PARP1 Inhibitors
2 drugsAbout PARP1
PARP1 (poly (ADP-ribose) polymerase 1) is an enzyme involved in DNA repair and other cellular processes. It plays a crucial role in repairing damaged DNA, making it a compelling target for therapeutic intervention, particularly in cancer.
Human genetic studies provide strong validation for PARP1 as a therapeutic target in diseases like clonal hematopoiesis (score 0.78) and cutaneous melanoma (score 0.77). Loss-of-function variants are associated with increased disease risk, supporting inhibition-based therapies.
PARP1 is targeted by two FDA-approved small molecule drugs, LYNPARZA (AstraZeneca) and TALZENNA (Pfizer), both used in oncology. LYNPARZA has 4 indications, while TALZENNA has 2, highlighting their clinical utility.
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 80% attractiveness score.
Human Genetic Evidence Strong
PARP1 has strong genetic support with a max score of 0.78 across 10 diseases.
Strong genetic support suggests a higher likelihood of clinical trial success for PARP1-targeting drugs.
Evidence Across Diseases
10 totalGWAS and other genetic studies link PARP1 to 10 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PARP1 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 concentrated, with AstraZeneca and Pfizer holding all approved drugs.
High market concentration suggests significant barriers to entry, requiring differentiated strategies for new entrants.
Drug Modality Landscape
Modalities
Routes of Administration
PARP1 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 PARP1 space.
Clinical Trials 440 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 170 | 74 | 24 | 71 | 76% |
| Phase 2 | 219 | 58 | 37 | 121 | 61% |
| Phase 3 | 43 | 16 | 3 | 24 | 84% |
| Phase 4 | 8 | 4 | 1 | 3 | 80% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
4 Phase 3 trials testing approved PARP1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PARP1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (2014 - 2018)
The approval timeline spans 5 years, with LYNPARZA approved in 2014 and TALZENNA in 2018.
The relatively short approval span suggests potential for further innovation and market growth in PARP1 inhibition.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 2 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 2-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • 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 386 clinical trials targeting PARP1.
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