Cancer resistance firm TP Therapeutics reaps $45M in third round

Could combination therapy end the targeted cancer therapy arms race?

California biotech TP Therapeutics has the funds on hand to take its drug for resistant cancer through the next stages of clinical development after raising $45 million in a series C financing.

The company was co-founded in 2013 by ex-Pfizer scientist Jean Cui, Ph.D., who was behind the development of the drugmaker's $560 million drug Xalkori (crizotinib) and is hoping to repeat that success with TP's lead candidate, TPX-0005.

Proceeds from the third-round financing, co-led by Lilly Asia Ventures, OrbiMed Advisors, and S.R. One, will be used to fund the continued development of TPX-0005 and "several preclinical pipeline projects," says TP.

TPX-0005 is in a phase 1/2 trial involving patients with solid tumors and non-Hodgkin lymphoma, and is billed by Cui as having the potential to "comprehensively address the drug resistance issues associated with acquired resistance mutations from targeting the ALK, ROS1, and NTRK family."

Kinase inhibitor drugs that target specific cancer mutations can achieve good clinical results but from the start have been undermined by resistance issues, with tumor cells developing ways to escape their effects through changes to the drug target or activating cellular pathways that allow them to downplay the drugs' effects.

If TP's prediction pans out, TPX-0005 would have the potential to make a play in the market for ALK inhibitors—which along with Xalkori includes Novartis' Zykadia and Roche's Alecensa—as well as emerging targeted cancer drugs in development at the likes of Loxo Oncology and Ignyta.

But there's more. Cui, TP's chief scientific officer, also thinks the candidate could be used in combination with other drugs to overcome bypass and epithelial–mesenchymal transition resistance mechanisms. Those are seen with a lot of targeted cancer therapies, including EGFR inhibitors.

The EGFR inhibitors are a perfect case study for the resistance seen with targeted cancer drugs. First-generation drugs like AstraZeneca's Iressa and Roche/Astellas' Tarceva transformed the treatment of non-small cell lung cancer, but often only keep the cancer at bay for a couple of years at best. What follows is an arms race, with new-generation inhibitors—such as Boehringer Ingelheim's Gilotrif and AZ's Tagrisso—brought to market to tackle resistant tumors. 

Cui hopes that with the right combinations of molecules, this arms race can be stopped in its tracks by addressing all the most common resistance mechanisms at the first strike.

Carl Gordon, Ph.D., general partner at OrbiMed, said the fund is "pleased to partner with TP Therapeutics and support their important work in creating new drugs and new hope for the numerous patients whose cancers have become resistant to initial protein kinase inhibitor drugs."