On November 12, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs, reported that data highlighting Actimab-A in combination with a CD47 blocking antibody immunotherapy are being presented at the 36th Annual Meeting of the Society for Immunotherapy for Cancer (SITC 2021) November 12th – 14th (Press release, Actinium Pharmaceuticals, NOV 12, 2021, View Source [SID1234595453]). The poster presentation highlights that in multiple AML cell lines, Actimab-A induced an increase in cell surface calreticulin as much as 3-times higher than control. When combined with a CD47 blocking antibody, enhanced pro-phagocytic immune response was seen in vitro across 3 AML cell lines. In vivo studies in disseminated AML tumor models showed a significant increase in survival with the Actimab-A plus CD47 immunotherapy combination compared to single agent therapy.
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Actimab-A is an antibody radiation conjugate (ARC) comprised of a CD33 targeting antibody armed with the alpha-emitting radioisotope Actinium-225, which has shown single agent anti-leukemic activity in a Phase 2 trial as well as synergy in combination with chemotherapy and targeted agents in Phase 1 trials. It has been shown that upregulation of CD47, which acts as a "don’t eat me" signal, is one mechanism in which AML cells can evade targeting and destruction by an innate immune response. The data presented at SITC (Free SITC Whitepaper) shows for the first time the potential to upregulate calreticulin, a pro-phagocytic "eat me" signal, with a CD33 ARC armed with the Actinium-225 radioisotope payload resulting in a potential synergistic effect with CD47 immunotherapy.
Dr. Avinash Desai, Actinium’s Chief Medical Officer, said, "As CD47 emerged as a highly attractive novel immunotherapy target, we rapidly identified the potential to combine Actimab-A with a CD47 blocking antibody. Based on the data to date with CD47 in patients with AML and MDS, we believe the potential exists to improve patient outcomes by combining with Actimab-A. Actimab-A is a highly differentiated agent for the treatment of AML as it uses radiation as the cytotoxic payload. AML, and many other blood cancers, are highly sensitive to radiation but cannot be properly targeted with standard external radiation sources due to their diffuse nature. With the increasing recognition of radiation’s potential to activate immune responses, we believe we are best poised to lead the field with our ARCs that can deliver and target the radiation with cellular precision and minimize systemic exposure and toxicities. By targeting CD33, we are targeting a validated marker that is expressed in a majority of AML patients with a radioisotope payload that is agnostic to cytogenetic or molecular markers. With initial mechanistic synergy demonstrated with CD47 immunotherapy, we look forward to exploring collaborations to advance this novel and differentiated combination from preclinical studies into patients in the clinic to further bolster Actimab-A’s potential as a backbone therapy for the treatment of AML."
SITC Poster Details
Poster Title: Anti-CD33 actinium-225 targeted radioimmunotherapy enhances the biologic activity of anti-CD47 antibody immunotherapy in preclinical models of acute myeloid leukemia
Poster Number: 590
Location: Poster Hall, Walter E. Washington Convention Center in Washington, D.C.
Dates and Times: 11/12/2021 – 11/14/2021, 7:00 am – 5:00 pm
The poster will be accessible on Actinium’s website on the Presentations & Webinars page: View Source