Learn how Inozyme is leveraging Genomenon’s custom genomic services to improve diagnostic rates for an ultra-rare genetic disorder
INZ-701 is the first therapy to be investigated in clinical trials for the treatment of ENPP1 Deficiency and is being developed by Inozyme. ENPP1 Deficiency is an ultra-rare mineralization disorder caused by variants in the ENPP1 gene and can present clinically as Generalized Arterial Calcification of Infancy (GACI) and/or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2).
As a result of its rarity and heterogeneous clinical presentation, prompt and accurate diagnosis of ENPP1 Deficiency remains a challenge but is critical to improve patient outcomes, especially for those presenting with GACI, which is often fatal in early infancy. Definitive diagnosis of ENPP1 Deficiency relies on genetic testing but is made difficult by an overall lack of awareness among clinicians and a high rate of Variants of Uncertain Significance (VUSs). These challenges combined can delay or prevent diagnosis and subsequently, appropriate treatment.
Objective
Inozyme was motivated to enable earlier diagnosis of ENPP1 Deficiency to improve patient outcomes. They recognized an unmet need for high-quality evidence to facilitate the resolution of VUSs and enhance clinicians’ understanding of the clinical and genetic features of the disorder as well as its prevalence.
Challenges
- Minimizing time and resource investment – Creating, analyzing, and disseminating a comprehensive database would require a significant investment, on the order of years, which a small biopharma like Inozyme could not spare.
- Preserving trust and compliance – Given Inozyme’s commercial interests in the treatment of ENPP1 Deficiency, the data would need to be assessed by an independent party with specific expertise in both genetics and data curation to ensure trust in the results.
The Solution
Inozyme partnered with Genomenon to overcome these challenges and rapidly develop and disseminate a wholistic package of high-quality evidence.
- Variant Landscape for ENPP1 - Genomenon used a unique combination of AI-driven indexing and expert curation to rapidly deliver a Variant Landscape for PIK3CD and PIK3R1. This included all published variants interpreted according to clinical guidelines with reference-cited evidence from the literature and other databases.
- Patient Landscape for ENPP1 Deficiency - Genomenon used a unique combination of AI-driven indexing and expert curation to rapidly deliver a Patient Landscape for ENPP1 Deficiency. This included all published patients alongside their demographics, phenotypes, and genotype.
- Genetic Prevalence Estimate for ENPP1 Deficiency - Genomenon leveraged the Variant Landscape and a proven methodology to produce an updated estimate of the genetic prevalence of ENPP1 Deficiency in collaboration with disease experts.
- Genetic Disease Sponsorship for ENPP1 Deficiency - Genomenon disseminated the Variant Landscape and links to Inozyme’s ongoing trials to over 25,000+ users of the Mastermind® Genomic Intelligence Platform across 2,000+ clinical labs in 140+ countries.
- Peer-Reviewed Publications - Genomenon wrote and managed the submission and review process for two publications in collaboration with Inozyme and disease experts.
Results
- Time Savings – Each component was developed within weeks-months, rather than years.
- Increased Actionable Variants – There are 3X more actionable variants in the Variant Landscape than are present in ClinVar, an alternative clinical variant database.
- Increased Genetic Prevalence – The updated estimate of genetic prevalence was 3.1X higher than the previous estimate at ~1 in 64,000 pregnancies (vs. 1 in 200,000)
Inozyme partnered with Genomenon to overcome these challenges and rapidly develop and disseminate a wholistic package of high-quality evidence.
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