firm.
The study concludes that it is feasible in various aspects to develop and commercialize an anti-cancer (thymoma as a rare disease with an orphan drug indication), and anti-Obesity & Diabetes therapeutics upto PhaseI-II clinical trials. Currently, the pharmaceutical product development process is at the TRL3 stage and the activities are projected to extend over the next 2 years with an expected completion of PhaseI-II clinical trials in 3 years. As MEISi, the research-use-only product is commercialised, its marketing activities will continue. These marketing activities for MEISi will also increase both the brand recognition and MEIS awareness. MEISi and MeisnibTM will benefit both from this marketing activity.
Given general failure rates of more than 90%, drug failure is closer to a certainty than a risk. In order to minimize this risk, differentiating commercialisation strategies for different product categories is one of the main points highlighted by this study. It seems reasonable that the best strategy for pancreas and leukemia cancer targeting molecules is to licence the drug candidate molecules both for preclinical and clinical trials because of the long lasting procedures of these cancer types. Licensing the drug candidate for lung, breast and prostate cancer types at the clinical trial stage is another strategy.
Meinox has summarised the most important risks into the following categories: business environment and industry, performance, commercialization, business strategy, finance, legal issues, intellectual property, human resources, IT/Technology, processes and operational management. These risk categories should be assessed, monitored and managed according to the Risk Management Procedures (Section 2.6). To minimize these risks, this feasibility study concluded that drug development could be facilitated by CROs with integrated drug development services as well as by establishing a co-development program with pharmas backed up with VCs.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Product development and industrialization plans for both research-use-only products and pharmaceutical drugs are laid out in detail. The production capacity is forecasted as 10,000 units for RUO product and reaching >400 patients as an investigational pharmaceutical product in PhaseI-II clinical trials in 5 years.
The feasibility study demonstrated that in the small molecule drug discovery market segments: Lead Optimization among other processes, Oncology among other diseases and North America as much as APAC among other regions have the highest market shares.
The study reveals that there is a growing demand for small molecule drugs due to the rising incidences of chronic ailments and limitations of chemotherapeutics. The utilization of small molecules in drug development is currently very popular and the majority of the economic mobility is concentrated in North America, Europe and APAC.
The feasibility study also concluded that there is a need for a diagnostic tool to distinguish which patients will benefit the most from MEIS inhibitors. This will also be needed to select patients that have MEIS+/high expression to include in Phase I-II clinical trials. To this end, MEIS specific biomarker analysis, validations, and diagnostic development will be done.

MEIS inhibitors in targeting cancers