Tyra Biosciences (TYRA) Study result summary

Study background and rationale

• Dabogratinib is positioned as the first potential oral innovation for intermediate-risk non-muscle invasive bladder cancer (IR NMIBC), aiming to address unmet needs in a largely undertreated patient population.

• Most IR NMIBC patients (~70%) do not receive adjuvant therapy despite high recurrence rates, highlighting a significant treatment gap.

• Sustained FGFR3 inhibition has shown durable responses in FGFR3+ patients, supporting the rationale for targeted oral therapy.

• Current adjuvant therapies require invasive procedures, while dabogratinib offers a non-invasive, daily oral alternative.

• Patient and urologist surveys indicate strong preference for oral therapies due to convenience, reduced invasiveness, and improved quality of life.

Study design and patient population

• SURF302 is a Phase 2 marker lesion study in adults with FGFR3-altered IR NMIBC, evaluating oral dabogratinib at 50 mg and 60 mg doses, with a cohort for upper tract urothelial cancer (UTUC) at 60 mg.

• The study enrolled a highly recurrent, elderly population, most with prior TURBTs and high tumor burden; 91% had FGFR3 mutations or fusions.

• Patients were randomized to 50 mg or 60 mg daily, with primary endpoint of complete response (CR) at three months and secondary endpoints including best overall response, recurrence-free survival, and safety.

• Most patients had no prior intravesical therapy and a majority had recurrent disease.

• Patients with single marker lesions serve as a strong predictor for adjuvant efficacy, aligning with prior THOR-2 study criteria.

Efficacy results

• At 60 mg, the overall response rate (ORR) was 79% and best overall CR rate was 64%; all three-month CRs were maintained at six months.

• Single marker lesion patients at 60 mg achieved 100% ORR and 75% CR, matching THOR-2 efficacy benchmarks.

• Multiple marker lesion patients showed lower response rates, with ORR at 40%.

• A clear dose response was observed between 50 mg and 60 mg, with higher efficacy at 60 mg.

• In UTUC, the first patient at 60 mg achieved a complete response with no significant adverse events.