Lenzilumab is a Humaneered® recombinant monoclonal antibody that neutralizes soluble granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine that drives the growth of certain hematologic malignancies – such as chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) – and perhaps some solid tumors. CMML is an orphan disease and JMML is a rare pediatric disease.

Phase I Lenzilumab Study Underway in CMML Patients.

Lenzilumab is a highly potent GM-CSF antagonist with a favorable safety profile. It has been tested in more than 90 patients and found to be well tolerated in previous clinical studies in either healthy adults or those with autoimmune diseases.

GM-CSF is one of the cytokines involved in the development and maturation of certain types of myeloid blood cells. Earlier data generated by a collaborator confirmed that hypersensitivity to GM-CSF plays an important role in the growth and survival of CMML cells. Such hypersensitivity is also a hallmark of JMML. Inhibition of GM-CSF may affect growth of leukemic cells in patients.

Currently available treatments in CMML are limited and produce inadequate responses, leaving these patients with high unmet medical need for effective and tolerable therapies.

Humanigen has started a Phase I trial focused on patients with previously treated CMML. The Phase I study is a multi-center, open-label dose escalation trial to evaluate the safety, maximum tolerated dose and preliminary activity of single-agent lenzilumab in CMML patients who are relapsed, refractory to, or intolerant to standard-of-care treatments. The first patient was dosed with lenzilumab in late July 2016.

The study will enroll up to 18 patients and is designed to identify the maximum tolerated dose –and a recommended Phase II dose – of lenzilumab in previously treated CMML patients. It will also assess preliminary efficacy of single-agent lenzilumab and provide additional data on pharmacokinetics, pharmacodynamics – including correlative biomarkers and mutational analysis – and safety.

CMML is a Rare and Aggressive Cancer of the blood.

CMML affects approximately 1,500 – 3,000 new patients per year in the United States. The cancer is considered a clonal disease which begins with one or more mutations to the DNA of bone marrow stem cell that multiplies uncontrollably. The change interferes with normal blood cell production, including red and white blood cells and platelets.

CMML patients often present with anemia, but can also experience low platelet counts leading to bleeding and abnormal white cell counts leading to infections, an enlarged spleen, bone marrow fibrosis and other symptoms. CMML patients have a shortened life expectancy and approximately 15-30 percent of patients progress to develop acute myeloid leukemia (AML).

The World Health Organization (WHO) reclassified CMML in 2008 into a separate disease from a therapeutic perspective. Prior to reclassification, CMML accounted for 10 percent of all myelodysplastic syndrome (MDS) cases for which hypomethylating agents (HMAs) have been approved. Treatment options are limited and include: blood transfusions; HMAs for non-proliferative forms; hydroxyurea for palliating symptoms related to massive splenomegaly and controlling elevated blood counts; and erythropoiesis stimulating agents for anemia.