Redx has hit pause on a phase 1/2a trial of its porcupine inhibitor after the first patient to receive the drug suffered “clinically significant” adverse events. The blow continues a rotten run for Redx, which spent half of last year fighting to resolve a debt crisis.
Investigators dosed the first patient in the advanced cancer trial last month. The drug, RXC004, targets the WNT embryonic signaling pathway to disrupt tumor processes including tumorigenesis, metastasis and resistance. However, the experience of the first patient to receive RXC004 suggests the inhibition of the WNT pathway may also cause significant adverse events.
Redx is yet to disclose details of the adverse events, but excitement about the potential of targeting WNT has long been tempered by concerns about on-target side effects. Whereas aberrant regulation of WNT is linked to key tumor processes, the effective operation of the pathway underpins essential bodily functions such as tissue homeostasis, organ repair and skin regeneration. Drugs that target the pathway must strike a balance between taking out the tumor and protecting healthy tissues.
Alderley Park, U.K.-based Redx thought its targeting of the porcupine enzyme that plays a central role in the WNT pathway would enable it to tread this fine line. But the drug performed surprisingly in the first patient, who experienced far more systemic exposure to RXC004 than Redx expected based on the preclinical data.
That finding gives Redx a potential path to the safe use of the therapeutic. The team is working on a protocol amendment that would allow the trial to resume at a significantly lower dose. Investigators would then start escalating the dose in search of a regimen that balances safety and efficacy. If that dose is found, Redx will move it into a monotherapy phase 2a and assess its use in combination with checkpoint inhibitors.
Those trials remain on Redx’s road map, but its plans are likely to be delayed by several months. There is also a risk doses of RXC004 that are high enough to kill tumors will cause on-target adverse events. But Redx remains outwardly confident in the potential of RXC004.
“The board continues to believe the overall risk/benefit assessment of RXC004 as an investigational drug is unchanged,” Redx executive chairman Iain Ross said in a statement.
Ross also thinks Redx has enough cash to progress RXC004, despite the delay. Redx’s finances landed the company in hot water last year when an unpaid debt caused it to go into administration. That led to the sale of a preclinical program to Loxo Oncology to raise money. Redx exited administration in November with £13.9 million ($19.6 million) in cash.
Shares in Redx opened down 51%.