On November 8, 2019 Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company focused on developing novel immuno-oncology and hematology therapeutics and Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy reported that new preclinical data for ALG.APV-527 are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting at the National Harbor, Maryland, November 6-10, 2019 (Press release, Aptevo Therapeutics, NOV 8, 2019, View Source [SID1234550769]).
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ALG.APV-527 is a novel immunotherapeutic candidate intended for the treatment of a variety of 5T4-positive solid tumors. It is designed to induce signaling through the co-stimulatory receptor 4-1BB (CD137), which is present on activated cytotoxic T cells and natural killer (NK) cells. Once activated, it is designed to promote potent and selective tumor-directed immune activation in the presence of the tumor associated antigen, 5T4, which is present on many different types of solid tumors.
The preclinical data presented at SITC (Free SITC Whitepaper) show that ALG.APV-527 selectively enhances T cell and NK cell responses in the presence of 5T4 in vitro and displays potent and sustained tumor suppression in vivo. The preclinical studies demonstrate that ALG.APV-527:
Enhances CD8+ T cell and NK function and proliferation preferentially over that of CD4+ T cells, upon 5T4-mediated crosslinking
In preliminary in vivo studies in a human 4-1BB knock in model, induces rejection of established murine bladder cancer cells expressing human 5T4 at doses of 20 µg in mice and induces anti-tumor immunological memory responses
Is well tolerated after repeated dosing in a GLP toxicology study above the expected human dose and displays an antibody-like half-life of up to 9.5 days
"We’re pleased that ALG.APV-527 continues to show promising preclinical results," said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo. "The ability of ALG.APV-527 to induce potent anti-tumor T cell and NK cell activity suggests 4-1BB is an attractive target for designing new immuno-oncology therapeutics. Monospecific 4-1BB-directed antibodies have been challenged by dose-limiting liver toxicities. As a novel bispecific antibody ALG.APV-527 may circumvent these challenges and minimize systemic toxicity by stimulating 4-1BB function only when co-engaged with the tumor antigen, 5T4."
"The presented preclinical data strongly support a potent effect of ALG.APV-527 without compromising on safety. The data further strengthens our CTA package and we are eagerly looking forward to discuss this candidate with potential partners to take this exciting asset further into clinical development," commented Christina Furebring, Ph.D., Vice President Preclinical Development at Alligator.
The Alligator/Aptevo poster presentation, entitled "Potent Tumor-Directed T Cell Activation and Tumor Inhibition Induced by a 4-1BB x 5T4 ADAPTIR Bispecific Antibody" is being presented on Saturday, November 9, 2019 from 7:00 am – 8:30 pm ET.
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 parts, one part activating tumor-specific T cells through the co-stimulatory receptor 4-1BB, the other part 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.