Surrozen Shares Early Phase 1a Results of SZN-043 in Healthy Volunteers and Liver Cirrhosis Patients at 2024 EASL in Milan

Surrozen, Inc. has recently shared promising early results from its Phase 1a clinical trial of SZN-043, a novel R-Spondin mimetic, at the 2024 European Association for the Study of the Liver (EASL) conference in Milan. The company, renowned for its work in targeted therapeutics that activate the Wnt pathway for tissue regeneration, reported that SZN-043 induced liver cell proliferation and exhibited a favorable safety profile in both healthy volunteers and individuals with a history of liver cirrhosis.

The Phase 1a trial was a randomized, placebo-controlled study involving 40 healthy volunteers and 8 patients with past liver cirrhosis. Participants received either single or multiple intravenous infusions of SZN-043 at doses ranging from 0.5 mg/kg to 3 mg/kg. The treatment was deemed safe and well-tolerated, with only mild to moderate, transient, and dose-related increases in serum transaminase levels, which normalized without any intervention. Importantly, these elevations were not linked to other markers of liver disease or damage.

Pharmacodynamic data from the study provided convincing evidence of Wnt pathway activation in the liver following SZN-043 administration. Increased levels of alkaline phosphatase (ALP) indicated effective binding of SZN-043 to its target, the asialoglycoprotein receptor (ASGPR) on hepatocytes. This interaction led to a transient reduction in ALP clearance, consistent with the engagement of other ASGPR-targeting agents. Furthermore, the methacetin breath test showed enhanced methacetin clearance after SZN-043 treatment, pointing to the activation of the Wnt target gene CYP1A2 in liver cells.

Additional liver function improvements were observed through HepQuant measurements, which showed increased portal hepatic filtration rates (HFR), likely due to Wnt-mediated stimulation of cholate clearance. This effect highlights the potential of SZN-043 to enhance liver function through the modulation of Wnt signaling.

Surrozen is progressing with the Phase 1b trial of SZN-043, enrolling patients with severe alcohol-associated hepatitis. This open-label study, which began in the second quarter of 2024, aims to recruit up to 30 participants. The trial will assess various parameters, including safety, pharmacokinetics, immunogenicity, and several efficacy endpoints such as MELD and Lille scores, both of which are predictive of clinical improvement and 90-day survival. Initial proof-of-concept data are anticipated in the first half of 2025.

In addition to SZN-043, Surrozen is developing SZN-413 for retinal diseases using its SWAP™ technology. SZN-413 targets Fzd4-mediated Wnt signaling and has shown promising preclinical results, including the stimulation of normal retinal vessel growth, suppression of pathological vessel growth, and reduction of vascular leakage. These findings suggest potential for not only halting retinopathy but potentially reversing the disease.

Surrozen has entered into a strategic partnership with Boehringer Ingelheim for the development of SZN-413. Under this agreement, Boehringer Ingelheim has an exclusive global license to develop SZN-413 and related molecules, with Surrozen eligible for up to $587 million in milestone payments and royalties on sales.

The company continues to focus on leveraging its innovative platform technologies to modulate the Wnt pathway, aiming to provide new therapeutic options for tissue regeneration and repair. Wnt signaling is crucial for the development, maintenance, and repair of various tissues, and Surrozen’s targeted approach holds significant promise for treating degenerative diseases and injuries.

Surrozen remains committed to advancing its pipeline and addressing unmet medical needs through its pioneering research in Wnt pathway modulation.