All right. I think we can get started. All right, great. Hi, everyone. Thanks for joining us for the Wells Fargo 21st Annual Healthcare Conference. My name is Sadia Rahman. I am one of the biotech analysts here at Wells Fargo, and it is my pleasure to introduce our first session here with Vor Bio. From Vor, we have the Chief Commercial Officer, Dallan Murray, and Chief Medical Officer, Jeremy Sokolove. I appreciate you being here. I am excited to have this discussion. You had a couple of announcements this morning. You also have a very important catalyst coming up in the first half of 2027, which is the myasthenia gravis phase III readout. I am looking forward to delving into that. Before we get into Q&A, I will hand it over to you for any opening remarks.
Well, thank you, Sadia, and thank you for having us. We are excited to be here, and it has just been just over a year since Vor 2.0 has rearranged itself the way we have, and we couldn't be more excited this morning. We have got the announcements that you spoke about, which speaks to a few things. It speaks to the execution that we have been able to generate very rapidly. It speaks to the KOL excitement about this new modality and this new agent, and speaks to the really great people we have been able to bring on board with Vor Bio. We are happy to be here, and Jeremy is going to walk through the exciting news that we have today. Thank you.
Great. Thanks. I will echo Dallan's thanks for the invitation and just take us through some of the events of the last week. As Dallan mentioned, Vor 2.0 has only been in existence for about a year, about nine months as an independent clinical development company. During that time, we have taken over and really rapidly executed on our upstream MG study, our phase III study of telitacicept in myasthenia gravis. We are proud to say that study has completed enrollment. That sets the clock for our 24-week outcome to come in the spring. We are super excited about that imminent event. Even in the meantime, we are doubling down on our confidence on telitacicept in this space. We have announced the plan to start our ocular myasthenia gravis study.
Ocular myasthenia gravis is a really important area because it is often a precursor to generalized myasthenia gravis, so it really opens up that space in the totality of the MG market, and for patients who have the spectrum of MG from ocular to generalized. We also would be presumably the third, only the third agent in MG and the first upstream mechanism. The other are FcRns. Efgartigimod has completed their study, and we believe that RYSTIGGO from UCB is conducting a study as well. However, they are both the same mechanism, FcRns, for which we think we have a significant advantage, especially as we move upstream in an earlier disease population where we hope to be able to show some degree of disease-modifying effect, where we prevent the progression from ocular MG to generalized MG. This is an outcome measure that has not yet been demonstrated.
We're still figuring out exactly how to show that, but in the meantime, we're confident we can show a significant benefit for patients with ocular MG in reduction of their symptoms and their morbidity. Finally, we are excited about the AANEM conference, which is upcoming. This is probably the largest neuromuscular conference, certainly in the U.S., and at that, we have an oral abstract, which will look at post-hoc data from our China MG study. That China MG study has been published, has been presented both the 24 and 48-week data with significant efficacy, a magnitude of which is relatively unprecedented in the MG space. What we're really going to be focusing in on here is both the depth, breadth, and durability of that response.
We're also looking now at minimal symptom expression, also known as MSE, and we're under embargo, but I'll just say that it's really important to how we look at MSE. Any point in time, having one day of MSE is probably not what patients want. I think what patients want is to be able to have minimal symptom expression for the duration of their therapeutic window. So what we'll be looking at here is the durability of MSE. So we're excited to present that data. We think it's important for patients and important to really demonstrate the efficacy of telitacicept in MG.
Great. Congratulations on completing enrollment. That's a major milestone. On the ocular study, is that starting soon? Can you say anything about timelines there?
It'll start in the first half of 2027.
Okay.
We're still working through the build. We wanted to really double down on our confidence and get it ahead of the MG readout.
Mm-hmm. Got it. Okay. Let's talk about the myasthenia gravis, the data that you showed in China and how you expect that to translate to the global trial. In China, we saw a really large effect size, 4.8 points on MG-ADL. Very impressive and substantially higher than what we've seen for other approved agents in MG. The expectation here for most is that that would compress in the global trial. Just wanted to talk about why that compression could occur, specifically on the placebo arm? Can you talk about what we saw in China, how that response compared to other global trials, and what could be different in a global trial as far as maybe background treatments, anything else that would push that placebo arm higher?
Sure. I think there's two things that will push the placebo higher. One is the baseline disease activity. So the patients in China had slightly higher baseline disease activity than has been seen in other global studies. The other is the duration of disease. Many of the patients had a shorter disease duration. Just the fact that none of them had seen any other advanced therapies. They hadn't yet been exposed to biologics such as FcRn or complement inhibitors. They just weren't available in China at the time. I think that that might do that. The other thing is, a lot of patients with other treatment options pushes things down the road. In any immunologic disease, and probably any disease, what we see is that as we get to a later line population, we get an increase in the placebo rate.
That's been true of global studies in MG across the board. So we think we'll probably look more like the representative placebo effects we've seen in recent global MG studies, somewhere in the two to three range. Now, that could compress your delta for your MG-ADL, but there's also a strong anticipation that we'll see an increase in the active arm. If we look at the China data we've seen, there's only a few examples, but in the few examples we've seen of data that went from China to global, what we do see is a lower placebo in China and a higher placebo when we go global. But the delta tends to stay relatively intact because we also see an increase in the active arm as we go globally, probably because the placebo effect is affecting both the placebo arm and the active arm.
The delta tends to remain relatively constant. We may see a compression, we will see a higher placebo, but we hope that there will be a roughly proportional increase such that we will maintain that depth of response we have seen.
Okay. And when you referenced the other trial where we have seen a similar delta, with placebo going up, even though placebo went up in a global trial, I guess you are talking about batoclimab.
Batoclimab, yeah.
Study?
Batoclimab was tested in China, and in China it had a delta of 2, or 1.9. When it went globally, it had a delta of 2. The placebo went up by over a point, the active arm went up by over a point, and the delta was almost exactly the same between China and global. That is just one example. Other examples in other diseases we have seen, BENLYSTA in China had a slightly lower placebo, but the same delta in lupus. We have seen the same with a subgroup of ianalumab, which is a drug for Sjögren's disease. In the China subset, we saw that the placebo was lower in China, the delta remained the same.
I think that this hopefully is a consistent message that we will be able to replicate similarly, because we really do think that the mechanism lends itself to that double depth of response, though we will have to wait and see until the data evolves.
Mm-hmm. Even in China on the telitacicept arm, the improvement in MG-ADL was higher than what we typically see from other agents. It was a 5.7 change from baseline. In other trials, we typically see 4 to 4.5 point improvement. Is that something that could actually maybe come down in a global trial if you go to maybe a more heterogeneous population or for other reasons? Is there any reason to think that that could change?
Anytime you move to a more heterogeneous population, you get some degree of dilution. Often it affects the placebo, but I think that MG is a nice indication, and part of the reason why we like it as our first indication is myasthenia gravis tends to be relatively consistent in its immunology across populations. Diseases like lupus can be very different in Asian, African American, white European, South American populations. MG tends to be very consistent in its immunobiology. So we think that that heterogeneity of the biology shouldn't be as much of a problem. The heterogeneity is more in the cultural interpretation of how people respond to the MG-ADL, and the cultural interpretation of how patients report placebo, which is just part of different cultures and how they deal with that.
That is the place where we could see some dilution. But again, our strongest anticipation is that we will see an increase in the placebo, but hopefully that placebo will carry through to the active arm.
Mm-hmm. That cultural interpretation piece, does that affect QMG less, possibly? Because with QMG, it was interesting to me that maybe it is a more objective measure of response, but you still saw a higher delta there compared to other agents as well, even though placebo was more in line with- global trials. Does that give you more confidence that that more robust efficacy we are seeing with telitacicept is real and could translate in the global trial?
Yeah. There is nothing better than orthogonal validation through a more objective outcome measure. I think that is exactly right. The QMG was almost spot on. A network meta-analysis done of QMGs across global populations. The investigators are administering the QMG with the same precision, and the patients are responding with the same level of baseline activity and the same level of response both in the active and placebo arms. We think that, again, provides that validation that the dual mechanism for telitacicept really gives the best of both worlds, upstream mechanism and downstream mechanism. Although I am hesitant to use the word additive, I think that that is what we are seeing is that additive efficacy of those two mechanisms.
Mm-hmm. Got it. A common question that we get on this class and skepticism of BAFF/APRILs in myasthenia gravis and the China data that we have seen from telitacicept comes from the observation that IgG does not decline as much with BAFF/APRILs as it does with FcRns. With BAFF/APRILs, we see 25%-35% reduction in IgG. FcRns, we see 60% or more. With FcRns, there is some evidence that suggests pushing that even deeper gets you deeper efficacy. Just wanted to understand how you would address that concern.
FcRns obviously mechanistically lower IgG. That is what they do, and it is all they do. There is going to be a directly proportional decrease in the pathologic antibodies as your total IgG. A 60% reduction in total IgG is roughly a 60% reduction in pathologic IgG. The first challenge is that it does not reduce IgA and IgM, and those have pathologic antibodies as well. That is a cap on the efficacy bar for that mechanism. I think with our mechanism, what is unique is that we do see a 30% reduction in total immunoglobulin, but across multiple diseases, we see double that reduction in pathologic immunoglobulin where we measure it. In lupus, we see a roughly 70% reduction in double-stranded DNA, even in the context of exactly 30% reduction in total IgG, or roughly 30% reduction in total IgG.
Similarly, in myasthenia gravis, in a mechanistic study, they showed roughly somewhere around a 60% reduction in anti-acetylcholine receptor antibodies, the pathologic IgG, again, in the context of a 30% reduction in total IgG. We think that there is the ability to more robustly and more, I do not want to say specifically, but relatively selectively reduce the pathologic IgG. It does that because autoreactive B cells tend to be highly dependent on BAFF for their survival. When you starve the system of BAFF, you end up with a preferential reduction in autoreactive B cells and a relative sparing of your homeostatic protected B cells. We think this is an opportunity, not a liability. I think, if you look at the data, it also supports that. What is really nice now, and again, we are happy that UPLIZNA is now approved for MG.
People are using it and getting experience, and again, very minimal relative reduction in total IgG, but still some degree of efficacy, if delayed and perhaps not as robust as we might have hoped. I think that speaks to the fact that when we move upstream, we are able to affect the pathobiology of the disease without significantly lowering the total humoral immunity.
Mm-hmm. With UPLIZNA, the IgG lowering there is only about 10% right?
Right.
Do you think that also gets to-- Because we're seeing meaningful efficacy-
Yeah.
Despite that. Do you think pathogenic antibodies are still being depleted to around that 60% level, or maybe other B cell actions are driving efficacy as well?
Yeah, I think it's a combination of that. I think there's definitely a reduction in pathologic antibodies. The degree to which is something I'm not aware, but I would guess that it's less than you'd get with a BAFF/APRIL inhibitor. We think of UPLIZNA as BAFF. We think of APRIL as FcRn. I think that that combination of upstream and downstream reduction in autoantibodies is really what's getting you that depth of response. The other thing is that there probably are antibody-independent mechanisms that drive the pathology of most autoimmune diseases. MG has always been thought to be one of those prototypic antibody-driven immune diseases. It responds to FcRns, it responds to IVIG, it responds to plasmapheresis.
I think what that data tells us from UPLIZNA is that, at least to some extent, the ability to decrease your B cell hyperactivity, those autoreactive, hyperactive B cells, is able to abrogate the disease. I think that by combining that upstream mechanism of B cell inhibition and the downstream mechanism of deep antibody depletion, there really is the opportunity for additive efficacy. We get the best of UPLIZNA, and we get the best of other mechanisms with deeper immunoglobulin depletion.
Mm-hmm. Yeah, and I think the kinetics, if you look at the kinetics of IgG depletion with UPLIZNA and the efficacy curve, it kind of tracks a little bit. That makes sense, what you're saying about deeper IgG reduction and then the B cell efficacy as well. Back to the question about translatability of China data into the global trials. Are there any differences in trial design, like patient mix or background therapy, between the China and global studies that you think could contribute to a different outcome in the global trial?
For the most part, the studies are very similar. I think the one thing that is different is the background therapies. We do allow prior exposure to biologic therapies, including FcRns and complement inhibitors. The number of patients is relatively small. We think it's the sweet spot where we have enough patients that we'll be able to draw numerical conclusions about the ability to respond to telitacicept in the setting of prior FcRn or complement inadequate response. Again, it would take a lot of those patients to dilute any effect size. That's always a risk, is that when you go to a more heavily pretreated population, you can reduce your effect size relative to a naïve population. That's the only one that might be different.
Mm-hmm. As far as just trial conduct in general, concerns about any issues in RemeGen studies versus in your global trial. We do have data from RemeGen and IgAN.
Sure.
That's very consistent with other BAFF/APRILs.
Yes.
In global trials, right?
Yeah.
Maybe, can you talk about that and how that makes you comfortable with the operational aspects of the China trial?
Sure. We're incredibly comfortable with telitacicept as a molecule. I think benchmarking, exactly as you suggested, Sadia, IgAN is an objective outcome measure. It's proteinuria measured in a lab. And what we see is that when dosed appropriately, we can get every bit the same efficacy and perhaps a little bit more than any other BAFF/APRIL inhibitor. Benchmarking molecule to molecule, telitacicept is potentially best in class at potency as an FcRn inhibitor using IgAN as the benchmark. The other thing it speaks to is the ability of RemeGen and the China investigators to execute at a clean global level. The placebo wasn't elevated. Not that you'd expect such with a hard outcome measure like proteinuria, but just the fact they were able to execute a study which basically benchmarked almost precisely to other optimized FcRns tells us that telitacicept is not a fluke China mechanism.
It's a mechanism that translates globally.
Mm-hmm. Even the eGFR stabilization that they showed, I think some people might have been skeptical.
Yeah.
Now we're seeing the eGFR is stabilized with these APRIL and-
Well, this actually is a very interesting point. We are not currently entering into IgAN, but I think that people have this debate of whether BAFF adds anything to APRIL and IgAN. At least when you look at the proteinuria reduction in Gd-IgA1 reduction, it's probably almost entirely driven by APRIL in that early portion of the disease effect. But one thing that people ignore is the fact that not all BAFF/APRILs are exactly the same, in the sense that the ratio of BAFF to APRIL is quite different. So telitacicept is slightly heavier for BAFF. It's 2:1 potency for BAFF to APRIL.
When we dose to APRIL, which is what most people do, you dose to APRIL because if you overdose on APRIL, you will end up with hypogammaglobulinemia, and if you underdose on APRIL, you might leave some efficacy on the table, especially early. But when we dose to APRIL, we are slightly overdosing on BAFF, and that is okay. As BENLYSTA taught us, 1 mg per kg, 10 mg per kg, minimal increase in efficacy, no change in safety. So you can hit your BAFF side quite hard and not end up with any toxicity, whereas if you overdose on APRIL, you will end up with hypogammaglobulinemia. So again, when we dose to APRIL, we are giving a much heavier dose of BAFF than other BAFF/APRIL inhibitors, or certainly than any APRIL inhibitor.
We think what that is going to do is going to really remodulate that upstream B-cell repertoire, and we would like to think that might be part of the reason why you saw that stabilization in eGFR in the China population that was not seen in the global population at 38 weeks. Now, also just to be transparent, patients in China tend to have slightly worse IgAN, so they have slightly more rapid progression. So that might have also been a reason why they were able to show that. But nonetheless, the mechanism was the first and only to show in their first part of their study, eGFR stabilization, really showing the benchmark efficacy of telitacicept relative to the other BAFF/APRILs in the class.
Mm-hmm. Compared to povetacicept.
Yeah.
They are running a phase II trial that could also read out in the first half of next year. How should we view read-through, and maybe talk about the difference in ratio of targeting BAFF and APRIL there, and what that might mean for dose selection for pove?
Yeah. We are worried not because of the competition. We are worried because they might read out negative, and we do not want that negative read-through because, again, they do not hit BAFF very hard when they dose to APRIL. They may also end up with hypogammaglobulinemia, especially at their higher dose, because of the amount of APRIL they are using. Again, it is simple PK/PD. If you dose to effect, you can overdose if you try to go too far. We are encouraged by the fact that they are following in our tracks. They are confident that the BAFF/APRIL mechanism was important to MG. We have a three-ish year head start, so that gives us a significant confidence in our ability to deliver, and Dallan can speak more to that. I think that from a mechanistic perspective, we think that their read-through should not be completely direct.
If they work well, we know we will work well. If they have challenges, I do not think any challenges that that molecule would have would directly read through to telitacicept because, again, they are underdosing on BAFF, most likely when they dose to APRIL. If they end up with overshooting on APRIL, we have already had about 3,000 patients dosed with telitacicept, and we have not seen any CF and hypogammaglobulinemia signal when dosed appropriately. We can get hypogammaglobulinemia, but we do not dose that far, and I think that the breadth of patients treated with telitacicept really gives us a very good exposure-response relationship such that we can avoid hypogammaglobulinemia.
Cool.
We think that three-year head start is very significant, and you only need to look at the MG market to see argenx had far less than a three-year head start in terms of the FcRn class, and yet they have had incredible success and really built a real beachhead in the disease.
That is what we hope to do.
Mm-hmm. Got it. Just on the hypogammaglobulinemia point, with the class, we do see pretty similar IgG reduction out to, let's say, one year or two years, right? IgG continues to decline, I think. It continues to trend down even past one, two years. Just curious how you are thinking about monitoring for hypogammaglobulinemia differences between agents, even though broadly IgG reduction looks similar.
Yeah. Again, on average, IgG looks the same. There's always going to be variability in populations. Again, if anything, the China population should have a slightly higher risk for hypogammaglobulinemia because they're a slightly smaller population in terms of BMI. But we don't see it. Again, across the IgAN study, the MG study, both at 240 mg as well as the lupus, RA, and Sjögren's studies at 160 mg, nobody had to stop for hypogammaglobulinemia during the 3,000 observed patients. Then even in the open label extensions out to a full year, there was no evidence of hypogammaglobulinemia followed every month to every three months, depending on the stage of the study. Then in the real world studies, this drug's been approved in China for six years across lupus, where patients do tend to get hypogammaglobulinemia, and patients are just not stopping.
If you look at the real-world experience, it doesn't seem to be a big challenge, and I think it's a testament to the early dose ranging, and a little bit of luck in how that balance of BAFF/APRIL came about with the molecular engineering.
In our global study, we're following the patients out in the open label extension for a full year, and then Jeremy has extended it beyond that. So we'll be generating good long-term data on both safety and efficacy because we believe both in the safety long term, but also the durability and that increasing magnitude over time.
Got it. Just to be clear on povetacicept on the readout, you think it could be negative maybe at the lower dose, but on the higher dose, do you think they are hitting BAFF enough, but we might see those safety signals pop up?
It is hard to speculate. Again, the question is, where do they have enough BAFF to really get a depth of response that mimics telitacicept?
That is an answer I just do not know.
Yeah.
But mechanistically, we are hopeful that we offer something different in the sense that by hitting BAFF heavily and APRIL to the adequate extent, we get that additivity of upstream and downstream mechanisms versus a drug which has a much more APRIL-dominant mechanism, which may under address that upstream mechanism that we think is, quite frankly, contributing not just to the depth of response, but that breadth of response and that durability. How many patients get a change of five in their MG-ADL? More importantly, as Dallan alluded to, how many patients get better at 24 weeks and continue to get better between 24, 48, 100 weeks?
Dallan, just commercially, can you talk about how differentiated this would be bringing that depth of response, even if it's similar to FcRns?
Yeah.
Because of that durability piece, and then also the dosing and convenience side?
Well, the gold standard for efficacy is the MG-ADL in the market. If we come close to replicating the Chinese data, you are looking at a drug that is double the efficacy of the entire rest of the field. So it would be very differentiating. As we have said before, though it is a rare market, it is not a one-time therapy. So the bar for physicians changing their patients out if there is a better therapy is pretty low. So we think just on the MG-ADL delta alone, as you asked, it is very, very significant efficacy difference. As we have talked about, we believe we have efficacy differences beyond the MG-ADL delta.
We were talking about the durability, and that is one thing that as Jeremy and I got out, started meeting the KOLs, they were excited about the MG-ADL, but almost more excited about the fact that patients continue to get better in that second six months. We can see from the UPLIZNA launch that despite a pretty modest efficacy at 24 weeks, you can see an increasing efficacy in the second six months for them. Despite what many doctors describe as disappointing primary efficacy, UPLIZNA's launch has been pretty good, and they have taken a lot of first-line business, and it just demonstrates what we believe is this unmet need in the market and a real strong excitement about targeting upstream and durability. So that is the second of our efficacy advantages. The third one, Jeremy alluded to it, is that the FcRns target IgG and IgG alone.
There is emerging data coming out of Yale and other labs showing that there is IgA and IgM, and that about a third of the patients roughly have IgA and IgM involvement. What we are seeing in the China data that we hope to replicate in the global data is a breadth of response that is also best in disease in that 100% of patients are getting at least some kind of modest response on the MG-ADL, like a response of two or three or greater. That is pretty significant.
That actually might even be the biggest of all three of our advantages, because if you think about it from a physician and patient standpoint, if there is a higher percentage you are going to have even some kind of a modest response versus if you are getting close to 100% of some kind of response versus two-thirds having a response, it is a really good reason to start with a therapy that gives you a better chance for some kind of a response. We actually think we are going to win on three elements of efficacy. All of the focus has been on MG-ADL to date, but the durability and what we are calling the breadth of response we think are also going to be big advantages.
Mm-hmm. Got it. Can you talk about the dosing volume in myasthenia gravis, and whether there is room to concentrate the formulation?
Yeah. It is a low volume injection. We will be launching with the current formulation, which is two shots once a week, but the team is moving very rapidly and executing well on a higher concentration formulation that will get us to one prefilled syringe once a week. We are going to move from that as rapidly as we can into an auto-injector.
We are moving as fast as we can. It will not be day one of launch, but we are continuing to develop that.
Mm-hmm. Got it.
We actually have the high concentration formulation. We are now just doing the CMC work on the devices, and it is in the device. It just takes time for stability.
Okay.
We will have it, but it will be a little after launch, unfortunately.
Mm-hmm. Just one difference between the China trial and the global study, in China, the drug was administered in-clinic, and in the global study, you have a mix of in-clinic and at home administration. Can you just elaborate on that mix in the global trial, and which one could be reflected in the label.
Yeah.
At the start?
The label will reflect both. Because we have done the option.
We'll have both in the label.
That is the anticipation. Obviously, to be determined, but that's the anticipation. We do find that patients who get injected in the clinic tend to have more smooth injections. Patients who inject at home, when they had any sort of an injection site pain or reaction, we bring them back, retrain them, and they tend to do very well. We think that the China population probably had a slightly lower injection site reaction rate because they had clinic administration. That said, we're also fairly confident that we can get patients who want to treat themselves at home to be well trained to treat themselves at home in an effective way.
That's where you see the market going, is having that flexibility for patients to be able to dose it at home, and we think that's critical. One of the things we talk a lot about the differentiation versus the current therapies, but the biggest opportunity in MG is the fact that only about 20%-30% of the patients have even gotten biologics. There's still a huge opportunity for that market to grow, and I think one of the big ways it can grow is allowing more flexibility for patients to dose at home. Because a lot of the patients that we're going to find as we grow the market are in areas that it's not going to be easy to get into the big MG centers to get their weekly injections.
Allowing them to dose at home is going to be an important advantage when we go into the market.
Mm-hmm. Got it. We only have a couple of minutes left, but I do want to touch on Sjögren's. We had the ianalumab data somewhat recently, and just talk about the placebo response in that trial, how you are trying to manage placebo response in your trial.
Yeah. We think the most important thing that really drives placebo is the ESSDAI efficiency of conducting the ESSDAI scoring, and we think, again, we do not know, one of the challenges that they may have met was a lot of new investigators who did not have experience with the ESSDAI. When you look at the baseline ESSDAI, it was probably slightly higher and slightly exaggerated, not by any conscious effort, just because of new investigators eager to get patients into a study of a drug that is really critical, a disease that is really critical to treat. As they got better at the ESSDAI over time, there was probably some degree of increased precision, which may have increased both the response in the placebo as well as the active. We think the most important thing that we have done is getting as many experienced investigators as possible.
Again, they had 600 patients in their study. They had to have three times as many sites as we did. We were able to pick up a lot of those sites from the ianalumab study, as well as people who have experience with nipocalimab, or other concluding studies to come over to our trial. We think what that gives us is much better precision, which will give less regression to the mean in terms of the placebo response. Will there be a higher placebo than China? Absolutely. Will there be a placebo as high as ianalumab? We are fairly confident we will be able to control for that.
Mm-hmm. As far as powering of the study, is it adequately powered for an effect size like we saw with ianalumab or no?
Well, it's not powered for a 1.1 directly. We have about an 80% power for a 1.5 change.
We have a 96% power for a two to 2.5 change, and we really think that, quite frankly, we need that to make any difference. The minimal clinically important difference for Sjögren's for the ESSDAI is probably in the range of three. Some people would lower that to two or 2.5, given the complexity of the ESSDAI and the unmet need in Sjögren's. So we're powering for the minimal clinically important difference that we feel would be clinically meaningful.
So we're well powered for that, and we're dramatically overpowered if we get anything that looks like the China data.
Just on dosing in Sjögren's, it's a lower dose than what-
Yep.
Was used in the IgAN?
Yep.
And myasthenia gravis trials, and that was selected based on RemeGen's dose-finding work in China.
Yep.
How confident are you that that dose will provide sufficient exposure in a Western population?
Yeah. At least if you look at the population PK analysis from China, BMI is not a significant variable in terms of exposure, nor in terms of efficacy at the exposure response. We are pretty confident that we have adequately addressed the target. Again, it covers enough BAFF because we think BAFF is a slightly more dominant mechanism in Sjögren's, but it also covers enough APRIL, as you can see from the immunoglobulin reductions of well over 25%, 30%.
They start with very high immunoglobulins in Sjögren's.
That is part of the disease pathology. We are fairly confident that we have got an effective dose, and we are not going to be going over, and we are enthusiastic to see the results. I will just make a plug. The great thing about Sjögren's is we took over MG with not a lot of patients after about a year and a half of the study. We have been in Sjögren's for about six months, and we have already basically, not capped out, but we have almost reached our goal for U.S. enrollment. It just shows the enthusiasm for Sjögren's across the population, as well as the impact we are having in influencing the Sjögren's community, which we think is critical.
Mm-hmm. Great. Well, unfortunately, we are out of time, so I will end there. But thank you both so much.
Thank you.
For joining us.
No, thank you, Sadia.
Thanks for having me.
Really appreciate it. Thank you for the invitation.