On February 5, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) ("Actinium" or "the Company") reported that its novel Phase 1/2 combination trial of Actimab-A and venetoclax has been initiated (Press release, Actinium Pharmaceuticals, FEB 5, 2019, View Source [SID1234533070]). Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program at the UCLA Medical Center will serve as Principal Investigator for this study. The Phase 1/2 combination trial will enroll patients with relapsed or refractory AML or Acute Myeloid Leukemia that have been previously treated with venetoclax and patients that have never received venetoclax.
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Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor that is jointly developed and marketed by AbbVie and Genentech. BCL-2 is one of several proteins encoded by the BCL2 gene family, which regulates apoptosis or programmed cell death. MCL-1 is another protein encoded by the BCL2 gene family that is also overexpressed in cancers, including relapsed or refractory AML, that prevents apoptosis and promotes resistance to venetoclax, which does not bind to MCL-1. It has been demonstrated that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium believes that the targeted radiation from Actimab-A can more effectively deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. In preclinical studies, Actinium demonstrated this synergistic effect when combining Actimab-A with venetoclax that led to increased cancer cell death, the results of which were highlighted in a webinar hosted by Actinium that can be accessed here.
Dr. Dale Ludwig, Actinium’s Chief Scientific Officer said, "The ability to deplete MCL-1, a known resistance mechanism to venetoclax, by selectively targeting AML cells that express CD33 with Actimab-A and hitting them with potent alpha radiation from Actinium-225 is very compelling. I am excited to see this study enter the clinic as I believe Actimab-A’s targeted radiation will prove to be synergistic with venetoclax as we have shown in our preclinical work. With our powerful Antibody Warhead Enabling technology platform we are excited to deploy targeted radiation as a weapon against cancer cells by exploiting their susceptibility to radiation and leveraging potential synergies with other therapeutic modalities."
Dr. Mark Berger, Chief Medical Officer of Actinium said’ "Despite advancements and recent approvals of AML therapies including venetoclax, there is a real need to improve their incremental benefits and produce more durable responses as well as curative outcomes for patients with relapsed and refractory disease. We are excited about this trial as our recent phase 2 study with Actimab-A demonstrated an ability to produce complete responses in difficult to treat AML patients. We attribute this efficacy to ARCs being agnostic to cytogenetic factors, the ubiquitous expression of CD33 in AML and potency of the Actinium-225 warhead. We are hopeful that the combination of Actimab-A and venetoclax will in the clinic will validate our preclinical studies showing synergy and result in improved patient outcomes."