Good morning. My name is Michelle, and I am your conference call operator. As a reminder, this call is being recorded. Before we begin, I would like to remind everyone that today's conference call will include forward-looking statements within the meanings of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, for example, statements regarding the potential efficacy and safety of Immunovant's product candidates and Immunovant expectations regarding the timing, design, and results of its clinical trials, including the timing of future data readouts and the announcement of future indications. These forward-looking statements are not guarantees of future performance and are subject to various risks, events and uncertainties, assumptions, known or unknown, which could cause actual results to vary materially from those indicated or anticipated.
For more information, investors are encouraged to review Immunovant's most recent quarterly report on Form 10-Q, filed with the SEC on August 10, 2023. Joining me on the call this morning is Dr. Pete Salzmann, Chief Executive Officer at Immunovant. Following his prepared remarks, we'll open the call up for questions. With that, I would like to turn the call over to Dr. Salzmann.
Thank you, Michelle. Good morning, everyone, and thank you for joining our call. At Immunovant, we are dedicated to enabling normal lives for people with autoimmune diseases. Today, I'm very excited to share new data with you that we believe substantially advances our vision. When we unveiled IMVT-1402, we shared data from cynomolgus monkeys showing that IMVT-1402 matched the IgG reduction of batoclimab, but without the albumin reduction or LDL increase seen with batoclimab. We said that we believed these observed differences in monkeys could be attributed to the different binding orientation of IMVT-1402 to FcRn, as compared to the binding orientation of batoclimab to FcRn. Both antibodies bind the IgG binding site of FcRn, but with a different three-dimensional orientation shown on this slide. IMVT-1402's orientation is consistent with avoiding steric hindrance of albumin binding to FcRn.
Given the prior consistency between cynomolgus monkey data and human data in terms of IgG and albumin across the anti-FcRn class, and given the differing crystal structures shown here, we said that we also expected to observe very meaningful differences between IMVT-1402 and batoclimab in humans with regard to their impact on albumin and LDL. Going into this phase I trial, we had several goals, which I've scored here based on the initial data. First, we wanted to show best-in-class IgG reductions similar to batoclimab. You're going to see that. Second, we wanted to show minimal to no impact on albumin. You're going to see that. Third, we wanted to show minimal to no impact on LDL. You're going to see that. And fourth, we wanted to show all of this could be done with a simple subcutaneous preparation. You're going to see that.
In sharing these data today, we are particularly pleased to be able to share data from the 300 mg MAD cohort. I'm incredibly proud of our team that was able to pull in this cohort well ahead of schedule. It's a tribute to their energy and capability. In terms of IgG lowering, 300 mg of subcutaneously delivered IMVT-1402 demonstrated a mean IgG reduction of 63% after four weekly doses in the MAD cohort. The SAD data was exciting, too, as IMVT-1402 demonstrated rapid and deep IgG reduction in both the 300 mg and 600 mg SAD cohorts. The second bullet is also very important. Allow me to read it. Initial 300 mg MAD data after four doses showed a favorable analyte profile of no decrease in albumin and no increase in LDL relative to baseline levels. That's exciting.
Finally, although we believe that the primary axis of differentiation for IMVT-1402 will be deeper IgG reduction without analyte changes, we're also excited to be developing IMVT-1402 as a simple subcutaneous injection designed to enable patient self-administration. This phase I trial is really interesting because in addition to evaluating the overall safety of IMVT-1402 at multiple doses, we're also observing whether IMVT-1402 lowers IgG without impacting albumin and LDL. Another key aspect of this trial is dose selection, since this study is designed to establish our going-forward doses. To achieve the goals on the prior slide, we designed the trial you see on this slide. It is a randomized, double-blind, placebo-controlled study. The IV SAD cohorts are primarily included to accelerate the path to the subcutaneous MAD cohorts.
The subcutaneous SAD cohorts give us an early read of IgG, albumin, and LDL levels after a single dose of IMVT-1402, delivered subcutaneously at 300 mg and at 600 mg. We expect 300 mg and 600 mg to be our two doses for future studies. Of course, the MAD cohorts are the most informative because in these cohorts, we can see how IMVT-1402 performs with continuous weekly dosing over four weeks. This is similar to the MAD design we used for batoclimab, making cross-trial comparisons possible. Finally, I should note that the 1,200 mg IV SAD cohort began a couple of weeks ago, but data is not yet available from that cohort. Similarly, most of the 600 mg subQ MAD cohort just began dosing this week, and we expect data from this cohort to be available in November.
Let me start with the SAD cohorts. This slide shows the mean IgG percentage change from baseline over time. After a single subcutaneous dose of 1402 at 300 mg and 600 mg, we observed mean IgG reductions of 37% and 45% respectively. The IgG reduction following a single dose of 1402 was observed to be as potent or more, more potent than batoclimab at every time point in the SAD data. Although this comparison is from two separate trials, we believe that 1402 can achieve maximum IgG suppression similar to batoclimab. In the 1402 arms, all time points showed a statistically significant decrease from baseline, with p-values less than 0.05. Here, we combine the two figures into one for easier comparison of the 1402 and batoclimab data.
In terms of IgG lowering, we predicted that 300 mg of IMVT-1402, in purple, would be at least as potent as 340 mg of batoclimab, in light green, and that is what we observed. We also predicted that 600 mg of IMVT-1402 would be as potent as maximum saturating doses of batoclimab. The batoclimab subQ SAD study didn't test 680 mg, but it did test a somewhat higher dose of 765 mg. Here we see that 600 mg of IMVT-1402, in blue, matched the 765 mg dose of batoclimab, in dark green. Again, this gives us confidence that we can achieve maximum IgG suppression around 80% with IMVT-1402.
Albumin data is shown on this slide with a side-by-side comparison of 1402 data on the left and batoclimab data on the right. Whereas batoclimab showed a decrease in albumin in both SAD cohorts, 1402 does not show a decrease in albumin, and the three curves for placebo, 300 mg and 600 mg, are basically on top of each other. No albumin data points in the 1402 treatment arms showed a statistically significant decrease from baseline, with all p-values well over 0.05. Consistent with the albumin data, we also observed no impact on LDL in the two SAD cohorts of 1402. No LDL value at any time point showed a statistically significant increase, with all p-values well over 0.05.
No comparison with batoclimab is shown because LDL was not measured in the batoclimab phase I, as this impact was not anticipated at that time. Excuse me. Moving on to the MAD cohorts. This slide shows initial results with the 300 mg cohort through four weeks of dosing. As I mentioned earlier, the mean IgG reduction from baseline for the 300 mg cohort was 63% after four weeks of dosing. Similar to the SAD data we just reviewed, the IgG data for this 300 mg MAD cohort of 1402 looks very similar to the 340 mg MAD cohort of batoclimab. You'll appreciate that even more on the next slide. Here we have overlaid the IgG data from the batoclimab phase 1 trial and the initial data from the 1402 phase I trial.
You can see the 300 mg 1402 cohort in purple is right on top of the 340 mg batoclimab cohort in light green throughout the dosing period. As I mentioned earlier, based on these data, we believe that the 600 mg MAD cohort, which just started dosing, will match the best-in-class IgG lowering of batoclimab 680, shown here in bright green. The 1402 albumin change from baseline chart is also impressive, showing albumin levels that are mostly above baseline for 300 mg of 1402, shown in purple, throughout the dosing period. Note that batoclimab begins to show clear albumin lowering 7-10 days into dosing and is peaking three to four weeks into dosing.
So the lack of any decrease in the 1402 arm throughout four weeks of dosing is an important observation. This is another very nice chart, and not at all surprising, given the lack of albumin changes observed in the 300 mg MAD cohort. After four weeks of dosing with 300 mg of 1402, the mean LDL change for the group ended below baseline. Moving on to safety. We included the IV cohorts in our safety analysis. The treatment-emergent adverse events that we observed were mild or moderate, with no serious adverse events observed across any arm to date. Also, we are not seeing any patterns where we did observe AEs, whether in 1402 or in placebo groups. They were mostly one-offs, meaning most unique AEs were experienced by zero or by just one participant per group.
The exceptions are shown at the bottom of the table. Here we list all AEs that occurred in two or more participants in a group. These three treatment-emergent adverse events were actually all more common on a percentage basis in the pooled placebo groups than they were in the pooled 1402 groups. For example, headache was observed in 3 out of 12, or 25% of placebo participants, while it was observed in only 4 out of 40, or 10%, of 1402 participants. Catheter site pain refers to pain from the catheter used for blood draws. Let me share with you my concluding thoughts before we open the call for Q&A. I hope you share our excitement after reviewing these encouraging data this morning. We believe these results strengthen 1402 as a potential best-in-class anti-FcRn.
I will note that in the ADAPT-SC study, IV efgartigimod showed a 62.2% reduction in IgG after four weekly doses. In the same study, Halozyme-enabled efgartigimod showed a 66.4% reduction in IgG after four weekly doses. Turning back to Immunovant, 680 mg of batoclimab has shown IgG reductions of about 80%, which we believe is best-in-class IgG lowering for a simple subQ. Based on the data reviewed today, we believe 600 mg of 1402, given weekly, will deliver IgG lowering on par with 680 mg of batoclimab, enabling the potential for greater efficacy across a range of autoimmune conditions. We're also excited by the albumin and LDL curves for 1402, which were both observed to be similar to the curves for placebo in all the initial data.
This slide highlights the emerging profile of 1402, a potentially best-in-class anti-FcRn, and provides the key points all in one place. I also want to remind everyone that we have a composition of matter patent that is pending for 1402, which, if granted, is expected to provide coverage into 2043. In closing, we are very excited about the initial data we reviewed today. We're also very excited about the many attractive potential indications, with 22 different indications being studied across the anti-FcRn class. This breadth of indications and the strength of IgG as a biomarker, both topics that we've been speaking about for a long time, make the data we re-reviewed today all the more important. With that, let's open the call for Q&A.
Thank you. If you'd like to ask a question, please press star one, one. If your question hasn't answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Derek Archila with Wells Fargo. Your line is open.
Great. Good morning, and congrats on the data. Well done. Just two questions from us. So maybe just discuss your reasoning to test the 1200 mg fixed dose in the SAD. If I recall, I believe that was originally an optional dose, so that would be great to know. And then just in terms of the 600 mg performing better than the 765 mg batoclimab dose in the SAD, I guess, would you expect now in the MAD trial to perhaps get greater than 80% IgG reduction? I guess, what's possible, and I know you just kinda compared to the other FcRns in the space, but you know, how does that compare to things beyond VYVGART and some of the other full-length antibodies? Thanks.
Yeah. Hey, thanks for those questions, Derek. So with regard to the 1200 mg SAD IV cohort, that's done to really round out our PK/PD models and help to answer, you know, some of the points you raised in your second question. That's really the only purpose for that cohort. The second question is interesting. You know, we're pretty convinced that 680 mg of batoclimab is maximally saturating the Fc receptor and therefore yielding the maximum amount of IgG reduction that can be delivered via this mechanism. That's consistent with what can be achieved with very, very high doses of nipocalimab given IV, for example.
So, the 765-mg dose of batoclimab would be, equivalent, obviously, to the 680-mg dose of batoclimab. We don't, we don't, see in the data we have that going above 680 of batoclimab would yield greater than 80% IgG reductions. So with all that said, we, we also believe that 600 is going to be fully saturating and that the, again, a fully saturating IgG reduction that we expect is, is around 80%. You know, I think those curves are probably, pretty close, even though there are a couple of time points where, you know, one's a little higher than the other.
Excellent. Thanks for the questions, and congrats again.
Thanks, Derek.
Thank you. Our next question comes from Yasmeen Rahimi with Piper Sandler. Your line is open.
Good morning, team, and congratulations on the great data. Extremely well done on the execution. A few clarification questions. Team, could you maybe comment on, sort of the variability, the error bars and IgG reduction along the SAD and the MAD, you know, whether it came in as expected, or, you know, or whether it was consistent with other studies? Any sort of commentary around variability in these measures would be helpful. Then... Second question is, is there any assumptions, like, as, thank you for predicting the 600 mg dose group. But is there any room that it could, I guess, what are the assumption that something could go wrong and then it doesn't show 80, 80% reduction?
You know, like, like, I guess, how confident can we be for the prediction of the 600 mg dose group? That would be really helpful. And then the third question that I think a lot of investors have is sort of, thoughts around which indications you're interested and what, when you hope to disclose sort of the next steps, post the full MAD data in November. And thank you for allowing me all, to ask all these questions.
No problem. Thanks, Yaz. So starting with the variability, I think, Yaz, what kind of variability are we seeing? So across the data set, we saw, albumin had a standard deviation of ±5. IgG, by the way, had a standard deviation of ±6, and LDL was ±16. As we said, prior to this data release, the albumin value was really the most important one, and that's because we believe the albumin data is most de-risking since the LDL changes seen with batoclimab happened because of the albumin changes. So with a flat albumin curve through four weeks of dosing in the 300 mg 1402 MAD, and with variability, observed variability of just ±5%, we have a lot of confidence in the data.
With regard to the 600 mg data, and how confident we are that that will saturate the receptor and yield maximum IgG reduction, we're very confident of that, based on a couple things. The translation of 340 to 680, that's based on... You know, we have a lot of PK/PD models for batoclimab that gives us confidence in being able to predict where batoclimab sits along the saturation curve. We used that model as well as a preclinical binding affinity of 1402, that's a little bit higher, to correctly predict that 300 would be the same as 340. And so doubling 300 will run up the curve to 600, obviously, just in the same way that 340 runs up the curve to 680.
680 is probably a little bit on the flat part of the curve. What I mean by that is, even a dose a little less than 680 of batoclimab would likely be saturating and deliver 80% IgG reduction. So several different points that we can use to triangulate give us confidence that 600 will be the maximum dose. Sorry, will yield the maximum IgG reduction. And then finally, you know, what indications do we plan to pursue? So, gosh, there's so many good ones, right?
That's right.
And, you know, our strategy is really to kinda attack, maybe there's three different types of indications that we're excited about. You know, in spite of 22 indications, you know, being studied, we still have some of the first, and some of ours are still first in class. And one that we're, we have a proof of concept that you know about with batoclimab is Graves' disease, and we're expecting data for that later this year. If that data is positive, I think Graves' disease is a really nice opportunity for 1402. And we've talked about that one pretty extensively before.
Looking at this emerging profile for 1402, which we believe is heading to best-in-class, you know, if you have the best-in-class asset, then that allows you to go after the best indications, based on a belief that the share market will ultimately be driven by the best-in-class profile of an asset, not so much the launch order in these indications. There's a whole variety of really good indications as defined by largest addressable market, most unmet need, and highest probability of technical success. Then we have some, you know, some emerging indications that are really interesting. J&J just reported a lot of data from their proof of concept study in rheumatoid arthritis, which I find to be very encouraging.
They had consistent signs of efficacy across many different clinical parameters. They achieved that with only a 58% reduction in IgG, so... And they showed a correlation between depth of IgG reduction, depth of ACPA, I should say, reduction, which is one of the pathogenic IgGs in clinical response. Even though that ACPA only was driven down by about 30% for nipocalimab, we believe we can get higher levels of IgG reduction, obviously, and therefore, you know, drive that clinical efficacy potentially higher in RA. So there's some other indications that are emerging that are really exciting. So a lot to think through now that we've got this data.
Thank you so much, and congrats.
Thanks, Yaz.
Thank you. Our next question comes from Robyn Karnauskas with Truist Securities. Your line is open.
Hi, guys. Thanks for the question, and congrats on the quality of the data, and your presentation was really well done. I guess I have two questions. How do you decide what indications to go for in financing those? 'Cause obviously, you can run a million trials at once and be competitive. How do you decide, like, where you go and what choices you make and where to capitalize your spend? And second, I'm glad you brought up the RA data. Given nipocalimab is not probably at the highest dose it could be, how do you comp that to 1402 and where you think you can go for RA? Thanks.
Yeah, thanks for the question, Robyn. So, I mentioned in response to Yaz's question, kind of how we're thinking about indications broadly and how there's so many that are exciting. Your question kind of follows up on that, which is: how do we prioritize which ones to start with? And I think there's a whole variety of factors to consider there that have to do with both, you know, the best indications are always gonna rise to the top. So that's gonna be probably the most important thing. And that's the - there, there's no, each indication is a little different on a different dimension. Some are more commercially attractive, some have a higher probability of technical success, some are at least a little bit easier to execute.
So we'll be looking at all that to basically decide which are our favorite few, to start with. And then in terms of RA, specifically, again, in one of the abstracts that Janssen submitted to ACR, which is on the website now, they report this 58% reduction in total IgG with about a 30% reduction in ACPA. And they state in the conclusion that ACPA reduction correlated with clinical remission, not just clinical response, but remission. These patients were pretty sick. They were, it had to be at least a minimum of one TNF failure, but probably they had many that were more than one TNF failure.
So to get to a clinical remission in that population over 12 weeks, even with only a 58% IgG reduction, and I know it wasn't statistically significant, but they're small numbers. I think that's really impressive. Where could we get, you know, going to 80% IgG reduction? Well, there's not enough data in RA to know for sure, but if we look across many, many other indications where deeper IgG reduction led to meaningfully more clinical response, you know, we think we can do better on all of the percentages that they reported in terms of like ACR 20, 50, 70, should we decide to pursue RA. So that's definitely one that we'll be considerations at.
Pete, one follow-up question for you. So when you think about catalysts, you mentioned Graves, but, you know, when do you think you could articulate when we get the indications you're going after, so we understand, we can model it better? I mean, I think a lot of clients are looking at MG, but, you know, they're way ahead. So, like, how do we think about when you disclose what indications you're going after so we can better model your company and the opportunities?
Yeah, great question, Robyn. There's always a tension between granular transparency, transparency on indication selection and the strategic value of waiting until the last minute to disclose an indication. And the last minute is usually defined by, you know, when you're posting it on ClinicalTrials.gov. And generally, the strategic advantage outweighs everything else. So I think we will disclose the indications probably as they're just about ready to go for 1402 on a case-by-case basis.
Okay. Congrats, and great job in the presentation. It's very clean. Thank you. I appreciate it.
Thanks. Thanks, Robyn.
Thank you. Our next question comes from Samantha Semenkow with Citi. Your line is open.
Hi, good morning, and let me add my congratulations on the data. Very well done. I wonder if you can maybe just talk about your next steps with FDA. I know you have an open IND. Do you think you'll be able to take this data directly into patients in the US with the safety database you have, or will you have to do any bridging work? Just curious on your thoughts there.
Yeah, thanks for the question, Sam. So first, we're gonna finish this phase I trial. We have another cohort to complete. It's just started, the 600 mg MAD cohort, and then, you know, that data needs to be all locked and cleaned so that we can use it for regulatory interactions. But in terms of bridging, there's not really a bridging concept between data from Western countries, at least, Europe, New Zealand, Australia, Canada, U.S. That data is essentially, you know, equally valid from an FDA perspective. So we'll take this data to the FDA, and in terms of which division, that depends on the indications that rise to the top. And, you know, different divisions have responsibility for different indications.
So as we make our indication prioritization decisions, then that will define, you know, which divisions at the FDA that we'll be going to next year.
Excellent. Thanks very much for taking the question.
Hey, you're welcome.
Thank you. Our next question comes from Sam Slutsky with Life Sci Capital. Your line is open.
Hey, good morning, everyone. Congrats on the update, and thanks for taking the questions. Just two for me. I guess, as it relates to the development in CIDP, just how are you thinking about the path forward for batoclimab versus IMVT-1402, depending on the scenarios for the initial CIDP data next year?
Yeah, thanks for that question, Sam. So, you know, when we launched the CIDP indication, we launched that with a lot of optionality. You probably remember those discussions. It has sort of a proof of concept built into the pivotal 2B design, in the sense that Period 1 is testing two doses. And our hypothesis at the time was that argenx would likely succeed in CIDP, as they have... and that there would likely be some additional room for efficacy based on some patients in the randomized withdrawal period relapsing, which we also saw. Then the third thing we hypothesized is that 680 of batoclimab would outperform 340 of batoclimab in our Period 1. So that we won't know until the first part of next year.
But, with all if all those things are true, then there's a compelling argument to be made to develop CIDP with 1402 through to registration versus batoclimab. So I think that's the way we're trending with regard to our CIDP program.
Got it. And then I guess on MG, obviously, batoclimab has the advantage versus currently marketed FcRns, that it could be self-administered versus healthcare administered for the currently approved products. Obviously, it has the LDL signal, whereas 1402 doesn't. I guess, does it make sense to study both in MG, and kinda what's the physician feedback been on batoclimab post argenx and Roza approval since we're healthcare administered?
Yeah, great question. So the, you mentioned one of the key differentiators that we believe our batoclimab program offers in myasthenia gravis, which is the simple subQ that we believe will ultimately lead to the ability for patients to self-administer. But the more important differentiator is the deeper IgG reduction, which batoclimab can also achieve, although for a shorter period of time than 1402 will likely be able to achieve it based on the analyte changes. Given the induction and maintenance paradigm in myasthenia gravis, then that shorter period of deeper IgG reduction, which is built into our the period one of our MG study, and which has an induction maintenance design, is very attractive to physicians.
I was at an investigator meeting for some of our a bunch of our clinical trial sites for myasthenia last week, and there's just a lot of enthusiasm for the trial design. It really resonates with neurologists to start with the more potent dose, and then after for those patients who will achieve a good response, they have the opportunity to titrate down their dose. So, we're really excited about what batoclimab can do for patients with myasthenia gravis. And, you're right that there will be some patients, particularly in the long-term extension, who may have a modest increase in their LDL, and that may require anti-lipid therapy in some cases.
But with the potential for additional efficacy and the potential for a better route of administration, we still see that program as really differentiated. All that said, you know, myasthenia is a really important indication for the anti-FcRn class, so I also wouldn't rule out that we'd eventually do a myasthenia study with IMVT-1402. But our short-term plans are to take batoclimab through to registration for myasthenia.
Got it. Thanks, everyone.
Yeah, thank you.
Thank you. Our next question comes from Thomas Smith with Leerink Partners. Your line is open.
Hey, guys. Good morning. Thanks for taking the questions, and let me add my congrats on the data. Just two quick clarification questions on my end. I guess first, can you share any color on what you saw with the single-dose IV cohorts on albumin and LDL, and particularly with the higher doses you explored there? And then, secondly, you mentioned, I guess just to follow up on, on your comments, Pete, you mentioned your standard deviation for LDL was ±16. Can you just comment on where that falls relative to your expectations and within the context of the assay variability?
Yeah. Yeah, thanks, Tom. So we didn't show the IV cohorts because they basically looked just like the subQ cohorts, and we had enough SAD data in the presentation, we thought already. We do expect the IV cohorts to provide some additional insight to us in terms of IgG reduction, and that's competitively sensitive since some companies are struggling to move from IV to subQ. But in terms of albumin and LDL, there wasn't anything interesting in the IV cohorts. And then what was your second question, Tom? Sorry, I missed it. I didn't write it down.
And then, yeah, it was just, you mentioned the LDL standard deviation was ±16.
Oh, yeah, very... Yeah, thanks.
Yeah.
Sorry about that. Yeah, so, you know, as I mentioned, in response to Yaz, I think the most important thing is that the observed variability for albumin was just as we predicted, ±5%. That's really the analyte of most interest here, because any LDL changes that we observe with batoclimab relate to changes in albumin. It's not an independent signal. You know, albumin was relatively easy for us to estimate the variability in advance of the trial because we have so much albumin data with batoclimab, because all of our batoclimab trials had multiple albumin measurements all along the way. Because that wasn't true for LDL. LDL wasn't measured in our phase I trial for batoclimab. It wasn't measured in the MG trial. It was measured infrequently in the TED 2b trial.
So we just had many fewer data points on LDL, and there's not that much in the literature. We found literature estimating LDL variability anywhere between, you know, 10%-16%. So this variability falls within that range. But the most important thing is the albumin variability, which is ±5%, and that gives us a lot of confidence.
Got it. That's super helpful. If I could just sneak in one other clarifying question. Just wondering if you could provide any additional color on the one AE-related discontinuation in the 300 mg cohort?
Right. That person had a mild AE that was not deemed related to study drug. It was an event. It was a preexisting condition that was mild and flared up, but just led them to discontinue the trial. Again, not related to study drug.
Got it. Super helpful. Thanks, Pete. Appreciate you taking the questions, and, congrats again on the data.
Yeah. Thanks, Tom.
Thank you. Our next question comes from Yatin Suneja, with Guggenheim. Your line is open.
Hey, guys. Thank you for taking my questions. Nice results today. Just a question on the regulatory part. Do we know if there is a regulatory path forward where you might be able to switch, you know, 1402 without running a pivotal study? Just curious if there is any precedent. Is that something you could do, you plan to do, or you would have to sort of run, pivotal study with 1402 in the indication where Bato is already ahead?
Thanks, Yatin, for that question. Yes, our assumption is that, anywhere we seek to get 1402 approved in the U.S., we'll need to run a registration trial with 1402. That said, there are some interesting pathways, including the model-informed drug development pathway, that the FDA just recently re-released some initial guidance on, and has been a big topic of conversation, which provides some interesting opportunities for leveraging data from a first-generation asset, where you have a good biomarker for a second-generation asset. And that pretty much exactly describes the situation here with anti-FcRn, batoclimab, and 1402. But at the end of the day, I do expect that any indication where we wanna get approval from the FDA in the U.S. will require a registrational program.
Again, that program could be a little bit optimized with the MIDD pathway, but you're gonna need a registrational study for sure.
Got it. Very good. Just one more. So if we look at the SAD 300 mg, it matches, especially if you look at the IgG reduction, it matches the 765, batoclimab, but in the MAD 300 is sort of more closer to 340. And what would be the plausible explanation there? Thank you.
Yeah, thanks, Yatin. I think the primary explanation for that situation is that you just have a lot more ability, variability after a single dose. And, you know, even in the MAD, you do see a little bit steeper at the very beginning drop with the 300. But I think if you look at the totality of the data from the 300, it... Again, it's just sort of right on top of the 300 and 340 mg of the batoclimab in the MAD. And the MAD curves are, you know, more reliable as a specific estimate of, you know, what you're gonna see with continuous dosing, since obviously you have continuous dosing there.
I think that's just a little bit of a fluke of variability in the SAD data.
Right. Very good. Congrats again. A very nice results.
Thanks, Yatin.
Thank you. Our next question comes from Jason Gerberry of Bank of America. Your line is open.
Hey, guys. Thanks for taking my questions. So firstly for me, and apologies if I missed this, but just curious in lieu of today's data, how you're thinking about this optional 450 mg dose in the MAD? If I recall, this could give you an option to have a single prefilled syringe as your high-dose option. And so just wondering if you're thinking about exploring that, and what is sort of the minimal IgG reduction you need to see for that to become your preferred, high dose? And then secondly, if you can just comment, were there any meaningful differences in baseline albumin levels, in this versus the batoclimab phase I studies? I know that other sponsors sometimes, have come in low, baseline, and that can kind of skew the percentages. So just curious if you can comment on that. Thanks.
Yeah, Jason, great question. And you noticed a difference between our prior SAD trial schematic and this one, because we've now advanced as we have more data in terms of our thinking. So you're right, we previously had listed that we had optional cohorts at either 150 or 450, and those were put in the protocol as optional cohorts in the case that the 300 mg, so 1402, yielded much deeper IgG reduction than we predicted. That's not the case. So 300 mg did what we predicted, which was it matched 340.
Those 450 and 150 cohorts were kind of in the unlikely case that we had much deeper IgG reduction with 1402, because you never know, we wanted to be ready for that. Then we could test the lower doses. So at this point, we believe 300 mg of batoclimab will be our sort of standard dose that yields sort of a standard degree of IgG reduction of around 65%, and 600 will be the high dose. So we're not planning on doing the 450 or 150 cohort. And then your second question, Jason?
Yeah, it was on the baseline albumin levels, this versus the batoclimab studies.
We didn't see any. There was nothing remarkable about that. This study done in New Zealand has a pretty unskewed population. It was a similar population to, you know, what you'd typically see in a healthy volunteer study, so nothing remarkable about baseline characteristics.
Okay. Thanks, guys.
Yeah. Thank you, Jason.
Thank you. Our next question comes from Louise Chen with Cantor. Your line is open.
Hi, team. This is Wayne, for Louise. Thanks for taking our questions, and congrats on the data. So there are two of those. First is, now that you have some IMVT-1402 data, are there any batoclimab indications that would be better suited for IMVT-1402? And then the second question is, have you ever considered, like, collaborations or partnerships for your anti-FcRn assets? Thank you.
Thanks, Wayne. So, in terms of our batoclimab studies, as I mentioned earlier, Graves, we have a proof of concept running with batoclimab, and data expected later this year. If that data is positive, then we would anticipate for future development in Graves to be done with 1402. And then I previously addressed in other questions our plan for CIDP and myasthenia gravis, and that just leaves our thyroid eye disease program. That's a fixed-duration therapy program, six months of fixed-duration therapy. And so for six months of fixed-duration therapy, the incremental advantage of 1402 versus batoclimab is less. So we plan to continue TED with batoclimab. In terms of collaboration, or maybe more broadly, you know, how do we maximize this amazing opportunity?
I think, you know, we're gonna look at every different possibility to maximize the potential of 1402, starting with our plan A, which is, you know, what we've done in the past, which is to raise capital in the equity markets and then use that to develop the indications ourselves. Thanks for the questions.
Thank you. Congrats again. Thank you.
Yeah.
Thank you. Our next question comes from Alex Thompson with Stifel. Your line is open.
Hey, great. Thanks for taking my questions. I guess for, for CIDP, I wonder if you could talk a little about, you know, what the functional path forward would be, post proof of concept with batoclimab transitioning into a 1402 study there. And then for subQ in particular, is there a path forward, to potentially having a high dose be a single injection there, at all, with formulation or something like that? But again, congrats on the data. Thanks.
Hey, thanks for those questions, Alex. So I think for CIDP, there's a lot of different, a lot of different options. You know, but most fundamentally, similar to my answer to Yatin, which was a little bit more general, assuming that our registration program for CIDP is with 1402, which is what I said we're probably trending towards, then we need a registrational study with 1402. How we can support that package, make that package most efficient by taking advantage of batoclimab, we have a lot of different, a lot of different ideas there, not the least of which is we have a lot of experience, now, a lot more experience, than we had a year ago running, running CIDP trials and working with investigators, around the world.
In terms of the injection presentation for 1402, our base case assumption is that it will be the same as batoclimab. So we have the standard dose in a single injection, a 2 cc injection with a 27-gauge needle, and that will be adequate for many people in many different indications. And then we can provide maximum IgG suppression with two injections, 2 cc, two 2 cc injections, similar to the way we do it in induction phase for batoclimab. At this point, the data so far in the phase I trial does not suggest that you could get to saturating levels of IgG suppression with a single 2 cc syringe.
Great. Thanks, Pete.
Yep.
Thank you. Our next question comes from Douglas Tsao with H.C. Wainwright. Your line is open.
Hi, good morning, and congrats on the data. Pete, maybe you talked a little bit about how you're thinking about some of the indications ongoing in development in terms of batoclimab versus IMVT-1402. I'm just curious, at this point, are there new indications that you would pursue with batoclimab, or should we think about now those efforts largely being focused on IMVT-1402? Thank you.
Yeah. Thanks for that question, Doug. I think that our primary focus in the near and medium term is likely to be in terms of new indications, likely to be 1402, primarily.
Okay. Great. Thank you very much.
Yeah, you're welcome.
Thank you. Our next question comes from Yaron Werber with TD Cowen. Your line is open.
Great. Thanks for including us and congrats as well. I think in the past, you've talked about having potentially a best-in-class profile, but also potentially having a few indications where you might just be able to be first-in-class with 1402. There's obviously multiple indications, including several that are not being developed yet by the competition. I don't want you to necessarily trump things here, but any sense you can give us which indications you think you can potentially have a fast path to market with? Thank you.
Yeah, thanks for the question, Yaron. I mean, I think, you know, the one we, that I, we can talk about because it's already been talked about is Graves' disease. You know, we can talk a little bit about how we selected that, and that would be a process that we would use to find other potentially first-in-class indications, and maybe not so much find them, but end up prioritizing them. Because I think, you know, the six or seven or eight indications that could well be studied with an anti-FcRn that are not currently in anyone's portfolio of announced indications, those probably aren't a secret to anyone. And Graves' wouldn't have been a secret, I don't think, before we announced it.
But, but, but what led us to have the conviction to start studying Graves', it was really, two things. And, and these are probably the most, two most important things for us, which is our assessment of the probability of technical success, even without any anti-FcRn data, and then secondly, our assessment of the unmet medical need. So in terms of the first assessment, you know, there's no, there's no data in Graves' yet with anti-FcRn, but, but it's a classic autoantibody condition. And so that, that gave us a, a lot of conviction. We also had some hints in our TED 2b trial that I've mentioned on prior calls.
For other indications that are, you know, involve different components of the immune system, the assessment would be a little bit different, but the basic idea is can we triangulate to a conviction on probability of technical success that's moderate, even without any anti-FcRn data? And I think the answer is yes for some remaining indications. Then the second question is equally important, which is our direct assessment of how much unmet need there. And this is something I think that we probably had a different assessment that's different than others, and I think it'll come into focus in a positive way for us.
We spent a fair amount of time, a lot of time actually talking to endocrinologists and even talking to people with Graves' disease to really appreciate that while there are many people who are well served with the existing, cheap, oral, generic anti-thyroid drugs, there's also another large group that is not well served by those medications and is not excited about radio ablation or surgery, which are basically the only other two options. So I think what led us to Graves' was really a deeper look at the patient experience, and that's an approach we'll take to other indications we're thinking about, where we could potentially be first-in-class.
Thank you. Our next question comes from David Risinger with Leerink. Your line is open.
Yes. Thanks very much. So just to follow on Graves', could you please add some additional color on the trial design, you know, key study considerations? And then also, could you please comment on the potential commercial overlap of Graves' with thyroid eye disease? Thanks very much.
Thanks, David. Two great questions. So in terms of the current trial, it's really designed to give us an estimation of the effect size, and effect size to do what? The effect size to take people who are insufficient responders to an anti-thyroid drug, as defined by they are still hyperthyroid in spite of anti-thyroid drug therapy. So they're an insufficient responder, they're hyperthyroid, and convert them to being euthyroid, which means normalize their thyroid hormone levels. That's essentially the definition of hyperthyroidism. You have high T3, T4, high thyroid hormones, and you normalize them, then you don't have hyperthyroidism anymore. So it's a nice condition from the standpoint of the biomarker is also the clinical endpoint.
Since there, as I mentioned, in the last question, there isn't any FcRn data in Graves', then estimating that effect size is an important part of the work you need to do prior to running a pivotal trial. There's some other things we'll learn from that trial that are important as well. In terms of the overlap with TED and Graves', actually, one of the things that drove us to Graves' were the advisory boards that we were running with physicians for thyroid eye disease, where they kept bringing up the idea that while thyroid eye disease is a really exciting indication for an anti-FcRn, Graves' is as well. Patients with Graves' are obviously the ones who get thyroid eye disease.
Graves' patients tend to be predominantly managed by endocrinologists, whereas patients with thyroid eye disease are managed by both endocrinologists and ophthalmologists, or more specifically, often oculoplastic surgeons. So having an anti-FcRn, even if it's two different anti-FcRns, to ultimately treat thyroid eye disease and Graves', provides a lot of kind of commercial and promotional synergy down the road. So that's a consideration for why we find these two indications attractive.
Thank you. Our next question comes from Brian Cheng with JP Morgan. Your line is open.
Hey, Pete and team, thanks for taking my question this morning. One question that we often get is, whether IgG reduction, deeper IgG reduction, will drive better responses and the balancing act of, you know, driving deeper reduction and, potential infection risk. So what, what is your latest view on, you know, those two key pushbacks, that we're hearing and, you know, especially on the back of today's data? Thank you.
Yeah. Hey, Brian, thanks for those questions. They're both really good and important. So deeper IgG reduction has been shown to correlate with more clinical response, essentially everywhere that anyone has looked with any amount of data. So if you look at all of the MG trials that have a difference in IgG reduction, argenx data has been interrogated and published in this regard. The large Phase II study with nipocalimab, Momenta published a strong correlation between depth of IgG reduction and decrease in MG-ADL. Our small 2a study in MG showed the same thing.
The UCB data in ITP, where they had a phase II trial with many different doses, a much wider range of doses than they've studied elsewhere, show the correlation between depth of IgG reduction and improvement in platelets. Our thyroid eye disease 2B trial, which had three doses plus placebo, so four different levels, including the null level of placebo. Pretty much every parameter correlated with dose and depth of IgG reduction. So, you know, in the pemphigus data from argenx as well, had some. They had some different doses in their pemphigus trial. Typically, they've just studied one dose, but their pemphigus trial had different, had multiple doses, and you saw a correlation with a depth of IgG response, and now the Janssen data in RA.
So, so just time after time after time, you see, you see this, correlation between depth of IgG reduction and clinical response. Second point I'd make is I don't think it's a surprise, the, the idea that you get a, a strong clinical response with 50% or 60% IgG reduction, you get a better clinical response with, with 80% IgG reduction. I don't think that's, that's surprising. So you have a sort of a non-surprising hypothesis supported by a, by a lot of data. Given the, severity, a lot of these, a lot of these conditions from a clinical standpoint, then the ability to get incremental efficacy is gonna be highly valued by many patients and, and, and all physicians.
Any individual patient can and should make a personal trade-off on risk-benefit, and that gets to your second question. You know, FcRn is a very selective and targeted immunosuppressant, but it's still an immunosuppressant, so you're likely to have higher rates of infection with deeper IgG reduction. But that's in the context of a mechanism that's really been pretty safe to date across all of the various trials that have been run now.
So I think there'll be a risk-benefit calculation, but the ability to offer, even offer that opportunity for patients to go for deeper, more potent IgG reduction and then have data of whether if there is an increased infection risk or not, and to characterize that, that'll all be, you know, important data that we can generate in our trials that have multiple doses and deliver to physicians, which they're excited about. So net, I see a really, really big opportunity for deeper IgG reduction to be a positive differentiator across this class.
Great. Thanks for taking my question.
You're welcome.
Thank you. This does conclude the question and answer session. Thank you for your participation. You may now disconnect. Everyone, have a great day.