Aadi Cuts 80% of R&D Staff as Fyarro Faces Phase 2 Tumor Setback

Aadi Bioscience recently announced significant changes following an unsuccessful phase 2 trial for its drug Fyarro, targeting solid tumors. The clinical trial, known as PRECISION1, aimed to evaluate Fyarro (nab-sirolimus), an approved mTOR inhibitor, in treating mTOR inhibitor-naïve malignant solid tumors with TSC1 or TSC2 inactivating alterations. However, the independent data monitoring committee concluded that the study was unlikely to meet its primary goal of demonstrating sufficient efficacy for accelerated approval, prompting the company to halt the trial.

The setback is notable for Aadi Bioscience, given that Fyarro is the sole drug in its development pipeline. Just two weeks prior, the company had expressed optimism, suggesting that PRECISION1 had the potential to significantly impact patients who had exhausted other standard therapies. Despite some monotherapy activity observed in the study population, Aadi's CEO, Dave Lennon, acknowledged that the trial did not achieve the necessary results to support accelerated approval for the TSC1/TSC2 mutation indication. He expressed gratitude for the effort of everyone involved in the trial and indicated that a comprehensive analysis of the study would be provided at a later date.

While discontinuing the PRECISION1 trial, Aadi will continue dosing patients in two other phase 2 studies involving Fyarro. These studies target mTOR-driven cancers, including neuroendocrine tumors of the lung, gastrointestinal tract, pancreas, and advanced or recurrent endometrioid-type endometrial cancer in combination with Novartis’ Femara. Enrollment of new patients in these trials will cease, but with 10 patients in the neuroendocrine tumor study and 20 in the endometrial cancer study, the company believes it can still evaluate Fyarro’s efficacy later in the year.

In conjunction with these clinical developments, Aadi announced substantial layoffs, indicating 80% of its research and development workforce would be affected. The implications for the total number of employees impacted remain unclear. As of the end of June, Aadi had $78.6 million in cash, which it expected would last until the latter part of 2025. However, the recent pipeline and workforce adjustments are projected to extend the company’s financial runway into at least the second half of 2026.

To conserve cash, Aadi plans to cancel or pause further enrollment in its remaining Fyarro trials. Additionally, the company aims to focus on “maximizing its commercial business” through the sales of Fyarro for its approved use in treating perivascular epithelioid cell tumors. In the second quarter, these sales generated $6.2 million in revenue for the company.

Aadi’s journey with Fyarro reflects the high-stakes nature of drug development, where clinical trial outcomes can significantly alter a company’s strategic direction and financial stability. The halted trial and subsequent layoffs underscore the challenges faced by biotech firms in navigating the complexities of bringing new treatments to market. Despite the setbacks, Aadi remains committed to evaluating Fyarro’s potential in other cancer indications and maximizing its commercial opportunities to sustain its operations and extend its cash runway into the future.