Mirati Therapeutics and Aadi Bioscience Partner to Evaluate the Combination of Adagrasib with Nab-sirolimus in Patients with Advanced Non-Small Cell Lung Cancer and Other Solid Tumors with a KRAS[...

SAN DIEGO and LOS ANGELES, Oct. 12, 2022 /PRNewswire/ -- Mirati Therapeutics, Inc. (Nasdaq: MRTX), a clinical-stage targeted oncology company, and Aadi Bioscience, Inc. (Nasdaq: AADI), a commercial stage biopharmaceutical company focused on developing and commercializing precision therapies for genetically defined cancers with alterations in mTOR pathway genes, today announced a clinical collaboration to evaluate the combination of adagrasib, a KRAS^G12C selective inhibitor, and nab-sirolimus, a small molecule mTOR inhibitor complexed with human albumin in KRAS ^G12C mutant non-small cell lung cancer (NSCLC) and other solid tumors.

The primary objective of this multi-center, single-arm, open-label Phase 1/2 trial is to determine the optimal dose and recommended Phase 2 dose for the combination of adagrasib and nab-sirolimus in patients with KRAS^G12C - mutant solid tumors. In addition, the study will investigate the safety, tolerability and efficacy of adagrasib and nab-sirolimus in combination in patients both with and without prior exposure to a KRAS^G12C inhibitor. The trial will build on preclinical data showing enhanced anti-tumor efficacy with the combination of adagrasib and nab-sirolimus relative to either agent alone.

"We are pleased to collaborate with Aadi on this clinical study of adagrasib and nab-sirolimus.  Our collaborative preclinical work has demonstrated that combinatorial mTOR and KRAS inhibition addresses key bypass and feedback pathways associated with either drug target and also results in enhanced efficacy in tumor models harboring KRAS^G12C mutations.  We believe the data from this trial may improve patient outcomes," said Charles Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "This clinical collaboration is an example of how Mirati is aggressively advancing the study of adagrasib both as a monotherapy and in rational combinations as part of our expanding development portfolio to benefit people living with difficult-to-treat cancers."

"KRAS and mTOR are closely linked and key pathways in oncogenesis and resistance to treatment. This collaboration builds on strong preclinical and mechanistic rationale supporting the combination of the two drugs to potentially provide greater benefit for patients with KRAS^G12C mutant NSCLC and other cancers," said Neil Desai, Ph.D., founder, president and chief executive officer, Aadi Bioscience, Inc. "We look forward to working closely with our Mirati counterparts to bring this treatment to those in need."

Under the terms of the collaboration agreement, Mirati will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Aadi, will oversee and share the cost of the study.

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Studies of adagrasib have shown that the drug has a long half-life, extensive tissue distribution and is well tolerated. Adagrasib has also shown, in clinical trials, CNS penetrance and single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors with KRASG12C mutations. Adagrasib is being evaluated in several clinical trials in combination with other anti-cancer therapies with strong scientific rationale in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science.

Nab-sirolimus is a novel albumin-bound nanoparticle form of the mTOR inhibitor sirolimus and is currently being evaluated in a tumor-agnostic registration-directed trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. In November 2021, nab-sirolimus was approved by the U.S. Food and Drug Administration (FDA) as FYARRO® for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

Mirati Therapeutics Inc., is a clinical-stage biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Mirati is using its scientific expertise to develop novel solutions in two registration-enabling programs: adagrasib (MRTX849), an investigational small molecule, potent and selective KRAS^G12C inhibitor, as monotherapy and in combination with other agents, and sitravatinib, an investigational spectrum-selective inhibitor of receptor tyrosine kinases in combination with checkpoint inhibitor therapies. Mirati is also advancing its differentiated preclinical portfolio, including MRTX1133, an investigational KRASG12D inhibitor, and other oncology discovery programs. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer.

For more information about Mirati Therapeutics Inc., visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook.

Aadi is a commercial-stage biopharmaceutical company focused on precision therapies for genetically defined cancers to bring transformational therapies to cancer patients with mTOR pathway driver alterations. Aadi received FDA approval in November of 2021 and in February of 2022 commercialized FYARRO® for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

Aadi has also initiated PRECISION 1, a Phase 2 tumor-agnostic registration-intended trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. More information on the Company's development pipeline is available on the Aadi website at www.aadibio.com and connect with us on Twitter and LinkedIn.

This press release contains forward-looking statements regarding the business of Mirati Therapeutics, Inc. ("Mirati"). Any statement describing Mirati's goals, expectations, financial or other projections, intentions or beliefs, development plans and the commercial potential of Mirati's drug development pipeline, including without limitation adagrasib (MRTX849), sitravatinib, MRTX1719 and MRTX1133, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to risks and uncertainties, particularly those challenges inherent in the process of discovering, developing and commercialization of new drug products that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.

Mirati's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati's programs are described in additional detail in Mirati's quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the U.S. Securities and Exchange Commission (the "SEC") available at the SEC's Internet site (www.sec.gov).These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

This press release contains certain forward-looking statements regarding the business of Aadi Bioscience that are not a description of historical facts within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding Aadi's current beliefs and expectations; expectations regarding the beneficial characteristics, safety, efficacy and therapeutic effects of nab-sirolimus; plans related to further development of nab-sirolimus; the clinical results and timing of additional clinical trials; and the timing and likelihood of regulatory filings and approvals of nab-sirolimus, including in potential additional indications and potential filings in additional jurisdictions. 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 uncertainties associated with the clinical development and regulatory approval of nab-sirolimus in additional indications, including potential delays in the commencement, enrollment and completion of clinical trials for additional indications; 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 collaborations with third-parties.

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 Quarterly Report on Form 10-Q filed on August 10, 2022, 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.

Aadi Contact
Investor Relations: ir@aadibio.com

Mirati Contacts
Investor Relations:ir@mirati.com

Media Relations:media@mirati.com

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