Oncology

We are investigating transformative scientific approaches to better treat deadly diseases.

In oncology, Chimerix is investigating smarter ways to treat  acute myeloid leukemia (AML), and potentially other hematologic indications. With more than 21,000 new cases of AML diagnosed annually in the U.S. and a five-year survival rate in elderly patients of less than 30%, there is a clear and urgent need for life-extending and life-saving treatment options.1

What is AML?

AML is a type of cancer in the blood and bone marrow that rapidly progresses and interferes with the production of normal white blood cells, red blood cells and platelets.

How is AML treated?

Currently, most patients receive chemotherapy, sometimes in combination with a targeted therapy, as treatment for AML. The goal is to eradicate as many AML cancer cells and leukemic stem cells as possible. If patients respond well, they may go on to receive a stem cell transplant.

What is the prognosis of AML with treatment?

Patients with AML receiving chemotherapy treatment may experience up to a 70% mortality rate within the first year of treatment, depending on age and comorbidities.2 Even patients who respond well to chemotherapy are likely to relapse in 12 months or less.3

Why is AML so difficult to treat?

  • AML is considered a heterogeneous disease, meaning there are a multitude of chromosomal abnormalities and gene mutations that can cause the disease
  • AML cells develop from stem cells that undergo both genetic and epigenetic changes resulting in subpopulations of cells with different phenotypes
  • Subpopulations of AML cells may contain distinct cellular abnormalities or mutations contributing to treatment resistance

What are targeted therapies?

  • Targeted therapies target specific genes, mutations and proteins that contribute to cancer growth and survival while conventional chemotherapies affect a broader population of rapidly dividing cells
  • Doctors often use targeted therapies in combination with chemotherapy to target and kill as many cancer cells as possible

Why do existing targeted therapies fall short?

  • Targeted treatments are designed to target specific mutations in AML
  • In many cases some of the diseased cells within a patient do not express the targeted mutation or the mutations themselves change during the course of the disease.
  • Relapse can occur if not all AML blasts and leukemic stem cells are eradicated

The Chimerix Difference

Dociparstat sodium (DSTAT)

Chimerix is currently developing dociparstat sodium, also known as DSTAT, a new chemical entity that has the potential to treat heterogeneous AML via multiple pathways that contribute to the growth and survival of the disease.

In contrast to targeted therapies DSTAT may affect multiple pathways that contribute to AML pathogenesis and treatment-resistance. Specifically, DSTAT may:

  • Mobilize AML cells out from the protective bone marrow environment, rendering them more susceptible to chemotherapy
  • Sensitize treatment-resistant AML cells for tumor cell death
  • Bind to multiple proteins to reduce AML chemotherapy resistance and enhance platelet recovery after chemotherapy a, b, c, d, e, f, g

These mechanisms suggest DSTAT will complement multiple existing and emerging therapies, including chemotherapy and targeted agents. DSTAT may play a role in improving long-term outcomes for patients with AML.

Read more about DSTAT.

Sources:

  1. NIH National Cancer Institute. Cancer Stat Facts: Leukemia – Acute Myeloid Leukemia (AML) Retrieved from https://seer.cancer.gov/statfacts/html/amyl.html
  2. Meyers J, Yu Y, Kaye JA, Davis KL. Medicare fee-for-service enrollees with primary acute myeloid leukemia: an analysis of treatment patterns, survival, and healthcare resource utilization and costs. Appl Health Econ Health Policy. 2013;11(3):275-286. doi: 10.1007/s40258-013-0032-2.
  3. Walter RB, Othus M, Burnett AK, et al. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. Leukemia. 2015;29(2):312-320. doi: 10.1038/leu.2014.242.

References:

  a,cZhang 2012 JBC 287(8); a,bKovacsovics 2018 Blood Adv 2(4); dYasinska 2018 Oncoimmunology 7(6); c,d,gRao 2010 Am J Physiol Cell Physiol 299;  dZheng 2016 Am J Cell and Mol Bio 56(1); dGriffin 2014 Am J Resp Cell and Mol Bio 50(4); c,eLakshmi 2010 J Biomed Mat Res 95(1); eYu 2005 Blood 105(9);  fLapierre 1996 Glycobiology 6(3); gTavor 2005 Blood 106(6); gKummarapurugu 2018 JBC 293(32)