Good afternoon, everyone. Thank you for joining the 21st annual Needham Healthcare Conference. My name is Joe Stringer, and I'm one of the biotech analysts at Needham & Company. It's my pleasure to introduce our next presenting company, Annexon Biosciences. Joining us today from Annexon is President and CEO, Doug Love. For those of you joining us on the webcast, if you wish to ask a question, please do so at any time. You can submit a question using the chat box at the bottom of your screen. With that, we'll go ahead and get started. I'll turn it over to Doug for some brief opening remarks, and then we'll go ahead and start with the chat.
Thanks so much, Joey. Really appreciate you and Needham having Annexon and myself with you this afternoon. Really excited about where we are as a company at this stage. I think you all are aware we're focused on the classical pathway, and we're squarely in phase II, phase III studies in multiple indications spanning autoimmune, neurodegeneration and ophthalmology. Importantly, our approach really is to provide more complete protection against aberrant complement-mediated activity in these three therapeutic areas. We've got nice evidence thus far in our ability to do so successfully. We've demonstrated in our most advanced autoimmune indication, Guillain-Barré syndrome, that our lead drug candidate safe, well-tolerated, and importantly, had meaningful impact on the key biomarker of neurodegeneration in NfL, as well as the clinical measures GBS Disability Scale, which is an approvable endpoint.
Now we've advanced that into a phase II/III study. Also on Huntington's disease, our most recent data set there, we demonstrated again full target engagement, both in the periphery and in the CNS. Importantly, was able to show meaningful impact on the clinical measures there. Again, the approvable clinical measure there, in a relatively rapid period of time. You will hear me refer to this theme again and again. Rapid impact on difficult to treat disease processes by providing more complete complement inhibition right at the start. I'll stop there. I'm sure we're gonna peel all of this back and look forward to doing so with you, Joey.
Yeah. Great. Thanks, Doug, for the nice company overview. Before we get started into some of the specific programs, just curious, you know, you're focusing on targeting complement here. What are your high level thoughts on the current state of the complement drug discovery? We've had a couple of recent approvals, each for a different target mechanism of action. Do you see this as a positive sign for the space in general or how do you view the space, current state of the space?
I do. Yeah, we're really quite encouraged by the target of complement altogether and this space. As you well know, we're dealing with aberrations in the immune system, which is quite important. To the extent you can really characterize the role of complement in a disease process, what we've seen time and again is the ability to produce significant data. We feel like targeting complement has, of course, been clinically validated in multiple diseases. The key in our view is just to, again, really well-characterize complement in the diseases for which we are pursuing. There are significant opportunities still available there or need, if you will, particularly as it relates to targeting indications where upstream aberrant complement activity is a key driver.
Where most of the success we've seen thus far has initially started downstream in and around C5. Increasingly, as you move into additional autoimmune and neurodegenerative indications, upstream immune cell activity, macrophage activity, microglia activity become more important. We think it's important to target both upstream and downstream, and we think it can be successfully done in complement as a whole, as has been seen heretofore with other approaches.
Yeah. I suppose that kinda touches on the therapeutic rationale for C1q. You know, recent approvals have been in, you know, of course, C5 and C3 and C5aR more downstream. But you know, what's the therapeutic rationale for targeting C1q? Is it just that it's further upstream, and you can sort of turn off the valve at a sort of more upstream location?
Yeah, great question. Certainly part of it. Well, you know, the role of the classical pathway is really well-known for 50+ years in antibody-mediated autoimmune diseases. In fact, C1q, the initiator of the pathway, is the key effector of complement activity there. Very well-known role there. Then as it relates to neurodegeneration, C1q in the classical pathway has been very well studied by us, pharma, academia, et cetera, with regard to removing functioning synapses as part of the neurodegenerative disease process. Looking at both of these two approaches, we've targeted C1q because it is indeed the initiator of the complement pathway. It is localized, importantly, on the disease tissue in the indications for which we are pursuing. For example, in Guillain-Barré syndrome, C1q is localized on neuromuscular junctions. It's on the striatal synapses.
In Huntington's disease, it's on photoreceptor cells and geographic atrophy. In all of those instances, it anchors complement, and it amplifies the complement system down from C1q through C3, C5, and C9. By blocking complement right at the start at C1q, you're in effect stopping a moving train before it gets started. That, of course, prevents the immune cell activity that's upstream, again, the macrophage and microglia activity associated with C1q, C4, and C3 activation. We think we're providing, again, a more complete role in protecting against aberrant complement activity with this approach upstream.
You touched on a couple of the programs at the top of the chat here, Doug, that you have programs in ophthalmology and autoimmune and neurology. How should we think about the Annexon approach? Is it focused on one type of indication over the other, or is it more broad-based?
Really good question. Yeah, it's broad-based. We're targeting aberrant classical complement activity where it appears, where we can characterize it in the body, the brain, and the eye. That's what lends us to pursuing specific indications in autoimmune neurodegeneration of the brain and neurodegeneration of the eye or ophthalmic indications. That is the way we think about it. We've put together this portfolio where we're targeting all three of these therapeutic areas in parallel, really taking advantage of the synergies between the three areas and the learnings across the three areas. We can certainly talk about that as we go through the indications.
We have learned by targeting all three in parallel how to fully engage the target in the respective compartments of the body, brain, and the eye, and how to assess the role of complement in specific patient populations. There's a fair amount of heterogeneity in many of these indications, and so being able to ferret out with objective biomarkers where complement is a key driver is really important. Anyway, we've got a portfolio with these three therapeutic areas. We have five fit-for-purpose drug candidates, or that's what we call it. What that really means is we are looking to inhibit target complement in specific compartments. We have drug candidates that target complement solely in the body, drug candidates that target complement in the body and the brain, and drug candidates that target complement solely in the eye.
We think this targeted approach allows us to really identify the patients who are most likely to benefit in a selective way so that we can optimize efficacy and still manage safely, appropriately. The last thing I'll say is that by targeting these three areas, we do have a portfolio that's targeting both orphan indications as well as large patient population indications. We have the potential to impact really targeted, significant orphan indications, but as well as millions of patients with just indications we're currently pursuing. We really quite like that.
Yeah.
Maybe I'll pause there, see if you got anything else for me.
Yeah, sure. Well, let's kinda jump into some of these programs, and we'll start with an autoimmune one, a phase II program that you have ongoing in warm autoimmune hemolytic anemia. Can you describe this indication, Doug, just unmet need, and then we'll get into the phase II design and things like that.
Yeah, happy to do so. WAHA, really an important severe autoimmune disorder where autoantibodies attack and destroy red blood cells, which results in anemia. It can be severe and life-threatening. I mean, it definitely impacts these patients' activities of daily living, if not more so. There are no approved FDA indicated treatments. Currently, you know, it impacts about just under 50,000 patients in the U.S., and patients are treated with blood transfusions, rituximab or chemotherapies, as well as steroids. Not all of the patients respond to these approaches. Some who do, you know, often relapse, and so it is an undertreated therapeutic area. I will also note, again, there's heterogeneity here, and so there are different disease processes that are driving this disease. It is important to understand those who have complement-mediated disease as we think about our approach.
In terms of the phase II design here, it has a little bit of a unique design. Can you sort of describe that and what types of patients are entering the treatment period?
Yeah, really important point. It picks up on my last point, which is, again, there's a lot of heterogeneity in this warm autoimmune hemolytic patient population. We are looking to target only those patients who have excess or aberrant complement activity as the key driver of their disease. This is a precision medicine approach that is really highly enriched for a higher PTS. As a result, we're running a clinical program that has two components to it. The phase 0 component of it is a non-interventional aspect of the study where we're screening patients for their complement signature. We've now screened more than 50 patients who meet this criteria. Only those patients who meet that criteria are being enrolled into the phase II. Again, a precision medicine approach. Again, you know, really quite like the way we designed and the way the study is being executed.
Great. Sticking with the phase II trial here, what types of changes in terms of an initial efficacy readout should we be looking for? Certainly, hemoglobin, LDH and bilirubin, some other measures. What would be sort of a kind of a clinically meaningful change in some of these metrics? Is hemoglobin and LDH the key efficacy measures here?
Yeah, it's a really good question. Again, one of the things we like about this, in addition to having a precision medicine approach to select patients, is the objectivity of the endpoint. We're looking at, you know, reduction or normalization of markers of hemolysis, as you alluded to, LDH and bilirubin, as a key aspect or a key outcome from the study, as well as improvements in hemoglobin. We think that's also very important, obviously. We wanna ensure that these patients are, you know, we're normalizing their hemolysis and improving their hemoglobin to ultimately improve their anemia.
Great.
One other thing I guess I would just say about this program.
Sure.
Just to put into context, we are doing this program with our lead drug candidate, ANX005. We'll talk more about it, full length monoclonal antibody. We do anticipate, upon good proof of concept data here, transitioning for a pivotal study with either our subcutaneous program, ANX009, that's also in the clinic, or our next generation drug candidate, ANX1502, which is a small molecule presentation. We think there's a lot of opportunity. We're gonna be bringing a great deal of convenience to patients. We're using this first study just to confirm the ability to inhibit complement and have a rapid impact on hemolysis and hemoglobin.
Okay. Sticking with ANX005 and the GBS program, Guillain-Barré, can you talk about sort of what the current standard of care and treatment paradigm is for GBS and how ANX005 would fit into that treatment paradigm?
Yeah, good question. GBS, another antibody-mediated autoimmune disorder. We consider it a higher PTS program. There are currently no FDA-approved therapies for this condition, and it's a gnarly condition. It is the number one cause of neuromuscular paralysis in the world. Patients have an autoantibody attack, which is mediated by complement, and it results in neuromuscular paralysis or other disability in a very rapid fashion. In fact, 5% of patients die from it, up to 25% of patients go on a ventilator, so very significant disease. Although there are no approved therapies, IVIG is used off-label in this space over a five-day course of treatment. Now, IVIG has never been studied in this disease versus a placebo, and so its true effect is not fully known.
Our aim with our approach, running a placebo-controlled large 180-patient study, is to displace IVIG as a monotherapy in this condition. A one and done type of course of therapy versus five days for hopefully a rapid improvement on the key measurements in this patient population.
You've had some initial phase I-B data in GBS. Can you describe the significance of that data and, more specifically, the improvements on the GBS Disability Scale? 'Cause that is the registrational endpoint. Just wanted to comment on the phase I-B results, how you think that will translate.
Yeah. Really important study for us, considered our proof of concept study. This is the first placebo-controlled study in Guillain-Barré syndrome in 35 years. Really kind of a landmark type of study for the field. We've worked very closely with the KOLs across the globe there. What we saw in addition to, you know, rapid inhibition of the target where ANX005 operates as an on/off switch is we first saw rapid improvement within the first week on muscle strength as measured by the objective MRC. That's really important because this again has been very well studied. Muscle strength improvement is a precursor to functional improvement, so it's a prognostic factor for future outcomes. We also saw statistically significant reduction, again very rapidly within two to four weeks in neurofilament light chain, key measurement of neuronal damage.
Then as you alluded to on the GBS Disability Scale, the approvable endpoint, we saw what we would consider to be an outsized effect versus placebo. The GBS Disability Scale is a six-point scale. It's very objective. One is normal, six is death, and in between there it gets progressively worse from one, patients who can walk unassisted or run, patients who can walk without assistance, patient who walks with assistance, patients who are admitted into ICU on a ventilator, et cetera. What we saw was a three-point change in roughly a third of our patient population on drug versus a zero point change on the placebo group. What that means is that patients came into our study who were, for example, on a ventilator in the ICU. Within eight weeks, they were able to walk with a bit of assistance.
It's very much on all fours with our mechanism of action that, where complement is a key driver of the disease, we're stopping it immediately with an on/off switch, and we're having a really important impact on all of the downstream components of complement. In fact, we shut them completely down. We're seeing a rapid, meaningful improvement there. With that data, we have now geared up into a phase II/III study. It's a large, properly powered study, randomized, 180-person study, and it's going really well. Enrollment is more than halfway through. We're really pleased with that. We're able to navigate through COVID and all of the other things really because of the demand for a new therapy in this population. We're working with the IGOS Consortium.
This is the International Guillain-Barré Outcome Study with 2,000 patients, more than 15 countries run out of Erasmus. They've been great partners with us in really understanding the disease, really understanding the role of complement, the specific patient populations, and how to intervene here.
Great.
Trying to-
Yeah, no. Yeah, no. In terms of the phase II/III study here in GBS, what are kind of typical placebo response rates and how should we think about the response rates on the GBS score from the phase II trial in terms of what types of patients—excuse me, the phase I-B. What types of patients were in that, and are you enrolling similar patients in the phase II/III trial?
Yeah, really good question and an important question. First, just turning to the placebo aspect of it is, as I said, you know, there had not been a placebo-controlled study run in 35 years, so we had to do some work here working with this IGOS Consortium as well as data from our study. What we see is that they do not have rapid improvement. Because of GBS's acute nature, you really wanna stop the disease immediately and allow for recovery. The longer it takes for that to occur, the greater disability that occurs to the peripheral nerves that do not regenerate and the greater likelihood that these patients are gonna have lifelong disability, if not die.
That's what we're seeing, that without an intervention, the placebo-controlled group, patients just do not recover as rapidly, if at all. The second part, as it relates to our study and the types of patients, what we've learned, again, with our initial proof of concept study and then working with IGOS is a few things. One, you absolutely wanna treat these patients within the first 10 days of onset of symptoms of their disease. Once you get too far beyond that, again, you have this damage to peripheral nerves, and they don't come back. We designed our study to ensure that we are capturing all patients within the first 10 days, and typically we're getting them much earlier than that, which increases the likelihood of success. We're stratifying patients also based on their baseline muscle strength.
We know that the worse your muscle strength upon entering into the study, the worse your prognosis or at least the longer it takes for you to improve. We wanted to make sure the treatment arms were balanced with regard to that. We've done some other things in this study to ensure we've got the right patient at the right time who's most likely to respond to our approach.
Got it. Now I guess we'll move on to one of the neuro programs, Doug, and this is the phase II Huntington's disease program with ANX005. You read out some phase II results, I believe it was like last year, or sorry, excuse me, early this year.
Early this year.
You know, you had some interesting results. I wonder if you could break down and summarize the efficacy data there, in a certain subset of patients, you saw improvements on the functional registrational endpoint, and not necessarily a change in sort of the biomarker, which was interesting to say the least. I'm just curious if you could dig a little bit deeper into what that data means and, you know, the types of patients who responded there.
Yeah, really good question. Look, this is a really important study for us and for the field. It is a first in kind study of complement in a neurodegenerative disease, a classic CNS neurodegenerative disease. You know, the approach, again, that's been really well-researched pre-clinically, and we have significant data, we and others, is that by blocking complement, you're able to preserve functioning synapses, which should translate into improvement both in cognition and motor skills. In fact, the number one correlation between deficit in cognition and motor, and motor function is loss of function synapses. It's our mechanism on all fours.
As you alluded to, what we saw in the study on the UHDRS, the Huntington's Disease Rating Scale, which is the approvable endpoint, is that we saw that in the full patient population, we were able to maintain function in that patient population versus an expected decline. In neurodegenerative disease, patients decline or worsen over time, and typically what you're looking to do is to slow that progression of the disease. What we were able to do in our study population was to maintain their function. There was no decline, and we're really pleased by that. We think obviously that's an improvable outcome in and of itself, and I think it's important for people to understand that. We showed more than that.
What we showed in more than half of the patients, they actually improved by month six in our study. When we looked further into the data, patients who we hypothesized would improve more quickly and more meaningfully, we saw that 75% of patients who had excess complement activity at baseline, as measured by objective biomarkers that were blinded to the patient, the physician, and the company, 75% of those patients actually showed improvement. I will note that the improvement is quite rapid. We saw improvement in six weeks, starting at week six, and all of the patients had improved, and this improvement or stabilization all occurred by month six, on the back end. We really are encouraged by what we saw there.
We saw a differentiated response in patients who had excess complement at baseline versus patients who had low complement. That was important for us to see because, again, excess complement activity is our mechanism. But it also suggests that this is not a placebo effect. If it were a placebo effect, the patients who had excess complement at baseline, as well as the patients with low complement at baseline, should have had a similar outcome. That is far from the case. In fact, the difference between the two groups is statistically significant on all of the endpoints that we looked at. We're encouraged by this data. As it relates to NfL and the biomarker, a really important learning there as well. NfL's an objective measure of neurodegeneration, and is really well known for measuring or assessing the stage of disease for a patient.
The more higher the NFL levels, likely the more progressed a patient is. Where it has been unknown or yet to be shown is whether NFL reduction or NFL is an actual surrogate for clinical outcomes, if you can reduce NFL. What we saw over the course of 2021, and as well as in our study, no one's been able to reduce NFL in a chronic neurodegenerative disease, slower progressing disease. We think the reason for that is that NFL is a measurement of neuronal death, the end of the disease process. It takes a while to get there. Our approach is of course targeting functioning synapses well before that occurs. It stands to reason that NfL is likely a lagging indicator for efficacy in this instance, and it'll definitely take longer than six months, at least thus far, to see a change.
Okay. Yeah, very helpful and interesting on the NFL versus sort of the functional output, the discussion there. Now you announced the topline results in January. You plan to announce sort of full data here in the second quarter of this year. That includes both the treatment and off-treatment periods for all patients.
Yeah.
It'll be interesting to see what happens to NfL and UHDRS, of course. Is sort of the base case scenario that you would expect to see minimal change in NfL when patients go off treatment and maybe potentially a return to baseline in the UHDRS as patients are taken off the drug? Would that kind of support some of the findings that you saw during the on treatment period that signal in UHDRS was a signal.
Right.
Positive efficacy signal.
Yeah. Really good question. Again, first in kind study, so won't say definitively what we will see until we actually see it. But you're absolutely right. The data that we initially released, the interim data, is for the on treatment arm. It included all of the patients on the clinical side, so all 23 patients. It included 16 patients on the NfL side on treatment. With this Q2 data release, we will have the full 23 patients on treatment, both clinical and NfL, and then the off treatment period of three months for all, both clinical and NfL. You know, we're gonna see one of two things, would be my estimation on this. It could be that what we see is a durable effect on the clinical measurements, and so not much change over that three-month period of time.
One of the reasons that you know I'm hypothesizing that is that ANX005 is indeed a really strong drug candidate. What we've seen is that patients are still inhibited, their complement is still inhibited once you stop the drug another month or so. What we you know designed to be a three-month off treatment period is now really about a two-month off treatment period. We'll see what that means. On the other hand, we know complement is a very powerful system, and removing it, even for that two-month period, may mean that patients begin to worsen who had previously improved. For NfL, patients who were stable on our program may actually begin to worsen as well. We'll just have to kind of wait and see. You know, our style is to put it all out there, and we will do that.
In terms of the safety from that trial, Doug, in terms of the safety profile for ANX005 in HD, there were higher AEs in the treatment patients who were administered ANX005. Is this something that you think is inherent to sort of systemic dosing of ANX005, or can some of these potential safety signals be mitigated through different dose levels or different types of administration? Just curious to get your comments on the safety here.
Yeah. Really good question and important question, because there are many aspects to it. The first thing I'll say is that ANX005 is a super strong drug candidate. In fact, it is by design a maximum inhibition of the classical pathway, both throughout the body, so in the body and in the brain. We did that purposely and led with that so that we could really characterize efficacy with this approach and then work backwards from there. We've begun that journey, and we're seeing that with GBS and HD, and we'll see that with additional other indications. But what we've seen thus far is we're pleased with the benefit risk profile of ANX005 in these devastating diseases for which there are no approved therapies.
We also know from literature that C1q deficient people who are born without C1q have a risk for lupus. That's what we saw in our study. I think everything else that we saw in the study was absolutely within range of what we would've anticipated, except for maybe one other case, and I'll come on to that. As it related to lupus, we anticipate that at some point you could see some level of C1q deficiency resulting in lupus. We saw that in our study in one patient who had a low grade lupus-like symptom. You know, it was rash and mouth, so again, it was very low grade. No end organ toxicity.
Importantly, once we stopped the drug, it fully resolved rapidly. We then dug deeper and realized that this patient actually entered the trial with high baseline ANA titers, and so it may have been uniquely susceptible to this outcome. We've modified all of our protocols, and I will say we treated more than 100 patients with ANX005, and we've not seen this before or since. So we're relatively encouraged that this, to the extent it will occur, is a low likelihood type of circumstance. But you also touched on other ways to think about safety and how we think about it. That is, the literature is also quite clear that if you have even low levels of C1q on board, 10% or so, you do not have risk for lupus.
When you think about the way we are advancing our drug candidates, one is dosing with dosing holidays, so to allow C1q to come back so that you can guard against potential untoward events. As you think about our other drug candidates, like ANX009, it only inhibits C1q in the blood, does not inhibit C1q in the tissue or across the blood-brain barrier. You always have C1q on board, should not have this lupus risk. ANX007 only inhibits C1q in the eye, should not have that risk as well. We think we've got a multi-pronged approach to safety. We have not been surprised by it whatsoever, and we're pleased with our ability to manage it thus far.
Okay. Just a quick one on HD before we move on to ALS, another neuro program. What are the next steps and the key learnings for the HD program? Now that you've seen the data and you're still kinda digesting it, and you'll get some additional data here coming up, what are the next steps from a clinical development perspective?
Yeah, really good question because we've learned a lot. One, you know, first-in-kind approach, we've learned that complement indeed has an important role in the neurodegenerative disease process. It's important to protect functioning synapses. We also learned that we can rapidly not only stabilize disease, we can show improvement, which is the holy grail of neurodegeneration, folks. I just cannot emphasize that enough. Like, that is a grand slam. You can get an approval on much less than that, but we saw that in more than half of the patient population. Then the third thing is that we saw rapid improvement starting at week six and then everyone through week six, you know, at six months.
Where we think about this is that we have an opportunity to run subsequent studies, and we've not landed on this yet, doing a lot of work with KOLs that are smaller, that are targeted based on potentially complement levels, that can be run for shorter periods of time. We think this is, you know, potentially a very enriched approach to run a chronic neurodegenerative disease in patient populations who are most likely to respond in a rapid fashion. We're gonna continue to work these things up, and then ultimately we will make all of that more known publicly.
Got it. Now kinda jumping straight into the ALS program here, another neuro program. In terms of any potential read-throughs, you know, given you've seen high target engagement, certainly different indications, but are there any read-throughs that you could take from the phase II HD trial into the ALS trial? And what are the key efficacy measures that we should be looking for in that phase II ALS trial?
Yeah, good question. Look, I will say we've been very intentional in the way we've built our portfolio, and we think the read-through to ALS is both from the Guillain-Barré study and the HD study. If you think about Guillain-Barré as a disease that causes peripheral nerve damage or death, very aggressive, and the hotspot for it is around the neuromuscular junction, which results in motor deficit. Really important there, and we had a really good outcome with regard to that in our proof of concept study. You think about HD on the other end of the spectrum, a slower progressing neurodegenerative disease where we showed improvement both on the TMS, the total motor score, as well as on the cognitive measures, both of which are really relevant for ALS.
ALS sits in the middle, so it sits between GBS and HD. We think that we've learned a lot with a very aggressive approach with GBS, a slower approach with HD, and now we're going after what is a reasonably aggressive approach with ALS. We've shown we can improve motor deficit and cognition in these studies, and we would anticipate seeing something similar in this patient population.
Okay. In terms of the change in the ALSFRS clinical outcome score here, what would give you confidence to sort of proceed with additional clinical development in this indication?
Yeah, good question. Of course, we are measuring both the ALS FRS as well as objective measures of respiratory function and muscle strength. We've got some objective measures in there as well with it. You know, as it relates to the ALS FRS, you know, if we see a slowing of worsening or decline of, you know, 15%, 20%, that would be really good in the space. If we show a stabilization or improvement, you're talking home run grand slam to outsize types of effects. One thing I should note with regard to ALS and our approach in complement, which is very different from the downstream approaches like C5. We've seen more recently a couple of C5 programs actually stop the studies for lack of efficacy. Again, this is why we think it's important to target upstream complement.
By targeting upstream complement, you are blocking this microglia and macrophage activity that results in inflammation, tissue damage, and disability. All of this happens before you get to C5. We think our approach is very different by providing complete complement inhibition, and we should have a different outcome. I just kinda wanted to make sure that was clear-
Yeah.
...because there are some folks who are probably looking at this and saying, "Well, complement's been used in ALS, but it's not been successful." Those are downstream approaches that aren't dealing with the upstream aspects or pathology of the actual indication.
Got it. For the sake of time, we have a few minutes left. You do have-
Okay, I'll be quick. Sorry.
...a program in lupus nephritis, which we'll maybe touch on that at the end. You had some recent news in your geographic atrophy program. You have a phase II trial ongoing-
Yeah.
...it recently completed enrollment, the ARCHER trial. Wonder if you could talk about, you know, given the recent success of a competitor program that's targeting C3 from Apellis in geographic atrophy, what are the read-throughs that you see to the C1q inhibition approach? What are the advantages and kinda differentiating features of Annexon's GA program?
Yeah, I'll be quick. Sorry, Joey. Yeah, listen.
No.
We like what the Apellis folks have done and the way they've run their studies. They're quite rigorous and well-designed. I think one of the most important read-throughs from that is that complement is playing a key role in a GA disease process. We all thought that, but I feel like they've confirmed that. Where we differentiate is that we actually are providing more complete complement protection. Again, by blocking at C1q, we're blocking all of the upstream opsonins involved in the disease process. As I alluded to at the outset, C1q is actually localized on the photoreceptor cells in geographic atrophy, as well as on drusen, the hallmark of the disease.
It anchors and initiates this whole complement process, and by blocking it there, we're providing more complete inhibition against this complement activity than the downstream approaches like C3 and C5. The other important learning from their study is just identifying this more aggressive patient population, the non-foveal. We had anticipated that. We actually structured our phase II study whereby we stratified for patients based on lesion size, lesion location, and CNV in the fellow eye. We ran our study in a way where we powered it, 270 patients, where half of the patients are non-foveal patients. What that means is we're designed to win in the full patient population, the foveal and non-foveal, as well as just only in the non-foveal population.
We took the learnings from those who came before us and built what we think is a really well-tailored study to answer the question with more complete complement protection.
Yeah. When can we expect the readout from that GA trial, Doug?
Good question. 12-month on-drug study, and then six- months off treatment. We will have the 12-month component of that in the first half of 2023. Really pleased with the way the investigators and patients have understood this approach and worked with us. We actually enrolled this study ahead of schedule by a fair amount. We're really pleased with that. We did a lot of partnering with folks to make sure they understood this aspect of early and complete complement inhibition.
Last question, it's on a preclinical program, but fascinating in terms of an oral complement inhibitor, which would be quite interesting for the field. Can you comment on sort of the status of that-
Yeah.
...of your oral complement inhibitor program? Have you thought about any indications, or when could we see one of these programs enter the clinic?
Yeah. Really good question. We love the program. First in kind, oral program in the classical complement space, targeting autoimmune indications initially. We are working on programs that'll target across the blood-brain barrier, but we started in the autoimmune space. We will be filing for regulatory approval to start our human studies shortly. Well, this quarter. We will get going into the clinic. We're really encouraged. We've got a full program behind us, not just the lead, but the backup programs as well. We're all in.
I think from an indication perspective in the autoimmune space, again, providing more complete complement protection, we will target both indications for which there are approved therapies, but perhaps with IVs and other types of approaches with the small molecule and oral, as well as therapies or indications for which there are no approved indications and may be a little more difficult to enroll with an IV type of an approach. We're going all in on the oral. We really like this opportunity.
Well, we're out of time for this section. Thanks so much, Doug, to you and the rest of the Annexon team for participating. Thanks everyone for joining us on the webcast. Have a good day.
Thanks, Joey. Really appreciate it.