Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 287

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 287
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 compared
to the other mTOR inhibitors. This is effectively illustrated in comparative experiments in animals bearing bladder cancer tumors or liver cancer tumors. Data from these tumor-bearing animal models showed many-fold higher tumor drug levels for
FYARRO at equal dose to the other mTOR inhibitors which was correlated with a greater degree of mTOR target suppression as indicated by inhibition of phosphorylation of S6 and 4EBP1 (downstream signaling nodes of mTORC1 that are known to play a role
in downstream activity of mTOR as well as resistance to mTOR suppression), and a correspondingly higher suppression of tumor growth.

We believe that
other mTOR inhibitors on the market or active in clinical development do not have the required favorable pharmacological profile to fully exploit the benefits of mTOR inhibition. We believe that FYARRO’s differentiated pharmacologic profile,
high tumor accumulation, and ability to effectively inhibit important targets in the mTOR pathway make it a well-positioned drug to address resistance and suboptimal efficacy of existing mTOR inhibitors.

We have studied FYARRO in cancers with known mTOR pathway activation, including indications targeting specific genomic alterations that activate the mTOR
pathway, such as our trial to evaluate adult patients with functional or non-functional, well-differentiated, locally advanced unresectable or metastatic NETs of the GI tract, lung, or pancreas who have
received ≤2 prior lines of therapy excluding somatostatin (SSTa). We have also conducted studies evaluating FYARRO in combination with other targeted agents, such as our study to evaluate the efficacy and safety of the combination of FYARRO
with letrozole for the treatment of advanced or recurrent EEC and our prior collaboration with Mirati to evaluate the combination of Mirati’s adagrasib, a KRAS selective inhibitor, and
FYARRO in KRAS mutant non-small cell lung cancer (NSCLC) and other solid tumors.

FYARRO - Commercial

Advanced Malignant PEComa.PEComas are mesenchymal neoplasms, composed of histologically and immunohistochemically distinctive cells, perivascular epithelioid cells (“PEC”s). Most PEComas are clinically benign and do not metastasize, but malignant PEComas can
demonstrate local invasion and aggressive metastatic

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spread. PEComas show a wide anatomical distribution, but most often arise in the retroperitoneum, abdominopelvic region