dabogratinib (TYRA-300) / Tyra Biosci - LARVOL DELTA

SURF303: Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=230 | Not yet recruiting | Sponsor: Tyra Biosciences, Inc

New P2 trial • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

Tyra Biosciences Reports Third Quarter 2025…Highlights (PRNewswire) - "Upcoming Clinical Milestones: (i) SURF302: initial three-month complete response data - 1H 2026; (ii) SURF303: initiate Phase 2 study - 2026."

New P2 trial • P2 data • Bladder Cancer • Urothelial Cancer

Dabogratinib (TYRA-300), an FGFR3 Isoform-Selective Inhibitor: Preclinical and Initial Clinical Evidence of Antitumor Activity. (PubMed, Mol Cancer Ther) - P1/2 | "In a xenograft model driven by an FGFR3S249C-activating mutation, dabogratinib treatment resulted in dose-dependent tumor growth inhibition with tumor regression observed at the highest doses. These preclinical findings are supported by the three case reports from the SURF301 study, which demonstrate early clinical activity in patients with advanced metastatic urothelial carcinoma with an FGFR3 fusion or activating mutation."

Journal • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

Next-generation isoform-selective fibroblast growth factor receptor inhibitors. (PubMed, Trends Pharmacol Sci) - "Pan-FGFR-selective inhibitors (erdafitinib, pemigatinib, and futibatinib) have been developed in clinical practice...FGFR2-selective inhibitor lirafugratinib, FGFR3-selective inhibitors LOXO-435 and TYRA-300, FGFR2/3-selective inhibitor ABSK061, and FGFR4-selective inhibitors are in clinical development. Additionally, novel isoform-selective FGFR-targeting degraders, FGFR2b/FGFR3-selective antibodies, and de novo-designed 'c' isoform-selective proteins provide novel treatment strategies. This review provides an overview of the current FGFR-targeted therapeutics and limitations and evaluates next-generation inhibitor development to guide future research."

Journal • Review • Oncology • FGFR • FGFR2 • FGFR3 • FGFR4

Dabogratinib (TYRA-300), an FGFR3 isoform-selective inhibitor: preclinical and initial clinical evidence of anti-tumor activity. (PubMed, Mol Cancer Ther) - P1/2 | "In a xenograft model driven by an FGFR3 S249C activating mutation, dabogratinib treatment resulted in dose-dependent tumor growth inhibition with tumor regression observed at the highest doses. These preclinical findings are supported by the three case reports from the SURF301 study, which demonstrate early clinical activity in advanced mUC patients with an FGFR3 fusion or activating mutation."

Journal • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

Discovery of Potent FGFR2/3 Inhibitors to Overcome Mutation Resistance and Treat Achondroplasia. (PubMed, ACS Med Chem Lett) - "Through structural hybridization of Tyra-300 and LY2874455, we developed compound 23, a new dual-target FGFR2/3 inhibitor demonstrating potent activity against both wild-type and mutant FGFR3. In preclinical ACH mouse models, compound 23 showed a dose-dependent improvement in growth rate, with significantly enhanced efficacy versus infigratinib at equivalent doses. This work presents a new structural scaffold for developing FGFR3 kinase inhibitors to target pathogenic FGFR3 mutations and treat ACH."

Journal • Endocrine Disorders • Genetic Disorders • FGFR2 • FGFR3

TYRA-300 Promotes Bone Growth In Two Mouse Models Of FGFR3-related Skeletal Dysplasia (ENDO 2025) - "The primary objectives of this study will be to assess safety and tolerability in children with ACH and evaluate change from baseline in annualized growth velocity to determine the dose(s) for further development. Secondary objectives will include evaluating change from baseline in height z-score, proportionality and pharmacokinetics."

Late-breaking abstract • Preclinical • Endocrine Disorders • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • FGFR3

Tyra Biosciences Doses First Patient in Phase 2 Study of TYRA-300 in Low-Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (SURF302) (PRNewswire) - "Tyra Biosciences...announced today that the first patient has been dosed in the Phase 2 SURF302 clinical trial of TYRA-300 in low-grade, intermediate risk non-muscle invasive bladder cancer (IR NMIBC)....SURF302 (NCT06995677) is an open-label Phase 2 clinical study evaluating the efficacy and safety of TYRA-300 in participants with FGFR3-altered low-grade, IR NMIBC. The study will enroll up to 90 participants at multiple sites primarily in the United States. Participants will be randomized initially to treatment with TYRA-300 at 50 mg once daily (QD) (Cohort 1) or treatment with TYRA-300 at 60 mg QD (Cohort 2)....Initial 3-month complete response (CR) data expected to be reported in 1H 2026."

P2 data • Trial status • Bladder Cancer

SURF302: Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Tyra Biosciences, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

SURF302: Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Tyra Biosciences, Inc

New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Tyra Biosciences Reports First Quarter 2025 Financial Results and Highlights (PRNewswire) - "Upcoming Anticipated Milestones and Events: (i) BEACH301: dose first child with ACH with TYRA-300 - Q2 2025; (ii) SURF302: dose first IR NMIBC patient with TYRA-300 - Q2 2025."

Trial status • Bladder Cancer • Genetic Disorders • Urothelial Cancer

GSC000829, a novel selective FGFR2/3 inhibitor, displays superior antitumor activity in preclinical FGFR-driven neoplasms models (AACR 2025) - "It also demonstrates enhanced antitumor activity at lower dosage in FGFR3-driven CDX models compared to the pan-FGFR inhibitor Erdafitinib, as well as other FGFR3-selective inhibitors such as TYRA300 and LOXO-435. GSC000829 exhibits favorable physicochemical and pharmacokinetic properties along with an excellent preclinical toxicity profile with no obvious phosphate increase at quite high exposure level in rats. Taken together, these findings bolster the rationale for advancing GSC000829 into clinical trials as a potential best-in-class FGFR isoform-selective inhibitors, offering an approach for treating advanced solid tumors harboring FGFR2/3 aberrations."

Preclinical • Oncology • Solid Tumor • FGFR1 • FGFR2 • FGFR3 • FGFR4

TYRA-300, an FGFR3 selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia. (PubMed, JCI Insight) - "Spinal stenosis is also a frequent complication, and TYRA-300 increased the lumbar vertebrae length and improved the shape of the intervertebral discs in both models. Taken together, these studies demonstrate that the selective FGFR3 inhibitor TYRA-300 led to a significant increase in bone growth in two independent FGFR3-driven preclinical models as well as in wild-type mice."

Journal • Endocrine Disorders • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • FGFR3

Tyra Biosciences Reports Fourth Quarter and Full Year 2024 Financial Results and Highlights (PRNewswire) - "Upcoming Anticipated Milestones and Events: (i) SURF302: dose first NMIBC patient with TYRA-300 - Q2 2025; (ii) SURF431: dose first HCC patient with TYRA-430 - Q2 2025."

Trial status • Hepatocellular Cancer • Urothelial Cancer

Tyra Biosciences Reports Fourth Quarter and Full Year 2024 Financial Results and Highlights (PRNewswire) - "Upcoming Anticipated Milestones and Events: BEACH301: dose first child with achondroplasia with TYRA-300 - Q2 2025"

Trial status • Genetic Disorders

A Relative Bioavailability and Food Effect Study of TYRA-300-B01 Capsule and Tablet Formulations in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Tyra Biosciences, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study of TYRA-300 in Children With Achondroplasia: BEACH301 (clinicaltrials.gov) - P2 | N=92 | Recruiting | Sponsor: Tyra Biosciences, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

A Study of TYRA-300 in Children With Achondroplasia: BEACH301 (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Tyra Biosciences, Inc

New P2 trial • Genetic Disorders

A multicenter, open-label phase 1/2 study of TYRA-300 in advanced urothelial carcinoma and other solid tumors with activating FGFR3 alterations (SURF301). (ASCO-GU 2025) - P1/2 | "The pan-FGFR inhibitor erdafitinib (erda) is approved for the treatment of mUC with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Phase 2 will enroll participants in FGFR3+ mUC and other tumor types to further explore the anti-tumor activity and safety of TYRA-300. SURF301 study began enrolling patients in November 2022 and is ongoing in Australia, the United States, France, and Spain."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR3

A Relative Bioavailability and Food Effect Study of TYRA-300-B01 Capsule and Tablet Formulations in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Tyra Biosciences, Inc | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: May 2024 ➔ May 2025

Trial completion date • Trial primary completion date

Tyra Biosciences Receives IND Clearance from FDA to Proceed with Phase 2 Study of TYRA-300 in Non-Muscle Invasive Bladder Cancer (SURF302) (PRNewswire) - "Tyra Biosciences...announced today that the U.S. Food and Drug Administration (FDA) cleared its Investigational New Drug (IND) application for TYRA-300 allowing the company to proceed with a Phase 2 clinical trial of TYRA-300 in low-grade, intermediate risk non-muscle invasive bladder cancer (IR NMIBC).....SURF302 will be an open-label Phase 2 clinical study evaluating the efficacy and safety of TYRA-300 in participants with FGFR3-altered low-grade, IR NMIBC. The study will enroll up to 90 participants at multiple sites primarily in the United States. Participants will be randomized initially to treatment with TYRA-300 at 50 mg once-daily (QD) (Cohort 1) or treatment with TYRA-300 at 60 mg QD (Cohort 2)."

IND • New P2 trial • Bladder Cancer

Tyra Biosciences Reports Third Quarter 2024 Financial Results and Highlights (PRNewswire) - "Third Quarter 2024 and Recent Corporate Highlights:...Phase 2 IND Submission for NMIBC on Track for Year-End 2024: TYRA plans to expand the clinical development of TYRA-300 into NMIBC to address the unmet needs in this cancer population with an efficacious, orally available therapy. TYRA remains on track to submit an Investigational New Drug (IND) application for a Phase 2 study of TYRA-300 in NMIBC before year-end 2024."

IND • Bladder Cancer

TYRA-300, an oral, FGFR3-selective inhibitor: Preliminary pharmacokinetic and pharmacodynamic analysis from SURF301, the multicenter open-label phase 1/2 study of TYRA-300 in advanced urothelial carcinoma and other solid tumors with activating FGFR3 alterations (EORTC-NCI-AACR 2024) - P1/2 | "In the ongoing SURF301 study, TYRA-300 has demonstrated exposures above the IC90 for FGFR3 inhibition that are below the IC50 for FGFR1/2/4 and led to changes in FGFR3 PD markers, a low incidence of hyperphosphatemia and decreases in plasma ctDNA fraction."

Clinical • Metastases • P1/2 data • PK/PD data • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3 • FGFR4

Tyra Biosciences Reports Interim Clinical Proof-of-Concept Data for TYRA-300, an Investigational Oral FGFR3-Selective Inhibitor, in Phase 1/2 SURF301 Study in Patients with Metastatic Urothelial Cancer (mUC) (PRNewswire) - P1/2 | N=310 | SURF301 (NCT05544552) | Sponsor: Tyra Biosciences, Inc | "Preliminary PK/PD analysis in 41 patients as of the data cutoff date: TYRA-300 plasma concentrations indicate adequate target coverage at ≥ 90 mg QD, with further pharmacokinetic characterization ongoing; In patients with FGFR3+ mUC who received doses ≥ 90 mg QD, anti-tumor activity was observed in all patients: 6 out of 11 (54.5%) patients at ≥ 90 mg QD achieved a PR, 3 of which are still ongoing. 5 out of 10 (50%) patients at 90 mg QD achieved a PR. 1 out of 1 (100%) patient at 120 mg QD achieved a PR. A 100% disease control rate (DCR) was achieved for all patients at ≥ 90 mg QD (PR + stable disease); Preliminary data from SURF301 suggest TYRA-300 to be generally well-tolerated, with infrequent FGFR2- and FGFR1-associated toxicities."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Tyra Biosciences to Host Conference Call on Interim Clinical Data of TYRA-300 from SURF301 Phase 1/2 Study on October 25, 2024, at 8am ET (PRNewswire) - "Tyra Biosciences...announced that it will host a conference call and webcast on October 25, 2024 at 8:00 am ET to share interim clinical results of TYRA-300 from the SURF301 Phase 1/2 study in metastatic urothelial cancer (mUC). These data will be presented in a late-breaking oral presentation at the 36th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics..."

Late-breaking abstract • P1/2 data • Urothelial Cancer