Date: 2018-05-08
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the PEGS meeting
Company: Alligator Bioscience (Sweden) Aptevo Therapeutics (USA - WA)
Product: ALG.APV-527
Action
mechanism:
- bispecific antibody/immunotherapy product. ALG.APV-527 is a bispecific agonistic antibody targeting 4-1BB (CD137), a member of the TNFR superfamily of co-stimulatory receptors found on activated T cells, and an undisclosed tumor-associated antigen (TAA) widely overexpressed in a number of different types of cancer.
- The co-stimulatory receptor 4-1BB is known to play an important role in modulating and augmenting the immune response to cancer by promoting the activation, expansion and enhanced effector function of tumor-specific T cells. It is, therefore, a promising target for new immunotherapeutic approaches for cancer treatment. If successfully developed, this new bispecific antibody candidate could have utility in the potential treatment of a broad spectrum of cancers including breast, cervical, non-small-cell-lung, prostate, renal, gastric, colorectal and bladder cancers. While this tumor antigen is widely expressed in multiple types of solid tumors, it shows limited expression on normal tissues, suggesting the potential for tumor-directed immunotherapy with improved efficacy and fewer side effects.
- ALG.APV-527 was co-developed with Aptevo Therapeutics. It was generated by proprietary binding elements obtained from Alligator’s ALLIGATOR-GOLD® antibody library, which were produced as a bispecific compound using Aptevo’s bispecific technology platform. ALG.APV-527 is based on Alligator’s first generation bispecific antibody, ATOR-1016.
- ALG.APV-527 is the subject of a collaboration agreement announced in July 2017.
Disease: 5T4-expressing solid tumors.
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On May 8, 2018, Alligator Bioscience and Aptevo Therapeutics announced the presentation of new preclinical data supporting ALG.APV-527 as a promising new immunotherapeutic candidate for the treatment of a variety of 5T4-expressing solid tumors. ALG.APV-527 is designed to simultaneously target 5T4 and the co-stimulatory receptor 4-1BB (CD137) to promote potent, tumor-directed immune T-cell activation. 5T4 is a well-defined tumor antigen expressed on many different types of malignancies including, non-small cell lung, renal, pancreas, prostate, breast, colorectal, gastric, ovarian and cervical cancers. Conversely, 5T4 has limited expression on normal tissues, making it an attractive target for cancer immunotherapy.
- New ALG.APV-527 preclinical data show that ALG.APV-527 has the potential to selectively activate and enhance tumor specific T cell responses at the tumor site without triggering systemic immune activation. Notably, the preclinical in vitro and in vivo data show that ALG.APV-527:
- -Stimulates increased T cell activation in the presence of 5T4-expressing cells
- -Localizes to the site of 5T4 positive tumors in an in vivo melanoma tumor model
- -Inhibits tumor growth in a 5T4 expressing in vivo human colon carcinoma model
- -Has an extended, antibody-like serum half-life of 9 days in an experimental model
The data were presented at the PEGS Summit 2018 and American Association of Immunologists (AAI) annual meeting.
- Aptevo and Alligator believe that the precise targeting of 4-1BB within the tumor microenvironment can overcome some of the limitations seen with other 4-1BB therapies. ALG.APV-527 employs a novel mechanism of action, 4-1BB x 5T4 binding, to direct the therapeutic immune response towards the tumor, thereby potentially reducing the harmful side effects of systemic immune stimulation while providing a strong tumor directed immune activation.
- • On August 17, 2017, Aptevo Therapeutics and Alligator Bioscience announced that the companies have initiated CMC activities for the manufacturing of clinical material in preparation for a future investigational new drug (IND) submission for the bispecific immuno-oncology antibody ALG.APV-527.
Is
general: Yes
