ASCO-GU 2026 – Protara gets that sinking feeling

Protara, the company that last year looked like it might challenge the likes of Johnson & Johnson in bladder cancer, has experienced a sinking feeling familiar to small-cap biotechs: having dosed more patients, its previously trumpeted level of efficacy has ebbed away.

The company’s update concerns the Advanced-2 trial of TARA-002, an inactivated Streptococcus strain, in non-muscle invasive bladder cancer patients unresponsive to BCG. With complete response rates falling from 100% last April to 66% now Protara shares lost 26% on Tuesday as investors took the view that TARA-002 no longer looked competitive against peers like J&J’s Inlexzo.

Inlexzo has been approved in the BCG-unresponsive setting, with a CR rate of 82% at any time in the Sunrise-1 study, while a key challenger that’s due to be filed this year, CG Oncology’s cretostimogene grenadenorepvec, has shown 76% in its Bond-003 trial.

Against such numbers Protara made a splash in December 2024, when the Advance-2 trial yielded data showing an 80% any-time CR rate, or 100% at six months. That concerned just five patients, but the headline number moved up to 100% when all five yielded CRs last April.

Now comes the shock: with 35 patients now evaluable, the any-time CR rate has crashed to 66%. The data also include a 12-month CR rate of just 33% (67% was the figure last year), though given the relatively few patients involved that number will likely change with more maturity.

The results are to be presented in a poster on Friday at the ASCO Genitourinary Cancers symposium, but have been released by Protara in advance. 

Cross-trial comparison in BCG-unresponsive NMIBC

Source: OncologyPipeline & Jones Research.

Protara does have a second string to its bow, with Advanced-2 also testing NMIBC patients who are naive to BCG therapy, and here at least numbers are holding up, with any-time CR rate of 72% and a 12-month CR rate of 58%.

However, the company now has a problem. It was prioritising the enrolment of BCG-unresponsive patients into Advanced-2, which is designed to be registrational in this population. It’s unclear whether, given the waning of that dataset, the results of Advanced-2’s BCG-unresponsive cohort can still back a filing.

Protara says it has now completed recruitment into the BCG-naive cohort, but here a phase 3 study, Advanced-3, needs to be carried out. It’s possible that Advanced-3 will now become the main focus for TARA-002, and on the plus side the FDA has apparently allowed this pivotal trial to compare against physician’s choice and not against BCG, wrote Jones Research’s Soumit Roy in a note to clients. 

But it’s also an open question whether a 72% CR rate is enough here. That number seems broadly in line with BCG, and being as good as BCG – a cumbersome and inconvenient treatment – without the need to combine with BCG might be enough of a win; however, the number will likely wane in a phase 3 trial, and CG’s creto-vec has shown an any-time CR rate as high as 88%, again eclipsing TARA-002 on a cross-trial basis.

The evolution of Protara’s dataset in BCG-naive NIMBC

Source: OncologyPipeline & company updates.