On December 5, 2016 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that results from its Phase 1 trial of Actimab-A were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) that is currently ongoing in San Diego, CA (Press release, Actinium Pharmaceuticals, DEC 5, 2016, View Source [SID1234516965]). Data from the previously conducted Phase 1 study pertaining to safety, efficacy and PB burden were highlighted during the poster session. Actimab-A is currently being studied in a 53-patient Phase 2 clinical trial as a monotherapy for patients newly diagnosed with Acute Myeloid Leukemia (AML) age 60 and above who are ineligible for currently used induction therapies. The Phase 2 trial is studying Actimab-A as a monotherapy administered via two fifteen minute intravenous injections of 2.0 μCi/kg/fraction of Actimab-A given a week apart. PB burden below 200 blasts/µL will serve as an inclusion criteria and patients above this threshold will be administered hydroxyurea to reduce their peripheral blasts counts prior to Actimab-A administration. Results from the Phase 1 trial showed that patients with PB burden below 200 blasts/µL who received a dose of 2.0 μCi/kg/fraction of Actimab-A saw a 50% response rate.

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Actinium’s PB burden hypothesis states that patients below the key threshold level of 200 blasts/µL have an increased response rate to Actimab-A while patients above the key threshold are unlikely to respond. An analysis of 2 clinical trials with Actimab-A totaling 38 patients, of which 36 were evaluable, showed that 42% (8 of 19) of patients with blasts counts below 200/µL responded to Actimab-A while no patients with blast counts above 200/µL responded to Actimab-A. The Phase 1 trial was a dose escalation study using a 3+3 design. Dose escalation proceeded if dose-limiting toxicities (DLT) were seen in less than 33% of patients. Maximum tolerable dose (MTD) was not reached in the Phase 1 trial.

Dr. Joseph Jurcic, Director of Hematologic Malignancies and Professor of Medicine at Columbia University Medical Center and Principal Investigator of the study said, "Older patients with AML, particularly those that have progressed from MDS, are difficult to treat and have very few treatment options since many have already received lower-intensity therapy with hypomethylating agents. The results from this Phase 1 trial were encouraging in regards to both the safety and efficacy of Actimab-A. We are particularly excited to have identified that patients with peripheral blasts below 200/µL have higher response rates to Actimab-A and that we can reduce blast counts in patients above that level using hydroxyurea. Actimab-A has shown promise in older AML patients, including those previously treated for MDS–a population excluded from trials with most novel agents, including ongoing studies with other CD33-directed therapies. We look forward to continuing to study Actimab-A in the ongoing Phase 2 trial and potentially meeting this critical need."

Of the 18 patients in the Phase 1 trial, 28% (5 of 18) had objective responses (2 CR, 1CRp and 2 CRi). Amongst patients with objective responses, median response duration was 9.1 months (range, 4.1-16.9 months). At the 3 highest dose levels in the Phase 1 trial (1.0 μCi/kg/fraction – 2.0 μCi/kg/fraction) objective responses were seen in 33% of patients (5 of 15). Mean bone marrow blast reduction amongst evaluable patients was 66% with 57% of patients having bone marrow blast reduction of 50% or greater and 79% of patients (11 of 14) had bone marrow blast reductions after Cycle 1 of therapy. The Phase 1 trial enrolled patients newly diagnosed with AML who are age 60 and above who were administered Actimab-A in combination with low-dose Cytarabine. Median patient age was 77 with 67% of patients having prior myelodysplastic syndrome (MDS) of which, 83% received prior therapy consisting of either hypomethylating agents (HMAs) or a hematopoietic stem cell transplant (HSCT).

A formal interim analysis will occur after 31 patients receive Actimab-A, which the Company expects to occur in mid-2017. The Company anticipates the Phase 2 trial to be complete by the end of 2017.

"Actimab-A, given its benign toxicity profile combined with potent efficacy as evidenced by the results presented today along with its ease of administration via 2 injections, represents an exciting therapy for elderly patients with AML," said Sandesh Seth, Executive Chairman of Actinium. "Due to our peripheral blast burden hypothesis and optimized Phase 2 protocol we have great excitement for the current Phase 2 clinical trial and future development pathways for Actimab-A."

About Actimab-A

Actimab-A, Actinium’s most advanced alpha particle immunotherapy (APIT) product candidate, is currently in a 53-patient, multicenter Phase 2 trial for patients newly diagnosed with AML age 60 and above. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 15-minute injections that are given 7 days apart. Actimab-A targets CD33, a protein abundantly expressed on the surface of AML cells via the monoclonal antibody, HuM195, which carries the potent cytotoxic radioisotope actinium-225 to the AML cancer calls. Actinium-225 gives off high-energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in almost 90 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML age 60 and above