22 Pre-Clinical Research Timeline Statistics Every Drug Development Leader Should Know in 2025

Comprehensive data on preclinical timelines, success rates, and costs shaping modern pharmaceutical development and personalized therapeutics

Key Takeaway

• Preclinical costs represent major R&D expenditure – Despite shorter duration than clinical trials, preclinical development requires substantial investment due to high compound screening volume and extensive safety testing requirements

• Attrition rates remain exceptionally high – A substantial proportion of candidates are discontinued before IND filing, with the overall likelihood of approval from Phase 1 approximately 8%, creating massive inefficiencies in traditional pharmaceutical development

• Rare diseases face unique development barriers – Traditional pharma lacks economic incentives for ultra-rare conditions, with an estimated 90-95% of rare diseases lacking FDA-approved treatments

• Regulatory requirements drive timeline length – Core IND-enabling nonclinical safety studies usually align with planned clinical exposure and can often be completed, alongside other IND-enabling work, in roughly 12-18 months (modality dependent)

• Reproducibility challenges persist – Major reproducibility concerns exist in preclinical research: only 6 of 53 landmark preclinical oncology studies were reproduced in one analysis, and an industry survey found only 20-25% of findings were reproducible

• New alternatives promise timeline reduction – Congress clarified that non-animal methods can support INDs, and FDA actively advances NAMs, enabling potential timeline compression

Preclinical Research Duration and Timeline Statistics

1. Formal IND-enabling preclinical work commonly spans 1-3 years

Formal IND-enabling preclinical work commonly spans about 1-3 years; discovery plus preclinical often totals 3-6+ years, modality dependent. This substantial time investment occurs before any human testing begins, as researchers establish safety profiles and biological activity in laboratory and animal models. Traditional pharmaceutical companies navigate these timelines for large patient populations, but for rare diseases affecting small numbers of patients, this lengthy process represents a barrier traditional pharma rarely overcomes. Source: Centre for Human Specific Research

2. Discovery and preclinical phases combined require four to seven years

When combining target identification, lead optimization, and preclinical safety testing, the complete preclinical timeline extends from four to seven years before IND submission. This represents approximately 40% of total drug development time, yet constitutes a disproportionate share of overall R&D expenditure due to high compound attrition. For families seeking treatments for ultra-rare genetic conditions, these timelines prove particularly challenging when no existing therapies exist and traditional pharmaceutical interest remains absent. Source: Biostock Drug Development Overview

3. Preclinical testing averages 31 months in pharmaceutical development

Analysis by the Congressional Budget Office found the preclinical phase averages approximately 31 months (2.6 years), followed by around 95 months for clinical trials—totaling 10.5 years from discovery to approval. This data encompasses traditional pharmaceutical programs but highlights the compressed timeframe needed for emerging personalized therapeutic approaches. Source: Congressional Budget Office

4. Core IND-enabling safety studies can be completed in 12-18 months

Core IND-enabling nonclinical safety studies usually align with planned clinical exposure and can often be completed, alongside other IND-enabling work, in roughly 12-18 months (modality dependent). Per ICH M3(R2), toxicology study durations generally match or modestly exceed the intended clinical exposure (e.g., up to 2 weeks clinical → ~2 weeks toxicology; 30 days clinical → ~3 months toxicology). This represents the majority of formal preclinical duration and generates the safety data required for IND applications to regulatory authorities. Source: Charles River Laboratories

5. Lead optimization to IND-enabling studies takes 12-24 months

Industry models estimate preclinical cycle times at approximately 12 months for the formal preclinical phase following lead optimization, though comprehensive IND-enabling programs often extend to 24 months when including formulation development and manufacturing process establishment. This critical period determines whether compounds advance to human testing, making efficient execution essential for managing overall development timelines. Source: Global Health Centre

Preclinical Success Rates and Attrition Statistics

6. Overall likelihood of approval from Phase 1 is approximately 7.9%

Across 2011-2020, the overall likelihood of approval from first-in-human (Phase 1) was about 7.9%. Preclinical-to-Phase 1 transition rates are typically on the order of two-thirds, varying by modality and therapeutic area. This success rate illustrates the substantial screening required in drug development approaches. For every 37 novel drugs approved, massive numbers of compounds enter the preclinical phase—with only a small fraction advancing to clinical trials. Source: Biotechnology Innovation Organization

7. A substantial proportion of candidates fail before IND filing

A substantial proportion of candidates are discontinued before IND filing due to safety, pharmacokinetic, or other issues; robust, standardized cross-industry estimates are limited. For clinical stages, the overall likelihood of approval from Phase 1 is approximately 6.7%. These high failure rates drive the substantial costs and timeline extensions that make rare disease development economically unviable for traditional pharmaceutical business models. Source: Norstella

8. Major reproducibility concerns affect preclinical research

Major reproducibility concerns have been reported in preclinical research: only 6 of 53 landmark preclinical oncology studies were reproduced in one analysis, and an industry survey found only 20-25% of findings were reproducible. This reflects poor predictive validity of preclinical experiments for human efficacy outcomes and highlights systematic inefficiencies in traditional target-based drug discovery approaches. Source: New Scientist

9. Preclinical transition probability reaches 69% for successful candidates

While overall success rates remain low, compounds that successfully complete preclinical evaluation demonstrate a 69% probability of transitioning to Phase I clinical trials. This higher transition rate for screened candidates demonstrates the value of rigorous preclinical evaluation in filtering unsuitable compounds before expensive clinical testing begins. Source: Global Health Centre

10. Over 20% of candidates fail in GLP toxicology testing alone

Industry data from AstraZeneca indicates over 20% of potential new medicines are stopped for safety reasons during the crucial Good Laboratory Practice (GLP) toxicology testing phase alone. This late-stage preclinical attrition represents particularly expensive failures, as compounds have already undergone extensive earlier testing. Analysis shows over 50% of these "stopping toxicities" emerge within two weeks of repeat dosing or relate to acute cardiovascular risks. Source: Drug Discovery Today

Preclinical Research Costs and Investment Requirements

11. Preclinical phase requires substantial investment

The preclinical phase requires substantial investment, primarily due to extensive laboratory studies and animal testing requirements. This significant expenditure precedes any human efficacy data, creating financial barriers for rare disease programs where patient populations cannot support traditional pharmaceutical return requirements. For personalized medicine approaches, operational complexity—not scientific capability—represents the primary cost driver that AI-powered platforms can systematically address. Source: Nome

12. Preclinical R&D constitutes disproportionate share of total spending

Although drugs spend considerably less time in preclinical development than clinical trials, the Congressional Budget Office found that a company's total preclinical expenditures typically constitute a considerable share of total R&D spending. This occurs because companies develop many potential drugs in the preclinical phase that never enter or complete clinical trials, spreading preclinical costs across far fewer successful candidates. This economic reality explains why traditional pharma avoids ultra-rare diseases where development costs cannot be recovered from small patient populations. Source: Congressional Budget Office

13. Poor preclinical predictive validity drives downstream costs

The reproducibility challenges in preclinical research contribute to overall drug development failure rates, generating massive downstream costs when flawed targets progress to expensive clinical testing. Preclinical experiments in isolated systems and animal disease models prove poorly predictive of human efficacy, yet regulatory frameworks still require extensive testing. This disconnect between regulatory requirements and predictive validity creates opportunities for alternative methodologies that better predict human responses. Source: Nature

Regulatory Requirements and Study Design Standards

14. Safety testing generally requires two species for small molecules

Generally two species (rodent and non-rodent) are used for small molecules; for biotechnology-derived products, one pharmacologically relevant species may be acceptable. These studies generate the comprehensive safety data regulatory agencies demand before permitting first-in-human studies. Source: Toxicology Research

15. Toxicology study durations align with clinical exposure

Up to 2 weeks clinical dosing typically requires ~2-week toxicology studies in two species; 30-day clinical dosing typically requires ~3-month toxicology studies. Pharmaceutical companies deliberately conduct studies aligned with anticipated human exposure to ensure comprehensive safety assessment. Source: FDA

16. Pivotal safety studies require GLP compliance

Pivotal nonclinical safety studies supporting an IND are expected to be GLP-compliant; early discovery and exploratory studies generally are not. These rigorous standards govern study conduct, documentation, and quality control, ensuring data integrity but adding procedural complexity and cost. GLP-compliant studies form the foundation of IND applications enabling clinical trial initiation. Source: eCFR

17. IND-enabling studies require multidisciplinary expertise

Comprehensive IND-enabling study planning requires multidisciplinary teams with expertise in pharmacology, pharmacokinetics, toxicology, chemistry, regulatory science, and biostatistics. This expertise requirement creates operational barriers for individual families and small patient advocacy organizations seeking treatments for ultra-rare conditions. When specialized teams in AI, genetics, rare diseases, and drug development unite around shared missions, this expertise gap can be systematically bridged. Source: Boston Biotech Advisors

Clinical Trial Phases Following Preclinical Research

18. Phase 1 trials enroll 20-100 participants over several months

Following successful preclinical completion and IND approval, Phase 1 clinical trials typically enroll 20-100 healthy volunteers to establish safety, dosing, and pharmacokinetics. Recent analyses show these first-in-human studies have a phase transition rate of approximately 63% to Phase 2, representing relatively high success probability. Phase 1 focuses on maximum tolerated dose determination and safety endpoint assessment rather than efficacy evaluation. Source: FDA

19. Phase 2 trials demonstrate 31% transition rate

Phase 2 clinical trials enroll 100-300 patients over 1-2 years to establish proof of concept and dose-ranging for efficacy, but demonstrate only approximately 31% transition rates to Phase 3. This dramatic success rate decline from Phase 1 reflects the transition from safety to efficacy assessment, where preclinical models often fail to predict human therapeutic benefit accurately. The lower success rate combined with larger patient populations makes Phase 2 substantially more expensive than Phase 1 on a per-program basis. Source: University of Cincinnati

20. Phase 3 trials require 300-3,000 patients over 2-4 years

Pivotal Phase 3 trials enroll 300-3,000 patients over 2-4 years to demonstrate confirmatory efficacy for regulatory submission, with transition rates of approximately 58% to approval. These large-scale studies generate the definitive evidence required for New Drug Application (NDA) submission to regulatory authorities. The substantial patient enrollment requirements explain why rare diseases with fewer than 200,000 affected individuals receive limited attention from traditional pharmaceutical developers focused on blockbuster drug economics. Source: University of Cincinnati

Emerging Trends in Preclinical Research Optimization

21. FDA advances non-animal testing methodologies

Congress clarified that non-animal methods can support INDs (FDA Modernization Act 2.0), and FDA actively advances NAMs, though no official 3-5 year timeline exists for making animal testing "the exception." This regulatory shift reflects growing recognition that alternative methodologies may provide superior human relevance compared to animal models. The FDA Modernization Act 2.0 explicitly authorized non-animal alternatives to support IND applications, removing previous requirements for animal studies in certain contexts. Source: FDA

22. Attrition rates are decreasing across all development stages

Recent research found attrition rates declining at all stages of clinical research in recent years, though they remain higher than in the 1990-1999 period. Studies also identified reductions in preclinical stage attrition rates over time, suggesting improvements in target validation, predictive models, and screening methodologies are gradually enhancing success probabilities. Multiple factors contribute including better target selection, improved biopharmaceutical understanding, and enhanced predictive models in discovery research. Source: Journal of Translational Medicine

Frequently Asked Questions

How long does preclinical research typically take before human trials begin?

Formal IND-enabling preclinical work commonly spans about 1-3 years; discovery plus preclinical often totals 3-6+ years, modality dependent. Core IND-enabling nonclinical safety studies usually align with planned clinical exposure and can often be completed in roughly 12-18 months. These timelines create particular challenges for rare disease patients without existing treatment options, where operational complexity rather than scientific capability often represents the primary barrier to therapeutic development.

What percentage of drugs that enter clinical trials ultimately receive FDA approval?

Recent analyses (2011-2020) estimate an overall likelihood of approval from Phase 1 of approximately 7.9%. Phase transitions averaged ~63% (Phase 1→2), ~31% (Phase 2→3), and ~58% (Phase 3→Approval), varying by therapeutic area. Preclinical-to-Phase 1 transition rates are typically on the order of two-thirds, though a substantial proportion of candidates are discontinued before IND filing due to safety or other issues.

Why do Phase 2 clinical trials have lower success rates than Phase 1?

Phase 1 trials achieve approximately 63% transition rates because they focus primarily on safety and tolerability. Phase 2 transition rates drop to around 31% because these trials assess efficacy for the first time in disease populations, where preclinical models often fail to predict human therapeutic benefit. The reproducibility concerns in preclinical research—with only 6 of 53 landmark studies reproduced in one analysis—mean many Phase 2 programs target mechanisms that prove ineffective in humans despite promising preclinical results.

How does the timeline for rare disease drug development differ from common conditions?

While preclinical timelines remain similar regardless of disease prevalence, rare diseases face unique barriers including limited natural history data, scarce animal models, small patient registries, and most critically, absence of pharmaceutical interest due to limited market size. An estimated 90-95% of rare diseases lack an FDA-approved treatment. Traditional pharma development timelines of 10+ years prove particularly challenging for rare disease families, as the operational complexity of coordinating geneticists, manufacturers, regulators, and clinicians without institutional infrastructure creates substantial barriers.

What are the main reasons preclinical research timelines get extended?

Preclinical timelines extend due to regulatory requirements, GLP compliance adding procedural requirements, late-stage toxicity failures requiring program restarts, and the multidisciplinary expertise needed for comprehensive IND-enabling study design. Generally two species (rodent and non-rodent) are used for small molecules with toxicology study durations that match or modestly exceed intended clinical exposure. Additionally, manual literature review and target validation processes consume substantial time in traditional development approaches.