Aadi Bioscience Breakthrough Therapy nab-Sirolimus (ABI-009) Preliminary Data Released from the AMPECT Registration Trial in Advanced PEComa

Highlights:

• 42% investigator-assessed ORR achieved in patients with advanced
  PEComa – a rare sarcoma with no currently approved therapy
• First prospective clinical study in advanced PEComa shows
  durable responses with nab-sirolimus with a manageable safety profile
• 62% of all responding patients continue to remain on therapy
• American Society Clinical Oncology (ASCO) Oral Presentation
  highlighted efficacy, safety and mutational analysis data from pivotal
  AMPECT study
• US FDA New Drug Application expected to be submitted late 2019
  or early 2020
• nab-Sirolimus leverages proven nanoparticle albumin-bound (nab)
  technology

PACIFIC PALISADES, Calif.–(BUSINESS WIRE)–Aadi Bioscience, Inc (Aadi), a privately held clinical stage
biopharmaceutical company, today released preliminary data on the
ongoing nab-sirolimus (ABI-009) registration trial (AMPECT) for
Advanced (metastatic or locally advanced) Malignant PEComa (perivascular
epithelioid cell tumor) – a rare form of sarcoma for which there is no
currently approved therapy.

Nanoparticle albumin-bound sirolimus (nab-Sirolimus), an
mTOR inhibitor, received Breakthrough Therapy Designation from the US
Food and Drug Administration (FDA) in Dec 2018, “for the treatment of
patients with advanced (metastatic or locally advanced) malignant
perivascular epithelioid cell tumor (PEComa).”

The AMPECT trial was conducted at 9 U.S. sites and enrolled 34 adult
patients, with 31 confirmed as PEComa by a central pathology laboratory.
PEComa origin sites in these patients included the uterus, pelvis,
retroperitoneum, lung, kidney, liver, brain, muscle, ovary, aorta and
small bowel.

These data, demonstrating a 42 percent confirmed investigator-assessed
objective response rate (ORR) across advanced PEComas originating in
various tissues, were released in an oral presentation at the American
Society of Clinical Oncology (ASCO) 2019 annual meeting in Chicago
(abstract 11005). AMPECT Principal Investigator Andrew Wagner, M.D.,
Ph.D., from the Dana Farber Cancer Institute, said nab-sirolimus
had delivered consistent and durable responses in advanced PEComa
patients. “These responses were achieved with a manageable safety
profile,” Dr. Wagner said. “We saw a majority of the responding patients
achieving a response by their first assessment at 6 weeks following
initiation of therapy. Cytotoxic chemotherapies and other drugs approved
for treatment of advanced sarcomas show only marginal benefit in
PEComas. Activation of the mTOR pathway is common in PEComa and case
reports have shown activity of mTOR inhibitors [1]. We are encouraged by
the outcomes in this first-ever prospective clinical trial in advanced
PEComa.”

“The Aadi Bioscience team is proud to have contributed to this important
study presented at ASCO,” said Neil Desai, Ph.D., Chief Executive
Officer of Aadi Bioscience. “We are grateful to the patients, families,
and clinical trial teams who help push the boundaries of available care
through their participation in clinical trials. These results are an
important milestone in the ongoing development of nab-sirolimus
across a wide range of diseases and therapeutic indications that are
driven by mTOR activation and for which there is a need for new
therapies.” Dr. Desai added: “Results from the AMPECT study will serve
as the basis for the ABI-009 New Drug Application (NDA) for nab-sirolimus,
which the company expects to submit to the FDA in late 2019 or early
2020. The primary analysis for the NDA will rely upon central,
independent radiology review, which will be performed in the second half
of 2019. The company plans to release these data at a scientific
meeting, which will also include additional patient follow-up, before
the end of 2019.”

Key Data Presented at ASCO

The primary efficacy outcome measure for the analysis presented at ASCO
is investigator-assessed objective response rate (ORR) as measured by
RECIST v 1.1. Key secondary endpoints include duration of response
(DOR), progression-free survival (PFS), PFS rate at 6 months (PFS6) and
safety. The data presented at ASCO employed a May 10, 2019 data cut-off,
summarized below, was based on response assessments as performed by each
respective clinical trial site (local, investigator-assessed radiology).
A separate response assessment performed by independent radiologists,
not yet completed, will be required to support global regulatory filings.

Consistent with agreements with the FDA, advanced PEComa patients
enrolled in the Phase 2 trial (AMPECT) contributed to the efficacy
analysis. The data presented are based on 34 patients evaluable for
safety and 31 patients evaluable for efficacy per defined criteria in
the protocol.

Sixty-two percent of patients (8/13) with responses are continuing on
treatment which include 3 patients on therapy for more than 1 year and 3
patients on therapy for more than 2 years. Median DOR has not been
reached; median time to response is 1.4 months (95% CI: 1.3, 2.7).
Median PFS is 8.4 months (95% CI: 5.5, –), PFS rate at 3 months (PFS3)
is 80% (95% CI: 60%, 90%), PFS6 is 61% (95% CI: 41%, 76%), and 32
percent of all patients enrolled remain on treatment.

For reference, per a meta-analysis of 10 years of phase 2 trials in
advanced soft tissue sarcomas (STS) published by the EORTC STS and Bone
Sarcoma Group [2], the PFS3 and PFS6 are widely accepted as a meaningful
measure of activity of drugs in STS and may be utilized to determine
acceptable criteria of benefit. Drugs yielding a PFS rate of ≥40% at 3
months and ≥14% at 6 months are considered to be ‘potentially active’ in
advanced STS [2].

A protocol prespecified exploratory mutational and biomarker analysis
was available for 25 patients on the AMPECT trial. Mutational status of
the suspect genes TSC1 or TSC2 in the mTOR pathway were
analyzed for association with patient response outcomes. Mutation or
deletion of TSC1 or TSC2 (no overlap) occurred in 5 (20%)
and 9 (36%) patients respectively, while 11 (44%) patients had no
alterations in TSC1 or TSC2. Responses occurred in 9/9
(100%) patients with TSC2 mutations, 1/5 (20%) patients with TSC1
mutations and 1/11 (9%) of patients with no mutations in TSC1 or TSC2.

The safety data presented at ASCO was available for all 34 patients
treated on the AMPECT trial. The most common treatment-related
hematologic adverse events of any grades included anemia (47%) and
thrombocytopenia (32%) and the most common nonhematologic
treatment-related adverse events of any grades included mucositis (74%),
rash (65%), fatigue (59%), nausea (47%), and diarrhea (38%). Most of
these events were grade 1 and 2, were manageable with dose modifications
and no grade 4 events were observed. Twelve patients (35%) required dose
reductions due to adverse events. Two patients (6%) discontinued nab-sirolimus
due to an adverse event.

The AMPECT Phase 2 registration trial for Advanced Malignant
Perivascular Epithelioid Cell Tumors completed enrollment in late 2018.
Aadi previously received agreement from the FDA that this open label
study in approximately 30 efficacy evaluable patients with a primary
endpoint of independently reviewed objective response rate could support
the submission of an NDA for approval to treat this rare disease.

About Aadi Bioscience and nab-sirolimus (ABI-009)

Aadi is a clinical stage biopharmaceutical company led by Dr. Neil
Desai, an inventor of ABRAXANE and the albumin-based technology
platform. Aadi’s lead product nab-sirolimus (sirolimus
albumin-bound nanoparticles for injectable suspension, ABI-009) is an
mTOR inhibitor complexed with human albumin that has significantly
higher tumor accumulation, mTOR target suppression and improved efficacy
over other mTOR inhibitors in preclinical models. mTOR as a therapeutic
target is well recognized in oncology, however Aadi aims to develop the
full potential of albumin-bound sirolimus in therapeutic areas and
diseases that are driven by mTOR activation and where the mTOR
inhibitors have not or cannot be effectively exploited due to problems
of pharmacology, effective drug delivery, safety or effective targeting
to the disease site. These indications include oncology, cardiovascular,
CNS, mitochondrial disease and diseases of ageing. Aadi’s ongoing and
planned clinical trials include Oncology (first-line treatment of
advanced colorectal cancer with respect to PTEN status, pediatric
tumors, advanced sarcoma, newly diagnosed and recurrent glioblastoma,
advanced neuroendocrine tumors), Cardiovascular indications (pulmonary
arterial hypertension), CNS indications (surgically refractory epilepsy)
and Mitochondrial disease (Leigh Syndrome).

About PEComa

Perivascular epithelioid-cell tumors (PEComa), defined by the World
Health Organization as ‘mesenchymal tumors composed of distinctive cells
that show a focal association with blood-vessel walls and usually
express both melanocytic and smooth muscle markers,’ are a rare subset
of soft-tissue sarcomas, with an undefined cell of origin. Malignant
PEComas may arise in almost any body site (typically the uterus,
retroperitoneum, lung, kidney, liver, genitourinary, and
gastrointestinal tract) and can have an aggressive clinical course
including distant metastases and ultimate death. Cytotoxic
chemotherapies typically used for sarcoma show minimal benefit and there
are currently no drugs approved for this disease. Malignant PEComas have
been shown to frequently harbor mutations in the TSC1 and/or TSC2
genes that result in the activation of mTORC1 pathway. Therefore, mTORC1
signaling is a promising therapeutic target for malignant PEComa.

References:

1. Wagner et al. 2010. J Clin Oncol 28(5): 835-840
2. Penel
et al. 2011. Ann Oncol 22(6): 1266-1272

The AMPECT study was funded in part by a grant from the FDA Office of
Orphan Products Development (OOPD).
ABRAXANE is a registered
trademark of Celgene Corporation

Contacts

Aadi Contact:
Nancy Jorgesen
Email: [email protected]
website:
www.aadibio.com