On December 15, 2021 Alligator Bioscience AB ("Alligator") and Aptevo Therapeutics ("Aptevo") (NASDAQ: APVO) reported publication of an article in the December 15, 2021, issue of the peer-reviewed journal, Nature Communications on the mechanism of action of CD137 (4-1BB) targeting bispecific antibodies (Press release, Alligator Bioscience, DEC 15, 2021, View Source [SID1234597187]). Nature Communications is an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, health, physical, chemical and Earth sciences.

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The article titled, CD137 (4-1BB) co-stimulation of CD8 T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation, details the mechanism of action of 4-1BB targeting bispecific antibodies. This work was published in collaboration by internationally renowned 4-1BB expert, Professor Ignacio Melero, and his team at the University of Navarra, Pamplona, Spain. Professor Melero’s data supports the bispecific antibodies, such as ALG.APV-527, targeting 4-1BB, and link 4-1BB signaling in cis (directly to tumor targets, such as 5T4), are more efficient at stimulating the anti-tumor response than bispecific agents that link 4-1BB signaling in trans to adjacent non-tumor cell targets such as the stroma.

"This study unveils an important mechanism for tumor-cell targeting therapies for cancer. Bispecific antibodies targeting 4-1BB offer a synthetic biology that can be very useful in cancer immunotherapy. In this study, we found a spatial requirement in regard to antigen recognition and 4-1BB co-stimulation. This means that the T cells can detect the antigen on the same cell that is providing natural or artificial 4-1BB co-stimulation. This type of co-stimulation, and the ensuing immune system activation and survival, is far more potent. The bispecific antibody from Alligator Bioscience and Aptevo Therapeutics, ALG.APV-527, is a tool that shows this potent 4-1BB co-stimulation in the tumor microenvironment and has the potential to provide a superior therapy to treat cancers," stated Ignacio Melero, MD, PhD, Cima and Clínica Universidad de Navarra, Spain.

"We are very pleased to have been selected for publication in a high-ranking peer-reviewed journal such as Nature Communications. This is very encouraging and validates the superior mechanism and design of ALG.APV-527. The data further highlights the strong positioning of ALG.APV-527 in the bispecific 4-1BB antibody field," said Søren Bregenholt, CEO at Alligator.

"The publication of Professor Melero’s findings further support the potential of ALG.APV-527 overall, to evoke an effective tumor-targeting immune response with fewer adverse events. This work highlights the potential differentiating benefit of ALG.APV-527 to induce stronger and more tumor-directed T cell responses with the potential for improved safety and efficacy in patients and represents a significant contribution from the scientific teams at Aptevo and Alligator. We are proud of their achievements and know their work will continue producing invaluable data going forward," commented Marvin White, CEO of Aptevo.

The complete article is available in print and in digital format which can be viewed via the following link: (link to article).

About ALG.APV-527

ALG.APV-527 is a 4-1BB and tumor-binding immunomodulatory antibody. 4- 1BB has the ability to stimulate the immune cells (anti-tumor specific T cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. The tumor-binding part of ALG.APV-527 targets the 5T4 tumor-associated antigen. 5T4 is a protein expressed in multiple tumor types, as well as certain types of aggressive tumor cells (tumor-initiating cells), but at low levels or not at all in normal tissue, making 5T4 a compelling target molecule for cancer therapy.

Alligator and Aptevo are advancing ALG.APV-527 into Phase I clinical development. The companies will continue to explore licensing opportunities as ALG.APV-527 moves into clinical development.