Actinium Highlights Improved Survival with Iomab-B in TP53 Positive Relapsed Refractory Acute Myeloid Leukemia Patients in the SIERRA Trial and Other Presentations at the 2024 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT® and CIBMTR®

Rhea-AI Summary

Actinium Pharmaceuticals, Inc. (ATNM) highlighted positive results from the Phase 3 SIERRA trial of Iomab-B, showing significant improvements in TP53 positive patients with a median overall survival of 5.49 months versus 1.66 months in those not receiving Iomab-B. The trial demonstrated Iomab-B's ability to overcome the negative impact of a TP53 mutation, leading to complete remissions in over 50% of patients. The company also presented promising data on radiopharmaceutical dosimetry and early results from a Phase 1 study using Iomab-ACT conditioning with CD19 CAR-T therapy.

Positive

• Significant improvement in overall survival with Iomab-B in TP53 positive patients
• Complete remissions in over 50% of TP53 positive patients receiving Iomab-B
• Positive results from Phase 1 study using Iomab-ACT conditioning with CD19 CAR-T therapy
• Upcoming oral presentations to further highlight trial outcomes
• No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in Phase 1 trial

Negative

• None.

Medical Research Analyst

The Phase 3 SIERRA trial results for Iomab-B highlight a significant advancement in the treatment of patients with TP53 mutations, a group traditionally facing poor prognosis and limited treatment options. The reported median overall survival increase from 1.66 to 5.49 months is a substantial improvement, which could signal a paradigm shift in the management of these patients. The robust hazard ratio of 0.23 and the compelling p-value of 0.0002 indicate a strong statistical significance of the trial's findings, underscoring the potential of Iomab-B to become a key therapy in this niche. The trial's impact extends beyond immediate patient outcomes, potentially influencing future clinical practice and healthcare policies regarding bone marrow transplants for this patient subset.

From a research perspective, the complete remission (CR) and durable CR rates are particularly noteworthy. These metrics not only reflect the efficacy of the treatment but also suggest a quality of life improvement for the patients, an aspect that is crucial in oncology. The absence of CR in the control group treated with conventional care starkly contrasts with the more than 50% CR rate in the Iomab-B treated group, emphasizing the drug's potential market impact. However, it is essential to consider the scalability of these results and the ability of healthcare systems to adopt this treatment, considering the specialized nature of radiotherapies and associated costs.

Oncology Doctor

The clinical results indicating that Iomab-B leads to complete remissions in more than half of the TP53 positive patients represent a breakthrough in treating this high-risk group. TP53 mutations are known to be associated with resistance to chemotherapy and poor survival rates, hence the improvement in outcomes with Iomab-B suggests a significant clinical benefit for these patients. The ability of Iomab-B to induce durable complete remissions is an important factor in considering long-term survival and could potentially change the standard of care for this patient population.

Furthermore, the early results from a Phase 1 study showing safety and lymphodepletion from Iomab-ACT conditioning with CD19 CAR-T therapy indicate a promising direction for future cancer treatments. The absence of immune effector cell-associated neurotoxicity syndrome (ICANS) in patients treated with Iomab-ACT is particularly encouraging, as ICANS is a common and serious side effect of CAR T-cell therapies. The data suggest that Iomab-ACT could enhance the safety profile of CAR T-cell treatments, which would be a significant development in the field of oncology.

Market Research Analyst

The data presented from the SIERRA trial has the potential to significantly affect the market dynamics for targeted radiotherapies, particularly within the niche of TP53 mutation-positive patients. Actinium Pharmaceuticals' Iomab-B, by demonstrating a marked increase in overall survival and complete remission rates, could see an increased demand as a preferred treatment option. The market potential for such therapies is contingent upon regulatory approval and reimbursement policies, which are likely to be influenced by the strong efficacy and safety profile demonstrated in these trials.

Moreover, the successful integration of Iomab-B into the treatment regimen of older patients and its compatibility with other therapies like CD19 CAR-T could expand the drug's applicability, leading to broader market penetration. As investors and stakeholders evaluate the implications of these clinical results, the company's valuation and stock performance could be positively impacted, provided the momentum continues into commercialization and the therapy becomes widely accessible to the patient population in need.

• Iomab-B significantly improved outcomes in TP53 positive patients with a median overall survival of 5.49 months versus 1.66 months in those not receiving Iomab-B (hazard ratio = 0.23, p-value=0.0002) in the Phase 3 SIERRA Trial
  
  
• The results demonstrate Iomab-B's ability to overcome the negative impact of a TP53 mutation in these patients who otherwise would have limited treatment options and dismal prognosis
  
  
• Five presentations include two upcoming oral presentations detailing improved outcomes in SIERRA trial patients ages 65+ and demonstration of robust engraftment with Iomab-B

NEW YORK, Feb. 23, 2024 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, today highlighted results from three poster presentations at the 2024 Tandem Meetings | Transplantation & Cellular Therapy (TCT) Meetings of ASTCT^® (American Society for Transplantation and Cellular Therapy and CIBMTR^®  (Center for International Blood and Marrow Transplant Research) being held in San Antonio, Texas. The posters detailed results and findings from the Phase 3 SIERRA trial of Iomab-B (¹³¹I-Apamistamab) including; improved rates of Complete Remission (CR), durable Complete Remission (dCR) and survival in patients with a TP53 mutation, key aspects of radiopharmaceutical dosimetry as related to Iomab-B, and early results from a Phase 1 study demonstrating safety and lymphodepletion from Iomab-ACT conditioning with CD19 CAR-T therapy.

Dr. Avinash Desai, Actinium's Chief Medical Officer, said, "Patients with a TP53 mutation have a desperate need for viable treatment options to improve outcomes. As seen in the SIERRA trial, Iomab-B led bone marrow transplant can overcome the negative impact of a TP53 mutation, producing complete remissions in more than 50% of patients as well as significant durable complete remissions. This is in stark contrast to the 0% complete remission and durable complete remission rate seen in the TP53 positive patients on the control arm who received best available treatment based on physician's choice. We are excited to further highlight these important outcomes to the transplant community and look forward to presenting additional findings from the SIERRA trial in our upcoming oral presentations."

The presented Iomab-B Phase 3 SIERRA trial results and highlights include:

Response Rate by TP53 Mutational Status and Treatment

	Iomab-B + Crossover		Conventional Care
TP53 Positive CR Durable CR	N=27 N=15 N=4	55.56% 14.81%	N=10 N=0 N=0	0% 0%
TP53 Wildtype CR Durable CR	N=93 N=54 N=15	58.06% 16.13%	N=23 N=4 N=0	17.39% 0%

CR = Complete Remission

Improved Survival with Iomab-B

	Iomab-B + Crossover	Conventional Care
	N=27	N=10
Median Overall Survival (95% CI)	5.49 (3.94, 8.25)	1.66 (0.99,2.96)
Hazard Ratio (95% CI)	0.23 (0.1., 0.52)
p-value (log-rank)	0.0002

Upcoming Iomab-B Phase 3 SIERRA Trial 2024 TCT Oral Presentations:

Title: ¹³¹I-Apamistamab Improves Outcomes in Patients 65 Years and Older with Relapsed or Refractory AML

Date & Time: Saturday, February 24, 2024, at 11:45 AM

Title: Targeted Myeloablative Radiation Using ¹³¹I-Apamistamab Prior to Allogeneic Hematopoietic Cell Transplant for Patients with R/R AML Results in Robust Engraftment

Date & Time: Saturday, February 24, 2024, at 10:30 AM

In addition, Actinium presented results from its ongoing phase 1 trial using Iomab-ACT as conditioning prior to CD19 CAR-T therapy for patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia or Diffuse Large B-cell Lymphoma. Importantly, no patients (0/4) developed immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade, a major safety measure of the study, as ICANS is observed in 25% or more of pts w/ R/R B-ALL and DLBCL treated with various CAR T-cell products. Iomab-ACT demonstrated transient depletion of peripheral blood lymphocytes and monocytes.  Persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities have been observed to date.

About the TCT Tandem Meetings

The Tandem Meetings I Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR are the combined annual meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR). Administrators, clinicians, data manager / clinical research professionals, fellows-in-training, investigators, laboratory technicians, MD/PhDs, nurses, nurse practitioners, pharmacists, physician assistants, and other allied health professional attendees benefit from a full scientific program that addresses the most timely issues in hematopoietic cell transplantation and cellular therapy.

About Actinium Pharmaceuticals, Inc.

Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA & MAA (EU)), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 220 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron.

For more information, please visit: https://www.actiniumpharma.com/

Forward-Looking Statements

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Investors:
investorrelations@actiniumpharma.com 

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SOURCE Actinium Pharmaceuticals, Inc.

What were the median overall survival rates in TP53 positive patients receiving Iomab-B compared to those not receiving Iomab-B?

The median overall survival was 5.49 months with Iomab-B versus 1.66 months without Iomab-B.

What percentage of TP53 positive patients achieved complete remission with Iomab-B?

Over 50% of TP53 positive patients achieved complete remission with Iomab-B.

What Phase 1 study results were presented by Actinium Pharmaceuticals?

Actinium presented results from a Phase 1 study using Iomab-ACT conditioning with CD19 CAR-T therapy.

What upcoming oral presentations are planned for the Iomab-B Phase 3 SIERRA trial?

Two oral presentations are scheduled to detail outcomes in patients 65+ and robust engraftment with Iomab-B.

Was immune effector cell-associated neurotoxicity syndrome observed in the Phase 1 trial?

No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed in the Phase 1 trial.