7217 Impact of INZ-701 on Bone and Mineral Metabolism Biomarkers and Clinical Outcomes in Adults with ENPP1 Deficiency - Results from 48-week Phase 1/2 Open Label Study
Bibliographic record
Abstract
Abstract Disclosure: K. Gunter: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. R.A. Wermers: Research Investigator; Self; Inozyme Pharma. R. Fuhr: Employee; Self; Parexel GmbH. Research Investigator; Self; Inozyme Pharma. D. Schnabel: Research Investigator; Self; Inozyme Pharma. A. Besancon: Research Investigator; Self; Inozyme Pharma. M.A. Nour: Research Investigator; Self; Inozyme Pharma. D. Wenkert: Stock Owner; Self; Inozyme Pharma. Y. Sabbagh: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. Background: ENPP1 Deficiency is a rare disorder due to inactivating mutations in the ENPP1 gene that result in low levels of inorganic pyrophosphate (PPi), a critical regulator of mineralization. Subsequent pathologic soft tissue calcification results in severe vascular calcification and ∼50% infant mortality. By early adolescence the majority of survivors develop FGF-23 mediated hypophosphatemic rickets, characterized by bone deformities, short stature, joint/ligament calcification and musculoskeletal pain. No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product. Purpose: To describe the safety, tolerability, immunogenicity, and exploratory efficacy (bone and mineral metabolism biomarkers and clinical outcomes) of INZ-701 in adults with ENPP1 Deficiency through the end of the phase 2 study period (week 48). Methods: Phase 1/2, multicenter, open-label, multiple ascending dose study including three adults in each of three dose cohorts (0.2, 0.6 and 1.8 mg/kg, total N=9) with genetic variants in ENPP1 and PPi <1300 nM (NCT04686175). Participants were dosed subcutaneously on Day 1, then twice weekly from Day 8 to end of study. Data through wk 48 as of July 6, 2023 are included; topline wk 48 data will be presented. Per protocol, participants may continue to receive INZ-701 beyond wk 48. Results: Rapid increase in mean PPi from baseline of 426±407 nM was noted in all patients, reaching the healthy volunteer range within 6 hrs of the first dose with sustained elevation through wk 48. Mean PPi across the 0.2, 0.6 and 1.8 mg/kg dose cohorts from day 32 to wk 48 was 1299±131 nM, 1356±136 nM, and 1282±81 nM, respectively. There were improvements from baseline to wk 48 in mean pooled FGF-23 (-22 pg/mL) and serum phosphate (+0.18 mg/dL), with dose-dependent changes in bone specific alkaline phosphatase consistent with bone healing. DEXA revealed improvements in spine BMD and BMC. There were trends towards improvement in mean % predicted change in 6MWT from baseline to wk 48: cohort 1, 76.7% (SE 10.5) to 85.0% (SE 3.0); cohort 2, 52.2% (SE 10.9 ) to 79.0% (SE 2.9); cohort 3, wk 48 data not available. Improvements were also observed in physician and patient global impression of change score (with no patients deteriorating) and PROMIS pain intensity score. INZ-701 was well tolerated with no drug-related serious or severe (> grade 2) adverse events. Low titers of non-neutralizing anti-drug antibodies (≤160) were observed in 7/9 patients. Long half-life of approximately 126 hours suggests the potential for once-weekly dosing. Conclusions: In adults with ENPP1 Deficiency, INZ-701 was well tolerated with no related serious or severe adverse events. INZ-701 demonstrated a rapid and sustained increase in PPi levels from baseline to week 48 with corresponding improvements in bone mineral biomarkers, functional performance, and patient and physician-reported outcomes. Presentation: 6/3/2024
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".