On November 4, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that two abstracts on the Company’s Antibody Radiation Conjugate (ARC) Iomab-B were accepted for oral presentations at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held virtually December 5-8, 2020 (Press release, Actinium Pharmaceuticals, NOV 4, 2020, View Source [SID1234569900]).

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"This is an exciting fourth quarter for the company and we are honored to have multiple oral presentations at this year’s ASH (Free ASH Whitepaper) conference. Our 3 oral presentations and one poster presentation demonstrate the clinical progress we have seen not only with Iomab-B, but our other programs including Actimab-A in combination with novel and approved therapeutic agents," stated Sandesh Seth, Actinium’s Chairman and CEO. "We look forward to presenting the Iomab-B data in further detail during the two oral presentations on the Iomab-B SIERRA study at ASH (Free ASH Whitepaper) in December. The company remains on track to report safety and feasibility data from 75% of the patients to be enrolled in SIERRA, as well as to complete the ad hoc interim analysis in the fourth quarter."

Mark Berger, Actinium’s Chief Medical officer, said, "We are encouraged that we continue to see positive ongoing results from our Phase 3 pivotal SIERRA trial in relapsed or refractory Acute Myeloid Leukemia (R/R AML) patients. In the Iomab-B Phase 3 trial we continue to see 100% engraftment in patients receiving a therapeutic dose of Iomab-B in the treatment arm whereas 83% of control arm patients failed salvage therapy, which includes the recently approved targeting agents such as venetoclax. This high failure rate demonstrates the significant need that exists in R/R AML and represents the paradigm shift we are looking to initiate with Iomab-B. The strong safety and feasibility data we have seen thus far gives us confidence that these older patients with active AML may benefit by undergoing a potentially curative bone marrow transplant which they could not receive otherwise."

Details & Highlights for Oral Presentations

Note: The two abstracts include SIERRA Phase 3 trial data available to the company from its CRO prior to August 10, 2020, the ASH (Free ASH Whitepaper) submission cutoff date. Per ASH (Free ASH Whitepaper) rules, updated data sets are permitted to be included in the live presentations.

Oral Presentation Title:

Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered

Publication Number:

193

Session Name:

721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities

Session Date:

Saturday, December 5, 2020

Presentation Time:

1:00 PM PT / 4:00 PM ET

53 patients (median age 64) were randomized to Iomab-B. 87% (46/53) received allogeneic transplant. 100% (46/46) Iomab-B transplanted patients engrafted, despite a pre-therapy median of 26% marrow blasts.
After randomization, 83% (44/53) of Conventional Care (CC) patients failed salvage therapy, including 45% (24/53) who received targeted agents. 44 CC patients were evaluated for crossover, with a median 33% marrow blasts, 59% (26/44) crossed over to Iomab-B followed by allogeneic HCT and 100% (26/26) of those patients engrafted.
Median time to neutrophil and platelet engraftment were 14 days (range 9-22) and 17 days (range 4-39) respectively, with 91% of evaluable patients achieving full donor chimerism (>95% by day 100). Neither the radiation dose delivered to the marrow (median 14.7 Gy; range, 4.6-32 Gy) nor the total administered activity (median 632 mCi; range, 354-1027 mCi) showed correlation with the time to neutrophil (p value=0.525) or platelet engraftment (p value=0.952).
Regression analyses, considering all of the variables individually, did not indicate a statistically significant correlation (p > 0.1) between days to engraftment and radiation dose delivered to the marrow.
Phase 3 SIERRA – Preliminary Results

Baseline Characteristics

Randomized to Iomab-B
(N=53)

Randomized to Conventional Care (CC)
(N=53)

Age (yrs, median, range)

64 (55-77)

65 (55-77)

Molecular & Cytogenetic Risk

Favorable: 2%
Intermediate: 33%

Adverse: 65%

Favorable: 4%

Intermediate: 30%

Adverse: 66%

% Transplanted
Intent-to-Treat Group

87% (46/53)

17% (9/53)

59% (26/44)

Results

Received Therapeutic dose of Iomab-B & Transplanted (N=46)****

Eligible to Receive Std. of Care Transplant Post-Salvage (N=9)

Evaluated for Crossover (N=44)*****

Cross-over Rate

n/a

n/a

Received Therapeutic Dose of Iomab-B (N=26)

Transplanted (N=26)

59% (26/44)

% Transplanted

100% (46/46)

17% (9/53)

100% (26/26)

BM Blast % @ baseline (median, range)

26 (4-95)

14 (5-97)

30 (6-87)

BM Blast % pre-HCT (median, range)

26 (4-95)

1 (0-3)*

32.5 (2-75)

Days to ANC Engraftment

14 (9-22)***

17 (13-83)#

14 (10-37)**

Days to Platelet Engraftment

17 (4-39)***

22 (8-35)#

19 (1-38)**

Days to HCT (Post Randomization)

30 (23-60)

66 (51-86)

65 (36-161)^

Myeloablative Dose Delivered to Bone Marrow

14.7 (4.6-32) Gv

n/a

14.4 (6.3-30) Gv

540 (313-1008) mCi

632 (354-1027) mCi

Chimerism >/= 95% by D100

91% (39/43^ Evaluable)

67% (4/6^^ Evaluable)

87% (20/23^^^ Evaluable)

100-day non-Relapse Transplant-Related Mortality

5% (2/40 Evaluable)

25% (2/8 Evaluable)

8% (2/24 Evaluable)

*1 pt with 8% BM blasts on D42 with CRp on D50, ** ANC engraftment data not available (N=3), platelet engraftment data not available (N=4); *** ANC engraftment data not available (N=4), platelet engraftment data not available (N=9), ^ 1 patient at 161 days had delayed transplant due to infection and respiratory failure, received Iomab & transplant when stable, # ANC and platelet engraftment data not available (N=2)

**** No Therapy Dose (7) due to: Declining KPS (4), Infusion Reaction (1), Unfavorable Biodistribution (1), Post-Randomization Eligibility (1); 1 Pending Treatment.

*****Ineligible for Iomab-B HCT after crossover evaluation – 13: due to Hospice Care/Progression (4), Declined/Ineligible for HCT (5), Died Pre-Crossover (4). 4 Received Dosimetry but No Therapy Dose due to Declining KPS; 2 Pending Evaluation for Crossover.

^ Did not achieve ≥95% chimerism (4); Data pending (2); Died (1); ^^ Did not achieve ≥95% chimerism (4); Data pending (1); ^^^Did not achieve ≥95% chimerism (4); Data pending (2);

Oral Presentation Title:

High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Publication Number:

135

Session Name:

721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities

Session Date:

Saturday, December 5, 2020

Presentation Time:

9:30 AM PT / 12:30 PM ET

The median dose of Iomab-B administered was 603 mCi (range 313-1027 mCi) and the median radiation dose delivered to the marrow in the Iomab-B group was 14.7 Gy (range 4.6 – 32 Gy).
All patients (n=45, median age 64) treated with a therapeutic dose of Iomab-B achieved neutrophil engraftment after a median of 14 days post-HCT (range 9-22), despite presenting with a median 26% marrow blasts prior to initiation of therapy.
No correlation between adverse events (AE) (FN, mucositis, sepsis) and administered Iomab-B activity (p=0.08), nor with dose delivered to GI tract (p=0.09) was observed. Furthermore, these AEs were not related to the dose of radiation received by the small intestine (median 2.7 Gy range 1.1-6.8 Gy) large intestine (median 2.6 Gy range 0.9-6.5 Gy), nor an average of 4 GI sites (median 2.8 Gy range 1.6-6.8 Gy).
About Iomab-B

Iomab-B via the monoclonal antibody BC8, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, B cells and stem cells. BC8 is linked to the radioisotope iodine-131 and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells.

Iomab-B is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on the Company’s Phase 3 clinical trial in R/R AML can be found at sierratrial.com.