Tyra Biosciences reports preclinical proof-of-concept results with TYRA-300

Tyra Biosciences announced preclinical proof-of-concept results with TYRA-300, an investigational oral FGFR3 selective inhibitor, in hypochondroplasia, or HCH. The results were presented at the 6th Annual Achondroplasia & Skeletal Dysplasia Research Conference, held June 28-30,in Baltimore. HCH is a skeletal dysplasia closely related to achondroplasia, or ACH, the most common form of dwarfism. HCH is most commonly caused by the N540K mutation in the FGFR3 gene. There are currently no approved therapeutic options for HCH. The design of TYRA-300 may inhibit the alteration driving FGFR3-related skeletal dysplasias including ACH, HCH and others. In an Fgfr3Asn534Lys/+ preclinical model, TYRA-300 was evaluated in FGFR3 wild-type and mutant animals to evaluate its potential effect on long bone length and skull size compared to vehicle-treated mice. TYRA-300 was administered daily at 1.8 mg/kg/day for 21 days starting at Day 3. TYRA-300 increased the length of the appendicular skeleton in the FGFR3 mutated mice: femur by 3.70% compared to the vehicle; tibia by 3.75% compared to the vehicle; humerus by 3.22% compared to the vehicle; and ulna by 5.03% compared to the vehicle. TYRA-300 also increased the size of the foramen magnum by 5.88% in mice. TYRA-300 demonstrated binding against the FGFR3 N540K altered protein and isoform selectivity for FGFR3 over other isoforms, as previously reported.