Tyra Biosciences, Inc. announced preclinical proof-of-concept results with TYRA-300, an investigational oral FGFR3 selective inhibitor, in hypochondroplasia (HCH). The results were presented at the 6th Annual Achondroplasia & Skeletal Dysplasia Research Conference (Pharmachon 2024), held June 28-30, 2024, in Baltimore, MD. HCH is a skeletal dysplasia closely related to achondroplasia (ACH), the most common form of dwarfism.

HCH is most commonly caused by the N540K mutation (~70-80%) 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 (p<0.01); tibia by 3.75% compared to the vehicle (p<0.05); humerus by 3.22% compared to the vehicle (p<0.05); and ulna by 5.03% compared to the vehicle (p<0.01). TYRA-300 also increased the size of the foramen magnum by 5.88% (p<0.05) in mice.

TYRA-300 demonstrated binding against the FGFR3 N540K altered protein and isoform selectivity for FGFR3 over other isoforms, as previously reported.