Angelini Research

Angelini has over 40 years experience in the R&D of small pharmaceuticals molecules, spanning from drug discovery to regulatory filing.

Several proprietary drugs have been fully developed by Angelini and two of them have gained the status of global products, marketed worldwide in more than 60 countries: the topical anti-inflammatory benzydamine and the antidepressant trazodone. In more recent times, Angelini, under license from Nippon Shinyaku, fully developed the antibacterial prulifloxacin, a fluoroquinolone, for the European market.
The Angelini research group has the capability of supporting the full development of a drug from the in silico model, through the preclinical characterization, up to a full clinical development. These activities are performed at the Angelini Research Center in S. Palomba, Rome, and at primary private and public institutions by collaborating with leading scientists worldwide 

The Projects

At present Angelini R&D is engaged in the development of new drugs, the finding of new indications for already marketed drugs and the extension of its line of products by applying new technologies to existing molecules. While R&D actively pursues the development of its pipeline, the R&D Search & Development Team works, in conjunction with the B&D Direction, to explore the occurrence of converging scientific and technical interests with potential partners. Partners are selected among start-ups and academic groups of high scientific profile in order to single out the best opportunities for either licensing or partnering.
Angelini’s R&D holds on to worldwide research visibility and co-operates with international research centers. Recently it entered a teamwork program – the Italian Drug Discovery Network (IDDN) – that includes other Italian pharmaceutical companies and public research institutes. The aim of IDDN, is to foster the interaction between public and private research in the discovery of new pharmacologically active compounds.
Angelini’s Research and Development ensures high competence and focus in research programs aligned with the company portfolio. The main projects are currently focused on the following research areas: pain/inflammation; CNS (mood disorders and insomnia); infection (antimicrobials).

Trazodone

Trazodone is an original Angelini’s antidepressant drug commonly prescribed by psychiatrists, neurologists and general practitioners as well.
It is a good example of what is nowadays conceptualized as a multifunctional drug: that is, medications endowed with more than one therapeutic activity depending on the dosage used. In general, multifunctional drugs act at low doses by means of biochemical mechanisms for which they have the highest affinities, while by increasing the dose other mechanisms are recruited, resulting in a different pharmacological activity that can complement that observed with a lower exposure.
At high doses trazodone acts as an antidepressant by increasing serotonin levels in the brain – as many other antidepressants do – and by modulating serotonergic transmission through selective serotonin receptor subtypes.
At low doses however trazodone retains mainly its antagonism on 5-HT2A receptor subtype and this biochemical profile appears to be the mainstay of the hypnotic activity recorded in experimental studies.
From a clinical point of view, the experimental use of trazodone in the treatment of insomnia is well documented in scientific literature.
All the above leads to the ongoing research and development project aimed to find the best dosage and the appropriate formulation for an application of trazodone in the treatment of mood and insomnia.

>R&D Pipeline

Angelini’s pipeline is predominantly focused upon our core therapy areas of Pain and Inflammation, CNS (Depression and Insomnia) and Anti-infectives. Angelini facilities include laboratories for primary investigation and discovery and technological platforms for computational chemistry and drug delivery.

Platforms

• POLGLUMYT® AND DERIVATIVES Bio-Polymers for drug delivery (oral and ophthalmic preparations), nutraceuticals and cosmetic formulations
• IN SILICO SCREENING Computational approach to screen compound libraries collections to identify virtual HITs. Selected target: 5-HT2A receptor; Poly ADP-ribose polymerase; Dipeptidyl peptidase IV; Aldose reductase; Epidermal growth factor receptor (EGFR); PPAR-gamma
• DRUG REPOSITIONING Re-assessment of drugs for new potential therapeutic applications (new indications and formulations) by means of in silico, in vitro and in vivo methodologies
• SPRAY DELIVERY Research of excipients able to dissolve high concentrations of poorly soluble drugs to be delivered through nebulization

Early Development Stage

• NANOCARRIERS FOR GENE DELIVERY Development of polymeric delivery vectors for genetic materials to obtain gene silencing.
• INTERACTOME In silico design of molecules which can block protein-protein interactions of bacterial divisoma and determination of in vitro and in vivo antibacterial activity. Therapeutic potential: antiinfectives
• DUAL GYRASE AND TOPOISOMERASE IV INHIBITORS Development of new class of GyrB/ParE and GyrA/ParC inhibitors. Therapeutic potential: antiinfectives
• NEW EICOSANOID MODULATORS (NEM) Development of new mPGES-1 selective inhibitors endowed of efficacy similar to that of cyclooxigenase inhibitors, but devoid of their collateral effects. Therapeutic potential: pain, inflammation & oncology
• GLYCOGEN SYNTHASE KINASE-3β (GSK-3β) INHIBITORS In silico design, in vitro evaluation and assessment of pharmacological effects of new GSK-3β inhibitors. Therapeutic potential: neurodegenerative diseases, inflammatory disorders, psychiatric diseases
• NEW MCPs INHIBITORS Identification and development of new MCPs inhibitors displaying activity on tumor progression and metastasis, in pain relief and in preventing ulcers. Therapeutic potential: oncology; pain and inflammation; gastroenterology.

Late Development Stage

PRULIFLOXACIN Antibacterial fluoroquinolone marketed in several European countries. New indications and/or posology: Acute exacerbations of chronic bronchitis (end of Phase 3); Traveller's diarrhea (end of Phase 3); Chronic bacterial prostatitis (end of Phase 3), Renal impaired subjects

TRAZODONE Original Angelini molecule, first member of SARI antidepressant class. New indications and/or posology: Once a Day formulation for Major Depressive Disorder (marketed in US and end of phase 3 in Europe); Insomnia (end of phase 2)

OMEOPRAZOLE Pump inhibitor associated with sodium bicarbonate in a sachet formulation. (pre-submission)

BINDARIT MCP-1/CCL2 production inhibitor. Indications: Diabetic Nephropathy (end of Phase IIa) and Restenosis (end of Phase IIa). Available for licensing

NON PHARMA High quality cosmetics, personal hygiene & female care products

LIFE CYCLE MANAGEMENT New formulations of marketed drugs and API development