BMN 401
(formerly INZ-701)

(701-007 [PROPEL])

Trial Status Recruiting

Condition

ENPP1 Deficiency, ABCC6 Deficiency

Technology

• Enzyme

Title

PROPEL – A Prospective Observational Patient Registry to Evaluate ENPP1 and ABCC6 Deficiency

Study Description

The purpose of this prospective registry is to characterize the natural history of ectonucleotide pyrophosphatase/phosphodiesterase1(ENPP1) Deficiency and the infantile-onset form of adenosine triphosphate (ATP) binding cassette transporter protein subfamily C member 6 (ABCC6) Deficiency longitudinally.

Primary Outcome Measure*

• Assessments will be collected during each subject’s routine visit. The assessments will be done per local standard of care.
  • Assessment of Patient Functional changes through a validated Patient Reported Outcomes (PROs) tools.*
  • Assessment of Health-Related Quality-of-Life (HRQoL) changes through validated PROs tools.*
  • Measurement of inorganic phosphate (PPi) levels in patients’ venous blood.*

Select Inclusion Criteria*

• Agree to provide access to relevant medical records
• One of the following genetic or clinical criteria:
  • A confirmed prenatal or postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (i.e., homozygous or compound heterozygous)
  • A confirmed monoallelic ENPP1 mutation with clinical symptoms
  • A confirmed prenatal or postnatal molecular genetic diagnosis of ABCC6 Deficiency with biallelic mutations

Secondary Outcome Measure*

• Not applicable

Select Exclusion Criteria*

• Patients who are currently participating in an BMN 401 (INZ-701) interventional clinical study.

* Additional measures/criteria may apply.; All PROs and PPi sampling are optional.

For comprehensive trial information, visit ClinicalTrials.gov NCT06302439

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-104 [ENERGY])

Trial Status Recruiting

Condition

ENPP1 Deficiency, ABCC6 Deficiency

Technology

• Enzyme

Title

The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency

Study Description

The primary purpose of this study is to assess the safety and tolerability of INZ-701 in infants with ENPP1 Deficiency or with ABCC6 Deficiency

Primary Outcome Measures*

• Number of Treatment Emergent Adverse Events
• Incidence of Anti-Drug Antibodies
• Left Ventricular Ejection Fraction

Select Inclusion Criteria*

• Confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency or ABCC6 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous)
• Have clinical manifestations of Generalized Arterial Calcification of Infancy (GACI) or GACI-2, which may include, but are not limited to, pathologic ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly
• <1 year of age at Baseline (Day 1)
• Weigh ≥0.5 kg at the time of the first dose of INZ-701

Secondary Outcome Measures*

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) Levels
• Area under the Plasma Concentration versus Time Curve (AUC)
• Maximum Plasma Concentration (Cmax)

Select Exclusion Criteria*

• Care has been withdrawn or study participant is receiving end of life care or hospice only
• Known malignancy
• Receipt of any non-Inozyme investigational new drug within 5 half-lives of the last dose of the other investigational product or within 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device, through completion of participation in the study

* Additional measures/criteria may apply.

For comprehensive trial information, visit ClinicalTrials.gov NCT05734196

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-106 [ENERGY3])

Trial Status Active, Not Recruiting

Condition

ENPP1 Deficiency

Technology

• Enzyme

Title

The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency

Study Description

The primary purpose of this study is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency

Primary Outcome Measure*

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration

Select Inclusion Criteria*

• Confirmed post-natal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous)
• ≥1 year and <13 years of age at Study Day 1
• Open growth plates of the distal femur and proximal tibia in both legs
• Plasma Inorganic Pyrophosphate (PPi) concentration of <1400 nM
• 25-hydroxyvitamin D (25[OH]D) levels of ≥12 ng/mL

Secondary Outcome Measures*

• Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score
• Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score
• Change from Baseline in growth Z-score (height/body length and weight)

Select Exclusion Criteria*

• Receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-fibroblast growth factor 23 (FGF23), and oral and/or IV bisphosphonates
• Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Study Day 1 and/or oral phosphate supplements within 36 hours prior to Study Day 1 if randomized to the INZ-701 arm
• Planned orthopedic surgery that may confound the interpretation of study results during the Randomized Treatment Period
• Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives of the last dose or within 4 weeks prior to Randomization, whichever is longer, or use of an investigational device

* Additional measures/criteria may apply.

For comprehensive trial information, visit ClinicalTrials.gov NCT06046820

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

BMN 401
(formerly INZ-701)

(701-304 [ADAPT])

Trial Status Recruiting

Condition

ENPP1 Deficiency, ABCC6 Deficiency

Technology

• Enzyme

Title

ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency

Study Description

The purpose of this study is to assess the long-term safety of INZ-701 in patients with ENPP1 Deficiency or ABCC6 Deficiency who have received INZ-701 in an existing clinical study and choose to continue dosing for the potential treatment of their condition

Primary Outcome Measures*

• Number of Treatment Emergent Adverse Events
• Incidence of Anti-Drug Antibodies

Select Inclusion Criteria*

• >1 year of age
• Completed the protocol-required safety and pharmacokinetic/pharmacodynamic and/or efficacy period(s) of a previous INZ-701 clinical study in ENPP1 or ABCC6 Deficiency
• Females of childbearing potential who are sexually active must be using or agree to use 1 highly effective form of contraception (per CTFG 2020) from at least 1 month before the first dose of INZ-701 through 30 days after last dose of INZ-701 (greater than 5 half-lives of INZ-701); participants must agree to not donate ova from the period following the first dose of INZ-701 through 30 days after the last dose of INZ-701
• Males who are sexually active must agree to use condoms from the period following the first dose of INZ-701 through 30 days after the last dose of INZ-701; participants must agree to not donate sperm from the period following the first dose of INZ-701 through 30 days after last dose of INZ-701

Secondary Outcome Measures*

• Mean change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentratio
• Time to maximum serum concentration (Tmax)
• Maximum Plasma Concentration (Cmax)

Select Exclusion Criteria*

• Concurrent participation in another interventional clinical study and/or has received an investigational drug other than INZ-701 within 5 half-lives or within 4 weeks prior to the first dose of INZ-701 in this study, whichever is longer, or use of an investigational device
• Pregnant, trying to become pregnant, or breastfeeding
• Males trying to father a child

* Additional measures/criteria may apply.

For comprehensive trial information, visit ClinicalTrials.gov NCT06462547

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4