On December 21, 2023 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs for cancer, reported the publication of extensive preclinical data on SON-1210 in Frontiers in Immunology (Press release, Sonnet BioTherapeutics, DEC 21, 2023, View Source [SID1234638755]). SON-1210, Sonnet’s lead proprietary bifunctional compound, combines the company’s FHAB construct with a novel single-chain IL-12 and fully human Interleukin 15 (IL-15). The paper, entitled "SON-1210 – a novel bifunctional IL-12 / IL-15 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy", demonstrated the robust binding affinity of SON-1210 to albumin and the anticipated in vitro activity and tumor model efficacy that might be expected from the body of research on native IL-12 and IL-15. In the B16F10 melanoma model, a single dose resulted in a marked reduction of tumor growth that was concomitant with increased IFNg and augmented immune cell numbers and activity in the tumor microenvironment. Repeat doses in non-human primates displayed excellent safety and tolerability and were similarly accompanied by increased IFNγ levels.

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"We are pleased to share these encouraging preclinical findings, which support the advancement of SON-1210 into future clinical development." said Pankaj Mohan, Ph.D., Founder and CEO of Sonnet. "These data support the impact of our proprietary engineering of SON-1210 to provide opportunity to target the tumor microenvironment (TME), redirect the immune response, and control tumor growth, positioning us to advance our mission to realize the full potential of this therapeutic class for cancer patients."

The manuscript can be accessed through the following link:

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1326927/full

About SON-1210

SON-1210 is an immunotherapeutic bifunctional drug candidate that links unmodified single-chain human IL-12 and human IL-15 with the albumin-binding domain of the single-chain antibody fragment FHAB separating the two cytokines with linkers to avoid steric hindrance. The FHAB single chain was selected to bind well at normal pH, as well as at an acidic pH that is typically found in the tumor microenvironment (TME). The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose-sparing, enhanced pK, and an opportunity to improve the safety and efficacy profile of not only IL-12 and IL-15, but a variety of other potent immunomodulators using the platform. We believe the two cytokines can orchestrate a robust immune response to many cancers and pathogens, particularly when presented together on the same molecule. Given the types of proteins induced in the TME, such as Secreted Protein Acidic and Rich in Cysteine (SPARC), several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1210 is designed to deliver IL-12 and IL-15 to local tumor tissue, with the intention of turning ‘cold’ tumors ‘hot’ by stimulating IFNg, which activates both innate and adaptive immune cells in the TME, as well as increasing the production of Programed Death Ligand 1 (PD-L1) on tumor cells.