• Five of six mTOR inhibitor-naïve patients with TSC1 or TSC2 inactivating alterations achieved confirmed partial responses to single-agent FYARRO
• Tumor-agnostic registrational trial of FYARRO in mTOR inhibitor-naïve solid tumors with TSC1 or TSC2 inactivating alterations to be initiated by the end of 2021

LOS ANGELES, June 04, 2021 (GLOBE NEWSWIRE) — Aadi Bioscience, Inc. (“Aadi”), a privately-held clinical-stage biopharmaceutical company focusing on precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, today presented preliminary data from its lead investigational product candidate, FYARRO™ (sirolimus albumin-bound nanoparticles for injectable suspension; nab-sirolimus; ABI-009), during the 2021 ASCO Annual Meeting being held virtually from June 4-8, 2021. The poster is entitled “Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations”.¹

Dr. Mark Dickson, Principal Investigator of the study at Memorial Sloan Kettering Cancer Center stated, “I am encouraged by the activity of nab-sirolimus in multiple solid tumor histologies with TSC1 or TSC2 inactivating alterations. These new data provide strong rationale for conducting a broader investigation of nab-sirolimus in a tumor-agnostic setting. If the observed activity were reproduced, this could represent a meaningful advance in treatment for these patients.”

Analysis from Expanded Access Patient Subset

Eight patients with malignancies and neoplasms bearing TSC1 or TSC2 inactivating alterations and representing histologies other than malignant PEComa were treated in a multi-institution expanded access program (NCT03817515) with FYARRO at 100 mg/m² on day one and day eight of a 21-day cycle. RECIST v1.1 criteria were used for response analysis. Data cutoff occurred in March 2021.

Patients had a median of 3.5 lines of prior therapy and 6 of 8 patients were mTOR inhibitor-naïve. Treatment duration for all patients ranged from 0.7 to 12.0+ months. Five of 8 patients continued on treatment as of the data cutoff and 3 of 8 patients discontinued. Reasons for discontinuation were progressive disease (2 patients) and an adverse event (1 patient with acute kidney injury possibly secondary to administration of contrast).

Of the 8 patients treated, 7 patients were evaluable for response analysis and 1 patient progressed before the first scan. Five of 8 patients (63%, 95% CI: 25%-92%) achieved a confirmed partial response (PR). Amongst the patients who were mTOR inhibitor-naïve, 5 of 6 (83%, 95% CI: 36%-99⁺%) achieved a confirmed PR. Duration of response at data cutoff ranged from 3.1 to 9.7+ months and 3 of 5 responders continue on treatment.

Treatment-emergent adverse events that were ?30% included edema, infections, mucositis, and pain (71% each), nail changes and vomiting (57% each), and hypertension and nausea (43% each). The majority of events were grade one or grade two. Treatment-related serious adverse events were reported in 2 patients and included hyperglycemia and infection; and acute kidney injury possibly secondary to administration of contrast. Three of 8 patients had a dose reduction from 100 mg/m² to 75 mg/m².

Dr. Neil Desai, founder and chief executive officer of Aadi, stated, “We are pleased to have provided FYARRO to patients through our expanded access program. Based on the data in this initial group of patients, and patients in the AMPECT trial with PEComa, we are planning to move forward with a tumor-agnostic registrational trial to confirm FYARRO’s activity in solid tumors with TSC1 or TSC2 inactivating alterations with planned initiation by the end of 2021.”

About Aadi Bioscience and FYARRO™

Aadi is a clinical-stage biopharmaceutical company developing precision therapies for genetically-defined cancers. Aadi’s primary goal is to bring transformational therapies to cancer patients with mTOR pathway driver alterations such as alterations in TSC1 or TSC2 genes, where other 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. Aadi’s product FYARRO^TM (sirolimus albumin-bound nanoparticles for injectable suspension; nab-sirolimus; ABI-009) is an mTOR inhibitor bound to human albumin that has demonstrated significantly higher tumor accumulation, mTOR target suppression, and enhanced tumor growth suppression over other mTOR inhibitors in preclinical models.²

Aadi’s registration trial of FYARRO in advanced malignant PEComa (the AMPECT trial) demonstrated meaningful clinical efficacy in malignant PEComa, a type of cancer with the highest known alteration rate of TSC1 or TSC2 genes. In long-term follow-up data presented on the AMPECT study at ASCO 2020³, an analysis of 31 RECIST-evaluable advanced PEComa patients treated with FYARRO demonstrated a 39% (95% CI: 22%-58%) independently reviewed confirmed overall response rate (ORR) including 1 complete response (CR) and 11 partial responses (PRs). The median duration of response had not yet been reached (range 5.6 to 42.4+ months, with 50% of the responders having a response duration that is 25.8 months or longer) and the majority of the responders were still on treatment. The response rate in the patients with metastatic disease was 46% (12/26, 95% CI: 27%-67%). In the patients with locally advanced, inoperable disease, 2 of 5 (40%) were able to undergo surgery following tumor shrinkage and remained disease-free in excess of 3 years. The median progression-free survival was 8.9 months (95% CI: 5.5 – not reached) and the one-year overall survival rate was 89%. In an exploratory analysis of the subset of patients with TSC1 or TSC2 alterations, the independently reviewed response rate was 64% (9/14, 95% CI: 34%-87%). Thirty-four patients were evaluable for safety. Most treatment-related adverse events (TRAEs) were grade 1 or 2. No grade 4 or 5 TRAEs occurred. The most common nonhematologic TRAEs of any grade were mucositis (79%), fatigue (59%), and rash (56%). The most common hematologic TRAEs were anemia (47%) and thrombocytopenia (32%). Noninfectious pneumonitis occurred in 18% of patients and was grade 1 or 2. Two patients stopped therapy due to a TRAE (grade 2 anemia and grade 1 cystitis). Dose reductions occurred in 13/34 (38%) of patients; 11 patients had a dose reduction from 100 mg/m² to 75 mg/m² and 2 patients had a dose reduction to 56 mg/m². FYARRO has received Breakthrough Therapy, Fast-Track and Orphan Designations from the U.S. Food and Drug Administration (FDA). A rolling New Drug Application (NDA) submission was completed in May 2021.

Based on the AMPECT trial and emerging data for FYARRO in other solid tumors with TSC1 or TSC2 inactivating alterations, and following discussions with the FDA, Aadi plans to submit an Investigational New Drug application (IND) for a tumor-agnostic registrational trial in mTOR inhibitor-naïve solid tumors harboring TSC1 or TSC2 inactivating alterations and initiate the study by the end of 2021. Aadi also has ongoing studies to evaluate dosing of FYARRO in combination regimens. FYARRO is an investigational drug that has not been approved by the FDA for commercial distribution in the United States. More information is available on the Aadi website at www.aadibio.com.

Forward-Looking Statements

Aadi Bioscience, Inc. (“Aadi”, “The Company”) cautions you that certain statements included in this press release that are not a description of historical facts are forward-looking statements. These statements are based on Aadi’s current beliefs and expectations. Forward-looking statements include statements regarding FYARRO, including expectations regarding the clinical responses and safety profile, and the timing of the initiation of additional clinical trials and Investigational New Drug (IND) application submissions. 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: risks related to Aadi’s ability to obtain sufficient additional capital to continue to advance FYARRO; uncertainties associated with the clinical development and regulatory approval of FYARRO, including potential delays in the commencement, enrollment and completion of clinical trials; the risk that interim results of clinical trials may not be reproduced and do not necessarily predict final results; the risk that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; the risk that unforeseen adverse reactions or side effects may occur in the course of developing and testing FYARRO; risks associated with the failure to realize any value from FYARRO in light of inherent risks and difficulties involved in successfully bringing product candidates to market; and risks related to the impact of the COVID-19 outbreak on Aadi’s operations, the biotechnology industry and the economy generally. 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 caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

References:

¹ ASCO 2021 Abstract: https://meetings.asco.org/abstracts-presentations/197602

² AACR 2019 Abstract: https://cancerres.aacrjournals.org/content/79/13_Supplement/348

³ ASCO 2020 Abstract: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.11516?af=R

Contacts

Investors & Media:

Investors:
Irina Koffler
ikoffler@lifesciadvisors.com

Aadi Bioscience, Inc.

Nancy Jorgesen
njorgesen@www.aadibio.com