Bank of America analysts said prior to Thursday’s readout that Tyra Biosciences’ TYRA-300 could rival Johnson & Johnson’s kinase inhibitor Balversa, which has suffered from safety concerns and poor tolerability.
Tyra Biosciences on Thursday unveiled early proof-of-concept data for its investigational and potential first-in-class FGFR3 inhibitor TYRA-300, touting “encouraging” anti-tumor action in heavily pretreated patients with metastatic urothelial carcinoma.
The findings come from the Phase I/II SURF301 trial, which is designed to conduct an initial assessment of the anti-cancer efficacy of TYRA-300 and determine its recommended Phase II dose. Interim results showed that all FGFR3-positive patients who received at least 90 mg of TYRA-300 experienced anti-tumor activity.
According to Tyra, 50% of patients on 90-mg TYRA-300 once-daily reached partial response, as did the sole patient treated with a once-daily 120-mg dose. Disease control rate, defined as partial response with stable disease, was documented in 100% of patients who were given at least a 90-mg dose of TYRA-300 once-a-day.
In terms of safety, SURF301 found TYRA-300 to be well-tolerated overall and resulted in “infrequent” adverse events associated with FGFR2 and FGFR1. In all TYRA-300-treated patients, there were four treatment-related serious adverse events, one dose-limiting toxicity and one study dropout due to a side effect associated with the study drug. There were no adverse events of grade 4 severity or higher.
Tyra CEO Todd Harris in a statement said that these interim data “are in line with our expectations” and “provide clinical support” for TYRA-300 to address the “difficult problem” of creating an effective FGFR3 blocker that matches the efficacy, but bests the safety, of pan-FGFR inhibitors.
“These data give us confidence to advance TYRA-300 through Part B in SURF301,” Harris said. Tyra will also “explore larger opportunities with Phase II studies in metastatic urothelial cancer, non-muscle invasive bladder cancer and achondroplasia.”
Tyra presented these at an oral late-breaking session at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, held this week in Barcelona, Spain.
Designed to be taken orally, TYRA-300 is a next-generation investigational precision therapy that selectively targets FGFR3. This mechanism of action allows TYRA-300 to sidestep current limitations of the FGFR inhibitor drug class, namely growing treatment-emergent resistance mutations and off-target side effects, according to the biotech’s website.
With Thursday’s readout, Tyra begins its long trek to challenge J&J in the FGFR3 arena. The pharma owns Balversa, which like TYRA-300, is an orally available kinase inhibitor that the FDA granted accelerated approval for locally advanced or metastatic urothelial carcinoma in 2019. In January 2024, the regulator upgraded Balversa to full approval, allowing its use in patients with susceptible genetic alterations to the FGFR3 gene.
However, unlike TYRA-300, Balversa‘s mechanism of action also involves targeting FGFR1, FGFR2 and FGFR4, which has resulted in substantial off-target effects.
Jefferies analysts in a Friday note to investors said TYRA-300’s preliminary proof-of-concept data “exceeded” their expectations on both the safety and efficacy fronts, with safety looking “much cleaner” compared to J&J’s Balversa “with the caveat that the safety is grouped together across 10-120mg doses.”
Last week, ahead of Tyra’s SURF301 readout, Bank of America analysts flagged these safety concerns for Balversa, saying that its “poor tolerability has made it largely a non-starter,” according to Seeking Alpha. Tyra, the analysts contend, could take advantage of this market gap and make safety its key differentiating factor versus other FGFR inhibitors for urothelial carcinoma.
