Tyra Biosciences (TYRA) investor relations material

Strategic program overview

• Lead drug Dabogratinib is advancing in three potential blockbuster indications: upper tract urothelial carcinoma (UTUC), intermediate-risk non-muscle invasive bladder cancer (NMIBC), and achondroplasia, with pivotal or phase 3 studies planned or underway and key data readouts expected this year.

• UTUC presents a high unmet need due to surgical challenges and high rates of kidney loss; the registrational path is rapid, modeled after Jelmyto, with a single-arm study design.

• NMIBC is the largest pursued indication, with phase 2 data expected mid-year to inform phase 3 design; Dabogratinib is the only oral option in development, targeting FGFR3-driven disease.

• Achondroplasia program aims to surpass current therapies by increasing annualized height velocity (AHV) through higher FGFR3 target engagement, with a 6-month safety sentinel readout planned for H2.

• Dose selection and efficacy optimization are guided by prior data and KOL input, aiming for high complete response (CR) rates with optimal tolerability.

Clinical development and data insights

• Phase 2 NMIBC study (SURF302) is enrolling rapidly, targeting 10-15 patients per dose; interim 3-month CR data will guide dose selection for phase 3.

• The study design leaves a marked lesion to assess dose efficacy, aiming for ≥70% CR at the most tolerable dose to enable long-term use.

• Lower doses (60 mg) show ideal safety with no discontinuations or significant adverse events, supporting their use in future pivotal trials.

• Phase 3 design for NMIBC may leverage a placebo-controlled approach, enabled by the oral formulation, and will be discussed with FDA following mid-year data.

• UTUC study uses a differential dosing strategy (60 or 80 mg) due to higher tumor burden, with a registrational path validated by FDA precedent.

Market opportunity and adoption drivers

• Oral Dabogratinib offers a transformative alternative to burdensome intravesical and surgical treatments, aligning with patient and physician preferences for convenience and reduced procedure load.

• Community urology practices, which treat 80% of patients, are well-equipped with in-office pharmacies, facilitating oral drug adoption and economic alignment.

• Academic centers may prefer procedures due to different economic incentives, but the majority of uptake is expected in the community setting.

• UTUC's high FGFR3 positivity and unmet need create a strong case for rapid adoption, with pricing expected to align with other bladder-sparing therapies.

• Achondroplasia patients and families seek greater efficacy than current options; the program targets higher AHV and improved proportionality, with dose response data expected to support phase 3 initiation.