TIE2 Inhibitors
7 drugsAbout TIE2
TIE2, also known as angiopoietin-1 receptor, is a receptor tyrosine kinase primarily expressed on endothelial cells. It regulates angiogenesis and vascular maintenance, making it a key regulator of blood vessel formation.
TIE2 is genetically linked to 16 diseases (max score 0.90), with strong evidence supporting its role in multiple cutaneous and mucosal venous malformations. Loss-of-function variants are associated with increased risk, suggesting activation may be beneficial.
Four FDA-approved small molecule drugs target TIE2, including STIVARGA, ICLUSIG, QINLOCK, and CAPRELSA. These drugs are approved for other therapeutic areas, highlighting the potential of TIE2 modulation.
TIE2 Genetic Evidence Strong
TIE2 has strong genetic support (score 0.90) linking it to multiple cutaneous and mucosal venous malformations.
Strong genetic support suggests that TIE2 has a higher probability of clinical trial success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 67% directional consistency across 3 traits
- • Strong signal in cardiovascular disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
67% alignedEvidence Across Diseases
16 totalGWAS and other genetic studies link TEK to 16 diseases.
Loss-of-function causes disease; activation may help
Gain-of-function causes disease; inhibition may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for TEK 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 TIE2 Drugs
Four companies have approved drugs targeting TIE2: DECIPHERA PHARMS, Bayer, Sanofi, and Takeda.
The presence of four companies indicates moderate competition, but also established market demand.
TIE2 Drug Modality Landscape
Modalities
Routes of Administration
TIE2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or fusion proteins could provide a competitive advantage.
TIE2 Clinical Trials 548 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on TIE2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 159 | 83 | 32 | 43 | 72% |
| Phase 2 | 316 | 130 | 60 | 124 | 68% |
| Phase 3 | 63 | 20 | 11 | 32 | 65% |
| Phase 4 | 10 | 5 | 1 | 4 | 83% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
7 Phase 3 trials testing approved TIE2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting TIE2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
TIE2 Drug Approval Timeline (2011 - 2020)
The first TIE2-targeting drug was approved in 2011, with the most recent in 2020.
The approval timeline suggests continued interest in TIE2, but potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 233 (47 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 TIE2. A trial counts if an approved drug acting on TIE2 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.