Hello, welcome to Annexon's Conference Call. At this time, all participants are in listen-only mode. There will be a question-and-answer session after the prepared remarks. Please be advised that this call is being recorded at Annexon's request. I will now like to turn the call over to Lori Murray, Senior Vice President, Investor Relations and Corporate Communications. You may begin.
Thank you, Jonathan. Good afternoon. Earlier today, we issued a press release outlining top-line data from our ARCHER Phase 2 clinical trial evaluating ANX007 in patients with geographic atrophy. The press release and the slides to which we'll refer are available under the Events and Presentations page within the Investor section of our website. On the call with me today is our CEO, Douglas Love, as well as our Chief Innovation Officer, Dr. Ted Yednock, and our VP and Head of Ophthalmology, Dr. Donald Baum. In addition, we are delighted to have Dr. Charles Wyckoff join us for the Q&A session. Dr. Wyckoff is the Director of Research at the Retina Consultants of Texas and an investigator in the ARCHER trial. Today's discussion will include forward-looking statements related to Annexon's current plans and expectations, which are subject to certain risks and uncertainties.
Actual results may differ materially due to the various important factors, including those described in our Risk Factors section of our most recent Form 10-Q and other SEC filings. These forward-looking statements represent our views as of this call and should not be relied upon as representing our views as of any subsequent date. We undertake no obligation to publicly update these statements. Now with that, I'd like to turn the call over to Doug.
Thank you, Lori. Thank you all for joining us today. We're excited to report the results of ARCHER, our Phase 2 clinical trial of ANX007 for the treatment of geographic atrophy, which demonstrated for the first time a statistically significant protection against vision loss across multiple endpoints in this patient population. These data are the realization of our founding hypothesis that we can treat complement-mediated diseases differently by stopping the classical complement cascade where it starts on diseased tissue. In the case of GA, that's C1q localized on photoreceptor synapses, resulting in damage and loss to photoreceptor cells and ultimately visual impairment. We'll come back to this concept. Our scientific founder, the late Dr. Ben Barres, a pioneer in complement-mediated neurodegeneration, trailblazed insights that fundamentally shifted the world's understanding of how our immune system can disrupt normal neuronal function in our eyes and brain.
Ben hypothesized that by blocking upstream classical complement activity via C1q, we could provide the most complete protection against harmful inflammation and tissue damage in the body, the eye, and the brain. This led to the founding of Annexon, and since then, we've made significant progress towards translating the scientific hypothesis into therapeutic reality. Ben's original discovery was in the eye, where he discovered that C1q led to aberrant removal of neuronal synapses or connections and tissue dysfunction. Over the last 2 years, we've presented clinical data in 2 difficult-to-treat diseases which support that hypothesis. Huntington's disease and ALS, where we showed that by stopping the complement cascade at its start, we can provide meaningful clinical outcomes for patients. Today, we're pleased to report the third supportive data set in a neurodegenerative disease, geographic atrophy or GA.
The top-line data from our ARCHER Phase 2 trial show that ANX007 is the first complement agent to demonstrate protection against vision loss following 12 months of treatment in pre-specified analyses. Today's top-line data support four key differentiators for ANX007. First, the data validate ANX007's unique mechanism of blocking upstream classical complement via C1q to preserve photoreceptor function and vision. Second, a statistically significant dose-dependent protection against vision loss was demonstrated in two pre-specified measures, BCVA, as measured by 15-letter loss, and LLVD, and was supported by multiple analyses, including protection against visual loss in both the foveal and non-foveal populations. Third, the primary endpoint of reduction and rate of lesion growth did not reach statistical significance.
We believe the results reflect the unique neuroprotective approach of ANX007 and its distinction from the biomarker measurement of lesion growth, that RPE clearance may be mediated in part by other complement pathways. Importantly, slowing of lesion growth has not been clinically correlated with visual function. Finally, ANX007 demonstrated favorable safety results in the 181 patients treated for 18 months, with no meaningful differences in CNV rates between the sham and treatment groups. In total, we believe these data strongly support the therapeutic potential and market opportunity for ANX007 by protecting against vision loss in GA patients. By way of background on slide 5, GA is an advanced form of age-related macular degeneration, or AMD.
It's a chronic and progressive neurodegenerative disease of the eye that, for more than 5 million people worldwide, leads to progressive and irreversible vision loss. GA is the leading cause of blindness in people over the age of 65 in developed countries, and the risk of developing GA increases with age. More than 1 million people in the U.S. have been diagnosed with GA, and another 4 million people outside of the United States. A person in the early stages of GA is likely to first notice problems with reading or low light vision. That's because photoreceptors or light-sensitive cells begin to deteriorate in the center of the eye, causing issues with fine vision and color perception. This damage, which starts as small spots, will eventually grow into larger patches. Ultimately, if the disease progresses to advanced stages, permanent blind spots will develop in the center of the visual field.
As the photoreceptor cells continue to die, the person will unfortunately lose their vision and the associated independence that goes with that. GA is a disease of vision loss due to damage and loss of functional photoreceptor cells, a type of neuron. Looking at the diagram in the retina in GA on slide 6, functioning photoreceptor cells, shown in green, have a rich synaptic network that links the retina to the brain for vision. Photoreceptors on the edge of the lesion in this diagram, shown in orange and in the actual microscope image below, are in clear decline. Annexon's seminal discovery by Dr. Barres was that C1q drives elimination of synapses in disease, leaving photoreceptor neurons dysfunctional and susceptible to elimination. In preclinical models, we have shown that blocking C1q protects photoreceptor cells synapses, and importantly, photoreceptor cell function.
We have also shown that blocking C1q leaves the normal clearance function of the lectin and alternative pathway in place, which is important for removing dysfunctional cells and maintaining tissue homeostasis. Fundus autofluorescence, or FAF, measures RPE cells, not photoreceptor, and loss of FAF is a measure of RPE clearance as a surrogate biomarker of lesion growth. Importantly, FAF is not a measure of photoreceptor cells or photoreceptor cell function. The goal of ANX007 as a C1q inhibitor is to protect against the loss of photoreceptor synapses to preserve photoreceptor cell function and vision. We demonstrated this in preclinical models and now in our pivotally designed ARCHER trial. Moving to the trial design on slide 7. Our ARCHER trial is a randomized, multicenter, double masked, sham-controlled study comparing safety and efficacy of ANX007 to sham patients with GA.
The study enrolled 270 patients stratified by GA lesion size, location, and fellow eye CNV to minimize biases or imbalances in the data. Patients were randomized to receive a 5-milligram intravitreal dose of ANX007, either monthly or every other month, or sham for a total of 12 months, followed by a 6-month off-treatment period. The primary endpoint of the study was the rate of GA things measured by fundus autofluorescence from baseline at 12 months. Importantly, the real-world clinical goal, however, is preservation of vision. Given the mechanism of ANX007, the ARCHER trial included multiple pre-specified endpoints to assess visual acuity. These are best corrected visual acuity, referred to as BCVA, low luminance visual acuity, or LLVA, and low luminance visual deficit, or LLVD.
BCVA is a widely established functional endpoint by the clinical community and regulatory authorities and represents the gold standard for assessing efficacy in many retinal diseases. In a BCVA assessment, visual acuity is tested using a specialized eye chart at a pre-measured distance and at a certain luminance. For veracity in our study, we defined vision loss based on two consecutive visits in which a patient had a loss of 15 or more letters compared to baseline, or if the loss occurred at the end of the study. This approach is designed to limit variability in vision and reading conditions by patients between visits, adding confidence to our data set. Low luminance visual acuity, or LLVA, involves standard BCVA testing in low light conditions, often by adding a neutral density filter in front of the testing eye.
Finally, low luminance visual deficit, or LLVD, is the difference between BCVA and LLVA and assesses retinal health and abnormalities in visual function that would not otherwise be apparent by measuring BCVA alone. In terms of patient demographics on slide 8, 270 patients were enrolled in our study were equally split between 3 arms. 89 in the ANX007 monthly group, 92 in the every other month group, and 89 in the sham group. The trial was predominantly conducted in the United States, with approximately 95% of study patients in the U.S. The overall demographics of the patient population were consistent with other GA studies, including age, gender, and ethnicity. The average age in the study was 80 years old, and enrollment was generally balanced between males and females. Importantly, patients were split almost equally between foveal and non-foveal.
As background, foveal patients are those with vision loss in the central portion of the macula, which is responsible for central vision. Non-foveal patients are those whose lesions are not yet affecting central vision. With that, let's turn to the ARCHER findings, starting with the most important functional endpoint, visual acuity. Starting with BCVA on slide 10. I'm sorry. Starting with BCVA, slide 10 shows the total number of patients with a 15 letter or greater loss at the end of the 12-month period for each study group. As shown in the bar chart on the left, out of the 181 patients treated with ANX007, only 15 patients, or 8.3%, experienced a 15 letter or more loss.
This means that treatment with ANX007, whether monthly or every other month, was able to protect against loss of 15 letters or more for 166 patients. This result was statistically significant with a P value of 0.002. We view these data as highly differentiated, especially when compared to the 21.3% of patients in the sham group who experienced a loss of 15 letters or greater at month 12. As noted, each patient's best corrected visual acuity was measured at each of their visits. Shown on slide 11 is an analysis of a risk, of the risk of a 15 letter or greater loss, defined as loss on 2 consecutive visits or at the end of month 12.
ANX007 reduced the risk of having a 15 letter or greater vision loss by 72% for those treated monthly, 48% for those treated every other month, and 59% for the pool of treatment group. This is compared to the sham group, which dropped substantially over the one-year period. These data were statistically significant in ANX007 monthly group with a P value of 0.006, non-significant in the every other monthly group with a P value of 0.064, and statistically significant in the pool population with a P value of 0.008. Over the last few years, there's been a significant amount of discussion in the industry on how patients might respond to treatment based on the location of their lesion.
Historically, it has been thought that foveal patients would not be able to benefit from a complement-mediated therapy, whereas non-foveal patients have been expected to see a greater benefit from treatment. We looked at a 15 letter loss for the monthly group compared to sham, separated by foveal and non-foveal populations, and the treatment effect was statistically significant at 0.0019. When we look at the same analysis for the every other month treatment group, the treatment effect was also statistically significant with a P value of 0.04. The ANX007 pool population also achieved statistical significance with a P value of 0.0015.
We saw a meaningful treatment effect in both the monthly treatment and every other month treatment groups, regardless of whether patients were foveal or non-foveal, which we believe strongly supports the therapeutic opportunity in an all-comer population. Moving to the next assessment of visual acuity on slide 13, we looked at LLVA, which is BCVA assessed in low light conditions. In this analysis, we observed that 20.3% of patients in the sham group had a 15 letter or greater loss versus 10% for those in the ANX007 monthly group and 11.8% for those in the every other month group. None of these reached a statistical reduction, this is the first geographic atrophy study that we are aware of that showed a trend in slowing the progression of LLVA.
On slide 14, we showed patients BCVA stratified by their retinal health status at baseline. For this assessment, we used the industry standard cutoff of 30 LLVD score. LLVD is a prognostic factor on the health of patients' retinas, and the evaluation assesses retinal function based on lighting conditions. Patients with a score greater than 30 are considered to have less healthy retinas, while patients with a score of lower than 30 are considered to have healthier retinas. When looking at patients with less healthy retinas, 30% of those patients in the sham group experienced a 15 letter or greater loss, compared to 16% of those treated with ANX007 either monthly or every other month.
Among patients with healthier retinas, 17% of patients in the sham group experienced a 15 letter or greater loss, compared with no patients in the ANX007 monthly group and only 6% in the every other month group. These data were statistically significant in all three ANX007 groups, with P values of 0.0016 for the monthly, 0.029 for the every other month group, and 0.0009 for the pool population. Comparing the data between ANX007 treatment groups and the sham group, the findings are striking. Treating patients earlier in their disease is always preferred, especially in neurodegenerative diseases.
When you look at the overall population of people with GA, those most likely to be treated first are those with an LLVD score of greater than 30, as they are showing rapid, challenging loss of vision. There's a large segment of the population with healthier retinas that is just starting to experience the impact of GA on their vision. These data show that those patients may benefit even more from ANX-007 with earlier treatment in their disease. In an assessment of LLVD on slide 15, we looked at patients in 2 ways. Patients with better vision as measured by BCVA score of greater than or equal to 55, and patients with impaired vision with a BCVA score of less than 55.
In the first group of those with better vision, 25.5% of patients in the sham group had a worsening of 15 letters or more, versus 9.4% in the ANX007 monthly group and 16.4% in the every other month group. Among those with more impaired vision, 17.9% in the sham group lost 15 or more letters, versus 17.7% in the ANX007 monthly group and just 3.3% in the every other month group. ANX007 monthly and pooled groups achieved statistical significance with P values of 0.0161 and 0.019 respectively. While the every other month group showed a non-significant trend with a P-value of 0.0597.
In total, when assessing all measures of a visual acuity, we are extremely encouraged by the preservation of visual function demonstrated by ANX007 in this GA patient population. Let's turn to GA lesion area. The primary endpoint of the study is based on the GA area. This is a measurement of the loss of RPE cells. RPE cells are needed to nourish photoreceptors, this loss has been hypothesized to loss of overlying photoreceptors, resulting in vision loss over time. However, meaningful function loss from this mechanism has not been consistently shown, this separation of loss of RPE and visual function is further confirmed in the ARCHER study.
As shown on slide 17, over the 12-month period, ANX007 had a relatively modest, non-significant effect of 6% on lesion growth reduction in the monthly treatment group with a P-value of 0.0526. 1.3% reduction was observed in the every other month treatment group with a P-value of 0.896. 3.7% reduction was observed in the pool patient population with a P-value of 0.673. These results did not correlate with the preservation of vision function seen on the functional measures. Finally, supporting ANX007 are the safety and tolerability findings. Turning to slide 19, ANX007 demonstrated favorable safety results when administered either monthly or every other month. CNV incidents, as determined by the investigator, was well balanced between sham and treatment groups.
There were 3 cases of endophthalmitis, all of which were determined to be by the investigator to be related to the injection procedure rather than the drug. There were also 3 cases of intraocular inflammation observed and thought to be mild. There was 1 case of uveitis treated with topical steroids and resolved within 48 hours. There was 1 case of trace vitreous treated only with topical steroids that resolved within a week, and there was 1 case of anterior uveitis that presented with cataract that was also treated only with topical steroids. In none of the cases was retinal vasculitis observed. There was 1 case of retinal artery occlusion, and retinal vasculitis was also not observed in this patient. Overall, we're quite pleased with the safety results observed with ANX007 in this trial.
In sum, the totality of the data with ANX007 in ARCHER trial are promising for the field and most importantly for GA patients. In our study, 20% of patients in the sham group lost at least 15 letters or approximately 50% of their vision in just 1 year. To put that in real-world context for patients, that would mean 1 in 5 had significant vision loss likely to impact their activities of daily living. Ultimately, without a treatment that protects against vision loss, millions of people are at risk of losing their sight, along with invaluable human attributes like the ability to see loved ones' faces or to maintain their own independence.
Based on the ARCHER findings, we plan to engage quickly with regulators to discuss next steps and determine the optimal path to advance ANX007 to our patients. In close, we believe that ANX007 represents a new and distinct product opportunity for patients with GA. It represents yet another important step toward achieving our mission here at Annexon of delivering game-changing treatments to patients living with complement-mediated diseases. This is only made possible by the passion and dedication of a lot of people. To our employees, collaborators, and advisors, these data are a great accomplishment, and I thank you sincerely for your warrior spirit and all for one commitment. To the physicians, medical teams, and most importantly, the patients, their families, and caregivers who participate in our clinical trial, we are eternally grateful and humbled by your support and contributions.
The GA field would not be where it is today without you. Before we open the call for your questions, we're delighted to be joined by Dr. Charlie Wyckoff, who will make a few comments from the treating physician perspective. Dr. Wyckoff, over to you, sir.
Thank you. Good afternoon, everyone. It's great to be here with everyone and with the Annexon team. Great summary of the data. Fascinating data, a lot to think about here. I think if I summarize this from my perspective as a clinician and as a clinical trialist in a very busy space of course, we have to look at this and think, it's frustrating to not meet a primary endpoint. Very quickly, I think, my takeaway is that we're learning something much more important here than just missing a primary endpoint. T his trial was structured around the primary endpoint of looking at a biomarker on fundus autofluorescence that has been validated now as a provable endpoint for a drug that can slow the progression of geographic atrophy at the anatomic level based on fundus autofluorescence.
That's an important biomarker for us as a field. What we're seeing here is a non-significant effect on that very specific biomarker. When you really step back and think, well, what are we trying to achieve as clinicians for our patients? We're trying to do what we're seeing here, which is a first time finding in geographic atrophy, at a significant, meaningful level like that, and that is preserve visual function. I think the key point for me is that while this is a complement inhibitor, we are seeing the complexities of the complement pathway. It's really important what those specific targets are.
A C3 inhibitor, a C5 inhibitor, clearly to me, have very different impacts on preservation of retinal tissue and functional outcomes than now what we're seeing with this 007 investigational product. To see preservation of vision in a way that we have not seen with any other study is quite meaningful. It's meaningful to the field because it shows that we really can impact visual function, which is what patients absolutely care about, through a 12-month endpoint, which is very meaningful. It also shows us that there's gonna be many different endpoints to consider for the host of drugs being studied in geographic atrophy. I t's overly simplistic to think that all drugs in geographic atrophy are gonna have the same effect on every biomarker.
F rom another perspective, I see this as complementary to, for example, the other agent that's already FDA approved, which has been shown to slow the progression of fundus autofluorescence-based lesion growth. This is quite distinct and very meaningful for patients in a very different way. Maybe I'll pause there. I'm happy to take any other questions.
Certainly. Ladies and gentlemen, if you have a question at this time, please press star one one on your telephone. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from the line of Tazeen Ahmad from Bank of America. Your question please.
Hi, guys. Good afternoon, and thanks for taking my questions. Just maybe a couple. If you were to compare your results that you got today versus what the C3s and the C5s have shown already, how would you think about the benefit that you saw in VA versus what the others have not been able to show? I guess, does that give you particular confidence that focusing on C1q could actually in the end end up better? Can you give us some thoughts this early on why you might have missed the primary endpoint and what you would change for the next study? Thanks.
Yeah. Thanks, Tazeen. Good questions. We appreciate that and appreciate you joining the call. Really good question. As it relates to your first question and the difference in what we've seen in our study versus some of the other, excuse me, downstream approaches, well, it's as Dr. Wyckoff really very nicely stated, we're focused on function, and that is ultimately what patients are concerned with maintaining their vision and their independent lifestyles. What we saw was, in this study, was an impact on function as measured in multiple ways, predominantly looking at BCVA at the 12-month time point. Over a 12-month period of time, we saw that functional benefit also demonstrated irregardless of patients' foveal status, whether they were foveal or non-foveal. We saw it in the healthier eye and the sicker eye.
That's our objective. We have not seen that in a single one-year study before. We're really encouraged by that across the board. I think when you turn to fundus autofluorescence and the measurement of that biomarker, it's just a very different mechanism, as we said, in our prepared remarks. There, you're seeking to protect against the loss of RPE cells that's really mediated through a clearance mechanism with downstream complement approaches, which is very different than targeting the photoreceptor itself, which is where function and vision is housed. We just candidly think it's a very different approach.
Our hypothesis is that the impact that we had there or the minimal impact that we had there is likely due to 1 of the other complement pathways playing a role in the clearance of RPE cells, which does not come into play as you attack or approach the photoreceptors.
Yeah. Okay.
I'm happy to jump in there too. I have a thought on that. I t's really important to move away from the concept of which is better, right? We live in a world where there's, for example, so many different anti-VEGF agents in retina, and so we've kinda gotten used to actually comparing this drug to that drug because at the end of the day, they all do something very similar, and we can definitely debate about distinctions between anti-VEGF agents. I think what we're seeing here, instead of a discussion of better, I think it's more of this question of differentiation.
There's meaningful differentiation here, and I think that there's a plausible mechanism that the Annexon team has been working on for many years, which I think can potentially explain why we're seeing preservation of visual function here, whereas other medications that are really targeted on slowing growth of lesions may not be seeing a visual function benefit. I deally, from a physician perspective, we would have seen much more robust visual function preservation with C3 inhibition, just to focus on the FDA-approved agent out there. There were some signals with microperimetry, for example, and the and the foveal occupancy data, but there wasn't a really strong overarching signal, and certainly none of the pre-specified endpoints seemed to show a signal.
That's frustrating as a field because we built this fundus autofluorescence story around the concept that eventually we would see a functional benefit, and we've certainly talked about that a lot over the years.
With that background, having enrolled a population of patients here that's actually very similar to the C3 and C5 inhibitor populations, and to see what I think is a, is a strong signal of visual preservation through a 12-month endpoint, I think is really meaningful. Because if this if this biologically is gonna continue to have protective effects, I would expect that differentiation between active treatment and sham to continue, for example, through an additional one year of treatment. To see this signal within 1 year, I think clearly differentiates this mechanism of action from the other complement inhibitors that we've been discussing.
Okay, thanks for all of that color. Maybe just 1 follow-up to what you said. H ow do you think about the every month dosing versus every other month? In the 1st year, it does look like the every other month had more meaningful impact on preservation of vision.
Yeah. We clearly saw a differentiated, a dose-dependent, impact on function based on every month and every other month. T hese data are new to us, so we'll dive into that, and hopefully learn more about that in the coming weeks.
Okay. Thanks, guys.
Thank you. One moment for our next question. Our next question comes from the line of Joseph Stringer from Needham. Your question please.
Hi, thank you for taking our question. Two from us, just given that there is now regulatory precedent in GA and endpoints that are established on lesion growth, what's your feeling on what the path forward is from a regulatory perspective and maybe your confidence level that FDA would be flexible on regulatory endpoints in GA?
I think we lost Joseph. Operator, are you still there?
Yeah. I don't hear him now. Oh, there he is. It seems like a poor signal.
I'm sorry. Can you hear me okay?
We can hear you now.
I can hear you now.
We heard the first part of your question regarding regulatory approach for vision. The second part we didn't.
Sorry, for the second part, for BCVA on slide 11, how does the risk reduction or the response rate for the sham group compare to that of the natural disease progression?
Yeah, great question. With regard to BCVA as an approvable endpoint, it is the gold standard for assessing vision and has been used as an approvable endpoint in other indications. We anticipate that it is an approvable endpoint here for geographic atrophy. Indeed, it is the most rigorous assessment for visual acuity in the marketplace. We're pretty confident on that. That being said, we will go down and talk to the regulators about all of this topic and many others related to this. Just with regard to the sham rate and natural history, the best example would be lampalizumab, where they've kinda published their longitudinal sham data. We haven't seen it from some of the other programs. Happy to look at it.
This is very much comparable with that, with about 20% of our patients had a 50% reduction, in under BCVA, so lost 15 letters at month 12, and that's very much close to what we saw in the lampalizumab study.
Great. Thank you for taking our questions.
Thanks, Joey.
Thank you. One moment for our next question. As a reminder, if you do have a question, please press star one one. Our next question comes from the line of Anupam Rama from JP Morgan. Your question please.
Hey, guys. Thanks so much for taking the question. I've got TWO quick ones. Do you believe that if you move forward with the pivotal study, that you would have to compare against SYFOVRE or IZERVAY? If it's not a BCVA endpoint and it is GA lesion size, which is kind of where currently the field is, would you be confident in spending resources on that pivotal study? For Dr. Wyckoff, you said that you view these agents, view ANX007 as potentially complementary to the existing agents. Could you expand on this? By that comment, did you mean, like, potentially sequencing these agents? Thanks so much.
Yeah. Maybe I'll start, Charlie, and then turn it over to you. Just with regard to running a study in comparison to the other programs, too early for us to speculate on that. We certainly don't think so, but we will go down and have the discussion with the regulators, with regard to that. Your second question, Anupam, Oh, would we advance the program on lesion growth alone? No, we would not. No. If we were required to only study fundus autofluorescence in the next study, we feel like we've got an answer at least over a 12-month period of time. We do think that over a longer period of time, certainly by protecting the health of photoreceptors, we will impact lesion growth over time. In a one-year study, we would not be advancing that program.
The third question, I'll turn over to you, Dr. Wyckoff.
T hanks. Anupam, great to connect with you here. T hat there's a lot of options forward, and obviously I don't have any data here to support this, but if you look at a lot of other fields of medicine, oncology, for example, it's pretty rare nowadays that we treat
A lot of common cancers with a single agent, right? We're using multiple agents. It's not to say that one agent when you're treating those cancers is quote-unquote better than another. It's that they're different, and they have complementary benefits to patients. I could see our field evolving in the same direction, right? We have so many shots on goal in GA as we broaden the discussion beyond just this data set. There's so many approaches. I don't see a reason why it has to be one versus the other in certain circumstances. Wouldn't it be great if there were different agents in a theoretical world that had different benefits for patients that we could combine them?
Of course, we have to study the safety, efficacy and figure out how that's gonna be done from a payer perspective and a sort of operational perspective. A lot of questions to answer, this data really lends itself to me to thinking about this as a differentiated mechanism of action and a different benefit for patients. It doesn't take away from the benefit of other drugs that can slow the progression of growth through one and two years. It does add to the story that now we can say, actually, we have a very significant visual impact for you, which is to slow the rate of vision loss, which I think will resonate strongly with patients. It doesn't take away from the anatomic benefit of other drugs.
I think in an ideal world, we could figure out moving forward how to potentially combine different agents for the benefit of our patients.
Thanks so much for taking the question, guys.
Thanks.
Thank you. One moment for our next question. Our next question comes from the line of Pete Stavropoulos from Cantor Fitzgerald. Your question please.
Hi, Doug and team. Thank you for taking my questions. First question I have is for the curves presented in slide 11. W hen you look at the monthly and every other month dosing curves, do you think there's an opportunity for a different treatment paradigm in the future where you can start off monthly dosing for a certain period of time followed by every other month dosing period? Or a different dosing paradigm for patients with a foveal and non-foveal lesions as a result of the data for the greater than or equal 15 letter loss measured using BCVA as in slide 12, I believe.
Astute observation, Pete. First thing I'll say is the data are new to us, and we do not have this all worked out yet, and we look forward to diving in much more deeply. As you're alluding to, you could see the rates of progression monthly and every other month early in the disease. In the first six months versus the second six months of the disease process with treatment. That may lend itself to varying ways in which to offer patients more convenience from a dosing perspective between monthly and every other month. More work to be done there before we can comment on that definitively.
I'll comment if that's all right, also.
No, sure. Please.
T his foveal. Thanks. This foveal, non-foveal story is really interesting to me, and I think we're still learning a lot here. I t's interesting to watch a lot of the GA programs pivot towards really focusing on non-foveal patients, right? The logic there is sound. It is that that's one of the biomarkers that predicts GA lesion growth, right? We know that if you're non-foveal involvement, those lesions overall progress faster, and therefore, if you have a drug with a modest benefit that you wanna pick lesions that are gonna have the fastest growth rate. It also makes sense 'cause then you can maybe preserve visual function and slow the growth rate of those lesions into the foveal center point. It makes sense that programs would do that.
What's really interesting to me is that in this data set, I mean, if you actually look at the absolute numbers, right, more patients in the sham arm seem to lose substantial vision in the foveal involved eyes than the non-foveal eyes. It could just be balance of numbers here. It's certainly not a meaningfully lower percentage. It really doubles down on the point that even if we have trials that are enrolling only non-foveal areas of GA, patients with all phenotypes of GA, including foveal involvement and non-foveal involvement, are still losing vision. They are unhappy losing that vision, and we shouldn't forget about those patients with foveal involved lesions. It's fascinating to me that this drug had a signal of meaningful benefit in both of those populations.
Okay. Thank you. Another question that I have is as visual acuity endpoint is perception. W hen designing a potential phase III study, I assume you're gonna take that into a consideration. Just like to know what that means in terms of sample size. Will 12 months be enough, or do you think you have to run a longer study?
Well, this certainly suggests that 12 months is sufficient. W e're likely to continue to look at patients thereafter. Can't really say more than that at this time, Pete. We're really just digesting this data. And we'll get going on the phase III program probably starting next week. Come back to us on that.
All right. Thank you for taking my questions.
Thank you.
Thank you. Once again, if you have a question at this time, please press star one one. One moment for our next question. Our next question comes from the line of Ernesto Rodriguez-Dumont from TD Cowen. Your question please.
Hi. thank you for taking my question. were you measure the change in average visual acuity and the certain improvement on that measure?
Ernesto, I'm sorry. Part of your call broke up. Could you repeat that?
Sure. Sorry about that. Were you able to measure the change in average visual acuity, and did you observe any improvement on the measure?
We have not done those analyses yet. We will do those analyses. Yeah, we don't have that yet.
Any other additional analysis or biomarker data that confirms that the proposed mechanism of action for the improvement initial function, like able signal to the protection of those synapses.
Pre-clinically. Oh, sorry. Yeah, Pre-clinically, we have a fair amount of data, that supports this mechanism of action in this disease. Clinically, what we've shown you, is the data we have.
Got it. Thank you. Thank you for taking my questions.
Sure. Thank you.
Thank you. This does conclude the question- and- answer session of today's program. I'd like to hand the program back to Doug Love for any further remarks.
Thank you. Thank all of you for joining us today. We're super encouraged by the progress we've made with ANX007. This is an important step for the company and for the GA population. These data today are really the first of multiple additional clinical catalysts we have over the next 18 months, including initial results from our Phase 1b ANX009 lupus nephritis trial that will read out mid-year. We'll have top-line data with our SAD and MAD phase i study with ANX1502, a first- in- kind small molecule approach in the classical complement space in the second half of the year, as well as additional data in our phase 2a trial with ANX005 in ALS in the second half of the year.
In the first half of next year, we'll have top-line results from our phase III trial in GBS in 2024. An exciting time for Annexon, and we're looking forward to sharing our progress in the weeks and months ahead. Thank you all for your questions and your attention and wish you all very well.
Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.