The Product

Aadi Bioscience’s first product, FYARROTM (sirolimus albumin-bound nanoparticles for injectable suspension; nab-sirolimus, ABI-009), is a form of sirolimus (rapamycin) bound to albumin that is based on similar technology as ABRAXANE® (nab-paclitaxel; Abraxis Bioscience acquired by Celgene Corp in 2010)

Albumin is accumulated in tumor tissues, either due to the leaky capillary system and defective lymphatic drainage of tumors [1] or through an active gp60/caveolae-mediated transport process across tumor blood vessel endothelium [2, 3]. Importantly, albumin is 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 [4]. The accumulation of albumin in solid tumors provides potential rationale for albumin-based drug delivery systems to preferentially target tumors. The nab technology enables sirolimus to associate with albumin through non-covalent hydrophobic interactions to create a suspension of nanoparticles with an average size of < 100 nm

[1] Kratz F (2008). J Control Release 132, 171-183.

[2] Desai N et al (2006). Clin Cancer Res 12, 1317-1324.

[3] Minshall RD et al (2000). J Cell Biol 150, 1057-1070.

[4] Commisso C et al (2013). Nature 497, 633-637.

Differentiation vs. Existing mTOR Inhibitors

The nanoparticle albumin-bound (nab) platform drives multiple advantages for FYARROTM in animal models vs. currently approved mTOR inhibitors including:

The nab platform allows for 12-43 fold higher intratumoral drug accumulation (P<0.0001) and mTOR target suppression (pS6) at equal doses for FYARROTM vs oral mTOR inhibitors (i.e., sirolimus, everolimus) resulting in higher anti-tumor activity in animal models.
At least 6-fold higher dose of oral mTOR inhibitors (clinically toxic doses) required to approach efficacy level of FYARROTM in animal models.