Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 286

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 286
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in 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))

FYARRO is a form of sirolimus bound to albumin. Sirolimus is a potent inhibitor of the mTOR
biological pathway and inhibits downstream signaling from mTOR, the activation of which can promote tumor growth. FYARRO is composed of nanoparticles of sirolimus bound to human albumin with an average size less than 100 nanometers. An artist’s
impression of these nanoparticles is shown below.

Figure 3 -Nanoparticle artist impression

The orally available mTOR inhibitors have poor and variable absorption, often require therapeutic drug monitoring, and have
incomplete target suppression. The combination of sirolimus with human albumin in FYARRO achieves higher area under the curve (AUC), Cmax and longer half-life in humans at its clinical dose when compared with published clinical data for other mTOR
inhibitors, demonstrating FYARRO’s differentiated clinical pharmacologic and pharmacokinetic profile.

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Figure 4- FYARRO PK Profile

These differences in pharmacology can result in advantageous differences in the clinical behavior of FYARRO when