PPI Pharmaceuticals develops cancer therapeutics by exploiting protein-protein interactions, focused on protein kinases deregulated in oncology. REPLACE is the technology that makes more of those targets accessible.
The current program is abbapolin inhibitors of the PLK1 polo-box domain, studied as potential therapeutics for colorectal cancer under a Phase I STTR from August 2025 to the present. National Cancer Institute grant R41CA298584 has two aims: medicinal chemistry optimization of the abbapolin leads, and testing their activity against colorectal cancers, including a panel of patient-derived organoids.
An earlier Phase I STTR, from May 2017 to November 2018, covered optimization of drug-like polo-box domain inhibitors. Orally dosed abbapolins showed no overt signs of toxicity, and 6369 and 6190 produced a statistically significant reduction in PC-3 xenograft tumor volume. In the NCI-60 panel, abbapolins 6157, 6171, and 6190 were active against prostate, CNS, and colorectal lines, but not breast lines. A Phase II grant applied for in September 2026, $2.5 million over two years, would determine in vivo activity in a colon cancer model.