Technology

EnePharma’s new drug is a combination of a xanthine oxidoreductase inhibitor (febuxostat) and inosine that enhances cellular ATP [ATP enhancer]. Since our drug is a combination of two active ingredients for which there is longterm experience in humans, we are targeting a 505(b)(2) pathway for speeding up the regulatory submission process with the FDA. We have evidence that it is effective to enhance cellular ATP from both pre-clinical and clinical studies.

Rationale

Energy (ATP) associated human genes comprise 8 % of all genes. So, many diseases must be caused by “energy shortage”, and there is large market potential for ATP enhancement therapy. Among rare diseases, mitochondrial disease is unequivocally caused by energy shortage, and among common diseases, mounting evidence from basic and clinical data strongly suggests that many of the neurodegenerative disorders including Parkinson’s disease are caused by energy shortage. By the intensive analyses of the association between genes and diseases, we have succeeded in designing a clever method to enhance the major purine compound ATP in humans by both providing more purine source and inhibiting purine degradation, i.e. by the administration of febuxostat and inosine.

In vivo disease studies in animals:  By the administration of febuxostat, the damage of mitochondria was suppressed. In transgenic model mice, progression of neurodegenerative disorders was suppressed.

Safety and efficacy supported by clinical data: Febuxostat and inosine have been co-administered to 65 subjects (18 healthy subjects and 47 patients), and the data supported the safety of this treatment. ATP and hypoxanthine were markedly increased in healthy subjects by the co-administration of febuxostat and inosine for 2 weeks but not by administration of either compound alone. In two patients with mitochondrial disease, co-administration of febuxostat and inosine for 2 weeks dramatically improved a biomarker of cardiac failure (BNP) in a mitochondrial cardiomyopathy patient and a biomarker of diabetes (insulinogenic index) in a mitochondrial diabetes patient. In patients with Parkinson’s disease, significant improvement (P = 0.0146) of the MDS-UPDRS Part III score with more than a minimal clinically important difference (MCID = -3.25) was shown in 26 patients treated for 8 weeks.

Current status of the development: Three leading professors in the US have agreed to become scientific advisory board members, and we are now preparing for pre-IND meetings with the FDA for mitochondrial disease and Parkinson’s disease based on our preclinical and clinical data.