Data support ability of AU-007, a computationally evolved, human IgG1 monoclonal antibody, to specifically block IL-2’s binding to CD25 and inhibit tumor growth in multiple cancer models
Data show potential of novel cancer treatment to break negative feedback loop caused by IL-2 and prevent Treg expansion
LARKSPUR, CA, USA I November 12, 2021 I Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of potentially best-in-class IL-2 therapeutics, today shared preclinical data for AU-007, a computationally evolved human antibody that leverages a highly differentiated approach to harnessing the power of IL-2 to eradicate solid tumors. Data were presented in a poster presentation at the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting.
“These positive preclinical data demonstrate the ability of AU-007 to tip the balance toward immune activation and away from immune suppression by preventing IL-2 from binding to T regulatory cells,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “While high-dose IL-2 has shown clinical benefit, associated toxicities have limited its therapeutic use. With AU-007, we are leveraging a mechanism of action unlike any other IL-2 therapeutic in development, with the potential for lower toxicity and a sustained anti-tumor response. Supported by these data, we are continuing to advance AU-007 into a Phase 1/2 clinical trial.”
AU-007 mediates human immune activation by precisely blocking an epitope on IL-2 that binds to CD25. This action redirects IL-2 to promote T effector cell expansion through binding the IL-2 receptor CD122/132 dimer while uniquely breaking the IL-2 negative feedback loop and blocking T regulatory cell (Treg) expansion, which requires activation through the CD25-containing IL-2 receptor trimer (CD25/CD122/CD132). Aulos Bioscience presented data at SITC establishing both the specificity and activity of AU-007. In preclinical studies, AU-007 was shown to bind human IL-2 with picomolar affinity and completely inhibit its binding to CD25 while preserving binding to CD122/CD132. When evaluated for activity in mouse models of cancer, administration of AU-007 complexed with human IL-2 resulted in expansion of CD8+ T effector cells, NK cells and NKT cells in a dose-dependent manner, but had no effect on the expansion of CD4+ Tregs. Additionally, AU-007 was shown to inhibit downstream signaling of IL-2 on human CD4+ Tregs, as measured by STAT phosphorylation, in a dose-dependent manner, but did not affect IL-2 signaling on human CD8+ T effector cells, NK cells and NKT cells.
Utilizing human peripheral blood mononuclear cells (PBMCs) activated only with anti-CD3/anti-CD28 co-stimulation, AU-007, but not an isotype control antibody, inhibited the proliferation of Tregs, indicating that AU-007 can capture endogenous IL-2 and prevent the Treg cell expansion negative feedback loop. By comparison, no inhibition of CD8+ T effector cell, CD4+ T effector cell, NK cell and NKT cell proliferation was observed under the same conditions. In murine models, AU-007 also demonstrated tumor growth inhibition in multiple cancers. AU-007 has been shown to be safe and well tolerated in primate toxicology studies (data not presented).
The poster presentation is available on the Aulos Bioscience website.
About AU-007
AU-007 is a computationally evolved, human IgG1 monoclonal antibody that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages the body’s own IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2 secreted by T effector cells from binding to trimeric receptors on T regulatory cells while still allowing IL-2 to bind and expand T effector cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to trimeric receptors on vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.
About Aulos
Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ own immune systems toward killing tumor cells. Matching world-class machine learning from founder and partner Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a computationally evolved human antibody that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and ATP with $40 million in Series A funding from ATP and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com.
SOURCE: Aulos Bio
Post Views: 29
Data support ability of AU-007, a computationally evolved, human IgG1 monoclonal antibody, to specifically block IL-2’s binding to CD25 and inhibit tumor growth in multiple cancer models
Data show potential of novel cancer treatment to break negative feedback loop caused by IL-2 and prevent Treg expansion
LARKSPUR, CA, USA I November 12, 2021 I Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of potentially best-in-class IL-2 therapeutics, today shared preclinical data for AU-007, a computationally evolved human antibody that leverages a highly differentiated approach to harnessing the power of IL-2 to eradicate solid tumors. Data were presented in a poster presentation at the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting.
“These positive preclinical data demonstrate the ability of AU-007 to tip the balance toward immune activation and away from immune suppression by preventing IL-2 from binding to T regulatory cells,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “While high-dose IL-2 has shown clinical benefit, associated toxicities have limited its therapeutic use. With AU-007, we are leveraging a mechanism of action unlike any other IL-2 therapeutic in development, with the potential for lower toxicity and a sustained anti-tumor response. Supported by these data, we are continuing to advance AU-007 into a Phase 1/2 clinical trial.”
AU-007 mediates human immune activation by precisely blocking an epitope on IL-2 that binds to CD25. This action redirects IL-2 to promote T effector cell expansion through binding the IL-2 receptor CD122/132 dimer while uniquely breaking the IL-2 negative feedback loop and blocking T regulatory cell (Treg) expansion, which requires activation through the CD25-containing IL-2 receptor trimer (CD25/CD122/CD132). Aulos Bioscience presented data at SITC establishing both the specificity and activity of AU-007. In preclinical studies, AU-007 was shown to bind human IL-2 with picomolar affinity and completely inhibit its binding to CD25 while preserving binding to CD122/CD132. When evaluated for activity in mouse models of cancer, administration of AU-007 complexed with human IL-2 resulted in expansion of CD8+ T effector cells, NK cells and NKT cells in a dose-dependent manner, but had no effect on the expansion of CD4+ Tregs. Additionally, AU-007 was shown to inhibit downstream signaling of IL-2 on human CD4+ Tregs, as measured by STAT phosphorylation, in a dose-dependent manner, but did not affect IL-2 signaling on human CD8+ T effector cells, NK cells and NKT cells.
Utilizing human peripheral blood mononuclear cells (PBMCs) activated only with anti-CD3/anti-CD28 co-stimulation, AU-007, but not an isotype control antibody, inhibited the proliferation of Tregs, indicating that AU-007 can capture endogenous IL-2 and prevent the Treg cell expansion negative feedback loop. By comparison, no inhibition of CD8+ T effector cell, CD4+ T effector cell, NK cell and NKT cell proliferation was observed under the same conditions. In murine models, AU-007 also demonstrated tumor growth inhibition in multiple cancers. AU-007 has been shown to be safe and well tolerated in primate toxicology studies (data not presented).
The poster presentation is available on the Aulos Bioscience website.
About AU-007
AU-007 is a computationally evolved, human IgG1 monoclonal antibody that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages the body’s own IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2 secreted by T effector cells from binding to trimeric receptors on T regulatory cells while still allowing IL-2 to bind and expand T effector cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to trimeric receptors on vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.
About Aulos
Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ own immune systems toward killing tumor cells. Matching world-class machine learning from founder and partner Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a computationally evolved human antibody that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and ATP with $40 million in Series A funding from ATP and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com.
SOURCE: Aulos Bio
Post Views: 29
