1. What is endometriosis?

Endometriosis occurs when cells similar to the lining of the uterus grow outside of the organ, sometimes causing pain, infertility and heavy menstrual bleeding. It is a chronic condition affecting 5-10% of reproductive aged women. The disease can present different characteristics depending on the patient including lesions, cysts, scaring, and adhesions. Official diagnosis is only permitted through visualization during surgery and thus accurate diagnosis takes years for many patients. Treatment typically involves surgery to remove or destroy all visible disease, however this does not always eliminate pain and there is no guarantee the disease will not return.

2. What are uterine fibroids?

Uterine fibroids are the most common tumor, affecting up to 70% of women. Fibroids size and count can vary between patient to patient. Although benign, fibroids are the lead cause of hysterectomies and cause severe gynecological dysfunction including heavy bleeding, infertility, and pre-term labor. Fibroids are initiated when normal myometrium stem cells are “induced” into tumor initiating stem cells and promote fibroid growth. The most common driver mutation of fibroids are MED12 missense mutations, but no therapeutics have yet been identified to treat the problem. For now, most women undergo surgery to have the fibroid removed, however, like endometriosis, there is no guarantee the fibroids will not return.

3. What is an uterine organoid?

Organoids are 3D models created from human cells that mimic the structure and function of real human organs, though in a simplified form. They offer more complexity than traditional 2D cell cultures, yet are easier to study than full tissue samples. Because they’re made from human tissue, organoids provide a more accurate and translatable model for drug testing than rodent studies.

At Opal Therapeutics, we’ve developed two types of uterine organoids: endometrial and myometrial. The endometrial organoids replicate the uterus's inner lining, while the myometrial organoids mimic the smooth muscle layer. Together, these models allow us to create human-relevant systems for studying endometriosis and uterine fibroids, laying the groundwork for our drug discovery platform. By closely replicating the unique cellular environment of these conditions, our organoids enable more accurate screening and identification of potential therapies, moving us closer to effective, targeted treatments for women’s health.

4. How do uterine organoids compare to rodent models for drug testing?

🧬 Rodent models are missing key pieces of human female biology - they don’t have a menstrual cycle. Rodents have an estrous cycle, which involves reabsorbing the uterine lining if fertilization doesn't occur. Humans have a menstrual cycle, characterized by the monthly shedding and regeneration of the endometrial lining. This process of breakdown and repair is central to diseases like endometriosis, and it does not naturally happen in rodents. Opal’s uterine organoids can be exposed to hormones like estrogen and progesterone to mimic the menstrual cycle and better replicate human uterine physiology.

🧪Inaccurate disease origin - artificial induction of endometriosis and fibroids. Animal models for reproductive disorders often require surgically or genetically induced disease.  In traditional endometriosis drug testing, human tissue is grafted into a mouse uterus [Rosa-E-Silva, A.C.J.S, et al., Reprod Sci, 2019; doi: 10.1177/1933719119859438], and efficacy is assessed by tracking lesion size or pain-related behavior over time. For fibroid studies, researchers often use the Eker rat model, which develops fibroids due to a TSC2 mutation [Halder, S.K. et al., Biol Reprod, 2012; doi:10.1095/biolreprod.111.098145]. In these models, treatment response is typically measured by tumor shrinkage after prolonged dosing. These approaches lack real-world relevance. In contrast, Opal’s human organoid platform enables direct evaluation of cellular, molecular, and phenotypic responses in a system derived from real patients, offering improved translatability and mechanistic insight - see our recent white paper.

⚙️Superior testing for drug screening - patient-specific and genetically relevant. Our organoids are derived directly from patient tissues and menstrual effluent, including healthy, uterine fibroids, and endometriosis donors. They retain the unique genetic signature of the patient and contain quantifiable phenotypes (image, biomarkers, omics).  Additionally, the organoid platform is highly scalable, allowing us to test hundreds of potential drug candidates simultaneously in a matter of a few weeks. This dramatically accelerates the pace of discovery compared to slow, costly, and ethically complex animal studies that can take 6-12 months to execute.

🧫A snapshot of a patient to study for years. From just one menstrual sample or biopsy, we can generate enough cells to run experiments for up to two years. Organoids can be cryopreserved, expanded, and re-tested across different conditions, without repeatedly burdening the patient. This enables standardized, head-to-head comparisons of drug responses, improving reproducibility and eliminating batch-to-batch variability seen in animal studies.

5. Are uterine organoids a New Approach Methodology (NAM)?

Yes, uterine organoids are a type of New Approach Methodology (NAM). NAMs include non-animal technologies such as patient-derived organoids, organs-on-chips, and computational models that better reflect human biology. These platforms are increasingly used to evaluate immunogenicity, toxicity, and drug response with higher accuracy and relevance to human systems. Animal models often fail to predict human outcomes. Over 90% of drugs that appear safe and effective in animals do not ultimately receive FDA approval, largely due to unforeseen safety or efficacy issues in humans. In fact, some drugs that passed animal testing have proven lethal in human trials.

With the passage of the FDA Modernization Act 2.0 in December 2022, the FDA officially approved the use of human-based alternatives to animal testing for preclinical research. This momentum continued in April 2025 when the FDA announced it would begin phasing out animal testing for monoclonal antibodies in favor of NAMs. In the same month, the NIH announced it would prioritize human-based models (including organoids) in its research funding decisions.
Uterine organoids offer an ex vivo method to rapidly study human biology at scale, reduce cost, reduce reliance on rodent models, and improve accuracy of drug study screening. 

6. How does the FDA regard organoid data?

The FDA increasingly recognizes the value of organoid-based data as part of drug development and regulatory submissions. A notable example is the Human Liver-Chip, which was accepted into the FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) pilot program. In a multi-center validation study, this Liver-Chip model accurately predicted 87% of known drug-induced liver injury (DILI) cases, demonstrating its potential to improve safety screening compared to traditional models.

More recently, in June 2024, Signet Therapeutics used data from its patient-derived organoid model to support IND approval of a compound targeting diffuse gastric cancer. This milestone shows that organoid-based data can be accepted in regulatory filings when well-validated and appropriately applied. To further encourage adoption of organoid models and other New Approach Methodologies (NAMs), the FDA has expressed support for:

• Welcoming NAM data (e.g. organoids or in silico models) as part of IND/BLA submissions

• Offering regulatory relief, such as reducing the number of required animal study replicates when strong human-relevant data is provided

• Piloting alternative paths, including waiving certain animal studies where organoid models are scientifically justified and validated

7. How can the uterine organoids be used for women’s health research?

Uterine organoids offer a powerful, human-relevant platform for advancing women’s health research. Derived from patient tissue or menstrual effluent, these 3D cell cultures replicate key features of the endometrium or myometrium, enabling a range of applications, including:

• Drug screening and hit identification: Test compounds against disease-relevant phenotypes (e.g. fibrosis, inflammation, hormone response) to identify potential therapeutic candidates.

• Toxicity and off-target effect assessment: Evaluate compound safety and off-target effects in a controlled human system, improving preclinical risk prediction.

• Mechanism of action (MOA) studies: Investigate how a drug influences molecular pathways, gene expression, and cellular behavior within diseased or healthy uterine tissue.

• Hormone response modeling: Simulate estrogen and progesterone cycling to study hormone-driven diseases like endometriosis and heavy menstrual bleeding.

• Biomarker discovery: Identify predictive or diagnostic markers from multi-omic analysis (e.g. RNA-seq, cytokines, imaging) of organoid responses.

• Precision medicine and patient stratification: Tailor therapies by testing drugs on organoids derived from diverse patient backgrounds, including responders vs. non-responders.

• Longitudinal studies: Organoids can be cryopreserved and expanded over time, enabling consistent analysis without repeated patient sampling.

8. I have a drug I want to test in women’s reproductive health, how do I work with Opal Therapeutics?

We’re always excited to collaborate with scientists and companies advancing women’s health. If you have a compound you'd like to test in endometriosis, fibroids, or related gynecological conditions, we’d love to connect. Opal Therapeutics offers flexible options tailored to your research needs. We can perform in-house drug screening using our validated organoid platform, providing high-content data including imaging, biomarkers, and transcriptomic outputs. Alternatively, we can ship cryopreserved organoid specimens directly to your lab, along with detailed culture protocols and media formulation support. To explore the best way to work together, please book an introductory call with our team.

9. Where is Opal Therapeutics located?

Our lab headquarters are in San Francisco, California.