Arog Pharmaceuticals Presents Crenolanib Clinical Data at 57th American Society of Hematology Annual Meeting

DALLAS, Dec. 9, 2015 (GLOBE NEWSWIRE) -- Arog Pharmaceuticals, Inc., a privately held, clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs to treat unmet medical needs in oncology, today announced that clinical data from its lead product candidate, crenolanib, continue to demonstrate best-in-class properties in the treatment of acute myeloid leukemia (AML) with FLT3 mutations. Analyses from Phase II clinical studies of crenolanib were presented at the 57th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.

Highlights of the presented data include:

  • Crenolanib is well tolerated and efficacious as single-agent therapy in AML patients who received a prior hematopoietic stem cell transplant
  • Good exposure of crenolanib is achieved in most patients using the recommended phase III dose of 100 mg three times daily. Crenolanib has predictable pharmacokinetics, with no drug accumulation, and no induction of drug metabolism.
  • Crenolanib is broadly effective against known FLT3 mutations, and effectively eliminates mutant leukemia cells in patients. Secondary mutations in FLT3 are a key mechanism of resistance to other FLT3 inhibitors, but not crenolanib.
  • Crenolanib has clinical activity in patients who previously progressed on other FLT3 inhibitors such as midostaurin, sorafenib, quizartinib (AC220) or gilteritinib (ASP2215)

Title: Full Doses of Crenolanib, a Type I FLT3 Inhibitor, Can be Safely Administered in AML Patients Post Allogeneic Stem Cell Transplant (Abstract #4359)

In a poster presentation of a retrospective analysis of patients who underwent HSCT prior to crenolanib treatment across two Phase II trials of crenolanib monotherapy in AML (Studies ARO-004 and ARO-005), Robert Collins, M.D., University of Texas Southwestern Medical Center, presented:

  • Across the two Phase II trials of crenolanib monotherapy, 16/65 patients had undergone prior hematopoietic stem cell transplant
  • Crenolanib was well tolerated among these patients: 0/7 patients receiving crenolanib at the phase III dose of 300 mg/day required dose reductions, and no patient required drug discontinuation due to crenolanib-related toxicities
  • Crenolanib demonstrated clinical activity in these patients, despite prior failure of other FLT3 tyrosine kinase inhibitors, including midostaurin, sorafenib, quizartinib or gilteritinib
  • Crenolanib was active against AML with primary and secondary FLT3 mutations, including FLT3-ITD, FLT3-D835, and compound FLT3-ITD+FLT3-D835 mutations

Title: Population Pharmacokinetics of Crenolanib, a Type I FLT3 Inhibitor, in Patients with Relapsed/Refractory AML (Abstract #3695)

In a poster presentation of pharmacokinetic data from two Phase II trials of crenolanib monotherapy in AML (ARO-004 and ARO-005), John Carl Panetta, Ph.D., St. Jude Children's Research Hospital, presented:

  • Crenolanib was rapidly absorbed, and good exposure of crenolanib was achieved in most patients
  • Crenolanib had predictable pharmacokinetics and did not induce its own metabolism
  • Crenolanib did not accumulate with extended use, making crenolanib well suited for combination therapies
  • Crenolanib 100 mg three times daily (TID) was established as the dose for randomized Phase III studies of crenolanib

Title: Exome Sequencing Informs Mechanisms of Clinical Resistance to the FLT3 Inhibitor Crenolanib (Abstract #2468)

In a poster presentation of whole exome sequencing of 42 AML patients treated with crenolanib, Jeffrey Tyner, M.D., Oregon Health & Sciences University, presented:

  • Crenolanib was broadly effective against FLT3-ITD and FLT3-D835 mutant AML. No secondary D835 mutations were identified.
  • Despite predictions of FLT3 gatekeeper mutations (or other secondary FLT3 mutations) as a primary mechanism of crenolanib resistance, these mutations were only observed in 5-7% of patients
  • A prominent signal of mutations in spliceosome (SF3B1), chromatin modifiers (ASXL1), cohesion complex (STAG2) and RAS pathway suggest a genetic/epi-genetic mechanism of resistance to crenolanib

About Arog Pharmaceuticals, Inc.

Arog Pharmaceuticals is a private, clinical-stage biopharmaceutical company that has leveraged its platform of benzimidazole derivatives to develop a robust drug pipeline of orally available, potent, and selective small molecule type I kinase inhibitors. Arog is poised to enroll patients in pivotal, randomized Phase III trials of its lead molecule, crenolanib. In addition to the four clinical trials it has already completed, Arog is also engaged in three ongoing Phase II clinical trials. For more information, please visit the company's website,

About Crenolanib

Arog's lead molecule, crenolanib, is currently being clinically investigated as a treatment for multiple cancers, including acute myeloid leukemia (AML), gastrointestinal stromal tumors (GIST), glioma, and non-small cell lung cancer (NSCLC). It is an orally bioavailable benzimidazole type I kinase inhibitor that selectively and potently inhibits signaling of wild-type and mutant isoforms of class III receptor tyrosine kinases FLT3 and PDGFRα/β. This molecule has an established record of patient safety and has been used to treat over 250 patients from around the world.

About FLT3

FLT-3 is a class III receptor tyrosine kinase, and its signaling is considered important for the normal development of hematopoietic stem cells and progenitor cells. The FLT-3 gene is one of the most frequently mutated genes (~35%) in acute myeloid leukemia (AML). One such mutation, internal tandem duplications of FLT-3 (FLT3-ITD), is a prognostic indicator associated with adverse disease outcome.

About PDGFRα/β

Platelet-derived growth factor receptors (PDGFR) α and β are cell surface tyrosine kinase receptors and are important factors regulating cell proliferation and cell development, as well as several diseases, including cancers like brain tumors and sarcomas. In clinical tests, crenolanib has been shown to inhibit both PDGFR α and β phosphorylation, thus preventing downstream signaling.


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