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Tyra Biosciences, Inc., a clinical-stage biotechnology company, announced that the US Food and Drug Administration (FDA) cleared its Investigational New Drug (IND) application for TYRA-300 allowing the company to proceed with a phase 2 clinical trial of TYRA-300 for children with achondroplasia (BEACH301).
TYRA-300 is a potential first-in-class, investigational, oral, FGFR3-selective inhibitor designed to avoid the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4. TYRA-300 is also being evaluated for metastatic urothelial cancer in the ongoing SURF301 study, where interim clinical proof-of-concept data were recently reported at the ENA 2024 meeting.
"IND clearance to proceed with BEACH301 is a significant milestone for the achondroplasia community and for TYRA, as we move into the clinic to treat our first rare skeletal dysplasia indication," said Todd Harris, CEO of TYRA. "We believe FGFR3 is the right target for achondroplasia, with almost one hundred per cent of cases being driven by a specific mutation in the FGFR3 gene. TYRA-300 has the potential to precisely engage FGFR3 to potentially achieve a higher annualized growth velocity, and lead to important functional outcomes and clinical benefits such as improvements in reach, gait and spinal disease."
Harris continued, "The currently available therapy is a once-daily injection that delivers modest increases in annualized growth velocity. As a highly selective FGFR3 inhibitor, we are hopeful that TYRA-300 may provide an improved therapeutic option for achondroplasia, and we are excited about our opportunity to potentially deliver improvements with our differentiated oral therapy in BEACH301."
BEACH301 will be a phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. Prior to initiation of Cohorts 1 and 2, the study will enroll a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10.
The primary objectives of this study will be to assess safety and tolerability in children with achondroplasia and evaluate change from baseline in annualized growth velocity to determine the dose(s) for further development. Secondary objectives will include evaluating change from baseline in height z-score, proportionality and pharmacokinetics (PK). TYRA is also planning exploratory assessments of clinical outcomes such as functional improvements, changes in the spine, and quality of life measures.
"We are excited to expand the clinical development of TYRA-300 into achondroplasia with BEACH301. Our existing database from the SURF301 oncology study includes information on doses significantly higher than what we are planning in achondroplasia. We believe this information suggest TYRA-300 may be well tolerated at low doses in children," said Doug Warner, MD, chief medical officer of TYRA. "We are continuing to engage with the achondroplasia community, including advocates and physicians, as we actively work to initiate the BEACH301 study and commence dosing in the first quarter of 2025."
In July 2023 and January 2024, the FDA granted Orphan Drug Designation (ODD) and Rare Pediatric Designation (RPD) to TYRA-300, respectively, for the treatment of achondroplasia. TYRA is committed to exploring the potential of TYRA-300 for functional impacts and quality of life measures in achondroplasia, hypochondroplasia and other skeletal dysplasia.
TYRA-300 is the company's lead precision medicine programme stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumours) (NCT05544552). The study is designed to determine the optimal and the recommended phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. Part A of the study included patients with all solid tumours who are FGFR3 +/-, and explored doses of TYRA-300 ranging from 10mg -120mg once-daily (QD). Part A of SURF301 is complete. The company continues to advance TYRA-300 through dose expansion in Part B, which includes patients with solid tumours who are FGFR3+, to evaluate potentially therapeutic doses in preparation for potential future phase 2 studies in metastatic urothelial carcinoma and non-muscle invasive bladder cancer. In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia and TYRA has received IND clearance from the US FDA to proceed with its BEACH301 clinical trial in children with achondroplasia.
Achondroplasia is the most common form of dwarfism with limited therapeutic options. It is estimated that 1 in 15,000 to 40,000 children are born have achondroplasia, with approximately 250,000 affected individuals worldwide. People living with achondroplasia may experience severe complications including foramen magnum and spinal stenosis, sleep apnoea and disproportionate short stature. An FGFR3 G380R gain of function mutation accounts for approximately 99% of achondroplasia. TYRA-300 is a first-in-class oral FGFR3 selective inhibitor whose design may have a meaningful impact on achondroplasia and other skeletal dysplasia.
Tyra Biosciences, Inc. is a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in FGFR biology.
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