On May 23, 2024 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, reported new nonclinical data demonstrating the significantly higher intratumoral drug concentration, stronger inhibition of mTOR targets and greater antitumor activity of nab-sirolimus compared to intravenous and oral mTOR inhibitors in a xenograft model (Press release, Aadi Bioscience, MAY 23, 2024, View Source [SID1234643636]). These data will be available as an abstract and published in the Journal of Clinical Oncology supplement to coincide with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 31 – June 4, 2024.

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"Our goal at Aadi is to unlock the full power of mTOR inhibition by combining nanoparticle albumin bound (nab) technology with sirolimus to improve delivery, stability, solubility and targeting," said Loretta Itri, MD, Chief Medical Officer at Aadi. "With superior findings across key markers, these important nonclinical data add to our growing body of evidence that nab-sirolimus may overcome limitations of previous therapies, including both orally and intravenously delivered mTOR inhibitors, with the potential to play an important therapeutic role in difficult-to-treat cancers."

Abstract details and highlights include:

Title: Antitumor activity of nab-sirolimus versus mTOR inhibitors temsirolimus, sirolimus, and everolimus in A549 NSCLC xenografts
Lead Author: Shihe Hou
Abstract: View Source

Despite the broad importance of the mTORC1 pathway in cancer cell growth and survival, mTOR inhibitors (mTORis) temsirolimus, sirolimus and everolimus have limited clinical application in the cancer setting.
In A549 xenografts, nab-sirolimus resulted in significantly greater suppression of tumor growth compared with IV temsirolimus and oral sirolimus and everolimus.
Average intratumoral drug concentrations 24 hours after IV mTORi treatment were significantly higher with nab-sirolimus (420-539 ng/g) compared with temsirolimus (34.9 ng/g) and its active metabolite (13.2 ng/g); similarly, tumor uptake of nab-sirolimus greatly exceeded that of sirolimus and everolimus at steady-state.
We believe these results support further clinical evaluation of nab-sirolimus as a single agent or in combination with other therapeutic agents.
In addition, Aadi will present a trials-in-progress poster on its Phase 2 trial in advanced or recurrent endometrioid-type endometrial cancer (EEC), a difficult-to-treat mTOR-driven cancer. Endometrial cancer is the most common cancer of the female reproductive organs and one of the few cancers with increasing mortality. There are an estimated 10,000 cases of EEC diagnosed annually.

Poster details and abstract highlights include:

Title: A phase 2, open-label, single-arm, prospective, multicenter study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer
Presenting Author: Lauren Dockery, MD, MS
Session Title: Poster Session – Gynecologic Cancer
Abstract Number: TPS5640
Date/Time: Monday, June 3rd, 9:00 am – 12:00 pm

This is a Phase 2 open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus and letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma, exploring the potential for this combination to produce additive anti-tumor activity in patients with EEC.
Dysregulation of mTOR signaling is implicated in the pathology of EEC, in which >80% harbor PTEN or PI3K/AKT/mTOR pathway alterations.
Prior clinical studies with mTOR inhibitors and letrozole in endometrial cancer patients have yielded promising results.
Alternative treatment options for patients with advanced or recurrent EEC remain necessary despite recent pivotal data demonstrating improved outcomes with immunotherapy plus chemotherapy.