Actinium Pharmaceuticals Inc (ATNM)

[GoodGuyBill]

Actinium Announces Completion of Enrollment of Second Dose Cohort in Actimab-A Venetoclax Combination Trial for Patients with R/R AML

- Proof-of-concept Phase 1 data expected in 2H:2021 will evaluate safety, response rates, MRD negativity and cytogenetic profiles
- Complete response in patient with TP53 and other mutations and one partial response reported in patient with poor risk adverse cytogenetics reported in first dose cohort with subtherapeutic dose of Actimab-A with venetoclax

NEW YORK, March 25, 2021 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") today announced that initial patient enrollment in the second dose cohort in the Phase 1 portion of the Actimab-A venetoclax Phase 1/2 combination trial in fit and unfit patients with relapsed or refractory Acute Myeloid Leukemia (r/r AML) has been completed. The Phase 1 portion of the trial is a 3 + 3 dose escalation study to determine the maximum tolerable dose of Actimab-A that is to be studied in the Phase 2 portion of the study. Based on the progress of enrollment, Actinium expects to complete the Phase 1 portion and present further proof-of-concept data in the second half of 2021.

First-in-human data from the first dose cohort of 0.5 µCi/kg of Actimab-A and Venetoclax were presented at the 62nd American Society of Hematology annual meeting in December 2020. Patients enrolled in the first dose cohort had a median of 2 prior therapies (range 2-3) and a median bone marrow blast percentage of 30% (range 20 - >60). All 3 patients had poor risk disease with adverse cytogenetics, and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation). One patient who had multiple genetic mutations including IDH2, RUNX1, TP53 and others, achieved a complete remission with incomplete blood count recovery (CRi) after the first cycle of Actimab-A and venetoclax. Next generation sequencing at the end of the first cycle showed that the patient was negative for the known IDH2 and RUNX1 mutations. In addition, another patient achieved a partial response after one cycle of Actimab-A and venetoclax. There were no Actimab-A related dose limiting toxicities or nonhematologic Grade 3 or greater related AEs reported in the first cohort.

Dr. Mark Berger, Actinium's Chief Medical Officer, said, "We are encouraged by the strong progress we are making in this novel combination trial and excited to be studying Actimab-A with venetoclax. Venetoclax has emerged as a standard of care and backbone therapy for patients with AML who are both fit and unfit, however, patients with relapsed or refractory disease have poor outcomes and therefore need better treatment options. Based on the synergistic mechanism of action and preliminary clinical evidence from the first cohort, we are optimistic that Actimab-A in combination with venetoclax can improve outcomes for patients with relapsed or refractory disease using the unique targeted radiation mechanism of Actimab-A. We look forward to presenting data from this cohort of patients as well additional clinical data from the Phase 1 portion of the trial and working to advance this novel combination in the clinic."

In a poster presentation at the American Association of Cancer Research (AACR) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting Mcl-1, a protein shown to mediate resistance to venetoclax. Further, the induction of direct AML cell death via double-stranded DNA breaks via the radioisotope Actinium-225 in Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Venetoclax is a B-Cell Lymphoma 2 (Bcl-2) inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML, Chronic Lymphocytic Leukemia (CLL), and Small Lymphocytic Leukemia (SLL). Despite its approval in AML, venetoclax has produced low response rates of 19% as a single agent in R/R AML.1 A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML.

Sandesh Seth, Actinium's Chairman and CEO, added, "This trial is an exciting evolution of our Actimab-A program and application of the isotope Actinium-225. Actinium-225 is a potent medical isotope that can kill a cancer cell with a single alpha particle hit, emits four alpha particles in its decay and can cause double strand DNA breaks for which cancer cells have no known repair or resistance mechanism. Its energy is also emitted over a very short path length equal to a few cells in diameter enabling precise cell killing while sparing normal cells to limit systemic toxicities. With clinical experience in nearly 150 patients, robust IP and a clinically validated supply chain, we are leaders in the rapidly growing field of targeted alpha radiotherapy and specifically Actinium-225. Through continued clinical progress and innovation driven by our R&D efforts, we are committed to advancing our leadership position in the field of Actinium-225 based therapies and applying them with the goal of improving patient outcomes."