About NMTrypI

The NMTrypI concept is based on the development of innovative drug leads by using a common drug discovery platform to study the mechanism-based combinations of known and investigational drugs and dual-target inhibition. The platform is established by experts in their respective fields from Small and Medium-sized Enterprises (SMEs) and the public research sector in Europe and disease-endemic countries.

The innovative concept is reinforced by the identification of preclinical biomarkers enabling the proteomic profiling of the compound to understand the mechanism of action (MoA biomarkers) and to detect the efficacy of the lead candidate (pharmacodynamic biomarkers).

The new NMTrypI platform will perform the screening of compound libraries, lead development, testing in mice, hamsters and dogs as a reservoir for the visceral leishmaniasis disease as well as toxicology and safety testing (in vitro against different cell types and in vivo in animals) to overcome current limitations in anti-trypanosomatid therapy.

The major strength of the Consortium lies in the complementary expertise of the partners and the integrated platform that will provide:

  • at least 1-2 innovative, less toxic and safer drug candidates for Trypanosomatidic infections compared to existing ones.
  • early phase biomarkers for efficacy prediction (to ensure overall improved efficacy and safety).
NMTrypI will translate drug leads into drug candidacy through 6 scientific work packages (WPs 1-6) supported by 3 transversal work packages (WPs 7-9) dedicated to project dissemination and management, and synergies with other similar projects within the community.


The application of the new NMTrypI approach is expected to lead to an adapted and affordable treatment of Trypanosomatidic Infections in disease-endemic countries. The NMTrypI project may contribute to a breakthrough in finding a suitable therapy for Neglected Tropical Diseases (NTDs).

Carrying out the project at an international level with the inclusion of EU and disease-endemic countries in the consortium provides a unique blend of experts to work in the field of Trypanosomatidae research which further increases the versatility of the project's outcome.

The research SMEs involved in the project aim at exploiting the results generated to create more revenues for the companies and therefore strengthen their competitiveness, allowing them to further develop their research and also to create more jobs.

  • Global international cooperation: The NMTrypI consortium will further develop partnerships/collaborations with international initiatives, existing research consortia or programs on NTDs - in particular the Geneva-based Drugs for Neglected Diseases initiative (DNDi) and the US-based Consortium for Parasitic Drug Development and Institute for One World Health (IoWH). These organizations proved formats to enable the progression of compounds through clinical trials, thus filling a gap created by the abandonment of these areas by the pharmaceutical industry. This cooperation will allow joining forces, avoiding duplication and speeding up development in an international cooperation context.

  • Increase in European competitiveness: NMTrypI results will contribute to the development of new scientific knowledge needed for the development of new drugs: therefore, the competitiveness of European pharmaceutical industries could be further reinforced, especially for the SMEs participating in the project.

  • Socio-economic impact: the final goal of the project is a step forward in the development of new therapeutic principles for anti-trypanosomal treatment that will directly lead to a benefit for human health. The exploitation of discoveries (target specific inhibitors/compounds) will translate into a direct improvement of the quality of life in developing countries as well as in Europe.


The aim of the NMTrypI project is the discovery of potentially useful drugs for trypanosomatid diseases affecting humans and dogs for which no satisfactory treatment exists.

The research project involves the use of experimental animals, namely mice, hamsters and dogs. The experimental approach includes the use of in vitro primary screening to reduce the need for animal experimentation or at least the number of animals needed.

However, the in vitro selection of hits and leads does not preclude the employment of limited numbers of animals as the final step of evaluation for the new treatments. Nonetheless, the selection model employed has drastically reduced the need for experimental animals.

European regulation and international codes of conduct

The use of animals in NMTrypI research activities will take into account and strictly adhere to:

  • Legislation for the protection of animals used for scientific purposes: http://ec.europa.eu/environment/chemicals/lab_animals/legislation_en.html
  • Council Directive of 24 November 1986 on the approximation of laws, regulation and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes (86/609/ECC), modified by Directive 2003/65/EC of the European Parliament and of the Council of 22 July 2003.
Furthermore, the NMTrypI consortium will apply the 3Rs:
  • Reduction refers to methods that enable researchers to obtain comparable levels of information with fewer animals or to obtain more information with the same number of animals.
  • Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.
  • Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
The Consortium considers the aims in all work packages ethically justified as the experiments will be carried out under ethical conditions, and the NMTrypI consortium will guarantee the compliance of all procedures with relevant European and national legislation by each Partner involved.


The Scientific Advisory Board (SAB) assists and facilitates the decisions made by the Steering Committee and provides scientific advice to the project.

The SAB is composed of four external key scientists:

  • Paul Selzer, Senior Research Executive at MSD Animal Health Innovation GmbH
  • Eric Chatelain Ph.D., Head of Drug Discovery at DNDi (Drugs for Neglected Diseases initiative)
  • Neena Goyal, Senior PI at the Central Drug Research Institute in Lucknow, India
  • José M. Coteron, Senior Scientist at GlaxoSmithKline (GSK)


The IP Committee is composed of one IP expert from UNIMORE (M. P. Costi), one from an SME (A. Venturelli, TYDOCK), and one from an academic institution (T. Calogeropoulou, NHRF).

The IP Committee is a consulting body to the project and consortium in IP topics and has three main functions:

  • Provide advice on IP issues to the Steering Committee and the Work Package Leaders.
  • Monitor the application of the IP elements of the Project Agreement.
  • Contribute to defining the most appropriate strategy to protect IP generated by the project.

WP1: Lead optimization & synthesis. Predictive ADME-Tox evaluation.

The overall objective of WP1 is to generate lead compounds belonging to three compound classes:
i) Synthetic folate pathway-targeting pteridine, benzothiazole and thiadiazole derivatives.
ii) Improved miltefosine analogs.
iii) Natural products.

WP1 leader: Dr. Theodora Calogeropoulou, NHRF

Main outcomes of WP1:

  • Synthesis of known and designed compound libraries filtered for ADME-Tox in silico (3-4 libraries for each compound class).
  • Lead compounds from natural product libraries.
  • 1-2 drug candidates of synthetic and/or natural origin.

WP2: Studies on purified targets. M/HTS assays for lead development.

WP2 integrates the screening of compound libraries. The target proteins will be obtained and inhibitor-target interaction studies will be performed using biophysical methods (X-ray crystallography, fluorescence spectroscopy, isothermal titration calorimetry).

The optimized leads will be identified through target testing in high-throughput screening (HTS), and combinations will be prioritized according to cellular liability assay results. In vitro toxicity, ADME and safety (in WP3) are prepared for delivery in animals (WP5).

WP2 leader: Prof. Dr. Maria Paola Costi, UNIMORE

Main outcomes of WP2:

  • Validated biochemical M/HTS assays.
  • Production of purified trypanosomal proteins.
  • Identification of compounds for further studies, 1-2 per class/parasite.

WP3: Phenotypic screening. M/HTS assays, ADME-Tox evaluation.

WP3 concerns the development of functional screening through cellular testing.

Natural compound mixtures are first tested on sensitive parasites and optimal mixtures are next re-tested against relevant drug-resistant strains. Only the selected mixtures from the dereplication process will be purified, and active compounds isolated and characterized. Final ranking and selection of the leads identified with related molecular and biological properties will be done based on Target Drug Lead Profile (TDLP) criteria.

Decisions on compound progression to WP5 for animal testing or WP1 for further chemical modification will be taken.

WP3 leader: Dr. Sheraz Gul, Fraunhofer IME-SP

Main outcomes of WP3:

  • Development of functional screening for parasite testing.
  • Development of compatible assays for targets and their use in screening natural products.
  • Ranking of compounds for further progression, based on activities and compound properties, to include suitable secondary assays and in vitro ADME-Tox data as appropriate.

WP4: Drug leads: mechanism of action, biomarkers, and resistance.

The aims of WP4 are to identify the mechanism of action and off-target effects for improving the design of optimized leads and to identify potential drug resistance that may evolve from the delivery of the leads to the parasites in vitro. The off-target information identified will be fed back into lead optimization in WP1. Combinations of two folate pathway proteins (pteridine reductase 1, PTR1 and dihydrofolate reductase, DHFR) inhibitors will be studied independently and then together, following the appropriate protocols.

Biomarkers of drug lead action on parasites will be obtained through a proteomic approach. The evaluation of the efficacy of drug candidates in T. cruzi (Chagas disease), T. brucei (sleeping sickness), L. major, L. infantum and L. donovani (leishmaniases) infections in animals will be performed in WP5.

WP4 leader: Dr. Joachim Clos, BNI

Main outcomes of WP4:

  • Drug target and off-target identification in drug-lead treated parasites
  • Mechanistic target and resistance information for feedback to lead optimization in WP1.

WP5: Evaluation of animal models of candidate drugs. Pharmacokinetic, toxicity and safety studies.

WP5 aims at determining the efficacy of non-toxic and safe selected leads (from WP2) against laboratory models of trypanosomatid infections (Trypanosoma spp, Leishmania spp).

Secondly, WP5 aims at evaluating the in vivo toxicity, safety, pharmacokinetic and pharmacodynamic parameters of selected drugs in different organs of the mice & hamster models.

Thirdly, WP5 aims at testing specificity and leishmanicidal activity in dog models for the most promising candidate drugs.

WP5 leader: Dr. Anabela Cordeiro-da-Silva, IBMC

Main outcomes of WP5:

  • Validation of trypanocidal activity, complete evaluation of pharmacokinetic properties, toxicity profile, safety and pharmacology.
  • Evaluation of the biological effect of the selected compounds on animals.
  • Pharmacokinetic profiles for 1-2 compounds/class.
  • 1-2 compounds tested on Leishmania-infected dogs.

WP6: Database design and data management.

The main objective of WP6 is to provide comprehensive data management for the project, i.e. a place to collect, structure and share data: experimental data, models, standard operating procedures (SOPs), as well as a participant directory.

WP6 leader: Dr. Wolfgang Müller, HITS

Main outcomes of WP6:

  • Database system to collect and share all the project data.
  • Software to store, manage, search and query all information.

WP7: Communication/Dissemination/Exploitation & International cooperation.

The main objectives of WP7 are the following:

  • To define the communication strategy and tools.
  • To actively pursue an exploitation and dissemination strategy for generated knowledge.
  • To ensure cooperation with Brazilian and Sudanese partners and with international initiatives against NTDs.
  • To set up an exploitation plan to maximize the value of exploitable outcomes.
WP7 leader: Dr. Stefania Ferrari, UNIMORE

Main outcomes of WP7:
  • Set-up of an NMTrypI Collaborative platform and the Project Public Website to ensure Consortium internal and external communication.
  • NMTrypI Communication and dissemination plan and Exploitation plan.