On April 18, 2023 Ashvattha Therapeutics ("Ashvattha"), a clinical-stage company advancing a new class of nanomedicine therapeutics that transverse tissue barriers to selectively target activated cells in regions of inflammation, reported preclinical data showing its potent macrophage switching nanomedicine, D-4559, reduces tumor growth in a mouse model of hepatocellular carcinoma (HCC) (Press release, Ashvattha Therapeutics, APR 18, 2023, View Source [SID1234630225]). The data was presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting taking place at the Orange County Convention Center in Orlando, Florida from April 14th through 19th.
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D-4559 is a new class of tyrosine kinase inhibitors referred to as Dendranibs, which specifically target activated macrophages and microglia in regions of inflammation. D-4559 is designed using the sorafenib backbone to selectively inhibit VEGFR tyrosine kinases in tumor associated macrophages (TAMs) leading to a functional reprogramming of TAMs toward a pro-inflammatory activated phenotype, allowing the immune system to better eliminate cancerous cells.
"We have combined the selectivity of our precision nanomedicine therapeutics with the ability to modulate the state of TAMs creating a unique approach to fighting cancer," said Jeff Cleland, CEO and chairman of Ashvattha Therapeutics. "We have observed with our other novel dendranib (D-4517.2) the ability to avoid the side effects of typical tyrosine kinase inhibitors. D-4559 offers an approach to safely creating a pro-inflammatory tumor microenvironment potentially improving anti-tumor immune response."
Key details and takeaways from the poster presentation include:
In vivo efficacy of D-4559 was examined in the subcutaneous Hepa 1-6 liver tumor mouse model and compared with sorafenib, a tyrosine kinase inhibitor used to treat kidney and liver cancers
D-4559 creates a pro-inflammatory tumor microenvironment which significantly reduced tumor growth when compared to vehicle-treated control group
D-4559-treated mice demonstrated a significantly greater M1:M2 TAM ratio compared to sorafenib-treated mice
D-4559 significantly increased plasma TNF-α and IL-8 cytokines, which has been correlated with better survival in patients with liver cancer