Neprilysin Inhibitors
3 drugsAbout Neprilysin
Neprilysin, also known as neutral endopeptidase (NEP), is a zinc-dependent metalloprotease that degrades various endogenous peptides, including natriuretic peptides. By degrading these peptides, neprilysin impacts vasodilation and sodium excretion.
Human genetic studies provide strong validation for neprilysin as a therapeutic target (max score 0.92). Loss-of-function variants are associated with diseases like Charcot-Marie-Tooth disease axonal type 2T (score 0.92) and spinocerebellar ataxia 43 (score 0.80), suggesting activation may be beneficial.
Neprilysin is targeted by three FDA-approved small molecule drugs, including SACUBITRIL AND VALSARTAN (ENTRESTO). These drugs, developed by Novartis and TORRENT, are approved for cardiovascular indications.
Strategic Insights
ℹ️ How we calculate- White space opportunity in HIV Infection with only 2 trials.
Human Genetic Evidence Strong
Neprilysin has strong genetic support with a maximum score of 0.92 across 26 diseases.
Strong genetic support suggests a higher probability of clinical success for neprilysin-targeting drugs.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in nervous system disease, phenotype, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link MME to 26 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for MME colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top Drugs
The competitive landscape is dominated by Novartis and TORRENT, with approved drugs.
The presence of only two companies suggests relatively high barriers to entry in this market.
Drug Modality Landscape
Modalities
Routes of Administration
Neprilysin is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests an opportunity to explore alternative modalities like antibodies or peptides.
Clinical Trials 158 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 28 | 21 | 1 | 5 | 95% |
| Phase 2 | 34 | 22 | 6 | 6 | 79% |
| Phase 3 | 36 | 20 | 5 | 10 | 80% |
| Phase 4 | 60 | 38 | 9 | 13 | 81% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (2015 - 2024)
The first drug targeting neprilysin was approved in 2015, with the most recent approval in 2024.
The recent approval indicates continued interest and potential for further development in this area.
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Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 120 clinical trials targeting Neprilysin.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities