Aptevo Therapeutics and Alligator Bioscience Present New Preclinical Data for ALG.APV-527 at the PEGS Virtual Interactive Global Summit
New Preclinical Data Show That ALG.APV-527 has Potential for a Favorable Safety Profile
Does Not Induce Systemic T-cell Activation at High Doses Which Were Observed in a Urelumab Analogue in a Side-by-Side Comparison
ALG.APV-527 is a Novel Immunotherapeutic Bispecific Candidate Designed to Treat Multiple Solid Tumors Expressing 5T4, a Tumor-Restricted Antigen
"Our latest preclinical data for ALG.APV-527 looks very encouraging and shows that ALG.APV-527 may overcome many of the limitations observed with other 4-1BB monoclonal antibody therapeutics by improving the biodistribution, efficacy and potential safety of this novel class of immunotherapies," said
ALG.APV-527 is a novel immunotherapeutic bispecific candidate intended for the treatment of multiple solid tumors expressing 5T4, a tumor-restricted antigen. 5T4 is an antigen that is highly expressed in a large percentage of solid tumors, including, non-small cell lung cancer (NSCLC), head and neck cancer and mesothelioma. ALG.APV-527 is designed to activate anti-tumor responses by inducing signaling through the co-stimulatory receptor 4-1BB (CD137), which is an immune receptor that is upregulated on activated T cells and natural killer (NK) cells.
The preclinical data presented at the PEGS Virtual Interactive Global Summit show that ALG.APV-527 may overcome many of the limitations of competitor 4-1BB antibodies as it selectively enhances the function of activated T cells and NK cells in the presence of the tumor antigen 5T4, as shown in vitro, and potently rejects tumors in an in vivo animal model.
In a high-dose toxicity human 4-1BB knock-in murine study comparing ALG.APV-527 with a urelumab analogue, ALG.APV-527 was well tolerated at high doses with no evidence of systemic T-cell activation and no impact on body or spleen weight, whereas the urelumab analogue induced weight loss, systemic activation of T cells, and signs of ulcerative dermatitis.
In summary, the data presented at PEGS demonstrate that ALG.APV-527:
- Enhances CD8+ T cell and NK function and proliferation upon 5T4-mediated engagement
- Accumulates at 5T4-positive tumors in preclinical models
- In an in vivo human 4-1BB knock-in model:
- Induces rejection of established bladder cancer cells at low doses
- Induces anti-tumor immunological memory responses
- Does not induce systemic T-cell activation at high doses, which were observed in a side-by side comparison with a urelumab analogue
- Is well tolerated after repeated dosing in a GLP toxicology study and displays an antibody-like half-life with a mean half-life of 8 days
"Our data supports that ALG.APV-527 has the potential to induce a strong anti-tumor immune response without systemic toxicity, which is exactly what we hoped to see," commented Christina Furebring, Ph.D., Vice President Projects at Alligator.
About ALG.APV-527
ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor-directed treatment of solid cancers. ALG.APV-527 was built using Aptevo's ADAPTIR™ bispecific platform and combines binding domains sourced from the ALLIGATOR-GOLD® human scFv library. The ALG.APV-527 bispecific antibody consists of two moieties, one moiety activating tumor-specific T cells through the co-stimulatory receptor 4-1BB, the other moiety binding to the 5T4 protein displayed on the surface of tumor cells. This enables the immune-activating effect of ALG.APV-527 to be directed specifically to the tumor and not against normal tissue.
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About Alligator Bioscience
Alligator Bioscience AB is a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs. Alligator's pipeline includes five lead clinical and preclinical drug candidates: Mitazalimab, ATOR-1015, ATOR-1017, ALG.APV-527 (co-developed with
For Further Information:
Alligator Bioscience
Phone +46 46 540 82 06. E-mail: cecilia.hofvander@alligatorbioscience.com.
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https://www.accesswire.com/593328/Aptevo-Therapeutics-and-Alligator-Bioscience-Present-New-Preclinical-Data-for-ALGAPV-527-at-the-PEGS-Virtual-Interactive-Global-Summit