Programs

What is Crenolanib?

Crenolanib is a small molecule investigational drug candidate that is being evaluated for safety and efficacy in Phase 3 clinical trials in acute myeloid leukemia (AML) and gastrointestinal stromal tumor (GIST). Crenolanib is a potent small molecule inhibitor of wild-type and mutant forms of FLT3 (FMS-like Tyrosine Kinase 3) and PDGFRα/β (Platelet-Derived Growth Factor Receptor).

FLT3 and PDGFRα/β are receptor tyrosine kinases (RTK) which play important roles in signaling cell growth and other processes. Dysregulation of RTK signaling is associated with a variety of diseases and cancers.

The lead indication for crenolanib is FLT3 mutated AML, an aggressive and deadly disease with limited targeted therapy options. FLT3 mutations are the most common mutations in AML, occurring in 25 – 33% of patients and are associated with increased rates of relapse and decreased survival.

We believe crenolanib has the potential to become a significant therapeutic advance for the treatment of FLT3-mutated AML, and that we have optimized the design of our enrolling global Phase 3 pivotal clinical trials to improve our chances to generate compelling efficacy and safety data that could establish crenolanib as a targeted treatment option for newly diagnosed and relapsed / refractory (R/R) FLT3-mutated AML.

Data from our Phase 1 and Phase 2 clinical trials of crenolanib with intensive chemotherapy have demonstrated encouraging rates of durable remissions in patients with newly diagnosed and as relapsed / refractory FLT3-mutated AML.

Additionally, crenolanib monotherapy has demonstrated encouraging activity in PDGFRA mutant GIST and is enrolling patients to a global Phase 3 study. Crenolanib is also being evaluated in phase I-II trials in advanced glioma as a monotherapy and in combination with CYRAMZA (ramucirumab) for advanced gastric cancer.

FLT3 Summary

AML is a highly heterogenous disease driven by multiple mutations. The most common driver mutations in AML occur in the gene FLT3 and are found in 25- 33% of all AML patients.

Multiple FLT3 mutations have been identified in patients and are generally regarded as poor prognostic markers in AML. Chemotherapy offers limited benefits in treating cancer cells harboring FLT3 mutations and are associated with high rates of relapse.

For patients with FLT3 mutations who have relapsed or were refractory to treatment there are currently no targeted agents approved in combination with standard of care salvage chemotherapy.

PDGFR Summary

Aberrations in PDGFR have an incidence of about 30% in cancer, including mutations, deletions, and amplifications. Tumor types for which PDGFR is altered in at least 10% of cases includes GIST, glioblastoma, lung, melanoma, bladder, prostate, colorectal and ovarian cancers.

Clinical Trial Pipeline

Indication	Patient subset	Phase I	Phase II	Phase III
FLT3 Pipeline
AML	Relapsed/Refractory (2L & 3L)			NCT03250338
	Newly Diagnosed (1L)			NCT03258931
	Post-Transplant maintenance		NCT02400255
Solid Tumor Pipeline
GIST	PDGFRa D842V mutated			NCT02847429
Glioma	PDGFRa amplification		NCT02626364
Gastric	Relapsed/Refractory	NCT03193918