Regulating calcification in multiple metabolic diseases.
Our lead candidate, INZ-701, is an enzyme replacement therapy (ERT) in the early stages of clinical development for the potential treatment of patients with a variety of calcification disorders linked primarily to mutations in the ENPP1 and ABCC6 genes.
In pre-clinical studies, the experimental therapy has shown potential to generate plasma pyrophosphate (PPi) and restore it to normal levels, which is believed to correct the underlying cause of these serious diseases for which there are no approved therapies.
INZ-701 is designed to increase PPi levels and regulate calcification in multiple metabolic diseases, including both ENPP1 Deficiency and ABCC6 Deficiency. Given the broad therapeutic applicability of the INZ-701 development program, the company may embark or is in the early stages of looking at other metabolic diseases with low PPi.
A team of researchers led by Dr. Demetrios Braddock published the ground-breaking preclinical proof-of-concept for INZ-701 for the treatment of GACI in a 2015 paper in Nature Communications, ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. The paper demonstrates the capability of a murine ERT (mERT) in preventing the lethal vascular calcifications of GACI in mouse models of the disease. The dramatic change induced by this ERT in enpp1asj/asj mice is illustrated in the image below. In untreated mice (a), the postmortem high-resolution micro-CT scans revealed the extensive calcifications in the heart, coronary arteries, and ascending and descending aortas. By contrast, there were no calcifications in these organs in the treated mice (b).
Additionally, data presented at the 45th European Calcified Tissue Society Congress in Valencia, Spain in May 2018 demonstrated that the same mERT used in the GACI mouse model is also capable of preventing the bone mineralization deficits in an ARHR2 animal model. Full publication of these ARHR2 data is forthcoming.
For links to relevant scientific publications and abstracts, please see the Publications landing page.