Company: WHWK
Filing Date: 2025-01-31
Form Type: DEFM14A
Source: 0001193125-25-018470
Chunk: 281

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-31
Form: DEFM14A
Chunk 281
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 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 albumin is known to accumulate in tumor tissues due to the leaky capillary
system within the tumor, defective lymphatic drainage of tumors, and active caveolae-mediated transport across tumor blood vessel endothelium. In addition, albumin can be taken up by proliferating tumor cells via endocytosis and macropinocytosis,
then catabolized by lysosomal degradation to support de novo protein synthesis, energy, and tumor growth. Ultimately, nabtechnology allows FYARRO to take advantage of albumin transport pathways to accumulate at high levels in tumors and
deliver sirolimus directly to cancer cells where it can effectively inhibit mTOR. The accumulation of albumin in tumors can be easily visualized by using evans blue dye which has a high affinity for albumin. Intravenous injection of albumin-evans
blue complex in animals bearing tumors resulted in rapid accumulation of the complex within the tumors which could be easily visualized a few hours after injection. Similarly, a fluorescent labelled albumin when injected into human glioblastoma
patients 24-48 hours before surgery resulted in excellent visualization of the tumors during surgery under fluorescent light and allowed the complete resection of the tumor margins in the majority of the
patients treated.

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Figure 2- Albumin Accumulation

Our Product

FYARRO®(sirolimus protein-bound particles for injectable suspension (albumin-bound