Tyra Biosciences Narrows Dabogratinib Focus, Teases Mid-Year NMIBC and 2H Achondroplasia Data

Key Points

• Tyra has narrowed dabogratinib to “highest-value” FGFR3-driven indications—intermediate-risk NMIBC, low-grade UTUC and achondroplasia—and expects NMIBC data mid-year and achondroplasia data in 2H, while SURF303 for UTUC (IND cleared) will be initiated with registrational intent.
• Tyra emphasizes dabogratinib’s selective FGFR3 profile to reduce FGFR1/2-associated toxicities; more than 100 patients have received the drug and main signals (diarrhea and asymptomatic AST/ALT rises) were mitigated by dose reductions with generally well‑behaved PK.
• In achondroplasia BEACH301, Tyra is testing 10–40 mg adult dose equivalents and expects a visible dose–response in small cohorts, targeting annualized height velocity outcomes around 7+ cm at higher doses versus competitors’ mid‑six‑centimeter ranges.

Tyra Biosciences NASDAQ: TYRA CEO Todd Harris said the company has narrowed its focus to what he described as the “highest value opportunities” for its selective FGFR3 inhibitor dabogratinib, emphasizing indications where FGFR3 alterations are clear drivers of disease.

Speaking at a virtual conference with analyst Matt Biegler, Harris highlighted three lead areas: two urothelial cancer settings—low-grade upper tract urothelial carcinoma (UTUC) and intermediate-risk non-muscle invasive bladder cancer (NMIBC)—and skeletal dysplasias, with achondroplasia as the lead indication. Across these diseases, Harris said FGFR3 is either constitutively active through somatic alterations in urothelial cancers or overexpressed in skeletal dysplasias.

Rationale for a selective FGFR3 approach

Harris argued that dabogratinib’s selectivity is designed to reduce toxicities associated with FGFR1 and FGFR2 inhibition, which have complicated the use of pan-FGFR inhibitors. He referenced historical validation of FGFR targeting in urothelial cancer, citing data generated over time with Johnson & Johnson’s erdafitinib, and described recent achondroplasia data from BridgeBio’s oral infigratinib as further validating the target.

In Tyra’s metastatic Phase 1 experience, Harris said the company saw what it had hoped for: a “significant reduction” in FGFR1/2-associated toxicities by focusing on FGFR3. He also said diarrhea appeared lower than what he characterized as another selective FGFR3 effort from Loxo.

Safety and dosing experience

Addressing questions about chronic dosing risk-benefit in earlier-stage disease and pediatric use, Harris said more than 100 patients have “touched the drug” across programs. He also underscored that Tyra completed an array of preclinical requirements needed for chronic dosing—multi-species chronic toxicology, reproductive toxicology, phototoxicity, genotoxicity, and QT interval assessments—which he noted are not always required prior to an initial oncology Phase 1 program.

Harris described dabogratinib as having “well-behaved PK” and said that expanding the clinical dataset reduces the risk of idiosyncratic toxicity. He said the main signals at the highest metastatic doses were diarrhea and asymptomatic AST/ALT increases, and that lowering the dose alleviated the liver enzyme findings and reduced diarrhea to low-grade and low-frequency levels.

Achondroplasia: BEACH301 dose exploration and efficacy expectations

In discussing achondroplasia, Harris called BridgeBio’s recent dataset a “Goldilocks” readout for the field and said Tyra is rooting for an oral therapy that can reach the annualized height velocity (AHV) benefits associated with CNP-based therapies. He added that Tyra believes further FGFR3 target engagement could translate into additional growth—he framed this as “another centimeter” of growth per year that could matter to families and potentially impact functional outcomes and longer-term clinical sequelae.

Harris contrasted dosing in metastatic cancer with dosing considerations in children. In metastatic urothelial cancer, he said 90 mg represented full target engagement and that Tyra observed an objective response rate of 5 out of 10 patients at that dose. For achondroplasia, he referenced case studies of children on full oncology doses of FGFR3 inhibition (including erdafitinib) experiencing extremely rapid growth (19 cm per year) alongside risks such as fractures, arguing this provides a data point for predicting dose-response but is not an appropriate chronic dose in pediatrics.

He said Tyra’s BEACH301 trial is testing 10, 20, 30, and 40 mg adult dose equivalents in children. Harris stated the company expects a visible dose-response even with small cohorts and said Tyra is looking for AHV outcomes that reach into “7 centimeters, and more potentially” at the higher tested doses, compared with competitive Phase 2 datasets he described as being in the low-to-high six-centimeter range over six months.

Bladder cancer: why intermediate-risk NMIBC and what Tyra hopes to show

Harris said the company’s focus on intermediate-risk NMIBC is driven by genetics: he stated that low-grade lesions in this setting can have FGFR3 positivity “north of 70%,” which he quantified as roughly 35,000 new patients per year with the alteration. By comparison, he said FGFR3 positivity is lower in high-risk disease (around 30%–40% by his description) and lower still in metastatic disease (15%–20%). He suggested that additional co-mutations may be required to produce higher-risk phenotypes, which may reduce responsiveness to FGFR3 inhibition.

He also described the patient burden in intermediate-risk NMIBC, including repeated cystoscopies, TURBT procedures, and intravesical chemotherapy schedules, and positioned an oral therapy as potentially reducing recurrence and treatment burden.

Tyra’s NMIBC study is a Phase 2 “signal-seeking” trial, Harris said, and is not designed like a Phase 3. He explained the protocol concept of leaving a marked lesion in place to assess whether it disappears on therapy, defining that as complete remission (CR). Harris said Tyra is aiming for a CR rate of 70% or greater with durability, and he described how that target could translate into an estimated disease-free survival rate in the mid-to-high 80% range in a future Phase 3, assuming an observation/placebo disease-free benchmark around 70%.

UTUC: kidney-sparing opportunity and registrational intent

Harris described low-grade UTUC as a significant unmet need, citing an estimate from a physician that about 40% of newly diagnosed low-grade UTUC patients may ultimately lose a kidney. He said tumor location in the ureter and kidney makes endoscopic management difficult and that existing approaches, including local delivery of chemotherapy, remain challenging and often ineffective.

Tyra plans to initiate SURF303 in UTUC soon, Harris said, noting the company has IND clearance. He characterized the trial as having registrational intent, with a structure including an expansion consistent with the approach used for UroGen’s gemcitabine approval in the indication. Harris said the primary endpoint would be initial CR, while the company also intends to evaluate the potential benefit of staying on drug to maintain kidney preservation.

In closing, Harris and Biegler noted Tyra has four open trials—SURF301, SURF302, SURF303, and BEACH301. Harris said the company expects NMIBC data mid-year and achondroplasia data in the second half of the year, with UTUC timing to be provided later. He also said Tyra intends to complete the metastatic urothelial cancer study and eventually publish a Phase 1 paper, but is not planning to invest in a Phase 2 program there at this time because it sees greater value in the earlier-stage urothelial and achondroplasia opportunities. Harris added that Tyra continues to run an active FGFR3 discovery program and has brought two other drugs into the clinic.

About Tyra Biosciences NASDAQ: TYRA

Tyra Biosciences NASDAQ: TYRA is a clinical-stage precision oncology company focused on the discovery and development of small-molecule therapies for genetically defined cancers. The company integrates bioinformatics, molecular biology and medicinal chemistry to identify oncogenic drivers and design targeted inhibitors. By leveraging large-scale genomic datasets and functional screening, Tyra Biosciences aims to advance therapies that address patient populations with high unmet medical need.

The company's pipeline includes multiple programs at various stages of development, each directed against distinct molecular vulnerabilities in cancer cells.

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