Surrozen's SWEETS Platform Shows Potential to Enhance Wnt Signaling in 'eLife' Study

Surrozen, Inc., a biotechnology company known for its innovative approaches in targeted therapeutics, has announced significant advancements in enhancing Wnt-signal activation through its unique targeted protein degradation (TPD) platform. The company's new findings were recently published in eLife, showcasing the development of two new ASGR-targeted SWEETS (Surrozen Wnt Signal Enhancer Engineered for Tissue Specificity) bispecific antibodies. These antibodies have demonstrated unique capabilities in promoting Wnt-signal activation, which is crucial for tissue repair and regeneration.

The newly developed ASGR-targeted SWEETS bispecific antibodies have shown promising results in enhancing Wnt-signal activation. This advancement builds on previous research by Surrozen scientists, which involved fusing a mutant RSPO2 protein to an antibody targeting the ASGR1 receptor. This fusion led to liver cell-specific enhanced signaling, proliferation, and restored liver function in mouse models. The new antibodies revealed distinct epitopes on both ASGR1 and ASGR2, resulting in robust and cell-specific Wnt-signal activation.

The unique TPD platform utilized by these SWEETS molecules functions through multiple mechanisms, expanding the potential applications of this technology in treating liver diseases. The targeted protein degradation approach offers an innovative way to enhance Wnt signaling, which could provide new therapeutic options for conditions with unmet medical needs, such as severe liver disease. Dr. Yang Li, Executive Vice President of Research at Surrozen, emphasized the importance of this work in boosting Wnt signaling through protein degradation technologies, highlighting the company's commitment to developing novel treatments for severe liver disease.

In addition to the eLife publication, Surrozen also announced the release of a review article in iScience. This article provides a comprehensive summary of the work done by Surrozen and other researchers in the field of Wnt signaling. It discusses the rationales and design rules behind various Wnt activating platforms and insights gained from studies on these novel molecules in different tissues. The review highlights the progress made in this emerging field and the potential of Wnt agonists in treating numerous tissue degenerative diseases.

One of Surrozen's key development candidates using the SWEETS technology is SZN-043, aimed at treating severe alcohol-associated hepatitis. Surrozen has completed a Phase 1a clinical trial for SZN-043, which included patients with a history of liver cirrhosis and healthy volunteers. The trial showed that SZN-043 was safe and well-tolerated in both single and multiple intravenous doses, with evidence of target engagement, Wnt signal activation, and positive effects on liver function. The Phase 1b clinical trial is currently enrolling patients with severe alcohol-associated hepatitis, and Surrozen expects to have proof-of-concept data available in the first half of 2025.

Wnt signaling plays a critical role in the development, homeostasis, and regeneration of essential organs and tissues, including the liver, intestine, lung, kidney, retina, central nervous system, cochlea, and bone. Modulating Wnt signaling pathways has the potential to treat degenerative diseases and tissue injuries. Surrozen's platform and proprietary technologies aim to overcome the limitations in utilizing the Wnt pathway as a therapeutic strategy, focusing primarily on severe liver and eye diseases.

Surrozen continues to pioneer in the field of targeted therapeutics, leveraging its expertise and innovative platforms to develop drug candidates that selectively modulate the Wnt pathway. The company's advancements in SWEETS bispecific antibodies and targeted protein degradation technologies represent a significant step forward in the development of regenerative medicines.