Scientists at Oslo University Hospital have developed a potent and specific inhibitor of tankyrase (OM-153), a master regulator of both WNT and YAP signaling pathways. These pathways are involved in the establishment and maintenance of cancer; at present the only major oncogenic signaling pathways without therapeutic options in the market. OM-153 displays good drug-like characteristics, anti-tumor activity as both mono- and combination-therapy and clean results in a 28-day toxicology study in mice. In summary, the results reveal OM-153 as an interesting first-in-class licensing opportunity.
The scientists have developed a class of novel WNT/YAP inhibitor compounds exhibiting high specificity for tankyrase and demonstrated proof of concept in mouse models for several cancer indications. The resulting preclinical candidate is highly potent in both cellular (pico molar range) and biochemical assays (single-digit nM range) and displays overall very favorable drug-like properties for an oral drug.
Good efficacy and proof of concept data are shown in a colon cancer xenograft model (COLO 320DM) as mono-therapy and in a checkpoint inhibitor-resistant melanoma model (B16-F10) in combination with anti-PD-1 checkpoint inhibitor. Both models show significant reduction of tumor growth.
A max tolerable dose study demonstrated that the lead candidate is well tolerated up to 2000 mg/kg BID PO. In a 28-days toxicity study in CD1-mice, no observed effect level (NOEL) was seen (200 mg/kg/day PO).
This outstanding data package is warranting an entry into IND enabling studies.
The class of molecules is protected by patent application with priority date of June 2018.
Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models, Waaler et al, April 2020, Communications Biology.