On December 11, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported four presentations at the 65th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) detailing results from the Phase 3 SIERRA trial of Iomab-B and Phase 1 trial of Actimab-A in combination with Venetoclax in patients with relapsed or refractory acute myeloid leukemia (r/r AML) (Press release, Actinium Pharmaceuticals, DEC 11, 2023, View Source [SID1234638442]). Iomab-B and Actimab-A are the only two clinical stage targeted radiotherapies in development for patients with AML, which is known to be highly sensitive to radiation.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "Earlier in 2023 we presented data from both Iomab-B and Actimab-A highlighting positive outcomes in patients with relapsed or refractory AML. We are particularly excited by these results as our trials enrolled patients with difficult to treat disease as they were heavily pre-treated, elderly in age, or had adverse cytogenetic or molecular mutations. As evidenced by the data presented at ASH (Free ASH Whitepaper) in the oral presentation of the Phase 3 SIERRA trial results, Iomab-B produced improved outcomes in patients with a TP53 mutation, which is associated with dismal outcomes. We are proud to have showcased Iomab-B and Actimab-A at ASH (Free ASH Whitepaper) and excited by the enthusiasm for which the data were received. We look forward to progressing both programs with key BLA and MAA filings for Iomab-B next year and advanced development for Actimab-A."

ASH Presentations and Highlights:

131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant Significantly Improves Overall Survival in Patients with TP53 Mutated R/R AML

Patients receiving Iomab-B had significantly greater median overall survival of 5.49 months compared to 1.66 months in patients on the control arm that received conventional care
24% of patients (37/153) enrolled on the SIERRA trial had a TP53 mutation, which is associated with the worst outcomes
Iomab-B produced response rates and overall survival in these very high-risk patients similar to those observed in patients without a TP53 mutation
131I-Apamistamab Effectively Achieved Durable Responses in Patients with R/R AML Irrespective of the Presence of Multiple High-Risk Factors

Patients receiving Iomab-B were able to receive a BMT and achieve durable Complete Remission (dCR), the primary endpoint in the SIERRA trial, irrespective of having multiple high-risk factors
Iomab-B met the dCR rate primary endpoint with high statistical significance (p<0.0001) with 22% dCR rate in the Iomab-B arm vs. 0% dCR rate in the control arm
53% of patients had 2-3 high-risk factors and 29% had 4-5 high-risk factors that included adverse-risk cytogenetics, age >65, prior treatment failure with Venetoclax, BMT comorbidity index > 3, and Karnofsky Performance Status < 90
There was no statistical difference in the rate of dCR in patients receiving Iomab-B across the high risk-factor categories (0-1, 2-3 & 4-5)
High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT Demonstrated a Dose-Response for Durable Complete Remission in Patients with R/R AML

Patients with higher bone marrow/liver absorbed dose ratios experienced considerably higher rates of dCR demonstrating a dose dependent response
27% of patients achieving dCR when receiving > 22 Gy to the liver vs 13.5% dCR rate in patients receiving < 22 Gy to the liver; maximum tolerable dose in SIERRA was 24 Gy administered to the liver
Rates of Grade 3 > treatment emergent events were similar between patients receiving < 22 Gy to the liver and those receiving > 22 Gy to the liver
Iomab-B led BMT produced to significantly higher rates of dCR with patients achieving dCR having a 92% 1-year overall survival and 60% 2-year overall survival
These results demonstrate the importance of maximizing the dose to target tissues within the established dose tolerances
Updated Results from Phase 1 Study of Targeted Radiotherapy with Lintuzumab-Ac225 in Combination with Venetoclax in Relapsed/Refractory AML

Actimab-A dosed up to 2.0 μCi/kg with Venetoclax in patients with relapsed/refractory AML was well-tolerated, with a manageable adverse event profile
Maximum tolerated dose was not reached with no dose-limiting toxicities observed at the 3 highest dose levels (1.0, 1.5 & 2.0 μCi/kg)
Complete responses were achieved including a complete response in a patients with prior Venetoclax treatment and a TP53 mutation
These results support the continued evaluation of Actimab-A in combination with Venetoclax-based treatment