On April 8, 2022 Asher Biotherapeutics (Asher Bio), a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, reported new preclinical data further demonstrating the profile of AB248, an engineered interleukin-2 (IL-2) immunotherapy that it intends to develop for the treatment of cancer (Press release, Asher Biotherapeutics, APR 8, 2022, View Source [SID1234611742]). The data will be presented on Tuesday, April 12 in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held in New Orleans, Louisiana.
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"We are pleased to share new preclinical data across our portfolio at AACR (Free AACR Whitepaper), including for AB248, our lead product candidate," said Ivana Djuretic, Ph.D., Chief Scientific Officer and Co-founder of Asher Bio. "AB248 highlights our cis-targeting strategy, which optimizes the use of immunomodulators by selectively focusing their effect to specific immune cell types. By precisely activating only CD8+ T cells, the primary immune cell subset that drives anti-tumor efficacy in response to IL-2 pathway activation, we believe AB248 has the potential to deliver a highly differentiated product profile, that could become a backbone of immuno-oncology treatment across a range of solid tumors."
High dose IL-2 was the first modern immunotherapy to show complete responses in a subset of cancer patients, however this and second-generation ("not α") cytokine-based medicines are generally limited by off-target effects that both suppress anti-tumor responses and drive toxicity. In order to overcome these challenges, new approaches have emerged, which include targeting IL-2 to the tumor microenvironment or leveraging a cis-targeting approach to deliver IL-2 to specific immune cell subsets. AB248 is a cis-targeted immunotherapy, which was specifically engineered to selectively activate CD8+ T cells, which drive anti-tumor efficacy. AB248’s design allows for the avoidance of NK cells, which can act as a pharmacological sink and contribute to toxicity, as well as Tregs, which are immunosuppressive.
The new preclinical data to be presented at AACR (Free AACR Whitepaper) detail these selective properties of AB248, underscoring key areas of differentiation compared to other molecules in development. In a poster presentation, titled "AB248 is a CD8+ T Cell Selective IL-2 Designed for Superior Safety and Anti-Tumor Efficacy," lead author Kelly Moynihan, Ph.D., Director and AB248 Program Lead at Asher Bio, presents experiments showing that AB248 demonstrated selectivity, with an approximately 1000-fold preference for the activation of CD8+ T cells over NK cells and Tregs, and induced dose-dependent, selective expansion of CD8+ T cells in non-human primates.
Laboratory data also demonstrated that AB248 avoided the NK cell-dependent IFNγ secretion by cultured human peripheral blood mononuclear cells (PBMCs) that has been observed with first-generation IL-2 or second-generation "not α" IL-2s. In addition, data demonstrated that AB248 augments effector cytokine production in CD8+ T cells that also receive a T cell receptor signal. Unlike NK cells, CD8+ T cells do not produce inflammatory cytokines following an IL-2 signal alone.
"This new data demonstrates our ability to deconvolute complex biology by separating cell types essential for anti-tumor activity, like CD8+ T cells, from those that are key drivers of toxicity, and to leverage this understanding to develop potentially best-in-class molecules," said Dr. Djuretic. "Together with the results of preclinical studies we’ve shared previously, the new data presented at AACR (Free AACR Whitepaper) substantiate our belief in the clinical potential of AB248. We look forward to advancing AB248 into human testing later this year, where we plan to evaluate it in multiple solid tumor indications as both a single and combination agent."
Asher Bio continues to advance AB248 through preclinical studies. Asher Bio expects to file an IND application with the U.S. Food and Drug Administration in the third quarter of 2022 and plans to initiate a Phase 1 clinical trial before year-end.
The poster presentation is now available in the "Presentations and Posters" section of Asher Bio’s website: View Source