Aadi Bioscience, a relatively under-the-radar biopharmaceutical company specializing in precision oncology, might be sitting on a goldmine. While their recent Q1 2024 earnings call focused primarily on the full enrollment of their PRECISION1 trial for nab-sirolimus in TSC1 and TSC2 mutated cancers, a subtle detail hinted at a potentially explosive commercial opportunity for their already approved drug, FYARRO.

FYARRO, currently indicated for malignant PEComa, a rare and aggressive cancer, saw a slight dip in sales for Q1 2024. The company attributed this to changes in distributor ordering patterns and fewer new commercial patient initiations. While these explanations hold water, a deeper dive into the transcript reveals a fascinating dynamic that could point to an off-label surge for FYARRO.

FYARRO Sales and PRECISION1 Trial Enrollment: A Curious Correlation

During the Q&A, CEO Dave Lennon addressed the lower commercial patient initiation numbers. He pointed out a peculiar correlation: some of the largest accounts seeing a reduction in commercial FYARRO orders were also the highest enrolling sites for the PRECISION1 trial. While he clarified that this couldn't be attributed to PEComa patients entering the trial (an exclusion criteria), it begs the question: where did these patients go?

A hypothesis emerges: could the promising early data from PRECISION1, particularly the 26% overall response rate in heavily pretreated TSC1 patients, be driving off-label use of FYARRO? Physicians, particularly those at the forefront of PRECISION1, are witnessing firsthand the potential of nab-sirolimus across diverse tumor types. Seeing these impressive responses, especially in patients with limited treatment options, might be leading them to explore FYARRO's potential off-label, particularly in late-line settings.

Off-Label Use: A Canary in the Coal Mine?

This hypothesis gains further traction when we consider the small number of patients driving the FYARRO sales figures. With around 90 patients on commercial FYARRO at any given time, and 80 patients enrolled in PRECISION1 over the past nine months, the overlap in physician experience between these two groups is substantial. It wouldn't take a large shift in prescribing behavior to create the dip observed in Q1.

Furthermore, Dr. Loretta Itri, Aadi's Chief Medical Officer, noted that enrollment into PRECISION1 actually saw a slight uptick after the interim data release. This suggests that the positive early data is driving enthusiasm within the medical community, further supporting the possibility of increased off-label FYARRO use.

The Potential Market for Nab-sirolimus: A Vast Opportunity

If this hypothesis holds true, it carries significant implications. A surge in off-label use for FYARRO, even in the absence of promotion, would be a strong indicator of its broader therapeutic potential. It would validate the market opportunity for nab-sirolimus beyond PEComa and bolster Aadi's pursuit of a tumor-agnostic indication.

Here's where things get even more interesting. The 16,000 new TSC1 and TSC2 patients diagnosed annually in the US only represent those with new mutations. The actual market size, including patients with existing diagnoses, is likely significantly larger. Add to this the potential for off-label use in other mTOR-driven cancers, and the total addressable market for nab-sirolimus becomes truly vast.

Aadi's Financial Strength: Ready to Capitalize

Aadi, with a cash runway into Q4 2025, is financially well-positioned to capitalize on this opportunity. They have the resources to navigate the regulatory landscape and, if needed, conduct additional trials to solidify the efficacy and safety of nab-sirolimus in broader patient populations.

PRECISION1 Trial Data: A Catalyst for Growth

While the PRECISION1 trial remains the company's primary focus, the subtle hint of off-label FYARRO use might be the canary in the coal mine, signaling a much larger commercial opportunity than previously anticipated. Investors would be wise to keep a close eye on future FYARRO sales figures, as they could be the harbinger of a blockbuster drug in the making.

FYARRO Net Sales (USD Million)

PRECISION1 Trial Enrollment

"Fun Fact: Aadi Bioscience's name is derived from the Sanskrit word "Aadi," which means "beginning." This is quite fitting, as the company is pioneering a new beginning in precision oncology with their innovative nab-sirolimus technology."