Pipeline & Targets
We are advancing a robust pipeline of discovery programs that leverage our rapid structure-based design process and unique insights into kinase family structures gained through internally derived co-crystal structures.
- FGFR3 (TYRA-300)
- FGFR3 (ACH)
Our lead discovery candidate, TYRA-300, is a potent and selective inhibitor of FGFR3 that is designed to address two critical limitations of current approved and investigational FGFR inhibitors: activity in the presence of treatment-emergent resistance mutations such as the V555 gatekeeper mutation, and selectivity for FGFR3 over FGFR1 and other FGFR isoforms to avoid off-target side effects.
Indication: Bladder and solid tumors
FGFR3 mutation incidence: The incidence of activating FGFR3 mutations in bladder cancer has been estimated to be as high as 75% in non-muscle invasive bladder cancer (NMIBC) and up to 20% in muscle invasive bladder cancer (MIBC).
We are developing a small molecule inhibitor of FGFR2 that is active against multiple acquired resistance mutations that arise during treatment with other FGFR inhibitors.
Resistance to currently approved FGFR inhibitors for FGFR2 fusion positive intrahepatic cholangiocarcinoma (ICC) has been reported due to acquired mutations in multiple regions of the molecule, including the gatekeeper and molecular brake regions of FGFR2.
Indication: Bile duct and solid tumors
FGFR2 mutation incidence: Approximately 15-20% of patients with ICC have genetic alterations in FGFR2, which are primarily gene fusions and activating mutations.
We are developing an oral, highly selective inhibitor of mutant FGFR3 to address long-term complications and improve quality of life in affected individuals with achondroplasia, a genetic disorder caused by a mutation in the FGFR3 gene.
Our drug discovery efforts are driven by structural insights into the FGFR3 selectivity we have observed with TYRA-300. The FGFR3 (ACH) program is in the discovery stage.
FGFR3 mutation incidence: Approximately 80% of cases of achondroplasia arise through spontaneous mutation of FGFR3.
We are developing a RET-specific inhibitor that is active in the presence of the V804 gatekeeper and the G810 solvent front mutations which arise from treatment with current RET therapies.
Our drug discovery efforts are driven by our ability to gain molecular-level detail and insights from internally derived co-crystal structures of current RET inhibitors bound to receptor tyrosine kinases. The RET program is in the discovery stage.
Indication: Lung and thyroid cancer
RET mutation incidence: In non-small cell lung cancer (NSCLC), 1 to 2% of patients who are negative for mutations or rearrangements in other common oncogenic drivers have RET fusions. In papillary thyroid carcinoma (PTC), the most common form of thyroid cancer, an estimated 35% of cases in North America and up to 65% of cases in other geographies are associated with RET fusions. In sporadic medullary thyroid carcinoma, or MTC, approximately half of patients have activating mutations in RET.
We are developing a FGFR4-specific inhibitor that is active in the presence of the V550 gatekeeper and the C552 Cys mutations.
Our drug discovery efforts are driven by our deep understanding of FGFR family structure and the FGFR4 protein specifically. The FGFR4 program is in discovery stage.
Indication: Liver and solid tumors
FGFR4 mutation incidence: FGFR4 gene alterations such as activating point mutations and fusions have been identified in rare populations such as pediatric rhabdomyosarcoma and a variety of other solid tumors.