From bench to first-in-human: an honest timeline of what happens between discovery and Phase 1

Getting from a validated target to a first human dose usually takes four to seven years. Discovery through candidate selection consumes two to five of them. IND-enabling work, meaning GMP manufacturing and GLP toxicology, takes another 18 to 30 months. FDA review of the IND takes 30 days. Site activation adds four to nine months. Most slippage comes from manufacturing, toxicology scheduling, and site contracts, not from FDA.

How long does it take to go from a validated target to a first human dose?

Industry data mostly measure the clinical years. The 2021 BIO analysis of 12,728 phase transitions found an average of 10.5 years from Phase 1 to approval, with Phase 1 alone averaging 2.3 years, and 2.7 years in oncology [1]. The years before Phase 1 are harder to benchmark because discovery start dates are rarely disclosed.

The best public estimate comes from a 2024 JAMA Network Open model that assigned the nonclinical stage a duration of 31.2 months [2]. That window covers roughly candidate selection through IND submission. It excludes the target validation, hit finding, and lead optimization that precede a candidate, which in my experience add another two to five years.

Four to seven years from a validated target to first dose is realistic for a well-funded program. Paul and colleagues estimated the cost of each new molecular entity at roughly $1.8 billion and argued that cycle time, alongside late-stage attrition, is a primary lever of R&D productivity [3]. The preclinical years are where a small company controls that lever most directly.

What happens in each stage, and what does it cost?

The table below is how I lay out the path. Durations reflect programs I have led or reviewed, not a statistical sample. Costs vary by modality by an order of magnitude, so I name the cost driver rather than quote a range.

Aggregate cost is well documented even where stage splits are not. DiMasi and colleagues estimated the out-of-pocket cost per approved compound at $1,395 million in 2013 dollars, or about $2.56 billion once capitalized with failures included [4]. Wouters and colleagues, using public filings for 63 products, put the median capitalized investment at about $1.1 billion in 2018 dollars after the authors' 2022 correction, with antineoplastic and immunomodulating agents highest at about $2.8 billion [5].

The preclinical share looks small in cash and large in risk-adjusted terms. In the 2024 model, the nonclinical stage was 6.8% of out-of-pocket spending but 40.2% of expected capitalized cost once failures and capital costs were counted [2]. Early years are cheap to spend and expensive to waste.

What does FDA actually require before the first dose?

The regulation lists what the IND must contain: a general investigational plan, an investigator's brochure, protocols, chemistry and manufacturing information, pharmacology and toxicology data, and any previous human experience. Each nonclinical safety study must carry a statement that it complied with good laboratory practice, or a brief explanation of why it did not [7].

The nonclinical package follows ICH M3(R2). Two-week repeat-dose toxicity studies in two species, one non-rodent, generally support a clinical trial of up to two weeks. The core safety pharmacology battery covering cardiovascular, central nervous, and respiratory systems should be completed before human exposure [8]. Longer trials require longer studies.

Oncology follows ICH S9, and the differences shorten the timeline. Genotoxicity studies are not considered essential before trials in advanced cancer, and stand-alone safety pharmacology studies are not called for absent a specific concern. A common small-molecule starting dose is one tenth of the rodent dose that is severely toxic to 10% of animals [9].

For non-oncology products, FDA's 2005 guidance derives the maximum recommended starting dose from the no-observed-adverse-effect level, converted to a human equivalent dose and divided by a default safety factor of 10 [10]. Phase 1 manufacturing is exempt from 21 CFR Part 211 under 21 CFR 210.2(c), but statutory CGMP still applies under FDA's 2008 guidance [11].

What slips most often, and why?

Manufacturing slips first. A GMP lot cannot be released without qualified analytical methods and enough real-time stability data to cover the trial. On the first-in-class biologic I carried to IND acceptance in a rare pediatric leukemia, the critical path was never the biology. It was the cell line, the process, and a CDMO slot booked months ahead.

Toxicology slips second, usually for an upstream reason. GLP studies need test article representative of the GMP process, and non-rodent studies at major CROs are scheduled months out. A dose-range-finding surprise forces a redesigned definitive study and a lost slot. On a radiopharmaceutical program I led, isotope supply and a dosimetry rework pushed the GLP start by two quarters.

Site activation slips last and most quietly. An Association of American Cancer Institutes survey of 61 centers found a median start-up interval of 167 days, and in one center's data each additional day of activation lowered the odds of accrual success by 0.5% [12]. A 2025 analysis described industry start-up as more than two months to select sites plus about eight months to activation [13].

FDA is rarely the bottleneck. If a clinical hold is imposed, the agency must respond in writing within 30 calendar days of receiving a complete response to the hold issues [14]. The sponsor's time to assemble that response, not FDA's clock, usually determines how long a hold lasts.

What can run in parallel, and what cannot be compressed?

Parallel work that pays: start CMC process development during lead optimization, not after candidate selection. Draft the IND's nonclinical and clinical sections while the GLP studies are in life. Build site contract templates before filing. Request a pre-IND meeting early. FDA classifies it as a Type B meeting, responds to the request within 21 days, and schedules it within 60 days [15].

What does not compress: the in-life phase of a GLP study plus histopathology and reporting, real-time stability time points, and the 30-day IND clock. Squeezing GLP reporting usually puts draft reports into the IND, and reviewers notice them every time.

Parallelization has a cost: it commits money before the candidate has earned it, and a GMP lot made ahead of definitive efficacy data may never be used. On the biologic program, the sequence ran IND acceptance, Fast Track designation two months later, then first-in-human dosing. Parallel work bought us months, not years.

This article is part of the Life Sciences Consulting practice at Hamilton Atlas Group — see the full capability list there.

References

1. Biotechnology Innovation Organization, Informa Pharma Intelligence, QLS Advisors. Clinical Development Success Rates and Contributing Factors 2011-2020. BIO, 2021.
2. Sertkaya A, Beleche T, Jessup A, Sommers BD. Costs of Drug Development and Research and Development Intensity in the US, 2000-2018. JAMA Network Open. 2024;7(6):e2415445.
3. Paul SM, Mytelka DS, Dunwiddie CT, et al. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nature Reviews Drug Discovery. 2010;9(3):203-214.
4. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics. 2016;47:20-33.
5. Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020;323(9):844-853.
6. Legal Information Institute, Cornell Law School. 21 CFR § 312.40 - General requirements for use of an investigational new drug in a clinical investigation. Cornell Law School, 2026.
7. Legal Information Institute, Cornell Law School. 21 CFR § 312.23 - IND content and format. Cornell Law School, 2026.
8. U.S. Food and Drug Administration. M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. FDA, 2010.
9. U.S. Food and Drug Administration. S9 Nonclinical Evaluation for Anticancer Pharmaceuticals. FDA, 2010.
10. U.S. Food and Drug Administration. Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. FDA, 2005.
11. U.S. Food and Drug Administration. Current Good Manufacturing Practice for Phase 1 Investigational Drugs. FDA, 2008.
12. Ratnayake I, et al. Evaluating the impact of delayed study startup on accrual in cancer studies. Contemporary Clinical Trials Communications. 2025;48:101562.
13. Hillery S, Majkowski R, Wang Y, et al. Accelerating start-up cycles in investigator-initiated multicenter clinical trials. Journal of Clinical and Translational Science. 2025;9(1):e249.
14. Legal Information Institute, Cornell Law School. 21 CFR § 312.42 - Clinical holds and requests for modification. Cornell Law School, 2026.
15. U.S. Food and Drug Administration. Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products. FDA, 2026.