TYRA-300 for Achondroplasia

Recruiting at 4 trial locations

Overseen By Kate Hogg Call

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Tyra Biosciences, Inc

Must not be taking: Cyp3A4 inhibitors/inducers

Disqualifiers: Endocrine conditions, Limb surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TYRA-300 for children with achondroplasia, a genetic condition affecting bone growth. The goal is to determine a safe and effective dose of TYRA-300 to improve growth in children with open growth plates, which are areas of growing tissue near the ends of long bones. Participants will receive different doses based on their weight, with adjustments every three months. Children aged 3 to 10 who have been diagnosed with achondroplasia and can take oral medication are suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in achondroplasia treatment.

Will I have to stop taking my current medications?

The trial requires that participants do not take medications that strongly affect a specific liver enzyme (cytochrome P450 3A4). If your current medications do not fall into this category, you may not need to stop them.

Is there any evidence suggesting that TYRA-300 is likely to be safe for children with achondroplasia?

Research has shown that TYRA-300 has promising safety results from earlier studies. Initial data suggest it is generally well-tolerated. Although detailed information on side effects remains limited, researchers have found no major safety concerns.

TYRA-300 targets a protein called FGFR3, which plays a role in bone growth. This is significant for conditions like achondroplasia, where bone development presents challenges. Although this trial is in an early stage, the treatment's safety appears encouraging. Participants will undergo regular monitoring to ensure safety and adjust doses if needed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for achondroplasia?

Researchers are excited about TYRA-300 for achondroplasia because it offers a new approach to managing this condition. Unlike current treatments that focus on surgery or growth hormone therapy, TYRA-300 is administered as sprinkle capsules or mini-tablets, making it easier to take, especially for children. The dosage is tailored based on the participant's weight, with adjustments every three months, ensuring personalized and potentially more effective treatment. This innovative delivery method and personalized dosing could lead to better outcomes and improved quality of life for those with achondroplasia.

What evidence suggests that TYRA-300 might be an effective treatment for achondroplasia?

Research has shown that TYRA-300, a drug specifically designed to aid bone growth, can be beneficial. In studies using a particular type of mouse, TYRA-300 significantly increased the length of bones such as the thigh bone (femur) and shin bone (tibia) by about 3.7%. This finding is important for conditions like achondroplasia, where bones grow more slowly than usual. The drug targets a key issue causing growth problems in achondroplasia, suggesting potential effectiveness in humans. Overall, TYRA-300 has demonstrated promising early results in improving bone growth, making it a potential treatment for achondroplasia. ^{2 3 4 6 7}

Who Is on the Research Team?

Doug Warner, MD

Principal Investigator

Tyra Biosciences

Are You a Good Fit for This Trial?

This trial is for children aged 3 to 10 with a confirmed diagnosis of achondroplasia, which is a bone growth disorder. They must have open growth plates, be able to walk and take oral medication independently. Consent from parents or guardians is required, and the child's willingness to assent if applicable.

Inclusion Criteria

I am between 3 and 10 years old.

I can stand and walk on my own.

I am between 3 and 10 years old and have not had treatment to speed up growth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Participants receive TYRA-300 in a dose-escalation format to determine safety and tolerability

12 weeks

Weight adjustments every 3 months

Dose-Expansion

Participants continue to receive TYRA-300 to identify potentially effective dose(s)

12 weeks

Weight adjustments every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TYRA-300

Trial Overview The study tests different doses of TYRA-300 (0.125 mg/kg up to 0.50 mg/kg) in children with achondroplasia to assess safety, tolerability, and effective dosing for promoting bone growth.

How Is the Trial Designed?

Group I: TYRA-300 0.50 mg/kg Experimental Treatment 1 Intervention

TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.

Group II: TYRA-300 0.375 mg/kg Experimental Treatment 1 Intervention

TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.

Group III: TYRA-300 0.25 mg/kg Experimental Treatment 1 Intervention

TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.

Group IV: TYRA-300 0.125 mg/kg Experimental Treatment 1 Intervention

TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.

Who Is Running the Clinical Trial?

Tyra Biosciences, Inc

Lead Sponsor

Trials

4

Recruited

500+

Published Research Related to This Trial

A spinal orthosis was tested on 19 achondroplastic children aged 11 to 52 months, resulting in a significant mean reduction of 23 degrees in the thoracolumbar curve and 15 degrees in the lumbosacral curve, indicating effective correction of spinal deformities.

In a larger group of 31 achondroplastic children and adults, the orthosis not only reduced spinal deformities but also provided symptom relief for back pain and neurological deficits, demonstrating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achondroplasia: effectiveness of an orthosis in reducing deformity of the spine. Siebens, AA., Hungerford, DS., Kirby, NA.[2007]

The pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 effectively reduces FGFR3 hyperactivity, leading to improvements in bone growth and structure in a mouse model of achondroplasia after just 10 days of treatment.

NVP-BGJ398 not only corrects abnormalities in the growth plate and skeleton but also inhibits key signaling pathways associated with FGFR3, suggesting it could be a promising therapeutic option for treating achondroplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. Komla-Ebri, D., Dambroise, E., Kramer, I., et al.[2020]

In a study of 6 patients with achondroplasia, surgical treatment involving posterior osteotomy and decompression effectively corrected thoracolumbar kyphosis from an average of 53.3° to 13.3°, achieving a 75% correction rate.

Patients also showed significant improvement in neurological function, with average JOA scores increasing from 4.5 to 8.5 points after surgery, indicating the procedure's efficacy in addressing both spinal deformity and associated neurological deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Posterior osteotomy and decompression for spinal deformity in patients with achondroplasia]. Sun, W., Zhang, JG., Qiu, GX., et al.[2011]

In a phase 3 trial involving 121 children with achondroplasia, vosoritide significantly increased growth velocity by an average of 1.57 cm/year compared to placebo, demonstrating its efficacy as a treatment.

The treatment was well-tolerated, with no serious adverse events linked to vosoritide, although the long-term effects and impact on final adult height remain unknown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Savarirayan, R., Tofts, L., Irving, M., et al.[2020]

In a study of 22 children with achondroplasia and genu varum, tension band plate (TBP) surgery effectively corrected knee deformities, with significant improvements in radiographic measurements over an average follow-up of 24.5 months.

Younger patients (average age 6.5 years) had better outcomes, highlighting the importance of early intervention for successful correction of varus deformities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements. Ulusaloglu, AC., Asma, A., Silva, LC., et al.[2023]

Citations

1. insight.jci.org insight.jci.org/articles/view/189307

TYRA-300, an FGFR3-selective inhibitor, promotes bone ... Treatment with TYRA-300 resulted in statistically significant increases in the appendicular skeleton, including the femur (+3.70%), tibia (+3.75 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06842355

NCT06842355 | A Study of TYRA-300 in Children With ... The purpose of this study is to evaluate the safety, tolerability, and identify potentially effective dose(s) of TYRA-300 in children with achondroplasia with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12128972/

TYRA-300, an FGFR3-selective inhibitor, promotes bone ... These data demonstrate that TYRA-300 was effective in increasing bone lengths in the Fgfr3 N534K–driven mouse model of HCH. Figure 4. TYRA-300 increased ...

4. ir.tyra.bio ir.tyra.bio/news-releases/news-release-details/tyra-biosciences-announces-first-child-dosed-beach301-its-phase

Tyra Biosciences Announces First Child Dosed in ... Dabogratinib is a first-in-class oral FGFR3 selective inhibitor whose design may have a meaningful impact on achondroplasia and other skeletal ...

5. tyrabio.investorroom.com tyrabio.investorroom.com/2025-06-30-Tyra-Biosciences-Doses-First-Patient-in-Phase-2-Study-of-TYRA-300-in-Low-Grade-Intermediate-Risk-Non-Muscle-Invasive-Bladder-Cancer-SURF302

Tyra Biosciences Doses First Patient in Phase 2 Study of ... TYRA-300 is an investigational, daily oral tablet that has shown encouraging preliminary safety and efficacy in an early phase trial and has the ...

6. ir.tyra.bio ir.tyra.bio/news-releases/news-release-details/tyra-biosciences-reports-interim-clinical-proof-concept-data

Tyra Biosciences Reports Interim Clinical Proof-of-Concept ... TYRA-300 has demonstrated favorable interim safety results as of the data cutoff date: Preliminary data from SURF301 suggest TYRA-300 to be ...

7. medchemexpress.com medchemexpress.com/tyra-300.html?srsltid=AfmBOoqNuOAZc2_SvjIxSkV3Pnh6_hktZ53M2nQOsogTbRb5kuWIAY_O

TYRA-300 | FGFR Inhibitor TYRA-300 is an orally active, selective inhibitor for FGFR3 with an IC50 of 11 nM in Ba/F3. TYRA-300 exhibits antitumor efficacy against urothelial cancers ...