Tyra rolls toward pivotal bladder cancer study even as midphase data deflates stock

Tyra Biosciences has reported initial phase 2 data on dabogratinib in bladder cancer, putting the biotech on course to start a registrational study next year. But the biotech’s stock slumped in premarket trading after the complete response rate fell short of the level targeted by analysts. 

The phase 2 trial is testing dabogratinib, an oral, FGFR3-selective inhibitor, in low-grade intermediate-risk non-muscle invasive bladder cancer. As of the Aug. 31 data cutoff, Tyra had three-month efficacy data on up to 12 patients in the 50-mg cohort and up to 14 participants in the 60-mg arm. The study is a test of Tyra’s belief that it can improve on the safety and efficacy of pan-FGFR inhibitors.

Tyra enrolled patients with single- and multiple-marker lesions. The complete response (CR) rates for the subset of single-marker patients were 63% in the eight patients who received 60 mg and 50% in a pooled analysis of 16 participants across both doses. Tyra plans to complete enrollment of patients receiving 60 mg, which it identified as the potential dose for its registrational adjuvant development strategy. 

The single-marker data are “a really high predictor of adjuvant success,” Tyra CEO Todd Harris, Ph.D., said on a call with investors to discuss the results. Adjuvant studies track patients for years to check if cancer recurs. By showing a single lesion disappears when exposed to its drug candidate, Tyra could provide a proxy for adjuvant efficacy in a shorter time frame.

Investors appeared unconvinced, sending Tyra's stock down 38% to $19.30 when markets opened Wednesday from a Tuesday closing price of $26.73.

In a note to investors last week, H.C. Wainwright analysts said they expected at least a 70% pooled three-month CR rate across the two doses. Guggenheim Securities analysts set 70% as the CR benchmark in a note sent back in April.

The benchmark reflects Johnson & Johnson’s THOR-2 study of single-marker patients. The study of J&J’s pan-FGFR inhibitor Balversa “was panned by [key opinion leaders] for off-target toxicity despite superb efficacy,” Guggenheim analysts said. J&J saw a 72% CR rate after three months, Harris noted, rising to 89% over time.  

Tyra aimed to avoid the toxicity of Balversa by designing dabogratinib to be more selective for FGFR3 over FGFR1, FGFR2 and FGFR4. H.C. Wainwright analysts expected to see Tyra validate dabogratinib’s safety and tolerability benefits by reporting low single-digit grade 3 or worse adverse events, dose reductions and discontinuations.

The safety cohort featured 44 patients, split evenly between the two doses. Tyra reported grade 3 or worse treatment-emergent adverse events in 9% of people in the 50-mg arm and 14% of participants in the 60-mg cohort. Investigators classed two of the adverse events as treatment-related, resulting in a rate of 4.5%. No dose reductions or treatment-related discontinuations were seen in the 60-mg arm. 

Tyra reported combined single- and multiple-marker lesion CR rates of 57% and 33%, respectively, for the 60-mg and 50-mg doses at the three-month assessment. The biotech enrolled multiple-marker patients to assess dabogratinib in an ablative setting. The results show that getting more “drug on board could be helpful for ablation,” Harris said, leading Tyra to commit to enrolling a 70-mg cohort. 

https://www.fiercebiotech.com/biotech/tyra-rolls-toward-pivotal-bladder-cancer-study-even-midphase-data-deflates-stock