Dive Brief:

• Shares in Tyra Biosciences declined nearly 20% on Wednesday after the company’s experimental bladder cancer drug fell short of Wall Street’s expectations in a Phase 2 trial. 
• Tyra’s drug, a daily pill called dabogratinib, is being tested in people whose tumors were driven to growth by an “FGFR3” mutation but haven’t spread beyond the bladder tissue. Study data revealed Wednesday show that, after three months, 57% of recipients had no visible signs of disease. Company executives had hoped 70% of patients would have this kind of “complete response.” 
• Tyra is positioning the drug as an alternative to a recently approved medicine called Zusduri and Johnson & Johnson’s drug-eluting device Inlexzo, both of which require patients to undergo invasive procedures in the urinary tract. Use of dabogratinib, executives have contended, could prevent recurrence in people who forego those alternative treatments. 

Dive Insight:

Tyra is developing dabogratinib in two types of bladder cancer involving FGFR3 mutations. Drugs targeting FGFR mutations have been approved for patients with more advanced disease. But Tyra seeks to make that kind of therapy available to people with “non-muscle invasive” disease — meaning their cancer hasn’t spread beyond the cells lining the bladder — earlier, following surgical removal of a tumor. It’s also evaluating use in a different urological cancer known as urothelial carcinoma.

Should Tyra succeed, it would compete with Zusduri. Marketed by UroGen Pharma, Zusduri is a liquid delivered to the bladder through a catheter. Once there, the drug warms to body temperature, thickens into a gel and gradually releases the chemotherapy mitomycin. Patients have to undergo the procedure once a week for six weeks.

Dabogratinib has a convenience advantage in that it’s a once-daily pill that doesn’t require office visits or an invasive procedure. However, Zusduri was associated with a 78% remission rate in testing, setting a high bar for dabogratinib. And though not approved in this specific setting, J&J’s Balversa induced complete remissions in 89% of enrollees with non-muscle invasive disease in a clinical trial.

In a statement, Tyra executives emphasized that dabogratinib appeared more effective in people with a single “marker lesion,” or tumor left behind after surgery for drug evaluation purposes, compared to those with multiple lesions. Six of the eight enrollees fitting this description reached a complete remission at the highest dose tested.

While Tyra’s market value fell on the results, analysts argued that the findings gave dabogratinib a path to success in a future Phase 3 trial. Tyra plans to test it in the “adjuvant” setting intended to prevent cancer recurrence, and enroll people without marker lesions.

“In that context, patients with a single marker lesion in [the Phase 2 trial] represent the closest analog to the intended Phase 3 population, given the relatively low residual disease burden compared with patients harboring multiple lesions,” wrote TD Cowen analyst Tyler Van Buren, in a client note.

Van Buren and other analysts also praised dabogratinib’s safety profile in the trial. The worst side effects, occurring in five patients, were categorized as “grade 3,” meaning they were severe but not life-threatening. No patients dropped out of the study or paused dosing either.