Tyra Biosciences Reports Preclinical Results for TYRA-300 in Hypochondroplasia

Tyra Biosciences, Inc., a clinical-stage biotechnology firm listed on Nasdaq under the ticker TYRA, has recently revealed promising preclinical proof-of-concept results for TYRA-300, an investigational oral FGFR3 selective inhibitor, in treating hypochondroplasia (HCH). These findings were unveiled at the 6th Annual Achondroplasia & Skeletal Dysplasia Research Conference, Pharmachon 2024, which took place in Baltimore, Maryland from June 28-30, 2024.

Hypochondroplasia is a form of skeletal dysplasia closely linked to achondroplasia, the most prevalent type of dwarfism. The condition is primarily caused by the N540K mutation in the FGFR3 gene, affecting approximately 70-80% of HCH cases. Presently, there are no approved treatments for HCH. TYRA-300 is designed to inhibit the alterations driving FGFR3-related skeletal dysplasias, which include achondroplasia, hypochondroplasia, and other related disorders.

Todd Harris, CEO of Tyra Biosciences, expressed optimism regarding the new preclinical data. He stated that these findings reinforce the potential of TYRA-300 to become a leading treatment option capable of addressing the unmet medical needs of individuals with skeletal dysplasias. According to Harris, the development of TYRA-300 for HCH is a logical progression from their efforts in achondroplasia. The company is preparing to submit an Investigational New Drug (IND) application in the latter half of 2024 to support a planned Phase 2 study focusing on pediatric achondroplasia.

In the Fgfr3Asn534Lys/+ preclinical model, TYRA-300 was tested on FGFR3 wild-type and mutant animals to assess its impact on long bone length and skull size compared to vehicle-treated mice. The treatment was administered daily at a dosage of 1.8 mg/kg/day for 21 days starting on the third day. Results showed that TYRA-300 increased the length of appendicular skeleton bones in FGFR3 mutated mice: femur length increased by 3.70%, tibia by 3.75%, humerus by 3.22%, and ulna by 5.03%, all showing statistical significance compared to the vehicle. Additionally, TYRA-300 enlarged the size of the foramen magnum by 5.88% in these mice. The compound demonstrated specific binding against the FGFR3 N540K altered protein and selectivity for FGFR3 over other isoforms.

Dr. Michael Bober, Vice President of Clinical Development and Medical Affairs at Tyra, commented on the significance of these findings. He noted that the improvements in growth plate function observed in the HCH model provide robust proof-of-concept for the further development of TYRA-300 as a treatment for hypochondroplasia. This supports the potential of TYRA-300 as a precision medicine for FGFR3-mediated skeletal dysplasia.

Susana Noval Iruretagoyena, Director of Fundación ALPE, highlighted the importance of continued research into skeletal dysplasias. She emphasized the necessity of exploring a variety of outcomes beyond height for affected families, mirroring the approach taken in studies on achondroplasia.

TYRA-300 is the company's lead precision medicine program from its in-house SNÅP platform. It is currently under development for treating cancer and skeletal dysplasias, including achondroplasia. In the field of oncology, TYRA-300 is being evaluated in a multi-center, open-label Phase 1/2 clinical study named SURF301. This study aims to determine the recommended Phase 2 dose and evaluate preliminary antitumor activity. TYRA-300 has shown positive preclinical results in both achondroplasia and hypochondroplasia, and Tyra Biosciences plans to submit an IND in the second half of 2024 to commence a Phase 2 clinical study in pediatric achondroplasia.

In 2023 and 2024, the FDA granted Orphan Drug Designation and Rare Pediatric Designation to TYRA-300 for treating achondroplasia, respectively. Tyra Biosciences continues to focus on developing next-generation precision medicines targeting significant opportunities in FGFR biology through its precision drug discovery engine. The company is headquartered in Carlsbad, California.