Annexon, Inc. (ANNX) May 13, 2026 Conference Transcript

Okay, good afternoon or still good morning, I think. Welcome back to the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I'm one of the senior biotech analysts at the bank. It's my pleasure to have our next presenting company with us at Nexon Biosciences. Presenting for Nexon this morning will be Doug Love, who is president and CEO. Doug, welcome back to Las Vegas.

Thanks so much, Tazeen. We're always happy to be here. We appreciate Bank of America.

So maybe we can just do a quick overview of an Exxon, your platform and your programs, and then we can go into a little bit more detail on some of the upcoming data catalysts.

Yeah, happy to do that. I'll be brief. An Exxon is a leading neuroimmunology company, Sarah, a little tongue-tied there. It has been already. Anyway, we're targeting complement, which many of you are familiar with, of a very differentiated approach. So we're targeting the classical complement pathway, and importantly, C1Q, the initiator of the pathway, it's completely different from any other complement approach people may be familiar with in that C1Q localizes and binds to diseased tissue and a host of neuroinflammatory diseases in the body, brain, and eye. We're 11 years into the journey, and we're more excited than ever at where we are. So after 11 years, we are led by two leading programs. One is in Guillain-Barre syndrome, an acute neuromuscular disease, in fact, the leading cause of acute neuromuscular paralysis in the world. There we were successful in a pivotal phase three study, really showing dramatic improvement in patients within a week and durable out to six months and beyond. And so we're really looking forward to making this drug available worldwide to patients. We have filed in Europe for approval, and we will be filing in the U.S. for this program as well. The second lead program is geographic atrophy, a separate drug candidate, intravitual administration via Bonaprumit. There, this is the only program to demonstrate significant vision preservation on all measures of visual acuity, including the gold standard measurement of best corrected visual acuity, 15-letter loss. We also showed, importantly, significant preservation of retina neurons in the eye responsible for visual acuity. These are photoreceptor cells and even more pronounced protection in the central retina. So really excited about this program. We're in a large phase three program, 659 patients that will read out in Q4. Last program is a really novel, first in kind, small molecule program. First small molecule program targeting the classical pathway. All three of our programs are designed to be market winners. And so as it relates to the small molecule, we're advancing it in a proof-of-concept study with the aim of ultimately taking it into a host of neuromuscular diseases that have currently been clinically validated but are being treated by antibodies, either by IV and more recently by subcutaneous approaches. So a holistic approach with the aim to treat millions of patients worldwide suffering from neuroinflammatory diseases, and we're energized by that.

Thank you for that overview. So maybe let's start off on geographic atrophy. You've got the pivotal study that's going to be reading out this year. Just mechanistically on C1Q, it's differentiated from the other two approved drugs in the market. We've talked about this in the past, but just remind us why mechanistically you think that there is a higher chance of showing a benefit on visual acuity, which is what your primary endpoint is for phase three?

Really good question. So as I said before, not all complement is the same, and targeting C1Q in the classical pathway is very different than the first-generation approach is targeting C3 and C5. What C1Q does is it binds to the locus of the disease, geographic atrophy, as it relates to visual acuity. These are photoreceptor synapses and neurons that are responsible for receiving light so that we can go forth and conquer c1q binds that and drives their removal this process happens prior to what the downstream uh complement um target components are targeting which are rpe or lesion growth it's really important to understand that so the way geographic atrophy works the photoreceptor neurons as i said before receive light and that's how we see underneath the photoreceptors are called RPE sales that provide trophic support for your photoreceptors to be healthy. These are durable sales. Unfortunately, for the programs that have already been approved, you lose your photoreceptor sales before you lose your RPE sales. The downstream approaches are targeting RPE sales after you've already lost your vision. And so as a result, you're not able to protect vision by protecting RPE sales, whereas by blocking C1Q, you are protecting your photoreceptor synapses in cells, which we've demonstrated preclinically and now clinically, and that's led to the vision preservation that we see in our studies.

So just remind us about powering of the study and how many patients do you have in each of the arms and what should we expect to see at the top line when the press release comes So as I said before, the data we'll read out in Q4.

The study is a 659-patient double-masked study. It's a randomized two-to-one treatment arm to the sham arm. It's the five-mid-muffly dose. And what we will read out in the top line is both outcomes on multiple visual acuity measures as well as the key structural measure in our study, which is protection of photoreceptors is measured by EZ or OCT analysis. So we're really encouraged by that.

So, if VA is the primary endpoint, you know, there's kind of one way to win on this, which is you show a statistically significant impact on that endpoint. With your discussions with FDA, I'm just curious, if the results come and it looks like it's a trend, but for whatever reason isn't stat sick, does that provide an avenue to continue to pursue an approval?

That's a good question. So we do think there are multiple ways to win. Our base case is that we will win on the primary endpoint, best corrected visual acuity, 15-letter loss. We are looking at key secondary measures, like I said before, OCT, low luminous, visual acuity, et cetera. The way the study is designed is it's a single protocol study of 659 patients. For approval in Europe, we need to win on that single analysis. In the U.S., in agreement with the FDA, we have two sub-studies that roll in under the single protocol. Each sub-study has been powered at a high phase three powering, so greater than 90%. And so our base position for winning is in Europe, we went on the overall study. In the U.S., we went on the two sub-studies. If we find ourselves in a circumstance where we went on the overall study and one of the sub-studies, I think that's a discussion we would have with the FDA for moving it forward as well.

Okay. Now, if you think about the uptake that you've seen with the other two approved drugs, what do you think has been rate limiting for those?

Yeah, it's twofold, actually. You know, the first is, of course, you are not providing visual benefit for patient population where vision is the key endpoint for these folks. This is what they're looking for. A point about best corrected visual acuting 15-letter loss, what that represents is 50% of your vision over whatever period of time in which you are assessing that. So that is quite significant. By law, you're having to turn in your driver's license. You, in effect, lose your independence. And so you can imagine as a person who is elderly, the average age of the patients entering our study is 80 years old. So if you're coming in to get a shot in the eye every month or every other month, you're looking for preservation of your vision. The drugs that have been approved, unfortunately, have not done that after four, four and a half years worth of data. And because they are targeting a lagging indicator of the disease, RPE lesion growth, it's unlikely that they are going to demonstrate vision preservation, certainly not in a reasonable period of time. We've already seen that. And so that's impacted the market uptake, if you will. We know 80% of patients are not being treated in the GA market currently with the current therapies of those 20 or so percent of patients who are being treated somewhere between a third and half of them are discontinuing treatment within a year of therapy. So the current first-generation therapies, they're an advancement, but they're not really solving the need for this patient population. On the other hand, with our approach with Vaughn and Prumit, by blocking C1Q and protecting retina neurons or photoreceptors in the eye, which result in functional preservation of vision. Again, we've measured that on every assessment, BCVA, low luminous visual acuity, etc. We are giving patients their independence and their life back. We expect the update to be quite, quite significant and early on because it's a complete paradigm shift. One other thing to note about our data in the phase two and what we're encouraged about with the phase three is that when you look at patients who are earlier in the disease process, excuse me, earlier in the disease process as described or defined by low luminous visual deficit of 30, zero out of 56 of those patients in our study lost vision. So this is early neurodegeneration. You want to stop the disease process so you can go forth and conquer the remainder of your life. Zero out of 56% lost vision, whereas in the sham group, about 17% of those patients lost vision. So why that matters for us is we anticipate rapid uptake just because we have vision preservation alone, but we think it's going to be even bigger because we're going to be able to punch into earlier stage disease and being able to attack neurodegeneration before it gets too far advanced. And that's what you see in all neurodegenerative diseases, whether it's Alzheimer's, Parkinson's, whatever. You want to treat patients earlier in the disease before you've had too much neuronal damage. And that expands your market opportunity as well. So we're really encouraged by the opportunity of this commercially.

Okay. What type of commercial footprint do you think you'll need to have, assuming that you're able to launch?

Yeah, good question. It's a really efficient opportunity here. So there are about 3,000 retina specialists here in the U.S. Most are in large practices, although not all. And we know that we can get to these physician practices in a multitude of ways, but in a very concentrated way. The thing I love about the retina community is it's very well integrated. There are a lot of conferences. There are a lot of communications. They read the publications, et cetera. We anticipate a really very efficient footprint overall, all, but it'll be reasonably sized to attack these 3,000 retina physicians. Two of the larger practices in the retina space see about 50% of the patients. So it's really quite nice, you know, being able to contract with some of these larger practice groups and then making sure we're doing the effective education with these sites around the country are really important. We're doing that now from a disease ed perspective, as well as educating on the mechanism of action with Vana Prumit. So we have a full med affairs team out, a full disease ed campaign behind that. So we're bringing them along now as we work through the phase three study. And then ultimately, we will launch with some bigger thereafter.

So maybe let's one more question about GA and then we can move on to VBS. For the other two drugs that were launched, over time, it became a little bit more apparent that safety became a little bit of a concern. now this might just be a numbers game um you haven't had any similar type of events as it relates to um infections with patients after injection but how how should we be thinking about that in a real world setting so this does get approved this does get adopted what should we think if over time you start to see similar um side effects as to what the other injectables have yeah you're well so really good question a really important question for this community against safety is very very important and you're right you know number of of just pokes in the eye

will help inform your safety profile over time but you're also right as we sit here today we just have not seen the types of safety events that have been seen with some of the downstream approaches and we you know we've got a few views on why that's likely the case first relates to the drug candidate itself von aprumit so this is a fab fragment it is a small fact fragment it is 50 KD, so really small with low viscosity, if no viscosity at all. The volume is about 25 microliters, about a quarter of what it is for syphovry, for example. So that allows for really simple and efficient ease of administration. And importantly, it's non-pegulated. So, you know, you're not getting kind of the viscosity and other issues that are associated with pegulation with our drugs. So that's really, really important. The second aspect from a safety perspective is our mechanism itself we are solely blocking the classical pathway we're allowing the lectin and alternative pathways to continue to function to perform their immune support for the eye that's really important from an immunologic perspective as a result what we are what we saw in our phase two study is we saw very little if no conversions to wet amd if you'll recall the approved drugs have conversions to wet AMD somewhere in the neighborhood of 10 to 15 percent of their patients come in to get treated for GA. They come out with GA and wet AMD. When you look at our phase two data, our conversion to wet AMD very much resembled CHAM and natural history over time in many other studies. So we're not seeing the conversion to wet AMD, which we think is really, really important. And then that coupled with allowing the other two pathways to perform their immune function we think over time this drug is going to have a really positive safety profile and i don't want to underestimate or under uh emphasize the route of it the way we are administering this drug at 50 kd and 20 micro 35 microliters is really really important just allows physicians to do a quick administration and move on and so you don't have you know at least thus far the infection risk that we've seen with other approaches okay so let's um move on to gbs um can you just give us an overview of that program yes and then we can talk a little bit more about the market opportunity and where you stand yeah we love this program this is a labor of love as i said before the number one cause of acute neuromuscular paralysis you're completely healthy it's an indiscriminate disease it can strike anyone at any time and anywhere you're completely healthy you get some preceding infection like food poisoning or something or another your immune system classical pathway kicks on to rid the body of the sick cells which is the appropriate role. For whatever reason, a month or so later, your immune system kicks on aberrantly, targeting peripheral nerves, which leads to, you know, ascending paralysis up your body, up through your body. One in four patients are on a ventilator within a matter of 10 days. So a really significant debilitating disease, and many, many patients never fully recover. In fact, 20% of patients with GBS, even with current treatments, are unable to walk without assistance It's a year after the disease. We know the mortality rate for GBS within a year after GBS, if you're 60 years or older, is around 25%. So this is a devastating disease. And we're really proud from a company perspective to be the only company to study this disease in a controlled study in over 40 years. And the reason we did it is because we know C1Q is the key effector driver of the autoantibody attacks that drive the disease. And so that's led to robust outcomes in our phase three study, as i alluded to before and so we really really want to emphasize that this is an important medicine for patients to give them their lives back in their families around the world where we are today having one on the phase three studies i said before we have filed for approval in europe we will file for approval in the u.s and i just want to make sure i'm answering your question yeah so let's talk in a little bit more detail so you filed for approval in europe um what what type of feedback have they given you so far yeah we've had really good engagement with europe um some initial responses from them in terms of questions, exactly what you would anticipate. And so really nice ongoing dialogue. They've also begun the inspection process of our facility or our sites in Southeast Asia, which we like. So it's a really active process. The thing I will say about Europe, which is a bit different than what we see in the States is there's a lot of expertise in Guillain-Barre syndrome in the European setting. There are multiple institutions in Europe that are studying GBS and there have been a round of studies that have been been conducted over the last 15 years they're not controlled studies but studies nonetheless none of that has happened in the U.S. why that's important is the regulators in Europe understand GBS at a depth that we've not necessarily seen here in the U.S. yet we will get there with that so we've had a round of discussions with them at the country level we've had rapporteur meetings and we've filed the document, and now we're engaged in discussions with them on our submission for EMA approval. So we really like where things are with Europe. I'm sure you're going to ask me about U.S., but I'll wait for you to do that.

Yeah. A couple more questions on Europe before we move on. So what type of treatment regimen do they have there that might be different from how their patients are treated here?

Yeah. In Europe, it's pretty much the same types of therapies are being used. So IVIG is used in Europe like it is here. IVIG is not approved in the U.S. It is approved in Europe, but it's proved on a compendia for use. It's not based on a study that's been run. About 80% of patients get IVIG. The other 20% get plasma exchange or plasmapheresis. So that's a really involved approach. IVIG is five courses of therapy over five days. And unfortunately, about a third of the patients get a second course of treatment. So they go five days, look and see how the drug's affected. If the drug's not working well, which happens in many, many instances, they'll then go an additional five days. Not ideal for patients, not necessarily a safe approach for patients, but it's what's done given, you know, the debilitating nature of the disease. And then for, you know, plasma exchange, you know, that's 10 days of plasma exchange. It is not at all comfortable versus our approach, which is a single infusion in a matter of hours, you're hospitalized, and you're really arresting the disease right away, you know, day one, if you will.

And how would you think about what reimbursement would look like in Europe?

Yeah, reimbursement in Europe is obviously an important topic and more relevant topic today than any other time I can think of. So very much like most drugs in Europe, and certainly rare drugs, you know, it's done at the country level. And so we've begun having those discussions at the country level, really educating on the disease and the burden of illness of the disease and the costs associated with the disease. So we've done significant and I would say the most extensive health economics work ever done in Guillain-Barre syndrome. There's one paper out there 20 some odd years ago from an academic institution. We've done robust assessments. We had multiple publications at AAN and you'll see additional ones out at P&S and other conferences upcoming. That's predominantly centered on the U.S. and we've now pushed into Europe with some of that work as well. so we are educating the payers in europe if you will on the advantage of using our drug and the cost savings associated with it europe is very much a value-based uh system in terms of reimbursement for for your drugs there so we like where that is today more work to be done from an education perspective okay but you expect to keep rights to europe you're not going to partner it that's a tbd okay so you know it would be much more efficient to put in the hands of the partnership we've had multiple partnering discussions in fact we've had multiple partnering term sheets i don't mind saying that we want to make sure we do this in a way where we take a global perspective on the overall availability of the drug and the pricing of the drug so mfn is relevant to us as it relates to an xus deal and so as we navigate through that that may or may not lead to a partnership they're certainly at the table i feel like there's a path forward for that but until we get a bit further we should kind of hold that back a bit okay all right so now let's talk about the status in the u.s just remind us about everything that's happened up until this point yeah so the for to get approval for Guillain-Barre syndrome both in the u.s and europe there are two requirements one is to demonstrate uh you know a substantial evidence of effectiveness the standard there because we ran the studies outside of the u.s and europe we have the additional requirement of demonstrating generalizability that is the patients in our study are consistent with the patients that would be treated in the west and the outcomes would be consistent so we did a real world evidence analysis of the patients in our phase three study we matched them with a 2,000 patient natural history data set run worldwide countries across the globe including the U.S. and Europe and Bangladesh and we were able to match our patients one for one in a propensity score matching so We feel very good about the patients in our study are consistent with what you would see in the West. We also compared outcomes with the patients who were matched in our study with patients who were treated with IVIG or plasma exchange from the natural history data set. And we show that we were superior on every measure as it relates to GBS. So that's really, really important. So those are the two requirements for approval, both in the U.S. and Europe. We've submitted a full package on both of those requirements in Europe. In the U.S., we are going to submit both of those. The U.S. appears to want some additional data in the U.S. as it relates to treating patients in the U.S. and Europe with our drug. That's an important concept for us. We've, of course, treated patients in the U.S. and Europe with our drug and other diseases like HD and ALS, but had not done so in GBS. So we took it on. We've got an open-label study that's ongoing called the FORGE study. Really pleased with how that study is going. We're able to kind of track that on a per-patient basis. And the purpose of that study is really a bridging-type study to show that the patients in the U.S. and Europe progress similarly as they do in Southeast Asia where we ran our Phase III studies. And the outcomes with our drug are similar. We're looking at things like PK and PD predominantly. We're also going to show efficacy data because we're encouraged by what we're seeing.

How long do you think it'll take to collect that data and show it's FDA?

We're well on the way on that. We still anticipate filing this year. You know, obviously there's been some adjustments in the FDA more recently.

Sorry, you do and you don't.

Yeah, we do anticipate filing on that this year. We're watching kind of the landscape within the administrative FDA to make that final determination. But we're, from a data perspective, we'll be in a position to file this year.

And then you mentioned it, the change that was announced yesterday as to head of FDA. Does that have any impact, do you think?

I wouldn't think so. I mean, I think, you know, one of the things we're in the neurodivision, And the thing I would say about the NeuroDivision and the FDA is that they are really well familiarized with our program. We've had more than 10 interactions with them over the course of the conduct of this program. And, you know, they're experts and, you know, they're showing up every day and doing their jobs. I expect they'll continue to do that.

So how do you think about the market opportunity in the U.S.?

Yeah, I love it. I mean, the thing about GBS, because of its devastating nature, everyone gets treated. 90 to 95% of patients currently are getting treated with IVIG or plasma exchange. Now, these patients are getting treated way too late, way too late to have a meaningful effect. In fact, we know one in four patients are diagnosed upon first presentation in the U.S., and that's because there's been no education for the physician community out here on the diagnosis of GBS, which is really straightforward. You really just have to capture a history of the patient. And then the protocols are very diverse across institutions around America. And again, because no one has centralized this. And so a new therapy is going to allow for better outcomes for patients across the board. From a market perspective, it's about 8,000 patients in the U.S. every year's incidence-based disease get GBS, another 15,000 in Europe or so. And given that 90% to 95% of these patients get treated every year, that's a meaningful market. That is a large, rare disease opportunity, one of the largest I've seen before, which we're really encouraged by. From a commercialization perspective, it's an incidence-based disease, which means these patients tend to show up in larger population areas. There are 50% of the practices in the U.S. see about 50% of GBS patients in larger centers. Because we're running this Ford study, we're in many of these practices. So we're working with them already, getting them familiarized with our drug, how to diagnose GBS a bit more efficiently, and making sure the protocols of moving the patients through the system are really, really efficient. So I really love the experience that's happening with this study as it relates this opportunity. From a commercial footprint, however, really, really small. And that is, we're not going to have a bunch of sales reps walking the halls in hospitals. They're not going to allow you to do it. So our focus is really twofold. one on the medical education side which again we're already out there with our MS cells and others with disease education education on our phase two or phase three program etc on that and so really making sure people understand that we have just started to educate on our health economics outcomes and really demonstrating the cost to the health care system at a system or hospital level basis for treating GBS on an annualized basis and the potential savings of a drug like ours where we showed patients get out of the hospital or they walk 30 days sooner they get off the ventilator 30 days sooner they get out of the icu 10 days sooner these are hard dollar savings to the health care system and so we're going through that burden of illness uh burden of cost um to these uh systems with them now so we really like this from a commercial setting in the u.s and then maybe on on the point of pricing what obviously you're not going to announce that right now but what's a range or what's a comp to look at yeah and we're not i appreciate you saying that yeah so we we are doing the work now on that i think the thing i think about when i think about pricing is i think this drug is quasi analogous to a cart t type of therapy the reason i say that is hospital based single treatment but it doesn't have all the downside kind of circumstances that go right like it's just an infusion you're not having to go through difficulty in terms of administering it you know have some issues with it we don't anticipate pricing anywhere close to where the car t's are when i look at the analyst reports covering it they have somewhere between 100 and 150 000 for course therapy for the drug that's probably not unreasonable um but we're continuing to do a lot of work the health save the value of the drug and getting patients back to their life sooner is where the opportunity is from a pricing perspective so this would be a little bit of a paradigm shift in terms of how patients are treated.

Not a little bit, it would be. Completely. Right. And so how do you anticipate what the initial, you know, responsiveness if this does become available would be by physicians?

Yeah, just based on what we're seeing in the study, I think it's going to be quite robust and exciting. What we're seeing is that patients are having a really rapid benefit. If you looked in our data in phase three, just by way of example, 86% of our patients showed benefit by week one, day eight. And we're seeing consistency in the FORGE study. You've never seen that with the current therapies that are out there. Well, firstly, it takes five days to infuse these therapies, five to ten days, right? So we are immediately arresting the disease and getting patients back on their feet. And the response to that has been really dramatic. We're really, really encouraged by that. More to do, but thus far, so far, so good.

Okay. In the minute that we have left, I wanted to quickly touch on 1502. So, you know, you've got a program, a proof of concept study that you're running in CAD. Can you just talk to us quickly about that and why you've chosen that indication?

Yeah, we chose that indication really as a tool indication, if you will. It's an objective measurement of impact on hemolysis by measuring bilirubin as well as complement levels, which are elevated in this disease. So really objective measures, and that's why we chose it. We will not advance commercially into codiglutin disease, but it really will allow us to understand our drug's profile.

So what would be good data?

Good data would show that you're normalizing bilirubin, and importantly, you've brought your complement levels down to normal in a reasonable period of time. and then so what safety as well right is there anything mechanistically to look out for on safety uh not that we're aware of or i've seen so what would be a next step if you see what you want to see yeah one of the things we have seen in the study is that we have seen a food effect with this formulation so what i'll need to see we'll need to see when we get all of the data pulled together should we stop and do a reformulation or do we advance as and move forward so that's a tbd otherwise the next step is to moving into a late stage study on one of the neuromuscular diseases like MG or CIDB.

We're about at the end of time, so we'll have to leave it there, but love to continue that conversation next time. All right, Doug, thank you for spending time. Thank you so much, Tazine. Thanks, everyone, for listening.