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DRUG:

AO-176

i
Other names: AO-176, Ti 176, AO 176
Associations
Trials
Company:
Arch Oncology
Drug class:
CD47 inhibitor
Associations
Trials
over3years
[VIRTUAL] The differentiated CD47 monoclonal antibody AO-176 exhibits significant in vivo activity against xenograft models of pediatric acute lymphoblastic leukemia (ALL) (AACR 2021)
Despite being tested in highly immune-deficient mice, the naked antibody AO-176 exhibited significant single-agent in vivo anti-leukemic activity against pediatric T-lineage ALL PDXs. The significant decrease in spleen infiltration elicited by AO-176 in 3/4 PDXs suggests on-target activity consistent with the known mechanism of action of CD47 targeting agents.
Preclinical • Late-breaking abstract
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CD47 (CD47 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CA 19-9 (Cancer antigen 19-9)
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AO-176
over3years
[VIRTUAL] AO-176, a highly differentiated clinical stage anti-CD47 antibody, is efficacious in pre-clinical models of lymphoma (AACR 2021)
Using a variety of cell based and in vivo models we show that AO-176 demonstrates increased binding to lymphoma cells at an acidic versus physiologic pH and that this binding and blocking of the do not eat me signal leads to enhanced phagocytosis of lymphoma cells either alone or in combination with rituximab. We also demonstrate that AO-176 is a potent tumor growth inhibitor in lymphoma xenograft models and appears to induce immune infiltrates as well as inflammatory cytokines.Taken together, these data show that AO-176 has strong therapeutic potential in lymphoma. AO-176 is currently being evaluated in clinical trials of select solid tumors (NCT03834948) and multiple myeloma (NCT04445701).
Preclinical
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CD47 (CD47 Molecule)
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CD47 overexpression
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Rituxan (rituximab) • AO-176
4years
[VIRTUAL] AO-176, a Highly Differentiated Clinical Stage Anti-CD47 Antibody, Exerts Potent Anti-Tumor Activity in Preclinical Models of Multiple Myeloma As a Single Agent and in Combination with Approved Therapeutics (ASH 2020)
When combined with the proteasome inhibitor bortezomib, AO-176 treatment at both 10 mg/kg and 25 mg/kg resulted in profound RPMI-8226 xenograft growth inhibition, near-total CRs (19/20 mice), and extended survival at both doses. Combining AO-176 and the anti-CD38 antibody daratumumab or immunomodulatory drugs (lenalidomide/pomalidomide) both produced significant enhancement of anti-tumor activity in xenograft models...In summary, the pre-clinical potent single agent activity and enhanced activity when combined with standard of care anti-MM agents, warrants further development of AO-176 in MM treatment. AO-176 is being evaluated in phase 1 clinical trials for the treatment of patients with solid tumors (NCT03834948) and with MM (NCT04445701).
Combination therapy • IO biomarker
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CD38 (CD38 Molecule)
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lenalidomide • bortezomib • Darzalex (daratumumab) • pomalidomide • AO-176