Redx stung by porcupine inhibitor flop in biliary tract cancer, setting biotech back before Jounce merger

Redx has hit a thorny patch. In the first data from a phase 2 program, Redx’s porcupine inhibitor RXC004 failed to improve progression-free survival in biliary tract cancer (BTC), prompting the British biotech to stop monotherapy development and focus on combinations in the indication.

RXC004 is designed to inhibit the porcupine enzyme, which is involved in the Wnt signaling pathway, and thereby both directly slow tumor growth and address immune resistance. Evidence of the two modes of attack on cancer led Redx to run a phase 2 program featuring monotherapy and checkpoint inhibitor combination cohorts.

The first phase 2 data have dented Redx’s monotherapy ambitions. The results come from PORCUPINE2, one of two midphase trials initiated by the biotech. One of the PORCUPINE2 modules enrolled patients with advanced or metastatic BTC who had progressed after first-line treatment.

After reviewing data on 16 patients in the module, Redx has called time on the monotherapy cohort. The biotech said some patients received durable clinical benefit from RXC004 but overall the results failed to support further monotherapy development in the setting. The setback wiped 26% off Redx’s stock in early trading in London, sinking its share price to 30 pence (35 cents). 

Redx still has other shots at finding a place for RXC004. The other modules of PORCUPINE2, which are testing RXC004 in pancreatic cancer and in combination with Merck & Co.’s Keytruda in BTC, are continuing. And another clinical trial, PORCUPINE, is testing RXC004 with and without Bristol Myers Squibb’s Opdivo in colorectal cancer. Redx’s confidence in the combinations is undimmed. 

“Our primary efficacy hypothesis is that in combination it can overcome immune evasion and anti-PD-1 resistance, which could open new patient segments. While today's results do not support further clinical development of RXC004 as monotherapy in recurrent BTC ... they are nonetheless consistent with the overall hypothesis that RXC004 has potential as an active component of combination therapy,” Jane Robertson, chief medical officer at Redx, said in a statement.

The setback comes as Redx prepares to merge with Jounce Therapeutics to secure a Nasdaq listing and cash for its R&D plans. RXC004 plays second fiddle in the R&D strategy to RXC007, a ROCK2 inhibitor that is in midphase development as a treatment for idiopathic pulmonary fibrosis.