PPi regulates bone health

Bones are complex tissues that grow with us and adapt to stressors like exercise or fractures. An important part of bone is hydroxyapatite, which is made up of calcium and phosphate, and gives our bones their strength and hardness. When hydroxyapatite is incorporated into our skeletons, this process is called bone mineralization.  

PPi (inorganic pyrophosphate) is a molecule that circulates throughout the body to ensure that the building blocks of bone end up in the right place. PPi regulates ongoing bone formation, keeping our skeletons strong and healthy.

PPi prevents calcium and phosphate from coming together and forming hard deposits of hydroxyapatite in places it shouldn’t, like our joints and arteries.

LEGEND: =hydroxyapatite,
=Phosphate, =Calcium, =Inorganic Pyrophosphate

Low PPi levels can lead to serious health issues

Low PPi levels can lead to the buildup of hydroxyapatite crystals in the arteries, making the arteries stiff and impairing blood flow. Bone minerals can also form deposits in other soft tissues such as the skin, internal organs, joints, and ligaments.

If minerals from the bone build up in these other parts of the body, they can cause medical problems ranging from pain and immobility to severe cardiovascular disease and in some cases death.

Maintaining balanced PPi levels is essential for our bones to stay strong and healthy while preventing too much mineralization that could damage soft tissues.

LEGEND: =hydroxyapatite, =Phosphate, =Calcium,
=Inorganic Pyrophosphate

Adenosine is a regulator of blood vessel health

Adenosine is a molecule in our bodies that helps control cell growth in blood vessels. Adenosine helps maintain proper blood flow by preventing the narrowing of blood vessels, which is called stenosis. Maintenance of wide blood vessels ensures tissues get enough oxygen and nutrients.

LEGEND: =Adenosine

Low adenosine levels can lead to serious cardiovascular issues

Low adenosine levels can lead to multiple severe issues with our blood vessels. First, low adenosine levels can contribute to intimal proliferation (excessive cell growth within blood vessel walls). This overgrowth can obstruct blood flow and increase the risk of cardiovascular events like heart attacks and strokes. Additionally, low adenosine levels can directly impact blood flow by promoting vasoconstriction (narrowing of blood vessels), which can also increase the risk of cardiovascular events.

Maintaining optimal adenosine levels is crucial for regulating both blood flow and cellular growth within blood vessels.

LEGEND: =Adenosine

The PPi-Adenosine Pathway

The PPi-Adenosine Pathway is important for keeping our bones and blood vessels healthy. This pathway generates ATP, PPi, adenosine, and phosphate – essential molecules with diverse functions in our bodies. Keeping these molecules balanced helps prevent harmful buildup of minerals and thickening of blood vessel walls. When this pathway doesn’t work properly, it can cause serious health problems. Here’s how it works:

1
2
3
4

ABCC6 and ANKH: Transports adenosine triphosphate (ATP) from inside the cell and into the blood.

ENPP1: Breaks down ATP outside of the cell into two smaller molecules: adenosine monophosphate (AMP) and pyrophosphate (PPi).

CD73: Converts AMP into adenosine and phosphate.

TNAP: Breaks down PPi into phosphate.

LEGEND: =Adenosine Triphosphate, =Adenosine Monophosphate, =Calcium, =Inorganic Pyrophosphate, =Adenosine, =Phosphate

INZ-701 is designed to restore balance across the PPi-Adenosine Pathway

INZ-701 is made by combining the active part of the ENPP1 enzyme with a fragment of a human antibody (Fc). This design allows INZ-701 to circulate all over the body and convert ATP into PPi and AMP. AMP is further broken down into adenosine and phosphate. Unlike traditional ERTs that treat a single disease by replacing a deficient or missing enzyme, INZ-701 targets the central role of ENPP1 in this key pathway. This unique approach offers the potential to treat multiple rare diseases driven by disruptions in the PPi-Adenosine Pathway.

In preclinical studies, INZ-701 prevented abnormal mineralization and intimal proliferation, which can lead to serious health problems in devastating disorders like ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. So far, clinical data have shown that INZ-701 was generally safe and well tolerated and that it meaningfully increased PPi levels in multiple clinical trials.

INZ-701 is an investigational product and that has not yet been approved by the U.S. Food and Drug Administration or any other health regulatory authority.