Greetings. Welcome to Annexon's GBS Program Update. This time, all participants are in listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero from your telephone keypad. Please note, this conference is being recorded. At this time, I'll now turn the conference over to Jen Lew, CFO of Annexon. Jen, you may now begin.
Thank you. Good morning, and welcome to Annexon's GBS Program Update Conference Call, and Webcast. Earlier this morning, Annexon issued a press release reporting top-line phase III results for the ANX005 in Guillain-Barré syndrome, or GBS. A copy of this press release is available on the company's website and through our SEC filings. Joining me on the call today are Douglas Love, President and CEO of Annexon, who will start with a brief overview of the program, followed by Dr. Jamie Dananberg, our EVP and Chief Medical Officer, who will discuss the GBS clinical program and new pivotal data. Dr. Ted Yednock, Annexon's EVP and Chief Innovation Officer, will then review the pathogenesis of GBS disease and mechanism of action for ANX005.
Finally, Doug will talk about next steps and the commercial opportunity for ANX005 before we open the call up for questions, where we will be joined by Dr. Hugh Willison, Professor Emeritus of Neurology at the University of Glasgow in Scotland, a recognized expert in autoimmune neuropathy, and Dr. David Cornblath, Professor Emeritus of Neurology at Johns Hopkins University School of Medicine, and a recognized expert in inflammatory neuropathy. Please note that on today's call, we will be making forward-looking statements, including statements relating to the existing clinical data and the therapeutic and commercial potential of our investigational product candidate, ANX005. These forward-looking statements are based on our current expectations and assumptions, which are subject to risks and uncertainties.
These statements reflect our views as of today, should not be relied upon as representative about views of any subsequent date, and we undertake no obligation to revise or publicly release the results of any revision to these forward-looking statements in light of new information or future events. These statements are subject to a variety of risks and uncertainties that could cause actual results to differ materially from expectations. For further discussion on the material risks and other important factors that could affect our financial results, please refer to our filings with the SEC, including our most recent annual report on Form 10-K and quarterly report on Form 10-Q. With that, I'll now turn the call over to Doug. Please go ahead.
Thank you, Jen, and thank you all for joining us on the call this morning. We're very excited to be reporting the positive outcomes from the first placebo-controlled pivotal trial in GBS in decades. Our third trial in this disease, our aim has remained steadfast to help scores of GBS patients suffering from this indiscriminate and devastating disease get better sooner. At Annexon, we are pioneering a novel and intentional approach to tackling an array of classical complement-mediated diseases. Founded ten years ago on the bold thesis that stopping the immune system's classical complement pathway where it starts could result in unique functional benefits, we are developing first-in-class therapies with game-changing potential for patients living with serious neuroinflammatory diseases.
Our foundational research and deep knowledge of the classical complement pathway have enabled us to translate important learnings into the development of multiple drug candidates and formulations tailored for complement-mediated diseases of the body, brain, and eye. We now have a late-stage clinical platform built on a well-supported mechanism of action that has consistently and robustly demonstrated functional benefits across multiple diseases. And we are poised for a transformative year and beyond, with several significant near-term value-creating catalysts. Today represents a step on the journey... and today represents an important step on the journey for the GBS community and for Annexon as we report positive top-line phase III pivotal data for lead candidate ANX005. Often striking without warning, GBS is a rapid and acute neurological emergency with a narrow therapeutic window that hospitalizes over 22,000 people annually in the United States and Europe.
Globally, it is the most common cause of acute neuromuscular paralysis and robs too many patients of their independence and ability to live their best lives. So we are encouraged that our approach and outcomes from the phase III trial potentially offer a new possibility to meaningfully impact a devastating disease for patients globally. With the potential to be the first FDA-approved treatment for GBS, ANX005 demonstrated consistent improvement and functional benefits in the phase III trial on key primary, secondary, and pre-specified endpoints important to patients and the healthcare community. After over 30 years of non-specific immunotherapy, ANX005 has achieved a breakthrough as a potential targeted and transformative treatment for GBS.
ANX005's treatment effect is evident by its demonstration of a 2.4-fold higher likelihood of being in a better state of health based on the FDA-accepted primary endpoint, GBS Disability Scale at week eight , and the data was highly statistically significant. The findings were supported by consistent and significant results from multiple pre-specified analyses, including ANX005-treated patients gaining muscle strength earlier, being able to walk earlier, and having less nerve damage over patients receiving placebo. Durable treatment effects were also observed across the full course of the 26-week study, and improvements over placebo were maintained at all time points across multiple measures, including enabling patients to spend less time on ventilation and having less overall disability.
As in our phase Ib study, ANX005 was generally well-tolerated with no new safety signals, no increased rate of infection, and no difference in all-cause mortality. Annexon is the first and leading company to target upstream classical complement pathway inflammation. The GBS phase III outcome represents an important scientific breakthrough, reinforcing our founding thesis that C1q inhibition is a powerful mechanism to stop the start of neural inflammation, and further underscores the potential of our platform to treat a host of complement-mediated diseases of the body, brain, and eye. Today, our team will review key efficacy and safety data in more depth and discuss the next steps of our program. We will present the phase III data at the upcoming Peripheral Nerve Society meeting later this month. Finally, we anticipate real-world evidence comparability data in the first half of 2025 in support of a BLA submission.
With that, I will now turn the call over to Dr. Jamie Dananberg, EVP and Chief Medical Officer at Annexon, who will discuss the pivotal top-line efficacy and safety findings of ANX005 for the treatment of GBS. Jamie, over to you.
Thank you, Doug, and good morning, everyone. This is an important day for Annexon, but more importantly, an exciting day for patients with GBS. I'll start with a brief overview of GBS, which, as Doug mentioned, is considered an acute neurologic emergency with long-term sequelae that requires an immediately effective and targeted intervention. It's the most common cause of acute paralytic inflammatory disease of the peripheral nervous system and typically follows an infection in otherwise healthy individuals. This infection leads to the generation of complement-activating autoantibodies that directly attack nerves, leading to their damage and acute paralysis. Importantly, GBS can happen to anyone at any time. The unmet medical need is high, with 7,000 patients in the United States and 15,000 patients in Europe diagnosed and hospitalized each year. Currently, there are no treatments that specifically and rapidly target complement-mediated nerve damage.
The current standard of care for GBS is plasma exchange and, more often, intravenous immunoglobulin, or IVIG, though the latter is not approved by the FDA for use in this disease. IVIG requires five days of treatment and has an ill-defined mechanism of action. GBS can lead to significant morbidity and mortality. Notwithstanding IVIG treatment, GBS results in severe weakness and paralysis that can require long stays in the ICU or even on a ventilator, and weeks or months to regain the ability to get out of bed or walk. Ultimately, the early nerve damage caused by GBS can result in poorly reversible or irreversible loss of function with incomplete recovery that prevents patients from returning to a normal life. There have been no advancements in the treatment in GBS in over forty years, and new targeted immunotherapies with rapid intervention are needed.
Let's begin with the trial design, which was consistent with previous trials in GBS and developed with input from global GBS experts, which led to a well-designed and executed pivotal phase III trial. This randomized, double-blind, placebo-controlled, multicenter phase III clinical trial evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of ANX005 at two doses compared to placebo in patients with moderate to severe GBS. It is important to note that this is the first standalone placebo-controlled trial in decades. These patients received Western-level best supportive care and were not otherwise treated with either plasma exchange or IVIG. The study was designed to determine the effective dose based on data from our early phase Ib study, showing early improvement in muscle strength and function at week eight, with doses providing between one to three weeks of full complement inhibition.
In this study, we evaluated two doses that provided either one or two to three weeks of complement inhibition to identify the effective therapeutic treatment window. Eligibility criteria included patients diagnosed less than 10 days from onset of weakness and who had a baseline GBS disability score of 3, 4, or 5, representing patients who could walk assisted, were bedridden, or on ventilation, respectively. Patients were stratified based on known prognostic factors of muscle strength and time from onset of weakness. Patients were treated with a single infusion of ANX005 at one of two dose levels or placebo, each given over a period of less than 24 hours and followed for six months post-treatment. The primary endpoint used was the GBS Disability Scale at week eight, which is a well-accepted clinical and regulatory measure assessing functional status.
Key secondary endpoints included assessment of muscle strength by MRC Sum Score, motor disability, as measured by the Overall Neuropathy Limitation Scale, or ONLS, and time requiring mechanical ventilation. The study was conducted in Bangladesh and the Philippines due to the high prevalence of GBS patients of all types, their internationally recognized scientific leadership in GBS, and the limited availability of IVIG in these areas, thereby enabling the conduct of the placebo-controlled trial. There were 241 patients enrolled and randomized in the study, with representation across the spectrum of GBS patients. The baseline characteristics of patients were well-balanced across treatment groups, and patients were stratified by key prognostic factors, including MRC Sum Score and time since onset of weakness. Both the AIDP and AMAN neurotypes were well-balanced as well. Of note, the overall time to treatment was rapid once the patients were randomized into the study.
On slide eight, ANX005 is designed to target multiple key aspects of disease mechanism of GBS, allowing patients to get better sooner. ANX005 is intended to deliver rapid and complete complement inhibition during an active disease progression to stop acute and ongoing complement-mediated nerve damage, while then allowing complement activity to return for its normal role in nerve repair. The therapeutic goals of ANX005 in GBS include rapidly blocking complement activity through C1q, which is expected to lead to an immediate reduction in nerve damage as assessed by the biomarker NfL, neurofilament light, leading to improved health status of the patient by multiple measures, including the GBS Disability Scale, the primary endpoint of the study, and early improvement in muscle strength as assessed by MRC Sum Score and a reduction in time on ventilator.
GBS-DS is an FDA-accepted and clinically used measure, and before the study, we gained FDA alignment on the statistical analyses used. Before sharing the data, it is important to understand the method used to analyze the GBS disability score at week eight as the primary endpoint. To help enhance clinical interpretability, we collapsed the seven-point scale to a three-point scale. The first category, including GBS-DS 0 and 1, represents a good state of health. The second category, including GBS-DS 2 and 3, represents the disabled state. The third category, including GBS-DS 4 through 6, represents a severely disabled state or deceased.
The rationale for this approach was to focus on a subject's actual health status at week eight after receiving ANX005 or placebo, and across all health states, so that the impact of the treatment can be assessed across the full range of the scale, compared to a dichotomy responder analysis that would only evaluate a shift at a single location on the scale. This offers the most efficient statistical analysis approach. For context, the eligibility criteria for the phase III study population was a GBS-DS score of between 3 and 5 at baseline. The study met its primary endpoint. ANX005 achieved a highly significant and clinically meaningful treatment effect on GBS-DS at week eight.
Patients who received ANX005 at 30 mg per kilogram were 2.4-fold more likely of being in a better state of health compared to placebo, which, as Doug mentioned earlier, is a resounding and much-needed win for patients with GBS. There is a higher proportion of patients treated with ANX that are in a good state of health, which can be observed by the green portion of the upper bar. This represents many more patients who were fully recovered or able to run by week eight. Further, there were fewer patients that were bedridden or requiring mechanical ventilation when treated with ANX005, as shown in the red portion of the upper bar. In a pre-specified analysis of GBS-DS at week eight, 28% of patients treated with ANX005 at the 30 mg per kilogram dose demonstrated...
I'm sorry, demonstrated a significant and clinically meaningful three-point or higher improvement in GBS-DS versus 13.6% of patients with placebo. This is an important pre-specified assessment corroborating the GBS-DS score. This three-point improvement represents a substantial improvement on the outcome score. As an example, it would represent a patient who required ventilation at the outset and was able to walk independently by week eight. Patients who achieve this level of function are often able to be discharged from the hospital and return to many aspects of their life. These findings are consistent with the results from our phase Ib study. Now let's turn to the MRC score, which is an important prognostic factor in GBS, and as such, was a key secondary endpoint of the study.
The MRC Sum Score uses a quantitative scale to measure muscle strength across 12 muscle groups in both arms and legs, with a maximum of 60 points. ANX005, 30 mg per kilogram dose, showed an early and meaningful 10-point improvement, a month faster than placebo. This early improvement in muscle strength suggests an early treatment effect and is associated with a faster recovery. This early improvement is particularly important given that the gain of muscle strength of this magnitude occurred a month earlier in ANX-treated patients than those on placebo. Moreover, the time advantage at every point of MRC gain continued to grow throughout the study between ANX005 treatment and placebo. At the 75 mg per kilogram dose, ANX005 was not statistically significant at the pre-specified primary endpoint.
It did demonstrate an early effect on muscle strength, performing similarly to 30 mg per kilogram up to the first four weeks, as seen on the right. These data suggest that for most patients, the prolonged inhibition of C1q with the 75 mg per kilogram dose is beyond the therapeutic window and limits C1q-mediated tissue repair. Ted will discuss this in more detail in a few moments when he discusses GBS pathophysiology and ANX mechanism of action. Another key endpoint, ONLS, is another key secondary endpoint. Using a 12-point scale, down is better in this case. ONLS measures the ability to perform daily tasks. Similar to MRC, we are seeing an early and significant, nearly 20% improvement in ONLS, which is occurring 20 days earlier with ANX005 compared to placebo. This improvement was sustained and even increased further throughout the study.
Importantly, these early improvements translate to major functional improvements in the arms and legs, which are extremely important to patients, their families, and the healthcare system, and further support how ANX005 is helping patients get better sooner. ANX005 accelerated the time to recovery across clinically important measures that have been used for decades, with the 30 mg per kilogram treated patients walking 31 days earlier and being off ventilation 28 days earlier. Importantly, what this means is that patients may require less intense resource utilization and be discharged from the hospital sooner, can be more independent, can return to work, and ultimately get their lives back.
Importantly, beyond just eight weeks, when a number of important measures were analyzed across all study points through 26 weeks, patients treated with ANX005, 30 mg per kilogram, had better outcomes relative to placebo and were more likely to be in a better state of health, have more muscle strength and be able to perform daily tasks. These GBS phase III results are highly relevant to Western populations. In fact, we are seeing a stronger effect with ANX005, 30 mg per kilogram, in patients with Western characteristics, which include lesser severity at baseline and the AIDP neurotype. Among U.S. and European patients, 80% have mild to moderate disease, with a baseline MRC score greater than 20 points.
In the phase III study, about 47% of patients had an MRC score above 20 and were three times more likely to be in a better state of health compared to placebo. Similarly, 60% of patients in the U.S. and Europe have the AIDP neurotype of GBS. Among the 21% of patients in the phase III study with the AIDP neurotype, those treated with ANX005, 30 mg per kilogram, were more than five times more likely of being in a better state of health at week eight. Turning to safety, ANX005 was generally well-tolerated, with no unexpected safety signals. Most adverse events were mild grade 1 to moderate grade 2 events. The most common related adverse events were infusion-related reactions, with the majority being mild, transient rashes.
There were no autoimmune-related adverse events reported, and infection rates were comparable across dose groups and consistent with typical hospital-acquired infections. Three patients discontinued the treatment, one in each group. There were no differences observed in incidence of all-cause mortality, with three deaths in each group, which were around 3.7% of all patients. Deaths occurred in older and more severe subjects. With that overview, Ted, our EVP and Chief Innovation Officer, will now further discuss GBS pathophysiology and the targeted mechanism of action of ANX005. Ted, to you.
Thank you, Jamie, and good morning, everyone. After hearing the data, let's take a closer look at GBS and its acute course of progression. GBS is an autoantibody-mediated disease, usually triggered by an infection from which the patient recovers. But antibodies generated by the infection cross-react with components of peripheral nerves. As autoantibody levels rise over subsequent weeks, their binding to peripheral nerves triggers the activation of the classical complement pathway, causing rapid nerve damage and paralysis. These initial days and weeks, highlighted by the blue column, represent the active phase of disease in which autoantibody levels reach their peak. Fortunately, the levels decline naturally, but then the acute active phase of disease transitions into a prolonged and variable phase of nerve recovery.
As shown on slide 21, the classical complement pathway is also known to play a role during the recovery phase, facilitating nerve repair by helping to clear the extensive level of tissue debris caused by acute injury. In designing the phase III trial, we examined two doses of ANX005, differing in their duration of complement inhibition. The idea was to identify the most effective treatment window, blocking aberrant function of C1q during the active phase of disease in the presence of nerve reactive autoantibodies, while allowing normal C1q function to return for debris clearance and nerve repair. The doses were chosen based on results from our phase Ib study, where we examined multiple dosing levels. As shown on slide 22, both doses provided the expected PK/PD results.
On the left, ANX005, 30 mg per kilogram, provided measurable drug levels for about one week, with inhibition of serum C1q during this time. C1q activity then returned to normal levels. The 75 mg per kilogram dose on the right provided drug levels and C1q inhibition for about two weeks. What we now know, based on the strong efficacy results that Jamie shared, is that the short duration of C1q inhibition with ANX005, 30 mg per kilogram during the active phase of disease, defines the most effective treatment window. Slide 23 shows that ANX005 targets C1q, the initiating molecule of the classical complement cascade. By blocking C1q interaction with autoantibodies on the nerve surface during disease, ANX005 shuts down the entire classical pathway before it starts, cutting off classical cascade amplification and expanding- and the expanding tissue damage.
This approach is differentiated from downstream complement inhibitors because it shuts off all inflammatory mediators of downstream complement components while avoiding potential bypass or breakthrough mechanisms. ANX005, with its rapid on-and-off mechanism, is ideally suited to address the narrow treatment window associated with the acute nature of GBS, while administered in a single 30 mg per kilogram dose. I will now turn the call back over to Doug, our CEO, to discuss next steps for our GBS program.
Thank you, Ted. As you heard today, this is a pivotal time for our GBS program, and we have several upcoming important value-creating catalysts related thereto. The phase III study was conducted in Bangladesh and the Philippines due to high prevalence of GBS and limited access to standard of care IVIG. Following our phase Ib findings and based on FDA feedback, Annexon has pursued a single pivotal study to demonstrate substantial evidence and comparability between the phase III patient population and Western patients for BLA submission. To support the comparability and relevance of our phase III findings to the Western population, we have initiated a real-world evidence comparability protocol with the International Guillain-Barré Syndrome Outcome Study, or IGOS, which is a global prospective observational multicenter cohort study that has enrolled 2,000 patients who were followed for one to three years.
Preparations for a matched cohort for comparison with IVIG are underway, and importantly, approximately 50% of all Western IGOS patients met the entry criteria for our GBS phase III study. We are very much on track to report real-world evidence data and submit our planned BLA in the first half of 2025. We at Annexon are very excited about the opportunity to potentially bring a new medicine to patients who've been waiting decades for something new and who deserve more than what they have today. ANX005 has the potential to be our first commercial launch as a company, which is a transformational event we have been working towards since our inception. We view a GBS launch as a significant commercial opportunity, with around 22,000 patients hospitalized with GBS every year in the U.S. and Europe.
Despite available treatments, there is significant unmet need for people stricken with GBS. Currently, 90% of patients with GBS in the U.S. receive off-label IVIG, excuse me, a nonspecific treatment approach requiring daily infusions over five days, a time period that consumes a significant portion of the active GBS disease window. Additionally, GBS results in greater than $2 billion a year in annual acute and long-term cost burden on patients, caregivers, hospitals, and payers. At Annexon, we are targeting ANX005, excuse me, as a first-line monotherapy treatment for GBS. As shown today, ANX005 help patients with GBS get better sooner. As a single infusion, ANX005 dosing is ideal for a neurological emergency like GBS.
It allows patients to get off a ventilator earlier and help them walk earlier, both of which are important drivers of long-term outcomes for patients and provide opportunities to reduce the cost burden of the disease. We intend to demonstrate this reduced cost of care through a robust Health E conomics and Outcomes Research plan. Since most patients are treated in major metro areas and large community hospitals, we can bring ANX005 to market through a focused and targeted commercial launch, if approved, and will supply our launch through a commercial manufacturing partnership with Lonza, a gold standard CMO. Finally, and importantly, our positive data in GBS is a beachhead for further investment into mechanistically related neurodegenerative and autoimmune indications, of which we are actively working on.
To close, the phase III data represent a profound moment for the GBS community by opening a new therapeutic area beyond the use of nonspecific approaches, with potential for ANX005 to be the first targeted therapy and first FDA-approved treatment for GBS. We are confident the results from our phase III trial demonstrate the potential for ANX005, with its novel and unique mechanism of action, to potentially change the treatment standard in GBS, and more importantly, help the tens of thousands of patients stricken with GBS around the world every year live their best lives. Our phase III trial met the primary endpoint, as you heard, the GBS Disability Scale at week eight, and patients treated with ANX005 were 2.4 times more likely to be in a better state of health compared to placebo.
ANX005 also helped patients with GBS get better sooner by delivering early, robust, and clinically meaningful benefit on multiple outcome measures by week eight, including ability to walk earlier and less nerve damage versus placebo. Durable treatment effects were observed over the course of the 26-week study, and moreover, these improvements were maintained over placebo at all time points across multiple measures, including less time on ventilation and less overall disability. The convenient single infusion of ANX005 was generally safe and well-tolerated, had a safety profile similar to placebo, and no increased rates of infection. And with our phase III data in hand, we are creating a clear path to BLA submission and launch. We are preparing to engage the FDA later this year to support a planned BLA submission in the first half of 2025.
Initial data from a real-world evidence study is on track for the first half of 2025 to support that BLA submission. We are preparing a powerful launch strategy with a focused commercial team. All in all, ANX005 is the most advanced candidate from our pipeline, and these positive data today further reinforce our platform approach, targeting upstream C1q in the classical complement cascade to stop neural inflammation at the start to effectively treat a host of diseases of the body, brain, and eye. We will be presenting the phase III data at the upcoming Peripheral Nerve Society meeting at the end of this month in June, and we hope to see you all there. Thank you. In closing, I want to specifically thank all of the patients, families and caregivers, physicians, and medical teams who participated in our trial.
We are eternally grateful for your support and contributions. I also want to thank our employees, collaborators, and advisors who whistle while you work with a warrior spirit and an all-for-one commitment. Finally, we would like to thank the GBS-CIDP Foundation International, IGOS, and the countless advisors, including our speakers here today, for their continued support and partnership. Lastly, we thank all of you for joining us today. With that, I will now ask the operator to begin the Q&A session, where we will be joined by Dr. David Cornblath, Professor Emeritus of Neurology at Johns Hopkins University School of Medicine, a recognized expert in inflammatory neuropathies, and Dr. Hugh Willison, Professor Emeritus of Neurology at the University of Glasgow in Scotland, also a recognized expert in autoimmune neuropathy. Operator, over to you.
Thank you. We'll now be conducting the question and answer session. If you'd like to ask a question at this time, please press star one from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please, while we poll for questions. Thank you. Thank you. Our first question is from the line of Anupam Rama with J.P. Morgan. Please proceed with your questions.
Hey, guys. Thanks so much for taking the question and congratulations on the data. A couple quick ones from me. Maybe for both KOLs on the line. Kind of with these data in hand, how do you think about incorporating ANX005 into your practice with, you know, IVIG potentially available in the U.S. and U.K.? And then, Doug, I wanted to maybe expand on one of the comments you said in passing, which was GBS is just sort of like the initial, maybe beachhead indication here for ANX005. What kind of optionality is there potentially in other acute complement-mediated diseases? And for the KOLs, if they could also comment on what other indications for ANX005 might be interesting? Thanks so much.
Thank you, Anupam. Really appreciate you joining and really good questions. I'll start and then turn it over to David and Hugh. So as it relates to your second question on what this data means, and the approach with ANX005 into other potential indications, GBS is an acute neuromuscular indication. It, in fact, is arguably the most aggressive neuromuscular disease out there, and we like to read through on this outcome into mechanistically related neuromuscular diseases in particular, many of which are chronic, like CIDP, often viewed as a cousin to GBS in a chronic form, myasthenia gravis, MMN.
And so there is a suite of indications that we've been doing work on for many years that are related to GBS mechanistically, and which we think, based on the data here, give us an opportunity to pursue with great vigor. With that, I'll turn it over to David and Hugh to answer two questions, one on what this might mean for treatment practices, as well as thoughts on other indications in which we may use ANX005. Maybe David, we'll start with you, and then we'll go on to Hugh.
So I think, from the standpoint of where this might fit into the future of armamentarium, once it gets approved and, goes through all the usual processes so doctors can order it, there are a number of advantages I see to, ANX005, including the single administration, during which time, the drug takes effect immediately, as opposed to IVIG, where you have to give it over five days and the effect is sort of slow-going. It's gonna be easily done, as you saw from the clinical trial data. You can give it essentially the same day that the diagnosis is made, and you're done. And it provides really robust evidence.
The other thing is this will be really the first approved drug in America, and so hopefully, this will set a standard by which we can use it to compare to other drugs, to see if adding to IVIG. There are a whole host of things that will come after it. I think Doug has mentioned the other indications. These are all complement disorders at some level, and they're being pursued by other companies as well. But I think there's plenty of room here in this space. CIDP, MMN, and myasthenia are the ones that come very quickly in mind.
Hugh, any thoughts on your end?
Hi. Hi, it's Hugh Willison here. I think David Cornblath has raised the main points. And I would add that ANX005 has a very good safety profile as well and could well be used in situations in which intravenous immunoglobulin is not appropriate or plasma exchange is not appropriate. So apart from being having many general features of benefit to GBS patients, it also has potential advantages over other existing treatments. Thank you.
I'd also like to just add that, that we have looked- are looking at this drug for other neuro emergency situations, such as traumatic brain injury, and we have publications there as well.
Thanks, Ted. Good to have.
Thanks so much for taking our questions.
Thank you. No problem.
Our next question is from the line of Andrew Tsai with Jefferies. Please just use your questions.
Hi, good morning. Congratulations. Thanks for taking my questions. So, two questions. The first one is, you guys have long said either dose arm in the study is needed to hit stat sig at week eight. I just wanted to reconfirm this was agreed by the regulators, including the FDA, in support of the filing. And then notice the secondary endpoints have nominal P values. Why are they nominal, and was there a testing hierarchy? And then, maybe for the doctors, to the best of your knowledge, what would IVIG monotherapy show on GBS as well as some of these secondary outcomes, out to week 26?
You know, are you guys in a position to say whether ANX005 is more comparable or even better than IVIG at this juncture, or do you feel like you're not in a position to make that assertion yet? Thanks.
Thank you, Andrew. Good questions, and appreciate you joining. Maybe we'll take these on turn, and I'll start and, and kick them around to others. So as it relates to two doses in the study, you're absolutely correct. We've taken two doses into the study with alignment with the FDA. The study was powered to win on either dose, so separately powered, with alpha attributed to either, to both doses. So we only need to win on one of the doses to move forward for a submission towards a BLA. So we're, we're really pleased with regard to that. I think I've lost track of your second question. Apologies.
[crosstalk]
It was the question in regard. Oh, it was around nominal. I get it. It was the question around nominal. Yes. So we did have a hierarchy with regard to endpoints in the SAP and missed on one of the endpoints in that hierarchy or did not achieve statistical significance, and so all of the endpoints thereafter were nominal, as we noted. And then the third question is with regard to IVIG. I'll turn it over to the doctors who are much more adept than me on this. The one thing I will say, though, is that there's far less information out there on IVIG.
Candidly, when you look at the studies, they go back many decades, and we have not seen an IVIG data set that provides a comprehensive review of all of the assessments that we have in our phase three study. Some of them are assessed, but, you know, in differing ways, like the GBS disability scale, which has often been looked at with a responder analysis, but not a proportional odds analysis. And we've not seen robust data, whether it be on NfL or some of the other endpoints, that we have in our study. But maybe I'll turn it over to you, Hugh and David, to respond to that question.
Yeah. So it's Hugh Willison here in Scotland. Thank you very much for that important question. Of course, I do think it's too early to definitively say whether or not this is more, ANX005 is more efficacious than current existing therapy. However, just looking, eyeballing the data without any formal statistical assessment, it does look to be at least as equivalent to existing therapies and possibly better. And I think there are a number of very, very specific advantages of having a targeted immunotherapy in the therapeutic armamentarium, rather than using nonspecific immunotherapies like plasma exchange and intravenous immunoglobulin. So this is a real extraordinary advance in our conceptualization of the therapeutic approach to GBS, and I'm pretty certain would be well taken up by the medical community when it becomes, assuming it becomes licensed and approved.
Got it.
Thank you.
Thanks very much. Congrats.
David, any thoughts on your end?
Yeah, I think the difficulty is that there is no placebo-controlled trial of IVIG in GBS, as the study done in 1990 was against the then standard of care, plasma exchange. So I think the real-world evidence study in which we can look at more data that's more current than, you know, 30 years ago or 25 years ago will give us the answer to your question specifically. But some of these endpoints are extraordinary. If you look at the time on a ventilator, you know, it was cut from 48 days to 20 days. I mean, that's an extraordinary the important view.
And the other thing that you mentioned that I failed was in people who are going to be older, where this is a much more common disorder in America, as you see from the age distribution in the ANX005 study, where it's mostly younger people. In the West, it's mostly a disorder of older people. There's going to be a reluctance to use IVIG when there's an alternative that doesn't have the potential IVIG side effects.
Thank you, gentlemen. Operator?
Yes, the next question is from the line of Phil Nadeau with TD Cowen. Please proceed with your question.
Good morning. Let us add our congratulations on the data. A few questions for us. First, a follow-up on the statistics. Doug, you mentioned that there was an endpoint that was missed, and that's why the secondaries were nominal. Was that endpoint the higher dose primary, or was there a separate secondary endpoint in the hierarchy that was missed, that made the subsequent secondaries nominal?
Yeah, it was a secondary endpoint, so it was. And maybe, Jamie, I should turn it over to you. You can answer this better than I. Yeah.
Yeah. Thanks, Doug. It was the ONLS at week eight, that, because of, as Doug mentioned, we split the alpha to get both doses in as the part of the primary. It's a pretty conservative threshold that had to be met, and it was only at week eight, so it missed that one, and so everything else is nominal beyond that.
That is very helpful. And then, second, in the presentation, you mentioned that there's early estimates for, or that, reduced cost of care will, will be a case that you'll make. Given the relatively dramatic, benefits on some of the secondary endpoints, like, like time on ventilation, do you have any early preliminary estimate of what the reduced cost of care is likely to be on, when, when patients use ANX005?
We don't. We're in the process of doing that now. I mean, our early read is it's, it's hundreds of thousands of dollars. Like, this, you know, because the cost associated with the disease is not drug costs, it is the cost of care. And so you think about days in the ICU, days on ventilation, days in the hospital, time for missed work, et cetera. So it is, it is a really significant number. As I think we said earlier, it costs more than $2 billion a year in the U.S. alone to treat, you know, roughly 7,000 patients. And so that, that is really due to the disability associated with it, the prolonged disability associated with the disease.
And so we, just based on this data, look like that we very much are going to improve upon that, but we'll wait until we complete the health economics work before we start coming out with specific numbers.
Great. And then last question for the-
Sorry.
Sorry, go ahead.
This is David Cornblath.
Yeah.
Let me just bring up, decades ago, when we did the plasma exchange study, the same thing was, the same question was asked, and I'll just give you the sort of answer that we gave then. That is, if you assume that, roughly a quarter to a third of the people who enter a hospital with GBS are going to be on a ventilator, and then the number of days on a ventilator is cut roughly in half or more, you can then multiply that number by, today, it's probably $10,000 a day to be in an ICU.
You can get a rough estimate of the number of dollars you can save in the healthcare system, and that's just on ICU care, not counting the days earlier to walk, which gets you out of the rehab hospital and home independently without home OT and PT.
That is very helpful. The last question, just a follow-up question for the physicians. And it goes into where ANX005 could be used in the standard of care. Would you imagine ANX005 will be used as a monotherapy when it's initially available? And if so, first-line, or just in those patients who can't go on IVIG or plasma exchange for some reason? Or do you imagine it would initially be used as combo therapy, just added on top of standard of care in those patients who are particularly severely affected?
Yeah. Hi, it's Hugh Willison here from Scotland. I think that's a very, very interesting question, and I think what this study has really shown us and brought to the into the headlights is that GBS is a medical emergency and needs to be very, very promptly treated as early as possible in the course of the disease with the fastest-acting treatment. And one of the fantastic things about this current study is that that early treatment was achieved. So I see this as being instituted as a monotherapy at first point of diagnosis in new patients presenting to hospitals, probably through their accident and emergency rooms very, very quickly after diagnosis or suspected diagnosis. It can be given extremely quickly by a single infusion and has immediate full inhibition of the classical complement pathway.
And the current therapies of plasma exchange, which of course is quite complex to deliver, an intravenous immunoglobulin, take days to weeks to fully complete those treatments, which is far too long. So it's this acute possibility of treatment with ANX005, which I think is such a useful addition to current care. Thank you.
Yeah, this is David Cornblath. The only thing I would add is that I think it's going to be unlikely, frankly, because of insurers, to try and give both of these at the same time. I just don't think in the current state of American medicine, they'll pay for them both. And so physicians will be forced to choose one or the other. And for the reasons you and I have already mentioned, we think, you know, that's gonna start to move fairly quickly toward ANX005.
That's very helpful. Thanks for taking our questions, and congratulations again on the day.
Thank you, Phil.
Our next question is from the line of Tazeen Ahmad with Bank of America. Please proceed with your question.
Good morning. Doug, congrats on the data. I just wanted to get some color on what is going to be looked for on this RWE comparability study. Now, based on the data that you've got in hand as of this morning, can you point to specific items that FDA might have been specifically looking for? And would there also have been certain thresholds that you would have agreed to FDA to look for? And then secondly, to just elaborate with the physicians about their view of the market opportunity, how do you think pricing will matter for this product versus what the average cost for IVIG is right now in order to help make the launch of the drug steep in the initial launch? Thanks.
Yeah, great, great questions, Tazeen, and thanks for calling in. I'll start on RWE and then kick it over to you, Jamie. So the FDA discussion is around demonstrating comparability of patients in our study with Western world patients. Given that our trial was run completely outside of the U.S., we need to demonstrate that GBS is the same all over the world, whether you're in Southeast Asia or you're in the U.S., and that matched patients progress similarly. And so that's what we will be doing. We're encouraged by the data we see in this study, particularly when you look at our baseline demographics, characteristics of the patients in our study, and knowing that a large portion of those patients in the IGOS dataset match those characteristics from which to do this comparability analysis.
But Jamie, I'll turn it over to you to see if you'd like to add anything to that.
Yeah, just a couple of things. Thanks, Doug. Thanks, Tazeen, for the question. So in general, we'll look at both just the baseline characteristics of the two populations. Understand, the real question the FDA is asking is whether this product would be... the data from this study is translatable to the Western population, and we'll use the IGOS comparison for that. But as we mentioned in the presentation, the data we have from this study already demonstrates quite good potential transferability of the results, given the fact that the patients who are milder, which is more common in the Western world, and patients with the AIDP neurotype are more common in the Western world. We had an even better effect in those patients, threefold better and fivefold better in the AIDP patients.
So I think we're off to a really good start on that, and we'll do that work with IGOS in terms of the direct comparison or the indirect comparison, using the IGOS dataset and do a direct comparison with IVIG as well. So I think we're in a really good place to conduct that work.
Thank you, Jamie. And then your second question related to the market opportunity and pricing. Maybe just a bit on pricing. So we are not gonna obviously disclose pricing until we get approval, but we certainly have the intent with pricing to match our overall mission as a company to help millions of patients around the world suffering from complement-mediated diseases live their best lives. We recognize the healthcare system today as it relates to that. And so we're gonna price this drug reasonably. Feel very confident in saying that at this stage. But again, the cost associated with Guillain-Barré is not drug costs. It really is the cost of care and missed time from living an independent life. So, I again, we'll be reasonable in our pricing.
We will recognize the significance of this disease and go after it from there. But I don't know if David or Hugh, if there's anything you guys want to add to for Tazeen's question.
It's Hugh here, and I would agree with what's been said. I think it's important to recognize that around the world there are over 100,000 cases of Guillain-Barré syndrome per year, and the lifetime likelihood of any one of us getting it is about one in 1,000. Once you have Guillain-Barré syndrome, you're off work for months. If you're self-employed or in other critical jobs or financial situations, this can really devastate your life and create huge financial burden. From a patient point of view, anything which has a rapid and effective inroad into the pathophysiology and leads to early recovery is very, very important indeed, irrespective of the massive hospital costs of people on intensive care and in rehabilitation for months.
So I think that it could have a profound economic effect. And in situations such as the Zika virus epidemic, which occurred not so many years ago, which produced thousands of cases of Guillain-Barré syndrome around the world, where hospital intensive care units become completely overwhelmed, which happened in Brazil, for example, an effective early drug like this could be really, really important in that kind of situation. Thank you.
Okay.
This is David Cornblath. Obviously, the drug pricing is very so complicated an issue in America, and the treating physician has such little impact, except when drugs are terribly overpriced, they have the option not to prescribe them. And this is something, for example, we could talk about at length, that you see in the myasthenia field. If this drug is reasonably priced, it will be used dramatically.
Got it. Thank you.
Thanks, Tazeen.
The next question is from the line of Derek Archila with Wells Fargo. Please proceed with your questions.
Hey, good morning, and congrats on the data. Two questions for management and then one for the physicians. So for management, I guess, you know, based on the data, is there any plan to file for breakthrough designation? And maybe you could discuss, like, what benefits that might bring at this step, you know, at this stage in the regulatory process. And then a second question is, you know, what additional data are you likely to be sharing at the PNS meeting later this month? And then for the physicians, just any commentary on kind of the baseline characteristics as you look at, you know, the GBS-D scores for placebo and the 30 mg per kilogram arms relative to MRC, I guess, which are more important here? Thanks.
Thanks, Derek, and thanks for joining us. So good questions. As it relates to breakthrough, we're, you know, we are assessing our regulatory strategy now. We've had the data a very short period of time. Breakthrough, obviously, is important for a closer relationship with the regulators and oftentimes speeds up review times, et cetera. So, more to come on that. We certainly are assessing that, in light of these data. I think it meets many, of those criteria as you think about the impact on important biomarkers like neurofilament light chain, as well as showing a real functional benefit, in this, in this study. And then, so as it relates to, what, I'm sorry, Derek, your second question was? I can't read my writing.
Just-
Oh, additional data, PNS. Yeah. I mean, we're certainly doing a ton of different sub-analyses, et cetera, but maybe, Jamie, I'll turn it over to you to, to comment on PNS and additional data that we may be looking at.
Yeah. Thanks, Derek. We're still going through the data, as you can imagine. We've had it for a very short period of time. Most importantly, we will be sharing some of the data, looking at the trends over time of these data, the relative impact of 30 mg per kilogram, especially on how much more quickly ANX005 achieved key milestones. So there's really some very important data to make sure we educate the world on in terms of how stopping classical complement at the start is extraordinarily relevant to downstream pathophysiology and why this works the way it does. So we're very excited about the engagements we have planned at PNS, which are extensive. And I'll turn it back to you, Doug.
Thanks, Jamie. Derek, did you have a third question?
Yeah.
Yeah, the third- t he third, It's Hugh here in Scotland. The third question that you raised was related to the use of these scales. I think what I'd say to you is that the MRC Sum Score, the GBS Disability Scale, the ONLS, are scales which all tell you slightly different things. And they've been meticulously developed by the GBS research community, clinical research community, over decades and are very, very widely accepted. I think what is important in this study is that they are all pointing in the same direction, and that is of substantial improvement and benefit. So it's not as if one has been cherry-picked over the other. They're all pointing in a successful direction, and that is an extremely important finding.
Unlike some diseases like multiple sclerosis, et cetera, where you can have, imaging, MRI imaging or other biomarkers, GBS is very much defined by its clinical characteristics rather than by any laboratory or imaging findings. And that's why we in the GBS community have spent so much time developing these clinical scales, because there is no, other alternative to that as things currently stand. The neurofilament data, which is the one biomarker that is being used in this study, is also pointing in the right direction. And I think it's when you collectively add all these, elements up, that we really see that this drug has had a dramatic effect on the disease. Thank you.
Thank you.
This is David Cornblath. The last comment is, in fact, this slide set that you've seen, most of the people in our community will not have seen, because they don't get on these kinds of calls. So my own view would be if they showed this slide set alone, given, as you said, all of these markers all going in the same direction, people will be wild.
Thank you. The next question is from the line of Pete Stavropoulos with Cantor Fitzgerald. Please proceed with your question.
Hi, Doug and team. Congrats on the data, and thank you for taking our questions. Just a couple from me. You know, I know the data is fresh, and you know, you're going to do more analysis. However, you know, is there anything you can speak to in terms of time to treatment and response? You know, was there a greater response in those that were treated earlier, or just dosing before day 10 key? Also, what was the distribution of patients between Bangladesh and Philippines? And you know, was there, was the efficacy comparable between the two groups?
Hey, Pete. Both good questions. Jamie, I'm going to turn that over to you, time to treat and then distribution. Yeah.
Yes. Yes. So, I'll just mention the distribution first, since that's the simple one. 80% of the patients were from Bangladesh and about 20% from the Philippines. In terms of time to treat, if you remember the slide on the baseline demographics, we actually were able to treat patients very quickly. So pretty much everyone got treated rapidly from the time point that they were diagnosed, and then followed up by the time to treatment. So that period of time was very narrow. There's not a lot of variation to see people who are treated earlier than later. We will be looking at some of those analyses. We do not have them to present at this point, but are considering what we can do for that on the PNS side.
I think in general, what we have shown, what's interesting about the 30 versus the 75, is that the treatment window is very well defined. And I think the design of the study helped us identify that getting in early, having an early treatment effect, and then having it come off, is essential to the long-term, the outcomes for the patients, which, we've established are predominant here. Even through all the way through 26 weeks, we can see the impact of treatment just in the very first day. The impact of treatment lasts all the way through the end of the study, and so that's a very encouraging finding for us and, and something that we think will be an important aspect that we highlight at PNS.
I don't know if I missed that. Apologies, if I did. The efficacy between Bangladesh and Philippines, was this comparable?
Oh, yeah.
[crosstalk]
Oh, yeah. Go ahead. I'm sorry. Yeah, when you adjust,
No, that's okay, go ahead. Go ahead. It was down.
Yeah. Yeah, there was no impact based on country, so it was, it was consistent between the two.
Okay.
And as Jamie said, just kinda quickly on the time to treat, really important, because in our mind, it really speaks to the quality in which the study was run. So these patients were treated, again, a median of six days. They came in on day six, and they were treated on day six. So they were immediately randomized and got into the study and dosed. And so we really are thankful for the many sites that just did a fantastic job in executing this study.
Okay. And just a quick question for the KOLs on the call. You know, you know, I think you briefly touched on it a couple of minutes ago, but, you know, where do you think the community's awareness is currently on ANX005 ? And, you know, especially as you speak to, you know, your colleagues who may not be at academic institutes, but community hospitals, and, you know, and, you know, with the background that they understand what complement inhibition is, you know, since they do treat patients with complement inhibitors.
Yeah, I would say, Pete, before these guys get going, we're on the front end of the curve in terms of educating the community on ANX005 and our approach. So we're just getting started. Lots of green fields in front of us with regard to that, but I'll turn it over to the physicians for their responses.
Yeah, it's Hugh here. Maybe I'll start first, and then David can follow. I think that the neuro community has well woken up to targeted immunotherapy. If you look at a disease like multiple sclerosis, which of course occurs in acute relapses and remissions, in addition to having chronic phases, there are a raft of immunotherapies now targeting all kinds of immune molecules, which are very widely used. The same applies to diseases like rheumatoid arthritis and all kinds of different things, cancer therapies, et cetera. So, I think it will be a breath of fresh air, and it certainly is to me, that finally, you know, we have a targeted immunotherapy available for Guillain-Barré syndrome, other than simply reversing back to immunoglobulin and plasma exchange, our historical favorites.
Yeah, the complement system is very well understood by most doctors. They may not know the details of all the different molecules in it, but it's a very clearly understood pathway. I think that I don't anticipate is going to cause any major sort of problems in it being appreciated by the non-specialist communities. Thank you.
All right. Thank you for taking my questions, and, congrats once again.
Thanks, Pete.
Thank you. Our final question is from the line of Joseph Stringer with Needham & Company. Please proceed with your questions.
Hi, good morning. Thanks for taking our questions. Just a follow-up question for the KOLs. Perhaps maybe asking a different way, which, which of the efficacy endpoints do you think will resonate most with, or be most important for both the treating physicians and importantly, payers in terms of real-world applicability and potential uptake? And then question for management. You're expecting the readout of the comparability results in the first half of next year. Is this gating to start the submission, or could you initiate potentially rolling submission given the data today and, and the fact that you do have fast track designation for ANX005 ? Thank you.
Hey, Joe, maybe we'll start with the regulatory first. So we will, as I said, we're just starting to assess what this data means in terms of our regulatory strategy, and we will be down with the FDA. So we'll update on that some point this year. We do think that these data warrant, you know, an emergent or a quick look at, right? So we want this to be as expedited as possible, but we'll work within the confines of partnership with the FDA. So over to the physicians for your first question.
Yeah, it's Hugh here. I think that's a very interesting question you've asked about whether one would prioritize any one of the outcome criteria over another. And what I would say is what is so powerful about this is that it is multiple outcomes. It's time on ventilation, time to walk, GBS- DS, ONLS, MRC Sum Score. And we as neurologists, you know, would put those together in a single and as I've already said, what's remarkable about this study is how they are all consistently moving in the right direction. So I wouldn't pick one out over another. Healthcare economists would obviously be maybe more interested in time on ventilators, whereas individual patients may be more concerned about time to get back to their work.
So there isn't a favored outcome. It's the fact that all are pointing in the same direction, and maybe David would like to add to that.
I think that's exactly correct. But if you looked at the one of their slides that was just showed the time to independent walking, which has been used since the first GBS trials as a primary outcome measure, and then if you look at the time on a ventilator, those two graphs alone will persuade people.
Great. Thank you very much.
Thank you. At this time, I'll now hand the call back to Douglas Love for final remarks. Mr. Love, the floor is yours for closing remarks.
Yes, sir. Yes, thank you, everyone. Really appreciate you making time to join us today and for the good questions. We're really quite excited by the outcomes from this study. As you've heard here today, there's not been a meaningful advancement in Guillain-Barré syndrome in multiple decades, and this targeted immunotherapy approach has the potential to really transform this landscape. We're working feverishly to do all that we can to get this drug to patients and improve their quality of lives. We look forward to continuing to update on this program as the year progresses. We thank you all and wish you all a very good day.
This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation.