Good morning, everyone. My name is Derek Archila. I'm one of the Senior Biotech Analysts here at Wells. I want to introduce my next company, Annexon. From the company, we have President and CEO, Doug Love. Nice to see you.
Thanks, Derek. Happy to be here.
Yeah. Well, why don't we just start off quick high level of the company, and then we can kind of start to dig into, you know, some of the exciting data that you guys presented in GBS and, you know, kind of the rest of the pipeline, but maybe just start with the high level.
Yeah, happy to do so. So for those who don't know us, I'm Doug Love at Annexon, focused on the complement system. You all may be familiar with complement based on the C5, C3 approaches. Our approach is quite differentiated from those. We are targeting C1q, the initiator of the classical complement pathway. Why that's important is classical complement pathway is really important in driving harmful inflammation in a host of autoimmune and neurodegenerative diseases. C1q, in particular, is a recognizing molecule. It recognizes transformation in tissue as part of the initiation of the disease process. It binds that tissue, anchors the complement system, and drives this inflammatory cascade. As a result, we've been able to pursue indications across a wide swath of diseases in the autoimmune space, as well as in the neurodegenerative space, in the eye and the brain.
And we've been exceedingly pleased with the consistency and robustness of the data that we've produced in these indications. In all the diseases we've been in, we've produced really robust functional outcome, meaning we're giving patients their lives back as it relates to whatever function disability is associated with the disease, as well as structural or biomarker data that supports that. And so we've got data in our lead indications, both Guillain-Barré syndrome, where we released a phase III data set. I'm sure we'll talk more about-
Sure.
as well as geographic atrophy, a phase II program. We're now into a large phase III program. What is very interesting about this, that I'll say, and then I'll shut up here and allow you to ask questions, is the diversity of the diseases, but the consistency of the outcome, because you are targeting the immune system. So in GA, a very slow progressing neurodegenerative disease in an elderly patient population that results in loss in vision. In GBS, a really acute neurological emergency and autoimmune condition in the body, neurodegeneration of the body, think of it that way. In patients, it's indiscriminate in both instances. By blocking C1q at the initiation of the pathway, again, we had very robust outcomes functionally and from a biomarker perspective. So we're encouraged.
Awesome. So yeah, let's talk about the GBS data, you know, for 005 . So, you know, maybe just a quick synopsis of the efficacy data and the safety data that you presented. But I guess the big question that we always hear from investors is kind of like biological rationale for that, you know, odd dose response that you kind of saw.
Yeah.
Right? So the lower dose performed better than the higher dose. You know, maybe dig into that as well.
Yeah, absolutely. So really pleased with this data set. This is the first placebo-controlled study in Guillain-Barré syndrome in 40 years, with the exception of our proof of concept study. The only other thing I'll say with regard to GBS, before I get into the data, is that we're not dabbling here. So we've run three studies in GBS, which is more than any other program in the history of the world, and so we know a lot about the disease. We understand complement in this disease and how our drug candidate works. What we showed on the primary endpoint, the Guillain-Barré Disability Scale, this is the approvable endpoint, is highly statistically significant on the endpoint at week eight, but we also looked at seven other additional assessments of the primary endpoint.
And what you see there is at every time point, we looked at week one, at week four, I mentioned week eight, and then week 26, we're showing rapid and powerful improvement on the disability scale, highly statistically significant. We did two sensitivity analyses there, where we showed percent of patients able to run, kind of the holy grail in this disease, where patients on drug were two and a half times more likely to show benefit versus placebo. Then we looked at patients who had a whopping effect on the disease. So a three-point improvement on the GBS Disability Scale . There, again, another two and a half times more likelihood of showing a whopping effect with our drug, meaning if you came into the study on a ventilator, by week eight, you were able to walk. So we're really pleased with the consistency of the data.
Last thing I'll say is that we got patients out of the hospital sooner, and that ultimately is what matters to patients and physicians. We got them on their feet 30 days sooner than placebo. We got them off the ventilator 30 days sooner than placebo, and of course, the ventilator is a precursor to death. So that's really, really important. As it relates to the drug response, dose and response, candidly, we're quite pleased by it. So folks refer to it as kind of a high dose and a low dose. It's not how we think about it. We think about it as a shorter inhibition of complement and a longer inhibition of complement. Both doses fully inhibited complement. The difference being that at the low dose, it inhibits complement for one week during the active disease phase of GBS.
So this is an acute monophasic disease that plays out over a matter of a week or two, with complement being the gas to drive autoantibody attack, activity and attack to peripheral nerves. You want to block complement during that period of time to stop that gas, if you will. However, after that acute process, you then have a recovery process, where you have nerve recovery. There you want complement to come back and be part of the cleanup mechanism to clear out debris from nerve damage, et cetera. What we saw in the low dose is it inhibited during the sweet spot. In the 75 mg, it inhibited during the acute phase of the disease into the recovery phase, which really slowed the drug's overall treatment effect. Two other things I'll just say about that quickly.
It's exactly what we saw in the proof of concept study. The low dose outperformed the higher dose in the proof of concept study, but it was a really small study. I mean, you're talking about a total of 18 patients, and so we took both doses into the phase III to really figure it out what is the most effective treatment window. Lastly, I'll say, IVIG has experienced the exact same thing. IVIG is the standard of care. They ran a large 200+ patient study out of Denmark that they reported in 2019. There, a single dose of IVIG gave you one treatment effect. Two treatments of IVIG gave you a different treatment effect that was far worse.
And so it really looks, makes clear that treating GBS through a specific window is the optimal way to go after this, and we feel like we've really defined the dose here.
Awesome.
with this program.
Very interesting. So I guess part of the, you know, phase III program is the IGOS study. So maybe just explain what that is, and ultimately, I guess, you know, now you said that the data is, you know, moved forward.
Mm-hmm.
If you pulled it forward to year-end 2024, what changed?
Yeah, great question. So for those who don't know, this study, our phase III program, was run in Southeast Asia. The reason for that is that the standard of care in the U.S. is IVIG to treat GBS. It's not an approved approach, but it is a standard of care over the last 40 years. FDA determined it would be unethical for us to run a study here in the U.S., where we're withholding IVIG. So we were required to go into jurisdictions where IVIG is not readily available. We did that in Bangladesh and the Philippines. These are world leaders in GBS, by the way. We can talk more about that. However. So to get a label, what we align with the FDA on is two components. One, we needed to demonstrate substantial evidence from our phase III program, ANX005 versus placebo.
Secondly, we needed to demonstrate that the patients in our study in Southeast Asia are comparable to the patients here in the U.S. Meaning GBS is the same disease worldwide, and it would play out similarly in patients in Southeast Asia as it would in the U.S. when you match them on baseline characteristics like your baseline muscle strength. And so we're doing both parts of the analysis. On the second part of the analysis, on this matching comparability aspect of things, we're using the IGOS Natural History Dataset. This is a 2,000-patient prospective registry that's been run over the last 10 years, in most all major jurisdictions in the world and many developing countries as well. It's run out of Erasmus over in Europe, and it's their data.
They're doing this analysis as an independent third party, pursuant to a protocol and a SAP that we have aligned with the FDA. And so we've given them a protocol and a bunch of resources to do this analysis. We did a test run of this analysis with our proof of concept data, which we published and presented at PNS over the summer. So this is our second time through it. We know a lot about it. What is speeding up Erasmus in doing this analysis is twofold. One, the team has done a really nice job in preparing them for what the analysis should be and how it should work, based on the prior work we've done. So second time through.
Two, we've given them a ton of resources, and so they've been super intentional about the way they've done this, after we got the phase III data, and they're just ahead of schedule, which we're really pleased by.
So we've seen some data from this, right? So we've seen, I think, a 1000 patients. So, like, what's going to be new in the new dataset? And I know there's all this push about like, okay, so what about IVIG and, like, how it will compare to IVIG. So why is that relevant?
Really good question.
Is it relevant for approval, or is it just relevant for the commercial?
Really good question. Maybe I'll start with the second one first. So for the approval, we are not required to show outcomes versus IVIG. IVIG is not an approved drug, and typically, companies who are going against IVIG, whether it's approved or not, do not show outcomes versus IVIG. The most recent example would be kind of a cousin or sister indication to Guillain-Barré, CIDP, which is a chronic form of GBS, if you will, where we saw recent approvals, both in complement as well as FcRn approaches, with no comparator to IVIG. That is the standard. That being said, we do think a comparison to IVIG is important from a marketability perspective. So we really want to make clear that there's very little data and information on IVIG and how it actually treats this population.
Mm-hmm.
Showing a comparison of our drug versus that, we think, really accelerates the adoption of our drug from a commercial perspective. IVIG is approved in Europe, and there may be a requirement to do a comparison against IVIG in Europe. We don't have that definitive yet, but we're preparing belt and suspenders in case that is the case. So that's what we're doing with regard to IVIG.
Gotcha. Okay. And so and then in terms of like, again, the data, what do we expect for that? And I guess also just to add on to that, how are you going to present it? So obviously, if we get the data, like how are you... Is it going to be a company event or-
That's a great question.
Yeah.
Really great question. So two forms of data. One will be just first, the matching aspect. The patients in our study, do they match with the patients in the U.S., and is GBS the same in both populations, or is it ethnically diverse? We do not believe that to be the case. There's no evidence of that. That is for approval.
Okay.
So we really will hunker in on that and really focus in on that because that's the path to a BLA. So that's one dataset. The second dataset that I referred to in the comparison against IVIG, we will do that as well, because again, I think it's important from a commercial perspective. How we'll release that data is a little bit TBD. What we will do is go have the discussion with regulators, make sure they're in alignment with what we are doing and that there's been no change there, and we will get it out. My guess is we will certainly do some type of company event. We will probably bring in KOLs and others to support that, but that's still a little bit TBD.
Gotcha. Okay. And so, you know, we've always heard, you know, some, I mean, maybe cautiousness around the fact that you ran this trial outside the U.S. I mean, you know, are there any precedents that you point to that are, you know, kind of in line with GBS for studies that have also been run outside the U.S.? Again, just any precedent or analogs.
Yeah, absolutely.
that you point to.
Yeah, multiple, multiple indications, multiple diseases or programs where this has occurred. In fact, six over the last six or seven years or so, programs have been run entirely out of the U.S. and approved by the FDA. Of course, these are diseases of significant high unmet medical need. More often than not, they're diseases of infectious diseases like you see with HIV or GBS, for that matter. And so for us, what's really important is that we ran it in jurisdictions that are experts in GBS. So when you think about GBS, Bangladesh has the highest incidence rate of GBS in the world. They are the largest contributors to this IGOS, 2,000 patient natural history dataset.
They've published extensively on GBS when you go into literature, more than any other country, certainly much more by orders of magnitude than here in the U.S. Many of their physicians and scientists have studied under the folks at Erasmus, as well as people here in the U.S. And they're currently, in fact, running a large NIH study that is sponsored by the U.S. government in GBS. So they are experts in this space. We've done multiple audits in Southeast Asia, both our sites from a CRO perspective, as well as hiring third parties to go over and do GCP audits in those jurisdictions. So we're really pleased by the caliber of the data.
In fact, the IGOS steering committee went over to visit the site in the middle of the phase III study and can attest to the quality of the program as well.
Got it. Understood. So I guess since the phase III, you know, results, like, what level of interaction have you had with the agency? And I know, you know, this is something that at least, you know, we've talked about, but, you know, this seems like it would be something that you could apply for or, you know, at least look for breakthrough. Like, is that-
Great question.
Is that a strategy you guys are looking to take or not necessarily?
Yeah, no, we're assessing all things under the sun. I mean, for us, what's most important, early days, excuse me, is to fully educate the FDA on both the disease, Guillain-Barré syndrome, as well as our data. This is a program that they've not seen or an indication they've not seen in 40 years.
Mm-hmm.
We're just taking no chances with regard to that. We will be in front of them shortly with a Type C type of meeting. We will provide more information on GBS, the disease, globally, as well as our specific data and the import of our data. I mean, there are meaningful aspects of our data that you've never seen before in GBS literature, like our impact on week one, which is the key prognostic factor for how patients are gonna do with the disease. It accounts for 80% of how patients fare with the disease. We just want to make sure they understand that. And then, of course, we have some really important questions for them, really on our path to getting to a BLA. One of the questions we will ask about is breakthrough designation.
It's important to note that breakthrough designation gives you kind of an accelerated review.
Mm-hmm.
Or we already have that as part of fast-track review.
Okay.
So there's not a ton there, but we do think it probably matters from a market perspective. One of the things required to get breakthrough is showing that you're likely to be better than the standard of care.
Mm-hmm.
So for part of this analysis, for breakthrough, we would need to put in front of them our outcomes versus IVIG. We, of course, don't have that yet.
Right. Okay.
And so we'll go in and have the discussion probably before we have that data, and then we'll make the assessment on breakthrough finally after that. Really, what's most important for us, though, is kind of a straight, rapid path to a BLA approval.
Gotcha.
Yeah.
Is that Type C meeting the pre-BLA or-
It's pre-
Oh, it is. Okay.
No, it's not pre-BLA.
Okay. So just-
So it's just a Type C meeting-
Got it
... with some questions that we want to clarify.
Okay.
Our objective, candidly, is to get into a pre-BLA meeting where we've worked out most all questions prior to the pre-BLA meeting to make that as smooth as possible. We just kind of want to take all surprises. Again, we're being a little conservative here because they've not seen a GBS program in many, many decades.
I mean, what are the big outstanding questions or the questions that you have? Is it mostly just around, like, regulatory or is it, like... Well, obviously, regulatory, but, like, again, the matching, like, what, where do you think the questions lie right now in terms of why you want us to seek a Type C?
Yeah. Well, I mean, again, the Type C meeting serving multiple functions. The first and foremost is just to make sure they understand the disease in our data.
Yeah. Got it.
So, I mean, so the questions aren't at large, but there are questions that we want to ask in and around the program, which I won't go into much detail here, but the number one thing is to make sure that they really, we're aligned on this is GBS.
Yeah.
GBS is the same worldwide, and here's how our data is affecting that. Again, you know, our assumption is that the FDA has done the research that all of us have on what IVIG does in this disease, but there's so little data on that.
Yeah.
We're gonna go in and educate on our drug. We'll educate on IVIG as well and just make sure everybody's at kind of a baseline understanding before we get into kind of the BLA-type discussion.
Understood. Okay, and then I wanted to ask about the opportunity here, so GBS, you know, unlike, you know, many chronic autoimmune disorders-
Right
... is very acute, right?
Mm-hmm.
Like, as you were talking about, it's this really acute. You have to catch it within a certain window to really have a meaningful effect. So I guess just walk us through how you think about the opportunity and, you know, kind of the specifics about, like, reimbursement right now for IVIG.
Right.
Not necessarily the cost, but, like, you know, what's kind of, like... I don't know if there's special codes that are kind of encompass, you know, GBS treatment that you would-
Right
… fall, you know, into.
Really great question. So firstly, I think this is a really meaningful indication from a marketplace perspective, much larger than I think what people may be aware of. So there are 7,000 patients in the U.S., 15,000 in Europe, 22,000 every year who get Guillain-Barré. That's based on the first claims assessment that's been done in GBS in decades. We did that here at Annexon, where we went back seven years and pulled claims data for patients who are hospitalized and treated for GBS. So it's a real number, does not need to be discounted. So that's. We love that. We also know that 90% of these patients get IVIG currently, because this is a neurological emergency. You show up in the emergency room, I've got to give you something.
Mm-hmm
... because in a matter of days, you are moving from, you know, weakness in your muscles to being on a ventilator. So it is an absolute emergency, if not dying. 5% of folks in the U.S. still die from GBS on an annual basis. So not a trivial disease. So they show up in the emergency room, they get prescribed IVIG. 30%-50% of those patients get two courses of IVIG because it has a limited effect. So what that says to you is this is not a watch and wait, or we can wait or do anything. I have to get treated immediately. That's your market. I love that. You don't see that all the time. Also, we'll say that because it's an incidence-based disease, it's really driven by population....
Two-thirds of the patients are in, you know, roughly five states, larger centers of excellence, as well as community centers where they are getting treated with GBS. That allows us to have a really efficient commercial footprint to get after those patients. We do have a mechanism to get after patients who are in more rural settings, but again, two-thirds are in these larger centers of excellence, as well as in large community practices, so we can have a targeted practice there. IVIG is reimbursed through a J- code, so it's hospital-based. It's administered in the emergency room. The overwhelming cost to treat GBS is not the cost of drug. IVIG is about $25,000 to treat GBS. If you get a single course of therapy, two courses of therapy, it's $50,000. The cost associated with GBS, however, is the treatment of the patient.
These patients are in the emergency room, they're in the ICU, they're in the hospital, skilled nursing facility, physical therapy, et cetera. These patients, on average, are hundreds of thousands of dollars per patient. In fact, there was a study, excuse me, that was published about 18 years ago, showing that for 6,000 patients in the U.S., it cost the healthcare system $2 billion a year to treat these patients. We're updating that assessment now, 20 years later, and we expect it's gonna be orders of magnitude higher. And so the opportunity with our drug is to not only save dollars.
is to save dollars in the overall treatment, to get patients off the ICU 30 days sooner, which we showed in our data, get them off the ventilator 30 days sooner, to get them walking 30 days sooner, which means you're getting out of the hospital, et cetera. So that's how we're going after it. We know we'll need to get a J-code. We're already in active discussions with the payers with regard to that.
Mm-hmm.
Done a number of focus groups, another number of surveys, a lot of market research, and now we're having very targeted messaging discussions around that. This is not a call center that they focused on as much because it is an ultra-rare disease, right? 7,000 patients a year. When you bring the numbers to light, though, where they're actually spending their dollars, they light up. And the opportunity, again, to save, you know, patients and get them off the ventilator, i.e., get them out of the ICU and out of the hospital, is huge. Not only in cost, but being able to make those beds available to other patients for different types of diseases. So J-code, probably a special exception to it as well, to do the pricing that we think is warranted for a drug like this.
Got it. I just want to go back to a comment you made.
Sure.
I don't know if I heard you right. Did you say two-thirds of the GBS patients are in five states?
They're about, yeah, two-thirds.
But is that because, you know-
Population-based.
Okay.
Highly population-
Because that seems interesting. Or does that mean it's underdiagnosed, and people are not just being treated in other states?
No, you know when you have GBS.
Okay, I was going to say-
I mean, GBS is indiscriminate. You are otherwise healthy, completely healthy. You typically will get some type of preceding infection, let's call it food poisoning. Your immune system or complement turns on to clear the food poisoning from your system.
Right.
It then shuts off. Everything's copacetic. Two weeks, three weeks later, for whatever reason, you're starting to feel tingling in your lower extremities. It moves up your body, and you literally go to bed at night, and you wake up the next day, and you cannot move. That's what's so scary about this disease. I mean, it's so hard to predict when that will occur.
Right
... but nothing looks like it.
Yeah.
When you show up in the emergency room-
They know
... it's really a very straight diagnosis. You know it. Nothing looks like it at all. And so... And then you actually do a lumbar puncture to confirm it. So yeah, it's a very straightforward diagnosis, but it really is population-based, which is very interesting, not only in the U.S., around the world. Where you see GBS is when you have larger concentrations of people.
Mm-hmm. Understood. Okay. So basically, before we shift to 1502 , so we're looking at the IGOS data towards the end of the year.
Mm-hmm.
Some type of event there and maybe, maybe feedback from a Type C meeting sometime-
Or more.
Or more by the end of the year.
Correct.
Okay, great. So yeah, maybe shifting gears to ANX1502. So, you know, you recently provided some, you know, color on the bridging study from the oral liquid suspension to the tablet.
Correct.
So maybe you can just, you know, provide a little bit more detail around that and how that went and why that's important.
Yeah. So for those who don't know, ANX1502 is our small molecule program. It is the first oral drug candidate in the classical pathway. We think that's really, really important. Again, it's stopping complement right up high in the cascade, and it offers just a more convenient dosing paradigm, as well as the mechanistic benefits of stopping complement high up in the cascade. What we love about it is there are a host of antibody-mediated autoimmune diseases for which this target, C1s, have been clinically validated and, in fact, approved, typically with IV formulations that require every other week IV. You see now sub-Qs coming on board. The opportunity to offer these patients to have significant neuromuscular damage or other types of damage in oral that they can take in the comfort of the home is game-changing.
All of our programs are designed to be best in class, just candidly, full stop. We completed our initial healthy volunteer study in a liquid suspension with patients and achieved our targeted drug levels in that study. Really pleased with that from a PK perspective. These are in healthies, where complement is relatively normal, so you don't get pharmacodynamic data out of that. You really just get PK data. We now have transitioned to a tablet form. That's the bridging study I referred to, Derek. There, we demonstrated that it was comparable, if not better, from a PK safety perspective than what we saw in our liquid suspension program. It's getting stronger. We're now moving into a proof-of-concept study in cold agglutinin disease . Very small study, really to confirm pharmacodynamic activity.
In this disease, complement levels are, of course, elevated, and we're looking to show with our treatment over a month period of time, that we're able to normalize hemolysis, which is really, really important, as well as downstream complement activity. Are we shutting down the pathway fully at a therapeutic dose? So that's kind of as fast as-
How... Like, what do those doses look like? Or I don't know how you've shared that much color on that, but, like, just kind of curious, like, how that, when you bridged it, you know, are those doses larger or, you know, again, the overall pill because of the excipients to make it more soluble?
Good point.
Like, what kind of happened when you did that?
Pretty similar in doses. I think we have it in our corporate deck. So this is a BID dosing, so twice-a-day dosing. I failed to mention that before, and I think it was. Our top dose is around 500-550 mg twice a day.
Okay.
Yeah.
Got it. Understood. So I think, you know, the other thing with this program that we always get feedback on is, like, if you look at the other C1s programs, again, on multiple antibodies.
Mm-hmm.
You know, relative to you guys as a, you know, I guess you didn't run this CH50 standard assay, so they always push back on that. So maybe-
We do a lot of that.
Yeah, yeah, just share for us why that's not really relevant for a small molecule.
Really good question. We get this question quite a bit, so first thing to note, we've been an antibody company first, so we've got four antibodies in the clinic. We understand the CH50 assay exceedingly well. We've looked at it with three of our sub Q or our IV drug candidates and one sub Q. So we appreciate the import of the CH50. What is different about a small molecule, however, are the target drug levels. So with an antibody, you dose up really high drug levels so that you can maintain coverage for a long period of time, once a month, if you will. With a small molecule, with BID dosing, your drug levels, by definition, are much lower because you're dosing twice a day. To run a CH50 assay, you have to do a dilution step, one to 100 .
When you dilute one to 100 , your drug levels with a small molecule just don't register. Your drug levels are lower there. So it's really kind of an apples to oranges analysis, and we looked at it four ways to Sunday, because we anticipated people would ask us the question, and we've shown CH50 with all of our antibodies already.
Got it.
So again, we understand it exceedingly well. As a result, that is why we are doing the CAD proof of concept study. That is where we're gonna demonstrate pharmacodynamic effects, et cetera, in an actual patient population. So it'll be a more robust data set at the end of the day.
Got it. So what should we expect in that CAD trial? Like, what's... I know there's a couple markers like bilirubin and looking at hemolysis and hemoglobin, but like, you know, what should we just see that kind of like normalize?
Yeah.
Like, what's the expectation?
It's a great question. Yeah, so we ran two, again, because we kind of take a rigorous step-by-step approach here at Annexon. We've already run a study in CAD with our antibody, ANX005, so we know what it's targeting upstream should look like in this disease. We're now taking a small molecule, and you said it, we wanna normalize complement activity downstream, so we want to block this downstream activation. C4a is the key kind of first activating component of the classical pathway that we'll be looking at. We've looked at it in a number of different diseases already, a number of different drug candidates, and then hemolysis is the second one. So this is, you know, looking at bilirubin, which you can normalize in a matter of days, right? And so we are looking to show normalization on that. We'll look at hemoglobin.
We don't really have a strong expectation on hemoglobin just because it's harder to predict. Maybe two-thirds to three-quarters of patients actually normalize with hemoglobin. In the case of our program, we're only dosing for a month. So we'll look at hemoglobin, but for us, it's not the key barometer.
Yeah.
It really is hemolysis and impact on complement measure.
I know this is like a really- it's like six patients, right?
It's a small study.
I mean, is this a very homogeneous population or heterogeneous? Like, is there any variability that we could expect that, like, you know, one patient just, like, doesn't respond for some reason?
Certainly, with hemoglobin.
Okay.
That's been the history.
Hemoglobin is the one that, you know-
That's the more variable one. Hemolysis is, it's been really objective, not only in our programs, but in other programs, and of course, inhibiting a complement pathway. Either you're fully inhibiting this thing or you are not, right?
Right.
So these are really pretty objective assessments for us.
Got it.
Yeah.
Then for CAD, I know you had, I guess, maybe flirted with the idea as pursuing that as an indication.
Yeah.
Then you're like, "We're gonna do a POC," but then you're kind of flirting with it again. So where are you-
Such a great question.
With CAD, in terms of... Is this, once you establish proof of concept, do you move forward, or you got to exercise, you know, looking at other indications?
Yeah. So both. Well, I shouldn't say both. We certainly are looking at other indications.
Mm-hmm.
There are many larger antibody-mediated autoimmune conditions that have been clinically validated, so high PTS clinically, and you're bringing forward a small molecule. We think those are market opportunities that are like no other, like myasthenia gravis, CIDP, et cetera. And there are a host of others that we like that you can target with a small molecule that are hard to get after with an every other week IV. So there are a host of indications there. As it relates to CAD, CAD is interesting to us. High probability of success based on what's been done with our program and others' programs.
Sure.
The issue with CAD is the market opportunity. So about 5,000 patients in the U.S., about half of them are really reasonably stabilized. However, when you look at the analysis that have been done by many bank analysts and others, you know, they've had a range of somewhere between $300 million and $800 million a year. That is not what we are seeing with the drug that's approved right now, sutimlimab, on the market, but it's also not being aggressively marketed. And so we're just assessing whether CAD could be low-hanging fruit for a really rapid path to an approval, to have some commercial attractiveness while you're pursuing the bigger indications. That's a TBD. We're doing the work now on that, so we'll come back on that.
So when you report the proof of concept in CAD, will you be also, you know, kind of highlighting which indications you look to pursue and kind of the development plans? Like, how robust of an update will that be?
Yeah, we do have indications that we do like definitively that we want to go into.
Okay.
And so we will be communicating those when we have the data as well. I don't know if CAD will be part of that mix at that point in time-
Okay
... if we've completed the work, but the others, two of them in particular, we've completed the work on it. So yeah, we, we will certainly be giving some direction with regard to that.
Got it. I guess, in terms of the expectation for that, like, is this something that you would like to go alone and develop those future indications, or would you look to partner?
Good question.
Do you think that POC in CAD is enough to partner?
Yeah. So we'll be opportunistic, right? I mean, we, we prepared this to kind of go along. These are, you know, rare or orphan diseases on the autoimmune space that we can readily take on, like many of the companies that have come before us to take on, both clinically and commercially, and with marketing appeals, very different to marketing an IV. We, we all know this, right? But we'll be opportunistic, and, and we do think that the POC data is the key de-risking data-
Mm-hmm.
for the program.
Got it.
Yeah.
Maybe with the last five minutes, I want to hit on 007 and GA. You know, getting studies underway and things there. Maybe just give us an update.
Yeah.
I guess the big question there is, well, not a big question, but, you know, you guys got, you know, designated with the PRIME designation, which no other, you know, kind of, GA therapeutic in development has.
Right.
That's in the EU. So, like, what is the EU seeing, you know, with you guys that, you know, obviously they're not seeing with, you know, other drugs that are approved or in development?
Yeah, great question. So again, for those who don't know, ANX007, this is a intravitreal administration drug into the eye, targeting C1q for geographic atrophy and a host of other neurodegenerative ophthalmic diseases, which we'll talk more about in time. There, we demonstrated statistical preservation against the loss of vision best in both normal conditions as well as in low light conditions. It's really, really important. That's a higher standard, both statistically significant. We also demonstrated impact on structure. There's this kind of belief that we're not impacting the structure of the eye. We've gone further than any company in showing impact on structure in the eye, and that we've shown impact in the center fovea of the eye, where your vision is housed. What's that mean? That's the association between structure and vision that we've demonstrated in our program that no other program has demonstrated.
Full stop. In fact, we've not even seen any company release structural data on the center fovea of the eye. We're the only program to do that. We're showing double-digit preservation of photoreceptor cells, 30, 40, 50%, whopping numbers. That is where vision is housed, so we love that data. That is what led to PRIME designation, which is, in effect, breakthrough for EMA. You guys are aware that EMA has rejected other programs that have only shown structural preservation of RPE cells, predominantly on the outer segment of the eye, that do not associate with vision. They only care about vision. These are 80+ year-old patients who are looking for function, and so that's what our program demonstrated in almost a 300-patient proof of concept study, highly statistically significant. And so that's what we were granted it on.
We anticipate, you know, we have really strong alignment. We're in a 630-patient, phase III global study that is underway now. Really excited about that. We have strong alignment with EMA as well as the FDA on that program, and so kind of all systems firing with GA.
How do you think that'll recruit, given, like, I guess there's a couple other options out there, but, I mean, are you gonna... And also, does your trial, you know, exclude patients who have been on, you know, Syfovre and Izervay?
Great question. Yeah, so we're not excluding patients. In the treatment eye, you've got to be washed out.
Okay.
In the non-treatment eye, you know, it's kind of up to the physician's discretion there.
Okay.
And the physicians are super excited, as well as the patients, to have an opportunity to preserve against the loss of vision. It's one thing to say you're preserving structure in the eye, but that doesn't matter to an 82 year old who can't see their loved ones, who can't make their eggs, who are losing their independence, who had to turn in their driver's license. They want to preserve their independence with vision, and so, recruitment is going really well right out the gate. We're excited about this. We're doing this globally in Europe and the U.S., as well as in Australia and New Zealand, and just really off to the races.
What do you think it means if Apellis... I mean, obviously, they got, you know, a negative opinion, trying to do the reexamination. So I mean, would that play well for you if they continue to, you know, kind of get, you know, stopped from the market there just because of the data that they have? And obviously, again, they don't have Prime designation, they don't have any of that.
Right.
So, like-
Right
... again, do you kind of see that as kind of like that hurdle is higher, and you guys have maybe met that hurdle already with some of the data?
It's certainly a higher hurdle, and again, we're not rooting against them. We appreciate the pioneering work that Apellis and others have done in this space, but ultimately, we're in this business to provide functional benefit to patients. The structural thing is a very odd thing. We're classic neurodegenerative folks. We've been in neurodegeneration for 20+ years. We're old-school Elan. Scientific discoverers of the A-beta approach in Alzheimer's, brought support for Tysabri, most efficacious drug in MS. We're about function, so you know, does it bode well for us that we're the only ones in Europe who can be dosed with, you know, kind of this type of drug? It does from a recruitment perspective, and ultimately, we hope it does so.
I mean, if they get approved, maybe the bar is lower, and then-
Right
It gets even better.
It works in either direction.
Yeah.
But, you know, from a recruitment perspective, right out the gate, they have-
Yeah
been looking for something to offer their patients.
Yeah.
You know, I say that, you know, it's really important in Europe, where they have twice as many GA patients as we have in the U.S. They've got over three million patients there, so a million and a half in the U.S. These are massive markets, which we're excited about. You know, candidly, and I'm sorry, I'm on a little tangent-
No.
But I'll just say as quickly as that. But our objective here, as I said, is to do a few things. One, we want to show functional improvement to all patients who are treating our drug with a mechanism that is very distinct from other complement approaches, and we've seen this now in multiple indications. Two, we want to be best-in-class in every disease we're in. We're not following a me-too model. So when you think about our data in GBS, never been seen before. We've run three studies, far and away the market leader. When you look at our data in GA, never seen statistically significant preservation of vision. Far and away, going to be the market leader if we replicate that.
And then the small molecule in the autoimmune space, we could have, when we brought forward ANX005, taken it into the small molecule or autoimmune conditions, of course, there are a bunch of IVs. Why would we do that? We're trying to win the market. It is our strategy. And so, you know, we're excited about where we are. We love what the future is, has ahead for us, but there's a lot of road-
Yeah
... like, we've got to do a lot more executing to kind of deliver on this promise.
All right. Well, maybe we'll leave it there. Thanks, Doug.
Thank you.
Good to see you. Appreciate it.
It's a pleasure.