Tyra Biosciences’ TYRA-300 Shows Promise in Metastatic Urothelial Cancer: Clinical Proof-of-Concept Data Released

Tyra Biosciences Unveils Promising Clinical Data for TYRA-300 in Metastatic Urothelial Cancer

Tyra Biosciences, Inc. (TYRA) has released encouraging clinical proof-of-concept data for its investigational drug, TYRA-300, in patients battling metastatic urothelial (mUC) cancer. The data, stemming from the ongoing SURF301 Phase 1/2 study, were presented at the prestigious EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, drawing significant attention from the medical community.

TYRA-300 stands out as a potential first-in-class, orally administered, FGFR3-selective inhibitor. It is specifically designed to target the FGFR3 protein, which plays a crucial role in the development and progression of mUC, while avoiding the toxicities often associated with inhibiting related proteins like FGFR1, FGFR2, and FGFR4. Notably, TYRA-300 remains effective regardless of the presence of FGFR3 gatekeeper mutations, making it a promising therapeutic option for a wider range of patients.

Encouraging Results from the SURF301 Study

As of the data cutoff date on August 15th, 41 patients had been enrolled in the Phase 1 portion of the SURF301 study, showcasing the robust recruitment efforts. The study included heavily pre-treated patients, further highlighting the potential of TYRA-300 for patients who have exhausted other treatment options.

TYRA-300 was evaluated across six dose levels, ranging from 10 mg to 120 mg once daily. Preliminary pharmacokinetic and pharmacodynamic (PK/PD) analysis revealed that TYRA-300 achieves adequate target coverage at doses of 90 mg or higher. This finding is crucial for ensuring the drug’s effectiveness in targeting and inhibiting FGFR3.

Anti-tumor Activity and Favorable Safety Profile

The most significant findings from the SURF301 study relate to the drug’s anti-tumor activity and safety profile. In patients with FGFR3+ mUC who received doses of 90 mg or higher, encouraging anti-tumor activity was observed across all patients:

*

≥ 90 mg QD:

6 out of 11 (54.5%) patients achieved a partial response, with 3 of those responses still ongoing.
*

90 mg QD:

5 out of 10 (50%) patients achieved a partial response.
*

120 mg QD:

1 out of 1 (100%) patient achieved a partial response.

Furthermore, all patients receiving doses of 90 mg or higher achieved a 100% disease control rate (DCR), indicating the drug’s ability to effectively control tumor growth and prevent progression.

Preliminary safety data from SURF301 suggest that TYRA-300 is generally well-tolerated, with infrequent toxicities associated with FGFR2 and FGFR1 inhibition. While there were 4 (10%) serious adverse events related to TYRA-300, only one dose-limiting toxicity (DLT) of grade 3 diarrhea at 90 mg QD was reported. Additionally, one grade 3 treatment-related adverse event led to discontinuation of treatment at 90 mg QD.

Importantly, no DLTs were reported at the highest dose evaluated, 120 mg QD, indicating a wide therapeutic window and further emphasizing the drug’s favorable safety profile.

Looking Ahead

These early clinical data from the SURF301 study hold great promise for TYRA-300 as a potential treatment for patients with mUC. The drug’s demonstrated efficacy, favorable safety profile, and ability to target FGFR3-positive tumors regardless of gatekeeper mutations make it a compelling therapeutic candidate. As the SURF301 study progresses, further data will be crucial to solidify these initial findings and evaluate TYRA-300’s long-term efficacy and safety in a larger patient population.

The release of this data has garnered significant attention from investors, resulting in a temporary dip in TYRA’s stock price. However, the overall outlook for TYRA-300 remains positive, with the potential to revolutionize the treatment landscape for patients with mUC.