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 an anti-HER2 antibody radiation conjugate (ARC) in combination with a CD47 blocking antibody immunotherapy in solid tumor models 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 [SID1234595458]). Actinium evaluated the anti-HER2 antibody trastuzumab (Herceptin) conjugated with either Actinium-225 (Ac-225) or Lutetium-177 (Lu-177) radioisotope payloads to explore potential synergies in combination with CD47 blocking antibodies. CD47 is a macrophage checkpoint which is upregulated in certain cancers, that acts as a "don’t eat me" signal on cancer cells to suppress phagocytosis and evade detection and destruction by the immune system. Actinium is exploring ARC combinations with CD47 blocking antibodies in solid tumors and blood cancers to evaluate mechanistic synergies including the ability to upregulate the cell surface "eat me" signal calreticulin via targeted radiotherapy.

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HER2-ARC + anti-CD47 SITC (Free SITC Whitepaper) Poster Highlights

HER2 targeting properties remained intact after radiolabeling trastuzumab with Ac-225 or Lu-177 as determined by binding to HER2 expressing cells
Calreticulin cell surface levels were increased in multiple cell lines after exposure to HER2-ARC
Phagocytosis was increased as much as 2-fold with the combination of a HER2-ARC and an anti-CD47 antibody compared to either as a single agent
Enhanced therapeutic efficacy with both improved tumor control and survival with the HER2-ARC and anti-CD47 blocking antibody combination compared to either as a single agent shown solid tumors in vivo models
Dr. Helen Kotanides, Vice President, Translational Research and Preclinical Development, stated, "We’re excited to present the first combination data from a CD47 targeting agent with an ARC in solid tumors. CD47 blocking agents hold tremendous potential but have yet to produce meaningful responses in solid tumors as monotherapies. Given our expertise in the area of targeted radiotherapy, we strongly believe that an ARC could synergize with CD47 blocking therapies given their immunogenic and cytotoxic properties. Specifically, we hypothesized that targeted radiotherapy could upregulate calreticulin, an "eat me" signal, to enhance phagocytosis and anti-tumor activity when combined with a CD47 blocking therapy. These results being presented at SITC (Free SITC Whitepaper) are highly encouraging and support not only our hypothesis of mechanistic synergy but also the continued development of this combination in HER2-positive and other solid tumor indications."

Sandesh Seth, Actinium’s Chairman and CEO, said, "We are excited to present this data at SITC (Free SITC Whitepaper) as it emanates from our renewed R&D focus on creating value by demonstrating the power of combining ARCs with immunotherapy for a better clinical effect by leveraging our platform capabilities. These data will support our pipeline expansion into solid tumors and combinations with immunotherapy. With the field of CD47 targeting agents growing rapidly, there is increasing competition not only in blood cancer indications but also in solid tumors, resulting in a need for differentiation. This data will also allow us to explore collaborations and partnerships with companies developing CD47 targeting agents with the goal of improving patient outcomes via the mechanistic synergy and highly differentiated profile of ARCs."

SITC Poster Details

Poster Title: Enhancement of the anti-tumor effects of CD47 blockade in solid tumors by combination with targeted radioimmunotherapy

Poster Number: 589

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