The company's core IP stems from a proprietary biobank of AML patient samples collected over 20 years at Oxford University. This historical dataset, containing samples from elite responders to stem cell transplants, is described as "very hard to replicate," creating a significant and durable competitive advantage in target discovery.
Researchers analyzed the Oxford biobank samples in an "unbiased way," without preconceived notions of what targets they would find. This approach surprisingly revealed that all 22 initial tumor-specific targets were HLA Class II-restricted, a category previously overlooked in favor of HLA Class I. This highlights the power of agnostic discovery to challenge existing scientific dogma.
The company not only identifies targets from its elite patient cohort but also isolates the corresponding T-cell receptors (TCRs). Because these TCRs have been circulating safely in patients for years, they offer a strong starting point for safety. They are also naturally "highly selected," providing significant initial affinity for their targets, which can accelerate development.
Instead of analyzing a broad patient population, Yellowstone focuses on a hyper-specific cohort: 15 out of 2,000 AML patients who were not only cured by stem cell transplants but also experienced no immune toxicity. This "elite responder" approach aims to identify therapeutic targets that are inherently both effective and safe, learning directly from ideal human outcomes.