Surrozen, Inc. Common Morgan Stanley 24th Annual Global Healthcare Conference

Sure. I'm Craig Parker. I'm the CEO at Surrozen.

I'm Dan Chao, Vice President and Head of Clinical Development.

Yeah. This is really a momentous year and great time for the company. We just filed an IND to start our first clinical trial with SZN-8141. The excitement about the molecule is about bringing together two mechanisms in one molecule to treat retinal vascular diseases. One is anti-VEGF. This is a well-established therapy, really has been a phenomenal, I think, breakthrough for patients with retinal vascular diseases, but it doesn't provide complete control for all patients. We started off as a Wnt biology company, and it turns out that Wnt has been implicated in normal function of retinal vessels. One of our competitors has shown some clinical data validating the approach of activating the Wnt pathway for retinal vascular diseases. I think we're really excitingly bringing together what we think are the two best mechanisms for treating these diseases into one molecule.

Dan and our clinical development team have designed a study we've called DUET, which we think has the opportunity to really reveal what could be a best-in-category or best-in-disease even control of fluid accumulation in these patients, potentially visual acuity, and potentially something which could really be breakthrough of reperfusing the retina in patients who have diabetic eye disease in particular. Really, it's a pretty unique moment for the company, and I think an exciting time for particularly the clinical development team to get this molecule into patients.

I'll let Dan answer that.

Yeah, sure. Thanks, Craig. I think when we think of the Wnt pathway, I think first of all, the Wnt pathway is a very ancient and conserved pathway important in many organ systems for regulation and repair, and that is no different than in the eye, and in particular, the retinal vasculature. It's been known for a very long time that these Wnt proteins are important for both the development of the normal vasculature as well as maintenance of the blood-retina barrier. In fact, there is actually human genetic evidence that some of the key proteins, such as the Wnt receptors Fzd4 and LRP5, are actually linked to human disease where there's incomplete development of the retinal vasculature. This leads to a really, I think, complementary approach as we think of anti-VEGF.

Now, vascular endothelial growth factor is a pathologic cytokine in the context of diabetic macular edema, which causes leakage, so kind of a pro-pathogenic cytokine. Whereas Wnt, we think of as more a restorative, reparative pathway, where we know that the Wnt pathway is important for upregulating tight junctions of proteins which are important for repair of the blood-retina barrier. So in fact, we think we're attacking this through very complementary mechanisms compared to anti-VEGF, where we're preventing leakage, and with Wnt, it's really more a restorative, reparative pathway. We think that combining these two then leads to additive and even synergistic effects in control of disease.

Yeah, absolutely. I think part of it is highlighting some of the data that Craig had mentioned. First, I think there's strong scientific rationale for targeting the Wnt pathway as a restorative pathway. In fact, a lot of preclinical data, including our own, shows that activating the Wnt signaling pathway can show actually strong efficacy in a number of preclinical retinal vascular disease models. In particular, I think the recent phase I, II data from first-generation Wnt agonist, Restoret, showed very robust increases in BCVA and CFT that are comparable to VEGF, and that level of efficacy has not been seen outside of any non-VEGF mechanism. So on the surface, the idea of putting together the two strongest mechanisms within disease, VEGF and Wnt, could have the potential to lead to better therapies beyond the standard of care.

I think the next piece of evidence is, what is the evidence that Wnt and VEGF are actually additive and not overlapping? I think that comes from our preclinical data where we've shown that when we compared our molecule, the SZN-8141 dual molecule versus a molecule where we've either inactivated the Wnt part of the molecule or the VEGF part of the pathway or even a co-formulation of the two is that our SZN-8141 combination molecule shows superior efficacy compared to all those. So suggests not only additive efficacy, but potential also synergistic efficacy. In a different preclinical model, in a wet AMD model, we've also shown that SZN-8141 was superior to aflibercept or EYLEA in reducing leakage, again, showing the additive benefit of these two pathways.

Then we've now designed the DUET trial to test and confirm whether these preclinical results translate into humans.