Annexon, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Yeah. Thanks, Pete. Thanks, Cantor. Happy to be here. I think this is our eighth year in a row, and always delighted to join this conference. I'm Doug Love, as Pete said, CEO of Annexon, founding CEO. I've been in the chair the past 11 years, and we're excited about the progress of the company since then. For those who are less familiar with Annexon, we are a complement-focused company, really stopping neuroinflammation right where it starts, on disease tissue in the body, brain, and eye. Over the course of 11 years, we've advanced multiple drug candidates. We're happy to be here today with two late-stage programs, one in Guillain-Barré syndrome, where we were successful in a large phase III pivotal study and are now on file in Europe and will file shortly in the U.S.

Following that, we have a large geographic atrophy program, the only program in the world to demonstrate significant vision preservation, both on all of the measures of visual function as well as significant protection of photoreceptor neurons responsible for visual acuity. So we're in a large phase III program there, which we'll read out in Q4. We're excited about what we've done over the last 11 years and more excited about what's ahead for us. Our mission is really to impact millions of patients worldwide living with devastating neuroinflammatory diseases for which there are no disease-modifying therapies. We're right on the cusp of doing that. So joining me today is Dr. Lloyd Clark, our SVP of Ophthalmology Strategy, and I don't know if, Lloyd, you'd like to just quickly introduce yourself.

Thanks, Doug. Pete, thanks for having us. 25-year career as a practicing retina specialist, extensive experience on the drug development side. Joined Annexon about a year and a half ago as we build out an ophthalmology business unit. Really excited to be here and excited about our opportunities with vonaprument.

Yeah. Unfortunately, the unmet need for geographic atrophy is immense. This is a disease with 8 million patients worldwide, leading cause of blindness, and the two first-generation drugs that are currently on the market really provide symptomatic benefit to the disease. That is, they are protecting against a structure in the eye that has not demonstrated protection of visual acuity. The opportunity is to do just that, to protect vision in patients with geographic atrophy with our therapy.

Yeah. Two components to the study. One was an aspect of structural assessment on RPE cells, which have historically been thought of as the structure in the eye that was necessary to protect to ultimately demonstrate visual preservation. There, we were not statistically significant on that particular endpoint. We did show a nice trend, which increased over the course of the 12-month study. However, what we did do in the study is demonstrate significant vision preservation, importantly, on best-corrected visual acuity 15 letter loss. This is the gold standard endpoint for visual acuity, and we demonstrated a dose-dependent response there on that endpoint, as well as its sister endpoint, low luminance visual acuity, or LLVA, and then LLD, et cetera.

In other words, we were statistically significant on all of the functional assessments of visual acuity in this study, all of which was dose responsive, which we think is really, really important. As I said before, associated with that, the how we ultimately demonstrated that, and that was by having significant preservation of the photoreceptor neurons in your eye that are responsible for visual acuity. It is important to note that your photoreceptor neurons are what are lost first in geographic atrophy. Following that, you lose your RPE cells underneath that. By protecting your photoreceptor neurons, not only are you strengthening the overall neuronal unit, which includes your RPE cells, it does translate to visual outcomes. From a safety perspective, the drug performed really nicely from that perspective as well.

Maybe I will bring that over to Lloyd as a treating retina specialist.

Well, first of all, I think it is important to understand that the endpoint is the most compelling piece. Losing 15 letters of vision typically renders a patient unable to drive, unable to read small print. This gold standard endpoint, confirmed 15 letter loss, first of all, is incredibly important to think about, and any statistically significant difference in that endpoint is highly clinically relevant for patients. Now, specifically, the risk reduction is incredibly important. That is a very, very easy number to talk to patients about. To be able to cut the likelihood of losing that clinically relevant endpoint by almost 75% is incredibly compelling data.

Or maybe said differently, three out of four patients had their vision protected in our study, and that's really a really high bar.