ANDOVER, Mass.--(BUSINESS WIRE)--DeuteRx LLC announced today the initial closing of a seed financing that will total approximately $2.8 million. DeuteRx is a research and development-focused biotechnology company dedicated to improving racemic small molecule marketed drugs and drug candidates intended for patients across multiple therapeutic indications. The funding supports the advancement of DeuteRx’s lead program, DRX-065, into human clinical trials for the treatment of adrenoleukodystrophy (ALD).
“This funding will allow us to aggressively pursue our lead program for ALD, a monogenic orphan disease for which there is no approved therapy,” said Sheila DeWitt, Ph.D., President and Chief Executive Officer of DeuteRx.
“The preclinical results that DeuteRx has obtained with DRX-065, the stabilized R-enantiomer of pioglitazone, have changed the interpretation of more than 25 years of R&D efforts, which define the mechanism of action for pioglitazone and related thiazolidinediones (TZDs) as PPARγ agonists,” said Dr. Lex Van der Ploeg, advisor to DeuteRx. “DeuteRx’s unique ability to study stabilized, single enantiomers has revealed surprising differences in the pharmacological properties of each enantiomer of pioglitazone. DRX-065 has the potential to be a disease-modifying and reversing treatment for ALD patients, without the side effects caused by S-pioglitazone.”
Dr. DeWitt will be presenting preclinical results obtained with DRX-065 and their relevance for the treatment of non-alcoholic steatohepatitis (NASH) at the American Association for the Study of Liver Diseases’ Liver Meeting on November 16, 2015, in San Francisco.
About Adrenoleukodystrophy (ALD)
ALD is an inherited disease in which there is a build-up of ‘very long chain fatty acids’ (VLCFA) in tissues around the body, mainly in the brain, spinal cord and adrenal glands. The condition, which affects mainly males, is caused by mutations in the ABCD1 gene, located on the X chromosome. When ABCD1 is mutated, the build-up of VLCFAs in the brain and spinal cord damages the protective sheath (myelin) around the nerves, causing a wide range of neurological problems that usually worsen over time. In the adrenal glands, the build-up prevents the glands from functioning properly and reduces their ability to produce hormones, such as cortisol. Symptoms of the condition can include behavioral, vision, coordination and cognitive problems.
The incidence of ALD has been estimated to be 1:17.000 newborns. ALD can manifest itself in children, where death or permanent disability occurs within two to five years of diagnosis. The adult form of ALD is known as adrenomyeloneuropathy (AMN) and the average age of onset is 28. Cerebral involvement occurs in 30 to 50 percent of AMN patients and leads to a poorer prognosis, including severe disability and death, when compared to patients without cerebral involvement.
There are currently no approved therapies for ALD or AMN. The most widely used treatment option is the dietary supplement, Lorenzo's oil, which is thought to aid in the normalization of VLCFA levels. However, this oil does not seem to alter the progression of the disease once the brain is involved. In 2013, L. Morató, et al. (Brain. 2013, 136(Pt 8), 2432-2443) reported that pioglitazone, a drug approved for the treatment of Type 2 diabetes, halted the locomotor disability and axonal damage in a murine model of ALD. A phase 2 trial of pioglitazone in AMN patients by the lead author, Dr. Aurora Pujol, is ongoing in Spain.
DRX-065 is the deuterated R-enantiomer of pioglitazone. DeuteRx’s preclinical in vitro and in vivo studies have demonstrated that the R-enantiomer exhibits glucose lowering through a novel mechanism of action, and modulates mitochondrial and anti-inflammatory activity, critical to the treatment of ALD. All of the PPARγ activity and the associated adverse side effects of pioglitazone, including weight gain and fluid retention, appear exclusively due to exposure to the S-enantiomer of pioglitazone. Issued U.S. Patent #8,722,710 includes composition of matter claims to deuterium-enriched pioglitazone analogs, including DRX-065. DeuteRx has a broad portfolio of additional issued and pending patent applications with claims to deuterium-enriched enantiomers of at least 15 families of TZDs.
About DeuteRx LLC
DeuteRx is pioneering ‘deuterium-enabled chiral switching’ (DECS), a revolutionary approach to improve racemic (a mixture of two mirror-image compounds or enantiomers) small molecule marketed drugs and drug candidates intended for patients across multiple therapeutic indications. Numerous drugs are still developed and marketed as racemic mixtures because the enantiomers are chemically unstable and rapidly interconvert in vivo. To date, DeuteRx has demonstrated the use of DECS to stabilize the enantiomers of many racemic active ingredients including bupropion, donepezil, pioglitazone, prasugrel, CC-11006, CC-122, and MSDC-0160. DeuteRx’s prioritized single enantiomer product assets are DRX-065 for ALD and NASH, DRX-164 for multiple myeloma and combination therapy with immuno-oncology drugs, DRX-194 for pediatric sickle cell disease, and DRX-184 for CNS disorders.
DeuteRx is a Boston-based biotechnology company founded in December 2012 as a spin-out company from Deuteria Pharmaceuticals Inc. Deuteria Pharmaceuticals was sold to a major biopharmaceutical company in December 2012.