Tyra’s bladder cancer drug candidate falls short in trial; shares plunge 38%

Tyra Biosciences’ bladder cancer drug candidate posted a complete response rate below expectations in a phase 2 trial, sending the company’s shares sharply lower.

According to Fierce Biotech on the 9th (local time), Tyra Biosciences released early phase 2 data for dabogratinib, an oral, selective FGFR3 inhibitor for bladder cancer. The company is preparing to start a registration trial next year.

Dabogratinib was tested in low-grade, intermediate-risk, non-muscle-invasive bladder cancer. As of the Aug. 31 data cutoff, 3-month efficacy data were available for up to 12 patients in the 50㎎ group and up to 14 in the 60㎎ group.

Among patients with a single marker lesion, the complete response rate was 63% in the eight patients who received 60㎎; analysis of 16 patients across both doses showed a rate of 50%. The company plans to select 60㎎ as the dose for the registration trial and complete patient enrollment.

Tyra Biosciences CEO Todd Harris said on an investor conference call that the single-marker data were “a very high predictor of adjuvant success.”

Investors, however, reacted coolly. At the market open, Tyra shares fell 38% from the previous day’s close of $26.73 to $19.30.

H.C. Wainwright analysts projected in a report last week that the 3-month complete response rate across both doses would reach at least 70%. Guggenheim Securities also set 70% as a benchmark in an April report.

The benchmark reflects the THOR-2 study, which evaluated Johnson & Johnson’s (J&J) pan-FGFR inhibitor Balversa. Harris said J&J recorded a 72% complete response rate at 3 months, which rose to 89% over time.

Dabogratinib was designed to act more selectively on FGFR3 than on FGFR1, FGFR2 and FGFR4, with the goal of avoiding Balversa’s toxicity issues. The safety cohort included 44 patients, split evenly between the two dose groups.

The incidence of grade 3 or higher treatment-related adverse events was 9% in the 50㎎ group and 14% in the 60㎎ group. Two of these events were classified as treatment-related, for a rate of 4.5%. No dose reductions or treatment-related discontinuations occurred in the 60㎎ group.

The 3-month complete response rate combining single- and multiple-marker lesions was 57% in the 60㎎ group and 33% in the 50㎎ group. Regarding the multiple-marker results, Harris said, “Increasing drug exposure may help with resection,” and said the company would pursue enrollment in a 70㎎ cohort.