First Health Pharmaceuticals has set its RNA Research priorities on the development of RNA Helicase inhibiting lead compounds


RNA molecules are a small and versatile tool to transport information within the cell and the organism, thus RNA represents an optimal way for viruses to store all the necessary information for their survival and replication in a minimal space and with minimal complexity.

Furthermore, the translation of RNA to proteins is fundamental for cell survival and replication, thus it is not surprising that RNA-related pathways are altered in pathological conditions as hyperproliferative diseases.

There have been identified several partners of RNA which contribute to transport, folding, unwinding, protection, lysis, expression and all its life cycle. Although the information carried is read from one strand of RNA, folding and annealing to double strand RNA is used to protect the molecule from lysis and to add a second structure for further recognition by partners. Therefore, a crucial step in the RNA molecule life cycle is the unfolding of double strand loops or molecules.


RNA helicases rearrange RNA secondary structure and RNA-protein interactions in an ATP-dependent reaction, performing crucial functions in all aspects of RNA metabolism.

DDX3 is part of the DEAD box proteins involved in RNA metabolism. Our DDX3 RNA Helicase inhibiting class of compounds do not target viral proteins but temporarily inhibit an enzyme of our own RNA cell biology that is of vital importance for the virus during its reproduction cycle. DDX3 RNA helicase has also remarkable oncogenic properties. Its overexpression has been verified in various forms of cancer, among which the most malignant types of Breast and Lung cancer.


Through the use of proprietary software, statistical analysis tools and machine learning algorithms, backed by substantial computer hardware facilities, First Health Pharmaceuticals brought computational drug development to an entirely new level


First Health Pharmaceuticals’ approach is a connubium of both “classical” and cutting edge Computer Aided Drug Design techniques and algorithms, which makes it possible to minimize the attrition rate of our drug discovery programs.  Classical techniques such as pharmacophore modeling and docking, which have a proven back track of successful applications, are integrated with proprietary statistical models based on Machine Learning algorithms, and modern protocols that accurately estimate the free energy of ligand / enzyme binding. The huge computational workflow involved in all of this is supported by a powerful water cooled hardware infrastructure with a total of 44 Teraflops and no less than 216 CPU core threads of calculating power.


Modeling of physical-chemical properties: Machine learning models (Random Forrest, Artificial Neural Network, Bayesian classifier).
Co-/Off-target identification: Reverse 3D-Pharmacophore screening of Protein Data Bank protein/ligand complexes, Polypharmacology profile by Tanimoto similarity search in PubChem/ChEMBL.
Drug re-purposing: Screening of known drugs by 3D Pharmacophore/Docking.
In silico study/understanding of protein inhibitor interaction: Metadynamics/Alchemical free energy perturbation.


In the last decade, the creation of publicly available data repositories such as Pubchem and ChEMBL as well as screening initiatives like the NCI Developmental Therapeutics Program (DTP) made a huge amount of drug discovery data available to the scientific community. To fruitfully mine this vast amount of information, both experienced researcher and advanced machine learning algorithms are required.

The main objective of First Health Pharmaceuticals is the identification of human RNA Helicases Inhibitors involved in both cancer pathogenesis and virus infection. By looking at the ADME (an acronym of Absorption, Distribution, Metabolism and Excretion) and physical-chemical properties from the first stages of the Research and Development (R&D) program, the research efforts are focused on the most promising compounds from the very start. The application of the aforementioned approach significantly accelerates the identification of good clinical candidates.


Since from the early stages, First Health Pharmaceuticals research and development pipeline, integrates a series of internally developed Artificial Intelligence predictive models to monitor the principal physicochemical properties such as water solubility and membrane permeability.

The Artificial Intelligence models based on algorithms such as artificial neural network and random forest, are constantly updated with experimental data coming from the tested compounds to increase the reliability of the predictions. In advanced phases the data on physicochemical properties and ADME characterization are combined to assess the probability of success (POS) for a specific compound, identifying the the suitable candidates for the further development process.


Considering the groundbreaking nature of the RNA Helicase targeting technology developed by our group, and the vast array of pathogens and malignancies that is targeted by our compounds, many research groups worldwide, directly or indirectly, participated in the research in our field of interest. Some of these collaborations are based on a joint development agreement.


HIV cure strategies

PARTNERSHIP: a multi-center public-private partnership (PPP) including First Health Pharmaceuticals along with other industrial partners and six high profile research groups from AUMC-Amsterdam University Medical Centre, co-financed with a PPP allowance made available by Health ~ Holland to Aidsfonds.
RESEARCH TOPIC: HIV cure strategies
OBJECTIVE: characterization of the dormant HIV in HIV reservoir and their removal with a combination of small molecules and antibodies.
DURATION: September, 2019 – September, 2021


HIV cure strategies

PARTNERSHIP: a multi-center public-private partnership (PPP) including First Health Pharmaceuticals along with Viiv Healthcare, Erasmus MC, UMC Utrecht, co-financed with a PPP allowance made available by Health ~ Holland to Aidsfonds.
RESEARCH TOPIC: HIV reservoirs reduction strategies
OBJECTIVE: developing different approaches to reduce the HIV reservoir by taking into account variation in the immune system and the virus.
DURATION: May, 2019 – May, 2022


Cancer treatment

PARTNERSHIP: First Health Pharmaceuticals and an Oncode Institute-affiliate
RESEARCH TOPIC: Glioblastoma, lung, breast cancer
OBJECTIVE: cancer research focused on advanced molecular oncology, translational research.
DURATION: May, 2019 –


Breast cancer

PARTNERSHIP: First Health Pharmaceuticals and ITT – Istituto Toscano Tumori

RESEARCH TOPIC: Breast cancer




Dengue virus

PARTNERSHIP: First Health Pharmaceuticals and AUMC-Amsterdam University Medical Center

RESEARCH TOPIC: Dengue virus

OBJECTIVE: DDX3 inhibitors in Dengue virus

DURATION: 2017 –


DDX3 Inhibitors in cancer

PARTNERSHIP: First Health Pharmaceuticals and the Department of Medical Biotechnologies and Translational Medicine (BioMeTra) of University of Milan, alongside the Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy.

RESEARCH TOPIC: DDX3 inhibition in cancer

OBJECTIVE: Assessment of the effects of a DDX3-inhibitor (DDX3-inh) on ECFCs obtained from cKS patients to investigate efficacy of DDX3 inhibition on ECFC.

DURATION: 2018 –


DDX3 Inhibitors in cancer

PARTNERSHIP: First Health Pharmaceuticals, Department of Medical Biotechnologies and Department of Medicinal Chemistry of University of Siena.


OBJECTIVE: the role of translation inhibitors compounds in RNA helicase DDX3 inhibitors

DURATION: 2015 – 2017

Past collaborations

Over the years, many highly specialised research groups around the world have been interested in testing our compounds, in order to gain more insight in the complex cellular RNA helicase biochemistry, related to the pathogens they are working on. We, from our side, also learn many new things about our field of research, but even in cases in which no direct benefit is to be expected for our company, we still aim to satisfy all requests that reach us from interested academic groups. We would like to specify that these groups are not affiliated to our company and neither do we wish to make statements about, or make any claims regarding the outcome of the research in question. We express our gratitude towards each of these highly respected groups that tested or continue to investigate our compounds. Some of the academic groups which researched the biological activity of our compounds are mentioned below.

  • University of Cambridge, Virology division, UK / Norovirus
  • US Army Medical Research Institute of Infectious Diseases, USA Ebola virus
  • University of Glasgow, UK / HCV
  • Nanjing Agricultural University, PRC / Japanese Encephalitis Virus
  • University of Rome La Cattolica del Sacro Cuore, IT / Toxicity and metabolism
  • John Hopkins University Hospital, USA / Breast Cancer
  • CNR - Italian National Research Centre, IT / HIV
  • Institut Pasteur, Lyon, FR / Ebola virus
  • Rega Institue, KU Leuven, BE / Flaviviruses
  • UC San Diego, USA / HIV, HCV