EPHA2 Inhibitors
3 drugsAbout EPHA2
EPHA2 is a receptor tyrosine kinase (RTK) involved in cell growth, migration, and differentiation signaling pathways. As a cell surface receptor, EPHA2 binds ephrin ligands to mediate cell-cell communication and regulate tissue organization.
EPHA2 is genetically linked to 18 diseases, including early-onset non-syndromic cataract (score 0.91). Loss-of-function variants are associated with increased risk of cataract, suggesting activation of EPHA2 may be therapeutically beneficial.
Three FDA-approved small molecule drugs target EPHA2 in oncology: DASATINIB (SPRYCEL), PHYRAGO. These drugs, developed by Apotex, HANDA THERAP, and Bristol-Myers Squibb, demonstrate the feasibility of modulating EPHA2 for therapeutic benefit.
EPHA2 Genetic Evidence Strong
EPHA2 has strong genetic support with a maximum score of 0.91 for early-onset non-syndromic cataract.
The strong genetic support and activation-likely-beneficial verdict may increase the probability of clinical success for EPHA2 agonists.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in genetic, familial or congenital disease, disorder of visual system, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
18 totalGWAS and other genetic studies link EPHA2 to 18 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for EPHA2 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 EPHA2 Drugs
Apotex, HANDA THERAP, and Bristol-Myers Squibb are the companies with approved EPHA2-targeting drugs.
The small number of companies suggests relatively low barriers to entry, but also a risk of direct competition.
EPHA2 Drug Modality Landscape
Modalities
Routes of Administration
EPHA2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage in the EPHA2 space.
EPHA2 Clinical Trials 218 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on EPHA2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 89 | 45 | 31 | 13 | 59% |
| Phase 2 | 112 | 49 | 26 | 36 | 65% |
| Phase 3 | 11 | 6 | 1 | 4 | 86% |
| Phase 4 | 6 | 2 | 0 | 4 | 100% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
EPHA2 Drug Approval Timeline (2006 - 2023)
The first EPHA2 drug was approved in 2006, and the most recent in 2023, spanning 18 years.
The recent approval suggests renewed interest in EPHA2, but also a risk of market saturation in oncology.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 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
- • Sponsors: 111 (13 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on EPHA2. A trial counts if an approved drug acting on EPHA2 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.