FDA Clears Tyra Biosciences' TYRA-300 IND for Phase 2 Achondroplasia Trial
核心洞察
The FDA has cleared Tyra Biosciences' IND application for TYRA-300, an oral FGFR3 (搜索)-selective inhibitor, to proceed with a Phase 2 trial in children with achondroplasia (搜索).
The BEACH301 trial will be a multicenter, open-label, dose-escalation/expansion study evaluating TYRA-300 in children aged 3-10 with achondroplasia (搜索).
TYRA-300 has received Orphan Drug and Rare Pediatric Designations from the FDA for treating achondroplasia (搜索), highlighting its potential impact on this rare condition.
Tyra Biosciences announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for TYRA-300, paving the way for a Phase 2 clinical trial (BEACH301) in children with achondroplasia (搜索). This clearance marks a significant step for TYRA-300, a potential first-in-class, oral, FGFR3 (搜索)-selective inhibitor designed to minimize toxicities associated with FGFR1, FGFR2, and FGFR4 inhibition.
BEACH301 Trial Design
The BEACH301 trial is designed as a Phase 2, multicenter, open-label study with dose-escalation and dose-expansion phases. It will evaluate the safety, tolerability, and efficacy of TYRA-300 in children aged 3 to 10 years who have achondroplasia (搜索) and open growth plates. The trial will enroll both treatment-naïve children (Cohort 1) and those who have previously received growth-accelerating therapies (Cohort 2) at multiple sites globally. Each cohort is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for a duration of up to 12 months. A safety sentinel cohort of treatment-naïve children aged 5 to 10 will be enrolled prior to the initiation of Cohorts 1 and 2.
The primary objectives of the BEACH301 study are to assess the safety and tolerability of TYRA-300 and to evaluate changes from baseline in annualized growth velocity to determine appropriate doses for further development. Secondary objectives include assessing changes in height z-score, proportionality, and pharmacokinetics (PK). Exploratory assessments will also be conducted to evaluate clinical outcomes such as functional improvements, spinal changes, and quality of life measures.
Significance of TYRA-300
TYRA-300 is also under evaluation for metastatic urothelial cancer (搜索) in the SURF301 study, where interim clinical proof-of-concept data were presented at the ENA 2024 meeting. Todd Harris, CEO of TYRA, emphasized the importance of this milestone, stating, "IND clearance to proceed with BEACH301 is a significant milestone for the achondroplasia (搜索) community and for TYRA, as we move into the clinic to treat our first rare skeletal dysplasia indication." He added, "We believe FGFR3 (搜索) is the right target for achondroplasia, with almost one hundred percent 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."
Addressing Unmet Needs in Achondroplasia
Achondroplasia (搜索), the most common form of dwarfism, affects an estimated 1 in 15,000 to 40,000 children worldwide, resulting in approximately 250,000 affected individuals. The condition is often characterized by severe complications, including foramen magnum and spinal stenosis, sleep apnea, and disproportionate short stature. Approximately 99% of achondroplasia cases are driven by an FGFR3 (搜索) G380R gain-of-function mutation.
Doug Warner, MD, Chief Medical Officer of TYRA, noted, "We are excited to expand the clinical development of TYRA-300 into achondroplasia (搜索) 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 suggests TYRA-300 may be well-tolerated at low doses in children." Warner also mentioned the ongoing engagement with the achondroplasia community, including advocates and physicians, as they actively work to initiate the BEACH301 study, with dosing expected to commence in the first quarter of 2025.
Regulatory Designations and Future Directions
The FDA has granted TYRA-300 Orphan Drug Designation (ODD) in July 2023 and Rare Pediatric Designation (RPD) in January 2024 for the treatment of achondroplasia (搜索). TYRA is dedicated to exploring the potential of TYRA-300 in addressing functional impacts and enhancing quality of life measures in achondroplasia, hypochondroplasia (搜索), and other skeletal dysplasias.