Inozyme Pharma Presents Preclinical Data Suggesting Utility of INZ-701 as a Potential Treatment for ABCC6 Deficiency

Results presented at the European Calcified Tissue Society Congress provide first evidence of increased plasma pyrophosphate (PPi) levels and reduced calcification with an enzyme replacement therapy in an animal model of PXE

BOSTON, MA, USA I May 07, 2021 I Inozyme Pharma, Inc. (Nasdaq: INZY), a rare disease biopharmaceutical company developing novel therapeutics for the treatment of abnormal mineralization, today presented preclinical data suggesting the utility of its lead clinical development candidate, INZ-701, as a potential treatment for ABCC6 Deficiency. The data, presented at the virtual European Calcified Tissue Society Annual Congress (ECTS, May 6-8), are the first to show that an enzyme replacement therapy (ERT) increased plasma pyrophosphate (PPi) levels and reduced calcification in an animal model of ABCC6 Deficiency.

ABCC6 Deficiency is a rare, inherited disorder that can present as generalized arterial calcification of infancy (GACI) type 2 in infants and as pseudoxanthoma elasticum (PXE) in children and adults. This is one of several disorders with significant decrease in plasma PPi levels, a potent regulator of mineralization. In patients with ABCC6 Deficiency, the abnormal calcification caused by low PPi can result in vision loss and life-threatening cardiovascular complications, among other morbidities. There is no approved treatment for ABCC6 Deficiency.

“In patients with ABCC6 Deficiency, the reduced levels of PPi that lead to pathological mineralization suggest an overlap between ENPP1 and ABCC6 Deficiencies,” explained Yves Sabbagh, Ph.D., Senior Vice President and Chief Scientific Officer of Inozyme Pharma. “This supports the rationale for an enzyme replacement therapy aimed at raising PPi to treat these serious genetic disorders. The data show that INZ-701 increased plasma PPi levels and prevented abnormal calcification in an ABCC6-deficient mouse model, demonstrating its potential for treating patients with PXE, a chronic form of ABCC6 Deficiency with no approved therapeutic options.”

This study was performed in collaboration with Thomas Jefferson University. Subcutaneous administration of INZ-701 (2 and 10 mg/kg every other day for two or eight weeks) was initiated in ABCC6-deficient mice at five to six weeks of age, the time where initiation of ectopic mineralization in this model is observed. INZ-701 led to a dose-dependent increase in plasma PPi levels at both two and eight weeks after initiation of treatment, leading to significantly lower levels of soft tissue mineralization. Histopathologic examination of tissue biopsies from vehicle-treated mice revealed extensive mineralization in the muzzle skin containing vibrissae, a biomarker of the mineralization process in this model. Compared to vehicle-treated mice, a quantitative calcium assay demonstrated that the amount of calcium in muzzle skin biopsies was reduced by 68% and 74% in mice receiving INZ-701 at dose levels of 2 and 10 mg/kg, respectively (p < 0.01).

“It is encouraging to see an ENPP1 enzyme replacement having an effect on tissue calcification in this PXE animal model. The patients suffering from this disease currently have no treatment options and collaborating with Inozyme to use our in-house expertise on this disease with their drug discovery efforts is exciting,” said Jouni Uitto, M.D., Ph.D., Professor and Chair of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Biology, at Thomas Jefferson University. "This study will help Inozyme further characterize the therapeutic potential of INZ-701 in PXE and other manifestations of ABCC6 Deficiency, which may offer hope to patient communities that have been waiting many years for a viable treatment option.”

About ABCC6 Deficiency and Pseudoxanthoma Elasticum (PXE)
ABCC6 Deficiency is a rare, inherited disorder caused by mutations in the ABCC6 gene, resulting in decreased or absent activity of the ABCC6 protein. A systemic and progressively debilitating condition estimated to affect more than 67,000 individuals worldwide, ABCC6 Deficiency leads to low levels of pyrophosphate (PPi) and is associated with pathological mineralization in blood vessels and soft tissues throughout the body. These effects can result in devastating medical problems including blindness, life-threatening cardiovascular complications, and skin calcification.

Some infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI) type 2, a vascular condition that resembles GACI type 1, the acute infantile form of ENPP1 Deficiency. In older patients, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), a rare, inherited disorder in which individuals develop calcification of soft connective tissues, including in the eyes, cardiovascular system, and skin. Individuals with PXE often have abnormalities in the eyes, such as changes in the pigmented cells of the retina; angioid streaks (tiny cracks in Bruch’s membrane, the inner layer of the retina); and choroidal vascularization (bleeding and scarring of the retina), possibly leading to vision loss. Patients with PXE may also exhibit yellowish bumps, papules, on the neck, underarms, and other areas of the skin which becomes leathery and sagging. The skin findings indicate a general, systemic, pathological process of soft tissue calcification.

About INZ-701
INZ-701 is an ENPP1 enzyme replacement therapy in development for the treatment of mineralization disorders of the circulatory system, bones, and kidneys. In preclinical studies, the experimental therapy has shown potential to generate plasma pyrophosphate (PPi) and to restore it to appropriate physiological levels, thereby preventing calcification in the vasculature and kidneys, while at the same time correcting bone abnormalities. Inozyme is developing INZ-701 for certain rare, life-threatening, and devastating genetic disorders such as ENPP1 Deficiency and ABCC6 Deficiency in which PPi levels are below the normal physiological levels.

Inozyme is preparing to initiate a Phase 1/2 clinical trial in patients with ENPP1 Deficiency in the first half of 2021 and a separate Phase 1/2 clinical trial in patients with ABCC6 Deficiency in mid-2021.

About Inozyme Pharma
Inozyme Pharma (Nasdaq: INZY) is a rare disease biopharmaceutical company developing novel therapeutics for the treatment of diseases of abnormal mineralization impacting the vasculature, soft tissue, and skeleton. Through our in-depth understanding of the biological pathways involved in mineralization, we are pursuing the development of therapeutics to address the underlying causes of these debilitating diseases. It is well established that two genes, ENPP1 and ABCC6, play key roles in a critical mineralization pathway and that defects in these genes lead to abnormal mineralization. We are initially focused on developing a novel therapy to treat the rare genetic diseases of ENPP1 and ABCC6 Deficiencies.

Inozyme Pharma was founded in 2017 by Joseph Schlessinger, Ph.D., Demetrios Braddock, M.D., Ph.D., and Axel Bolte, MSc, MBA, with technology developed by Dr. Braddock and licensed from Yale University. For more information, please visit

SOURCE: Inozyme Pharma

La Merie Biologics

FREE Weekly News Bulletin

Sign Up

2020 Sales ofAntibodies & Proteins

New Product Alert

For La Merie Publishing

Sign Up