Iomab-B produces high response rates and significant improvement in overall survival in relapsed or refractory AML patients with active disease overcoming TP53 mutation.- Actinium Pharma

The oral presentation highlighted significantly improved survival in patients with a TP53 mutation receiving Iomab-B.

Iomab-B is a targeted radiotherapeutic comprised of an anti-CD45 monoclonal antibody with the Iodine-131 radioisotope payload. The Phase III SIERRA trial enrolled 153 patients with active relapsed or refractory acute myeloid leukemia (AML) and compared outcomes of patients receiving Iomab-B and a bone marrow transplant (BMT) to those of patients receiving physician's choice of care in the control arm, which was intended to reflect current best practices. Patients not achieving a Complete Remission (CR) in the control arm who were unable to proceed to a BMT were offered to crossover to receive an Iomab-B led BMT.

Iomab-B achieved the primary endpoint in the SIERRA trial of durable Complete Remission (dCR) of at least 6 months with high statistical significance (p<0.0001), with 22% of patients randomized to the iomab-b arm achieving dcr and 0% of patients in the control arm achieving dcr, irrespective of tp53 mutational status. in addition, iomab-b significantly improved event-free survival, a secondary endpoint, with a hazard ratio of 0.22 and median overall survival (mos) was doubled.></0.0001),>

Median OS was 6.37 months in TP53 negative patients receiving Iomab-B and 5.72 months for TP53 positive patients demonstrating Iomab-B's ability to overcome TP53 gene mutations.

Dr. Hannah Choe, Assistant Professor of Medicine at Ohio State University and SIERRA trial investigator, commented, "Patients with a TP53 mutation have notoriously poor outcomes due to resistance to anti-leukemic therapies and are rarely offered access to potentially curative transplantation. Iomab-B can grant patients increased access to transplant and induces high complete remission rates despite active, relapsed/refractory disease and even in those with a TP53 mutation. This speaks to the novelty and safety of a CD45-directed radiotherapy. More importantly, we see that these response rates translated into improved overall survival, overcoming the increased risk associated with TP53 mutation while no other viable treatment options exist. We are excited to present these results that further support the use and safety of Iomab for disease control."

Overall, twenty-four percent (37/153) of patients enrolled on SIERRA had a TP53 mutation. In total, 27 patients with a TP53 mutation received Iomab-B and accessed BMT on the SIERRA trial either after initial randomization or following crossover after not being able to access a BMT on the control arm. Only 1 patient with a TP53 mutation was able to access a BMT on the control arm via conventional care.

Dr. Avinash Desai, Actinium's Chief Medical Officer, added, "The SIERRA trial data support that regardless of advanced age, prior therapy, or high-risk cytogenetics including a TP53 mutation, Iomab-B provides unprecedented access to a potentially curative BMT. The results also show that on a population basis and across subgroups, an Iomab-B led BMT may result in improved survival. We are incredibly excited for the potential of Iomab-B and what it represents for patients with relapsed or refractory AML. The international enthusiasm for the SIERRA data amongst key medical and scientific communities is evidenced by the eight oral presentations at some of the most prestigious medical conferences held this year including TCT, EBMT, ONS, EHA, SNMMI, EANM, SOHO and now ASH is highly motivating, and we are committed to bringing Iomab-B to transplant physicians and their patients globally."

About Iomab-B and the Pivotal Phase III SIERRA Trial : Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative BMT by simultaneously and rapidly depleting blood cancer, immune and bone marrow stem cells that uniquely express CD45. Multiple studies have demonstrated increased survival in patients receiving BMT, however, an overwhelming majority of patients with blood cancers do not receive BMT as current approaches do not produce a remission, which is needed to advance to BMT, or are too toxic. Studied in over 400 patients, prior studies with Iomab-B have demonstrated nearly universal access to BMT, increased survival and tolerability in multiple clinical trials including the recently completed pivotal Phase III SIERRA trial in patients with active (leukemic blasts greater than 5%), relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above.

Iomab-B met the primary endpoint of durable Complete Remission (dCR) of 6 months after initial remission post-BMT in the pivotal Phase III SIERRA trial with high statistical significance (p<0.0001). iomab-b produced a 75% post-bmt cr rate (44 59 patients), which is 12-times greater than the post-bmt rate of 6.3% (4 64 patients) in the control arm. patients receiving iomab-b had a 78% lower probability of an event, defined as not achieving a cr crp, crossover, not receiving a bmt, relapse or death, with a hazard ratio of 0.22 (p><0.0001). iomab-b doubled 1-year overall survival with 26.1% compared to 13.1% in the control arm for patients who did not crossover as well as median overall survival with 6.4 months vs 3.2 months. overall survival statistics are confounded by the crossover arm. crossover patients had a 35.8% 1-year overall survival rate. due to its targeted nature, iomab-b was well tolerated with four times lower rates of sepsis compared to the control arm (6.1% vs. 28.6%) and lower rates of bmt associated adverse events including febrile neutropenia, mucositis and graft versus host disease (gvhd). actinium intends to submit a biologics license application (bla) seeking approval for iomab-b in 2024 to address patients age 55+ with r r aml who cannot access bmt with currently available therapies. iomab-b has been granted orphan drug designation from the fda and has patent protection into 2037.></0.0001).></0.0001).>

The pivotal Phase III SIERRA (Study of Iomab-B in Elderly relapsed or refractory AML) is a 153-patient, randomized, multi-center clinical trial, studying Iomab-B compared to the control arm of physician's choice of salvage therapy. Control arm options included chemotherapies like cytarabine and daunorubicin and targeted agents such as a Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2 inhibitors. The SIERRA control arm reflects real-world treatment of r/r AML patients with over 20 agents used alone or in combination as no standard of care exists for this patient population. The SIERRA trial enrolled patients at 24 leading transplant centers in the United States and Canada that perform over 30% of AML BMTs.

Developed at the Fred Hutchinson Cancer Research Center, a pioneer in the field of BMT, Iomab-B is supported by data in six disease indications including leukemias, lymphomas and multiple myeloma, which afflict over 100,000 patients annually. Actinium intends to pursue additional indications for Iomab-B beyond AML. Actinium also intends to pursue international regulatory approvals independently and through partnerships. In April 2022, Actinium licensed the European, Middle East and North African commercial rights for Iomab-B to Immedica Pharma AB, a fully-fledged independent pharmaceutical company headquartered in Sweden. In exchange, Actinium received an upfront payment of $35 million USD with the potential for an additional $417 million USD in regulatory and sales milestones and mid-twenty percent royalties. Europe represents a commercial opportunity approximately double the size of the United States by number of patients with AML receiving BMT. Iomab-B has been granted Orphan Drug Designation by the European Medicines Agency (EMA) and has received positive Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the EMA indicating that the Phase III SIERRA trial design, primary endpoint and planned statistical analysis are acceptable as the basis for a Marketing Authorization Application.