nab-Sirolimus demonstrated significantly
greater intratumoral drug concentration, stronger inhibition of
mTOR targets and greater antitumor activity compared to IV and oral
mTOR inhibitors in a xenograft model
Data support further clinical exploration of
nab-sirolimus as a single agent or in combination
LOS
ANGELES, May 23, 2024 /PRNewswire/ -- 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, today
announced 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. 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) Annual Meeting
taking place May 31 – June 4, 2024.
"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:
https://meetings.asco.org/abstracts-presentations/235617
- 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.
About Aadi Bioscience
Aadi is a
commercial-stage precision oncology company focused on the
development and commercialization of therapies for cancers with
alterations in the mTOR pathway, a key regulator of cell growth and
cancer progression. To unlock the full potential of mTOR
inhibition, Aadi uniquely combines nanoparticle albumin-bound
(nab) technology with the potent mTOR inhibitor, sirolimus.
Aadi received FDA approval and commercializes FYARRO® for the
treatment of adult patients with locally advanced unresectable or
metastatic malignant perivascular epithelioid cell tumor
(PEComa).
Aadi is exploring nab-sirolimus in PRECISION1, a Phase 2
tumor-agnostic registration-intended trial in mTOR inhibitor-naïve
malignant solid tumors harboring TSC1 or TSC2
inactivating alterations. Aadi is also exploring
nab-sirolimus in two single-indication Phase 2 trials for
difficult-to-treat mTOR-driven cancers: neuroendocrine tumors
(NETs), and advanced or recurrent endometrioid-type endometrial
cancer (EEC) in combination with letrozole. More information on
Aadi's development pipeline is available on the Aadi website at
www.aadibio.com and connect with us on Twitter and LinkedIn.
Forward-Looking Statements
This press release
contains certain forward-looking statements regarding the business
of Aadi that are not a description of historical facts within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements are based on Aadi's current
beliefs and expectations and may include, but are not limited to,
statements relating to: expectations regarding the beneficial
characteristics, safety, efficacy and therapeutic effects of
nab-sirolimus; expectations regarding the beneficial
characteristics, safety, efficacy, therapeutic effects and the size
of the potential targeted markets with respect to
nab-sirolimus, including in EEC; and the sufficiency of
Aadi's existing capital resources and the expected timeframe to
fund Aadi's future operating expenses and capital expenditure
requirements. Actual results could differ materially from those
anticipated in such forward-looking statements as a result of these
risks and uncertainties, which include, without limitation, those
associated with the uncertainties associated with the clinical
development and regulatory approval of nab-sirolimus in
additional indications; the risk that non-clinical results may not
be reproduced and do not necessarily predict clinical results; the
risk that unforeseen adverse reactions or side effects may occur in
the course of commercializing, developing and testing
nab-sirolimus; and risks related to Aadi's estimates
regarding future expenses, capital requirements and need for
additional financing.
Additional risks and uncertainties that could cause actual
outcomes and results to differ materially from those contemplated
by the forward-looking statements are included in Aadi's Annual
Report on Form 10-K for the fiscal year ended December 31, 2023, including under the caption
"Item 1A. Risk Factors," and in Aadi's subsequent Quarterly Reports
on Form 10-Q, and elsewhere in Aadi's reports and other documents
that Aadi has filed, or will file, with the SEC from time to time
and available at www.sec.gov.
All forward-looking statements in this press release are current
only as of the date hereof and, except as required by applicable
law, Aadi undertakes no obligation to revise or update any
forward-looking statement, or to make any other forward-looking
statements, whether as a result of new information, future events
or otherwise. All forward-looking statements are qualified in their
entirety by this cautionary statement. This cautionary statement is
made under the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995.
Contact:
IR@aadibio.com
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SOURCE Aadi Bioscience