Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 285

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 285
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 the 12-kDa FK506-binding protein 12 (“FKBP12”), and the complex directly and strongly inhibits mTORC1.

Figure 1 - mTOR Pathway

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Currently approved mTOR inhibitors are limited in their applicability due to poor and variable absorption of
the oral drugs (sirolimus and everolimus) or variable conversion from prodrug to active drug (temsirolimus) and premedication requirements (temsirolimus). These drugs have a narrow therapeutic index and a reduction from the labelled dose can result
in decreased efficacy. Preclinical study comparisons with FYARRO showed significantly higher tumor uptake, greater downstream mTOR target suppression and increased suppression of tumor growth for FYARRO compared to the oral mTOR inhibitors. A
literature comparison of the clinical pharmacokinetic profiles of the drugs shows that FYARRO has a longer half-life, higher peak blood concentration and greater total exposure than the other approved mTOR inhibitors. FYARRO is administered in
cycles that are given weekly for two weeks followed by a week off and does not require therapeutic monitoring to ensure adequate blood levels.

Nanoparticle Albumin-Bound (nab) Technology

The
nanoparticle albumin-bound, or nab, technology was created and developed by Neil Desai, our founder and Executive Chairman, and former colleagues while at Abraxis Bioscience, LLC. This technology takes advantage of the protein albumin, a
natural carrier of water insoluble molecules (e.g., various nutrients, vitamins and hormones) found in humans. Due to various active and passive transport processes in the body, albumin can accumulate preferentially in different tissues including
tumors, areas of inflammation, or areas of tissue remodeling, i.e., at sites of disease. The nabtechnology takes advantage of these transport properties of albumin and its affinity of binding to certain drug molecules to increase the
efficiency with which these molecules may be brought to these sites of disease. The first clinical and commercial validation of this technology is BMS’s Abraxane , which is approved in
the United States and worldwide for the treatment of breast cancer, non-small cell lung cancer and pancreatic cancer.

We are applying the nabtechnology to the molecule sirolimus, a potent inhibitor of the mTOR pathway that is hindered in large part by a poor
pharmacologic profile (e.g., poor and variable absorption with incomplete target suppression). The relevance of albumin transport in cancer has been extensively studied and album