CG-806 for Myeloid Tumors

Pipeline

Product Mechanism Ownership Indication Preclinical Clinical Proof-of-Concept Pivotal
CG-806 FLT3 (wildtype and mutant) Aptose: WW
Crystal Genomics: Korea
AML & MDS
complete
AML & MDS Preclinical Phase complete
in progress
Clinical Proof-of-Concept Phase in progress
not started
Pivotal Phase not started

The Story Behind CG-806 in Myeloid Tumors

We believe that CG-806 truly represents an entirely new class of drug. It is a genotype-agnostic and mutation agnostic agent that targets clusters of related kinases, yet with a precision that avoids known targets typically associated with toxicity.

The role of FLT3 in Acute Leukemia

Approximately one third of AML patients harbor a constitutively activating internal tandem duplication (ITD) in the FMS-like receptor tyrosine kinase 3 (FLT3), which is associated with poor prognosis. Additional point mutations occur in FLT3, commonly in the activation loop residue D835 and the “gatekeeper” residue F691, which can result in drug resistance to existing therapies and disease relapse. As demonstrated by the success of FLT3 inhibitors approved by the FDA or in late-stage development, the inhibition of FLT3 is a validated strategy in this patient populations. Yet, the clinical benefit of dirty agents is limited due to the challenges of titration due to their toxicity, while the clinical benefit of more selective agents is not overarchingly durable due to the emergence of resistance.

CG-806: A Potent Mutation-Agnostic Inhibitor of FLT3

CG-806 inhibits FLT3-ITD and all other known mutant forms of FLT3 with IC50’s in the pM to low-nM range. CG-806 is more potent than other FLT3 inhibitors, including midostaurin, sorafenib, sunitinib, dovitinib, quizartinib, crenolanib and gilteritinib against primary samples from patients with AML containing wildtype or mutated FLT3. In murine xenograft models of AML, including a PDX model with cells from the bone marrow of an AML patient with dual FLT3/D835 mutations, CG-806 demonstrated highly potent anti-leukemic efficacy and cures, and was well tolerated with no toxicities. Importantly, CG-806 targets other oncogenic kinases which may also be operative in FLT3-ITD AML, thereby potentially allowing the agent to become an important therapeutic option for difficult-to-treat patient populations. Importantly, oral CG-806 has a desirable safety profile in GLP toxicology studies of rodents and dogs, in rodent respiratory and central nervous safety studies, and in dog cardiovascular studies, and has exhibited no myelotoxicity in animals or humans to date.

Clinical Development

Aptose plans to seek allowance from the FDA to move CG-806 into patients with relapsed or refractory AML in a separate Phase 1 trial in the first half of 2020. Since relapsed and refractory AML patients are acutely ill, we did not wish to dose this patient population with a sub-therapeutic dose that likely would not provide clinical benefit. Therefore, at this time we continue to collect safety and PK data from the initial cohorts of our study of CG-806 in patients with B-cell malignancies in order to identify a dose that we believe has the likelihood to deliver therapeutic benefit immediately to AML patients.

For the upcoming trial in relapsed and refractory AML patients, we plan to include patients having the ITD mutation in FLT3 (typically referred to as FLT3 positive patients), patients having mutations within the tyrosine kinase or gatekeeper domains of FLT3, as well as AML patients that have wild type FLT3 status. Moreover, we plan to include AML patients who are resistant to other FLT3 inhibitors or venetoclax, or those having mutations in IDH1 or IDH2 and other relevant genotypes.

Posters & Presentations

Posters & Presentations

Our robust library includes numerous publications, including presentations, posters, and other media that provide additional information on our drug candidates, pre-clinical and clinical studies.

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