Surrozen Highlights Wnt Retina Pipeline, SZN-8141 IND Timeline at H.C. Wainwright

Key Points

• Surrozen is advancing a Wnt-based retina strategy centered on Frizzled-4 signaling, with CEO Craig Parker saying human genetics support the target in retinal vascular disease and that the approach may complement existing anti-VEGF therapy.
• SZN-8141 showed encouraging preclinical synergy by combining Wnt agonism and VEGF inhibition, with data suggesting better efficacy than either mechanism alone and potential benefits for reducing avascular areas in diabetic macular edema models.
• The company plans to file an IND for SZN-8141 in the second half of this year and said differentiation could come from stronger drying effects, addressing retinal non-perfusion, and potentially supporting less frequent dosing if human data are positive.

Surrozen NASDAQ: SRZN Chief Executive Officer Craig Parker outlined the company’s rationale for developing Wnt-targeting retinal disease therapies during H.C. Wainwright’s 6th Annual Ophthalmology Investor Conference, emphasizing the company’s focus on Frizzled-4 signaling, anti-VEGF activity and, in one preclinical program, IL-6 inhibition.

In a discussion moderated by Matthew Caufield, a senior biotech analyst at H.C. Wainwright, Parker said the company’s interest in Frizzled-4 is rooted in human genetics tied to rare pediatric retinal vascular diseases. He said mutations in the Frizzled-4 receptor, the ligand Norrin and the LRP co-receptor have been linked to loss of Wnt signaling in retinal vascular endothelial cells, leading to leaky and poorly developed vessels.

While those childhood diseases do not exactly resemble wet age-related macular degeneration or diabetic macular edema, Parker said they share overlapping features, including leaky vessels and impaired blood-retinal barrier tight junction proteins. He said that history helped establish Frizzled-4-mediated Wnt signaling as a target for retinal vascular disease.

Surrozen Highlights Dual- and Tri-Specific Retina Programs

Parker discussed Surrozen’s preclinical SZN-8141 program, which combines Frizzled-4-mediated Wnt activation with VEGF inhibition. He contrasted the program with SZN-413, a bispecific Wnt agonist antibody previously licensed to Boehringer Ingelheim, and said the company’s retina strategy reflects an evolving field in which developers are pursuing multifunctional antibodies aimed at multiple disease contributors.

“VEGF is foundational therapy,” Parker said, noting that VEGF-targeting agents are effective in improving visual acuity and reducing retinal vessel leakage. However, he said other contributors to disease have been identified, including Wnt signaling and inflammatory mediators such as IL-6.

Surrozen is also developing SZN-8143, a preclinical tri-specific candidate designed to activate Frizzled-4 while inhibiting VEGF and IL-6. Parker said IL-6 became relevant in retinal disease following observations in autoimmune patients with uveitic macular edema, as well as biomarker studies showing elevated IL-6 in conditions including uveitic macular edema and diabetic macular edema.

He said Surrozen believes there is evidence that IL-6 contributes to uveitic macular edema and, in some diabetic macular edema patients, inflammatory disease components. Parker described SZN-8143 as a “quite complex, large antibody” intended to preserve VEGF inhibition, IL-6 inhibition and Wnt activation in a single molecule.

Preclinical Data Suggests Potential Synergy

Parker said preclinical data presented at ARVO suggested synergy between Wnt agonism and VEGF inhibition in SZN-8141. He described experiments using oxygen-induced retinopathy, a model associated with diabetic macular edema, and choroidal neovascularization, a model of wet AMD.

In those studies, Surrozen tested SZN-8141 against versions of the molecule that either retained Wnt agonism without VEGF inhibition or retained VEGF inhibition without Wnt agonism. The company also tested a mixture of the separate Wnt agonist and VEGF antagonist components.

Parker said the combined SZN-8141 molecule showed better efficacy in the oxygen-induced retinopathy model than either Wnt agonism or VEGF inhibition alone at the same concentration. He added that the full molecule performed better than the mixture of the two separate components, suggesting what he called an “intrinsic benefit” to combining the mechanisms in one molecule.

A key finding, Parker said, was reduction of avascular areas in the model, which he linked to the clinical concept of retinal non-perfusion in diabetic macular edema. He said current VEGF drugs work well on leakage and visual acuity but “don’t really do anything” to areas of retinal non-perfusion, which are associated with more active disease and disease progression.

Differentiation Could Depend on Drying and Reperfusion

When asked how SZN-8141 could differentiate itself from other Wnt pathway therapies, including Merck’s Restoret program, Parker said the most important measures would include whether it can act as a better “drying” agent and whether it can address retinal non-perfusion.

He said retinal fluid can be assessed through optical coherence tomography, with measures such as central subfield thickness, absence of macular edema or complete absence of fluid. Parker said a therapy that is both a superior drying agent and able to reperfuse areas of non-perfusion could be “transformative” for the field.

Parker cautioned that the current data are preclinical and based on mouse models, though he said those models have been validated by approved retinal drugs. He said human data will ultimately determine whether the preclinical findings translate.

He also said a highly competitive profile in diabetic macular edema could include a high percentage of patients with no macular edema or intraretinal fluid, along with a less frequent injection schedule. Parker said the company is optimistic SZN-8141 could potentially support less frequent dosing than every other month, but added that animal and human data will dictate durability.

Clinical Development Considerations

Parker said the current regulatory path in diabetic macular edema is primarily focused on treatment-naive patients. He said registrational studies would be expected to include a preponderance of treatment-naive patients, potentially around 75%, because that population is considered the cleanest for observing a treatment effect.

He also acknowledged unmet need among patients who remain incomplete responders to current therapies such as Eylea or Vabysmo. Parker said a study in such patients could be meaningful if switching to SZN-8141 resolved residual fluid, though he noted there is no precedent for such a design leading to a label in that specific population.

Caufield noted that Surrozen is targeting an investigational new drug application for SZN-8141 in the second half of this year, and Parker confirmed that timing. Parker said clinical proof-of-concept could involve established endpoints and imaging tools, including ETDRS visual acuity testing, OCT fluid measurements, OCT angiography and ultra-wide fluorescein angiography. He said Surrozen also plans to evaluate aqueous humor samples for soluble biomarkers of treatment response or Wnt pathway activation.

Broader Wnt Opportunity in Eye Disease

Looking beyond SZN-8141, Parker said the company believes Wnt signaling may have broader applications across retinal vascular diseases, including wet AMD, diabetic macular edema, uveitic macular edema and retinal vein occlusion. He said Wnt activation upregulates tight junction proteins in retinal vessels, which could directly reduce vessel leakage.

Parker also said there are other Wnt-responsive tissues in the eye, including potential front-of-the-eye targets, though he noted Surrozen has not emphasized other funded programs in that area. He said success with SZN-8141 could lead the company to pursue additional ocular cell types and targets involving other Frizzled receptors.

About Surrozen (NASDAQ:SRZN)

Surrozen, Inc is a clinical-stage biopharmaceutical company focused on developing novel therapeutic antibodies that target the Wnt signaling pathway for applications in tissue repair, regeneration and oncology. Founded in 2012 and headquartered in South San Francisco, California, the company leverages its proprietary SurroBody platform to design bispecific antibody molecules capable of modulating Wnt receptor activity with enhanced tissue specificity.

The SurroBody platform enables the generation of high-affinity, dual-binding antibodies engineered to either activate or inhibit Wnt signaling, a pathway critical to cell proliferation, differentiation and homeostasis.

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