Aadi Biosciences has instituted cash-saving measures after the company decided to halt the registrational Phase II PRECISION1 trial for its mTOR inhibitor, nab-sirolimus.
The company’s decision to discontinue the trial was made after an analysis done by the Independent Data Monitoring Committee (IDMC) found the “study was unlikely to exceed an efficacy threshold necessary to support an accelerated approval”.
Concurrently, Aadi also decided to pause enrolment in two other Phase II trials of nab-sirolimus for advanced or recurrent endometrioid-type endometrial cancer (EEC) and neuroendocrine tumours (NETs), respectively.
As part of the cash savings initiative, Aadi is also reducing its research & development headcount by 80%. The pipeline and workforce restructure are expected to extend Aadi’s cash runway into H2 2026. The company reported cash reserves of $78.6m as of 30 June 2024.
The news broke after markets closed on 20 August, causing Aadi’s stock to also take a significant hit. The company’s stock was down by more than 30% in premarket trading today.
This is not the first time that the PRECISION1 trial (NCT05103358) data significantly impacted Aadi’s stock price. In December, the company stock fell by almost 57% after it released interim data from the PRECISION1 study. In the analysis done with the first 40 participants, at a minimum of 4.5 months of follow-up, 22 and ten participants in the TCS1 and TCS2 arms achieved an overall response rate of 26% and 11%, respectively. Despite the data being largely positive, it did not sway the company’s investors.
“While nab-sirolimus showed monotherapy activity in the study population, the trial fell short of delivering what we believe would be required to support an accelerated approval in the broad TSC1/TSC2 inactivating mutations indication. We look forward to providing the full trial analysis at a later date," said David Lennon, president and CEO of Aadi Bioscience.
"Given the change in the development pipeline, we have taken the necessary steps to immediately preserve cash runway, and have hired an advisory firm to explore all options to maximize value for shareholders."
The open-label Phase II trial (NCT05997056) of nab-sirolimus in NETs has enrolled 10 out of the 21 expected participants. The Phase II study (NCT05997017) of the therapy in advanced or recurrent EEC has enrolled 20 out of 29 expected participants. Aadi noted that the current levels of recruitment in the two trials are expected to be “sufficient” to assess initial efficacy signals, which is expected by the end of the year.
Nab-sirolimus is a sirolimus protein-bound particle that targets the mechanistic target of rapamycin (mTOR), which plays a pivotal role in cell growth and proliferation. Aadi’s nab-sirolimus is marketed as Fyarro and was approved by the US Food and Drug Administration (FDA) for adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa), in 2021.
Following the pipeline restructure, Aadi plans to shift its focus to commercial activities Fyarro in PEComa. The therapy generated $24.4m in sales last year, as per the company’s financials. While Fyrro sales dipped by 8.8% in Q1, these were back on track and grew to $6.2m in Q2 this year.
