SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Asher Biotherapeutics, a biotechnology company developing precisely-directed immunotherapies for cancer, autoimmune, and infectious diseases, today announced new preclinical data demonstrating proof of concept for its cis-targeting platform and lead program AB248. AB248 is an engineered intereukin-2 (IL-2) immunotherapy, designed to selectively target CD8+ effector T cells. The data will be presented at the Society for Immunotherapy of Cancer 36th Annual Meeting (SITC 2021), being held in Washington D.C. and virtually, November 10-14, 2021.
“We are pleased to share two presentations at SITC, providing further evidence that our cis-targeting approach enables us to craft exquisitely selective molecules, which activate only the desired immune cell types. This approach allows us to deliver immune activators to the cell types that drive efficacy, while avoiding other cell types that can lead to increased toxicities or other undesired consequences. These data provide further validation for our platform, which has now generated multiple lead molecules against high value targets and support our efforts to advance a pipeline of immunotherapies to provide better outcomes to patients,” said Andy Yeung, Ph.D., Chief Technology Officer and Founder of Asher Bio.
Ivana Djuretic, Ph.D., Chief Scientific Officer and Founder of Asher Bio, added: “Historically IL-2 has proven to be a very potent immunotherapy capable of inducing durable complete responses in some cancer patients, but IL-2’s potential has been severely limited by toxicities, which arise due to non-selective activation of many different cell types. Our approach is to focus IL-2 to selectively activate CD8+ T cells, the primary immune cell subset that drives anti-tumor efficacy in response to IL-2 pathway activation. We are encouraged by the preclinical results presented at SITC, which demonstrate the potential for AB248 to deliver both enhanced anti-tumor efficacy and improved safety and reinforce our confidence in AB248’s potential as a best-in-class IL-2 immunotherapy. We look forward to advancing AB248 into clinical studies across multiple solid tumor types next year.”
In an oral presentation titled, “CD8-targeted IL-2 drives potent anti-tumor efficacy and promotes action of tumor specific vaccines,” Bob Schreiber, Ph.D., Professor of Pathology & Immunology; Director, Bursky Center for Human Immunology & Immunotherapy Programs; Washington University School of Medicine and a scientific founder of Asher Bio, reviewed new preclinical data from studies of CD8-IL2, a murine surrogate of AB248, which was evaluated in a T3 sarcoma model. The data showed that:
- In an anti-PD-1 resistant tumor model, a single dose of CD8-IL2 resulted in complete tumor rejection in 90% of treated mice. In contrast, high dose IL-2 produced minimal efficacy.
- Treatment with CD8-IL2 led to the expansion of antigen specific T cells with increased expression of activation-associated markers and reduced expression of exhaustion-associated markers.
- CD8-IL2 monotherapy was well-tolerated, demonstrating therapeutic activity without inducing body weight loss.
In a poster titled, “Selective activation of CD8+ T cells by a CD8-targeted IL-2 results in enhanced anti-tumor efficacy and safety,” lead author Kelly Moynihan, Ph.D., Associate Director and AB248 Program Lead at Asher Bio, described the design of cis-targeted CD8-IL2 molecules and reviewed preclinical in vitro and in vivo data, which showed that:
- Treatment with a single dose of CD8-IL2 resulted in a majority of complete responses in established MC-38 tumors, and superior efficacy as compared to a “not α” IL-2. CD8-IL2 also showed marked synergy in combination with an anti-PD1 against established B16F10 melanomas, inducing complete responses in 100% of treated mice.
- Efficacy with a “not α” IL-2 in mice cannot be achieved unless “not α” IL-2 is dosed to levels that drive a high degree of toxicity-induced body weight loss (>10%). In contrast, treatment with CD8-IL2 drives strong anti-tumor efficacy without inducing body weight loss.
- Treatment with CD8-IL2 led to selective expansion of CD8+ T cells in both the peripheral blood and tumor compartments in mice, and in cynomolgus monkeys, showed strong and selective expansion of CD8+ T cells.
Both presentations will be available in the “Presentations and Posters” section of Asher Bio’s website: https://asherbio.com/pipeline/presentations-publications/.
About Asher Bio
Asher Bio is a biotechnology company developing precisely targeted immunotherapies for cancer and other diseases. Our cis-targeting platform aims to enable selective activation of specific immune cell types, addressing the inherent limitations of otherwise pleiotropic immunotherapies that act on multiple cell types. Our approach has the potential to precisely direct different immune mediators against a range of target immune cell-types and create best-in-class immunotherapies in cancer, autoimmune and infectious diseases. Asher Bio was founded by Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit www.asherbio.com and follow us on Twitter @AsherBio and on LinkedIn.
