Bringing the NAMs Revolution to Women's Health
Last week, I attended a one-day conference hosted by the Pharmaceutical & BioScience Society (PBSS) in South San Francisco titled “New Approach Methodologies (NAMs): Minimizing Animal Studies for Pharmacology, ADME, and Toxicology in the Context of the FDA Roadmap.”
While discussions about regulatory frameworks don’t usually excite a room, this meeting was an exception. It was an opportunity to speak directly with leading scientists, regulators, and pharma about a question central to my work at Opal Therapeutics: How can organoids truly accelerate drug discovery and help us get safer, more effective drugs to patients faster?
Definitions:
NAMs: New Approach Methodologies: Includes organoids, organs-on-a-chip, in silico digital twins.
CIVMs: Complex In Vitro Models
FDA: U.S. Food and Drug Administration
NIH: U.S. National Institutes of Health
Context: A Broken Drug Development Pipeline
Drug discovery has reached a crisis point. Despite record R&D spending, 90% of drugs still fail in clinical trials, and the cost of bringing a new molecule to market now exceeds $1.8 billion per drug. The majority of these failures occur because animal models (rodents, dogs, and mini-pigs) simply don’t predict human biology accurately enough. Without a step-change in R&D productivity, pharma cannot sustain innovation at the pace needed to offset patent expirations or rising development costs [1].
NAMs and CIVMs are emerging as the solution to this bottleneck. By providing human-relevant, data-rich platforms, they can improve predictivity, reduce attrition, and ultimately accelerate safe, effective therapies to market.
NAMs: The FDA Wants Change Now, but Biotech R&D Must Build the Path
With the passage of the FDA Modernization Act 2.0 (2022), the agency formally endorsed the use of human-based testing methods as alternatives to animal models for preclinical research. This momentum continues:
April 2025: FDA announced plans to phase out animal testing for monoclonal antibodies in favor of NAMs.
May 2025: The FDA Center for Drug Evaluation and Research NAMs Coordinating Committee was formed to drive strategic engagement, standard-setting, and culture shift toward NAM adoption.
September 2025: NIH announced the first Standardized Organoid Modeling (SOM) Center, dedicated to advancing reproducible, human-based preclinical systems.
Despite this progress, industry adoption remains slow. Drug developers (always a risk-averse bunch) are hesitant to shift from entrenched animal-based workflows. A common misconception persists that NAM-generated data must be pre-qualified by the FDA before use, which is not the case.
As one ex-FDA speaker put it: “The FDA is looking for the data, people just aren’t submitting it.”
Notable success stories highlight what’s possible. HUB Organoids (acquired by Millipore Sigma in 2025) cut the time to clinic in half for a colorectal cancer drug candidate using tumor organoids. Similarly, Emulate Bio’s Liver-Chip and InSphero’s liver organoids have demonstrated exceptional predictive power for drug-induced liver injury (DILI), outperforming traditional models.
NAMs: From Academic Curiosity to Industry Utility
Several talks noted that organoids and organs-on-chips aren’t new, they’ve been in development for nearly two decades. But translating academic models into standardized, industry-ready tools has been challenging. As one Genentech speaker described it, the field faces a “Paradox of Choice”: too many models, each highly customized, with little harmonization across platforms.
To drive adoption, pharma wants fewer “over-engineered” models and more robust, automated, and QC-validated systems that can deliver consistent results across sites. Most efforts so far have focused on safety (toxicology and DILI prediction), but efficacy-based models, those that predict whether a therapy will work in humans, are equally critical. For example, researchers are developing tonsil organoids to model immune responses to avian flu vaccines an application animal models cannot capture [2].
Where Opal Therapeutics Fits In
The conference themes of standardization, validation, and regulatory readiness were central and directly align with what Opal Therapeutics is building. The industry’s call for reproducible, QC-driven, and automation-compatible NAM systems reinforces the importance of our work. At Opal, we are developing standardized SOPs, assay workflows, and data pipelines for uterine organoids to make them scalable, validated, and industry-ready. Our goal is to ensure that human-based reproductive models can be integrated into the same regulatory and commercial frameworks now emerging for liver, tumor, and lung organoids.
However, while progress in these other organ systems has been rapid, women’s health remains far behind in efficacy-based modeling. Since 2023, outside of cancer therapies, only 3.3% of drugs have been approved by the FDA for women’s health conditions and none address the underlying causes of fibroids or endometriosis [3]. This gap underscores the urgent need for validated NAM platforms that not only assess safety but also model therapeutic efficacy in reproductive disease. The NAMs we are developing at Opal are designed for high-throughput drug screening and in silico uterine digital twin modeling, providing a powerful bridge between biological data and computational prediction.
3. Young WB. Women’s Healthcare: Call for Action. J Med Chem. 2024. doi:10.1021/acs.jmedchem.4c01135
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