Inozyme Pharma Shares Preclinical Data on INZ-701 for Rare Bone and Blood Vessel Diseases

Inozyme Pharma, Inc., a biopharmaceutical company at the clinical-stage, has announced promising preclinical data regarding their lead therapy, INZ-701. The data indicate the potential of INZ-701 to treat a variety of diseases influenced by the PPi-Adenosine Pathway, which plays a crucial role in regulating both mineralization and the proliferation of vascular smooth muscle cells inside blood vessels, known as intimal proliferation.

The findings were published in the journal Cells under the title, “Inhibition of Vascular Smooth Muscle Cell Proliferation by ENPP1: The Role of CD73 and the Adenosine Signaling Axis.” Yves Sabbagh, Ph.D., the Chief Scientific Officer of Inozyme Pharma, commented on the significance of the data, emphasizing the potential of INZ-701 to inhibit intimal proliferation and thus provide treatment options for various rare diseases linked to the pathological overgrowth of these smooth muscle cells.

The PPi-Adenosine Pathway is essential for maintaining both bone health and the function of blood vessels. The ENPP1 enzyme is a key component of this pathway, responsible for the production of inorganic pyrophosphate (PPi), which regulates mineralization, and adenosine, which controls intimal proliferation. Disruptions in this pathway can cause severe musculoskeletal, cardiovascular, and neurological disorders, including ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament (OPLL).

INZ-701 is designed to increase the levels of PPi and adenosine, correcting the deficiencies in these molecules and potentially treating several rare diseases caused by disruptions in the PPi-Adenosine Pathway. The Cells publication detailed preclinical findings with INZ-701 (ENPP1-Fc) through both in vitro and in vivo experiments.

In vitro experiments demonstrated that ENPP1-Fc, when applied to vascular smooth muscle cells (VSMCs), led to the production of AMP, which was then converted to adenosine. This conversion reduced cell proliferation. Both AMP and adenosine independently inhibited the growth of these cells. Additionally, blocking the CD73 enzyme, which converts AMP to adenosine, diminished the accumulation of adenosine and suppressed the anti-proliferative effects of ENPP1/ATP.

In vivo experiments using a mouse model with a ligated carotid artery revealed that treatment with INZ-701 could prevent or reduce intimal proliferation in both ENPP1-deficient and wild-type mice. These results suggest that maintaining a certain level of adenosine is essential to preventing or reducing intimal proliferation.

The conclusions drawn from these experiments highlight that ENPP1 not only produces PPi but also plays a significant role in generating adenosine, which inhibits intimal proliferation. This dual function positions INZ-701 as a potentially broader therapeutic application beyond traditional enzyme replacement therapy.

INZ-701, an ENPP1 Fc fusion protein, is being developed as an enzyme replacement therapy to address rare diseases associated with the PPi-Adenosine Pathway. INZ-701 metabolizes adenosine triphosphate (ATP) to produce inorganic pyrophosphate (PPi) and adenosine monophosphate (AMP), which can then be converted to adenosine. Adenosine is a natural inhibitor of intimal proliferation, while PPi is a natural inhibitor of pathological mineralization. Preclinical studies indicate that INZ-701 can prevent abnormal mineralization and intimal proliferation, both of which contribute to the severity of diseases like ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament (OPLL).

Inozyme Pharma is committed to developing groundbreaking therapeutics for rare diseases affecting bone health and blood vessel function. With a focus on the PPi-Adenosine Pathway, Inozyme aims to address the significant morbidity and mortality associated with these severe disorders. Their lead candidate, INZ-701, is in clinical development and has shown potential to correct the pathological processes underlying these diseases.