Tyra Biosciences Announces Interim Proof-of-Concept Data for TYRA-300 in Phase 1/2 mUC Study

Tyra Biosciences, Inc., a biotechnology company based in Carlsbad, California, has recently announced promising clinical proof-of-concept data for their investigational drug TYRA-300. The study, part of the ongoing Phase 1/2 SURF301 trial, focuses on patients with metastatic urothelial cancer (mUC) who have undergone extensive prior treatments. The findings were shared at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics held in Barcelona, Spain.

TYRA-300 is an oral, FGFR3-selective inhibitor developed to avoid the toxicities linked with inhibiting FGFR1, FGFR2, and FGFR4. This drug aims to treat urothelial cancers with FGFR3 alterations, which play a significant role in tumor development for a subset of these patients. Current pan-FGFR inhibitors, though beneficial, are often associated with intolerable side effects that limit their use.

Dr. Ben Tran of the Peter McCallum Cancer Centre in Melbourne emphasized the potential of TYRA-300 to improve both longevity and quality of life for patients with FGFR3-altered urothelial cancer. He noted the drug’s high selectivity for FGFR3, suggesting that it could offer better anti-tumor activity and tolerability compared to existing treatments.

As of August 15, 2024, 41 patients with advanced malignancies were enrolled in the Phase 1 study. These patients, some of whom had previously been treated with erdafitinib, received various doses of TYRA-300 ranging from 10 mg to 120 mg once daily. Notably, 44% of the participants had undergone three or more lines of therapy before trying TYRA-300, and 76% of those with FGFR3+ mUC had received at least three prior treatments.

Preliminary data from the study showed that TYRA-300 achieved adequate plasma concentration levels at doses of 90 mg or higher. The anti-tumor activity was evident in all patients with FGFR3+ mUC at these doses. Specifically, 54.5% of patients achieved a partial response, with an overall 100% disease control rate observed. The safety profile of the drug was also encouraging, with infrequent toxicities related to FGFR2 and FGFR1.

Doug Warner, Chief Medical Officer of TYRA, highlighted that the data align with expectations, showing that TYRA-300 is generally well-tolerated with fewer toxicities. The results support further development of the drug for mUC and potentially other FGFR3-altered cancers.

CEO Todd Harris expressed confidence in advancing TYRA-300 through the next stages of clinical trials. He noted that the interim results validate their approach to creating an FGFR3-selective inhibitor capable of addressing the limitations of current pan-FGFR inhibitors. The company plans to proceed with Phase 2 studies in metastatic urothelial cancer, non-muscle invasive bladder cancer, and achondroplasia.

The SURF301 study is designed to determine the optimal and recommended Phase 2 dose of TYRA-300 and to evaluate its preliminary anti-tumor activity. Part A of the study, which included patients with various solid tumors, is now complete. The focus has shifted to Part B, which will evaluate the drug in patients with FGFR3+ solid tumors.

TYRA-300 has also shown positive preclinical results for skeletal dysplasias such as achondroplasia and hypochondroplasia. The FDA has granted Orphan Drug Designation and Rare Pediatric Disease Designation to TYRA-300 for treating achondroplasia.

In summary, the interim data from the SURF301 study of TYRA-300 are promising. The drug has demonstrated potential as a next-generation targeted therapy for patients with FGFR3-altered urothelial cancer, offering improved anti-tumor activity and tolerability. Tyra Biosciences remains committed to advancing this investigational drug through clinical development to meet the needs of patients with these challenging conditions.