Preclinical tests support FGFR3 inhibitor in skeletal dysplasia

Fibroblast growth factor receptor 3

Biotechnology company Tyra Biosciences has announced preclinical proof-of-concept results with TYRA-300, an investigational oral fibroblast growth factor receptor 3 (FGFR3) selective inhibitor, in hypochondroplasia (HCH).

The results were presented at the 6th Annual Achondroplasia & Skeletal Dysplasia Research Conference (Pharmachon 2024).

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. The design of TYRA-300 may inhibit the alteration driving FGFR3-related skeletal dysplasias including ACH, HCH and others.

“The new preclinical data presented at Pharmachon 2024 are very encouraging and continue to support our belief that TYRA-300 has the potential to become a best-in-class agent with the potential to address unmet medical needs for people with skeletal dysplasias,” said Todd Harris, CEO of TYRA. “We look forward to submitting our IND in the second half of this year to support our planned Phase II study in paediatric achondroplasia.”

An exciting time for research in skeletal dysplasia

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 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.

The drug also increased the size of the foramen magnum by 5.88% in mice. It demonstrated binding against the FGFR3 N540K altered protein and isoform selectivity for FGFR3 over other isoforms, as previously reported.

Susana Noval Iruretagoyena, Director, Fundación ALPE, commented: “It’s an exciting time for research in skeletal dysplasia and movement into hypochondroplasia. Like with achondroplasia, it will be important for companies to study more outcomes beyond height for these families.”

Diana Spencer, Senior Digital Content Editor, DDW

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