Inozyme announces publication of preclinical data on INZ-701

Inozyme Pharma announced the publication of preclinical data supporting the potential of INZ-701, the Company’s lead ENPP1 enzyme replacement therapy fevelopment candidate, to treat a broad range of diseases mediated by the PPi-Adenosine Pathway, which regulates mineralization and intimal proliferation. The article titled, “Inhibition of Vascular Smooth Muscle Cell Proliferation by ENPP1: The Role of CD73 and the Adenosine Signaling Axis”, published in the journal Cells. Overview of Findings: The PPi-Adenosine Pathway is critical for regulating bone health and blood vessel function. The ENPP1 enzyme is a vital component of this pathway and plays an essential role in generating inorganic pyrophosphate, a key regulator of mineralization, and adenosine, a key regulator of intimal proliferation. Disruptions in this pathway impact the levels of these molecules, leading to severe musculoskeletal, cardiovascular, and neurologic conditions, including ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament. INZ-701 is designed to increase PPi and adenosine, addressing deficiencies in these molecules and offering the potential to treat multiple rare diseases driven by disruptions in the PPi-Adenosine Pathway. The Cells publication highlights the following preclinical findings with INZ-701: In vitro Experiments: ENPP1-Fc was tested on vascular smooth muscle cells which are the major cells in the walls of blood vessels. Adding ENPP-1-Fc and ATP to VSMCs led to the production of AMP, which was subsequently converted to adenosine, reducing cell proliferation. Both AMP and adenosine independently inhibited VSMC growth. Blocking the CD73 enzyme, which converts AMP to adenosine, reduced the accumulation of adenosine, and suppressed the anti-proliferative effects of ENPP1/ATP. In vivo Experiments: In a mouse model where the carotid artery was ligated, treatment with INZ-701 prevented or reduced intimal proliferation in a prophylactic or therapeutic setting, respectively, in both ENPP1-deficienct and wild-type mice. These results suggest a certain level of adenosine is necessary to prevent or reduce intimal proliferation. Conclusions: In addition to producing PPi, ENPP1 also plays an important role in the production of adenosine, revealing the mechanisms by which ENPP1 prevents both abnormal mineralization and inhibits intimal proliferation. These results suggest that INZ-701 may have broader therapeutic applications beyond traditional enzyme replacement therapy.