ZUG, Switzerland I September 22, 2016 I Turing Pharmaceuticals AG today announced that it has advanced several experimental compounds into pre-clinical development. The selected compounds come from a library of small molecules, discovered as part of Turing’s research efforts in toxoplasmosis, with significantly improved potency and selectivity over current treatments in animal models of the disease.
With its discovery, Turing has initiated the regulatory safety studies and pharmaceutical development activities needed for an Investigational New Drug Application (IND) to the US Food and Drug Administration (FDA). This will be Turing’s fourth IND since the company’s founding last year. Clinical trials with the new compounds are expected to begin in 2H2017.
“There’s a definitive need for new and improved therapies against toxoplasmosis,” said Turing President of R&D, Eliseo Salinas, MD, MSc. “Current therapies target a protein family that is required by both the parasite and its human host. Consequently, treating physicians are limited in the doses of the current products they can use to eliminate the parasite. The ability to selectively engage the parasite would maximize the opportunity to eliminate infection without harming the patient.”
Toxoplasmosis is caused by Toxoplasma gondii – one of the most commonly found parasites worldwide. It is carried by about one in five Americans, with one million new infections each year. In most cases the infection produces minor symptoms, if any. But in a small subset of patients it can have serious, sometimes fatal consequences. Despite the severity of the disorder, there have been no significant pharmaceutical advancements in its treatment since the introduction of currently utilized therapies over 50 years ago.
Turing’s most advanced ongoing discovery program in toxoplasmosis focuses on developing inhibitors of dihydrofolate reductase (DHFR) – an essential enzyme for folate metabolism and cellular proliferation. Current treatments target this pathway with modest selectivity for the parasite over its human host.
Applying state of the art computational chemistry, in silico screening and structure-based drug design to first identify a library of novel compounds, Turing subsequently optimized and tested the selected drug candidates in relevant disease models. These included compounds with low nanomolar potency and significantly higher selectivity for the parasite DHFR over human DHFR. This profile should enable a substantially greater therapeutic window and may eliminate drawbacks of current toxoplasmosis treatment, while potentially expanding the addressable patient population.
Early efforts from the DHFR inhibitor program were published this month in ACS Medicinal Chemistry Letters by the American Chemical Society. An abstract of the article ‘Discovery of Potent and Selective Leads Against Toxoplasma gondii Dihydrofolate Reductase Via Structure-Based Drug Design’ is available at http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.6b00328. Turing’s research team also reported the first-ever crystallographic data of a novel inhibitor bound to T. gondii DHFR. These data have been deposited in the Protein Data Bank and are publicly available. Turing plans to submit additional manuscripts detailing drug discovery and development efforts for publication in peer-reviewed journals in the near future.
Toxoplasmosis is a potentially serious, sometimes fatal infection caused by the Toxoplasmsa gondii (T gondii) parasite. The Centers for Disease Control and Prevention (CDC) considers toxoplasmosis to be one of the five neglected parasitic infections. Although many people are infected, only a small number may experience serious complications. Most suffer no more than passing flu-like symptoms until the parasite is controlled by the immune system. The organism can, however, be reactivated in people, including those with compromised immunity. Active infection can cause encephalitis (inflammation of the brain), blindness and death. In some cases, a mother can transmit the infection to her fetus, who might suffer serious and sometimes irreversible complications.
Turing Pharmaceuticals AG is a privately-held biopharmaceutical company with offices in Zug Switzerland and New York, NY. Turing focuses on developing and commercializing innovative treatments for serious diseases and conditions across a broad range of therapeutic areas, for which there are currently limited or no treatment options.
SOURCE: Turing Pharmaceuticals