Good morning. My name is Sherry, and I will serve as your conference call operator. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this call is being recorded. Joining me on the call today is Dr. Pete Salzmann, Chief Executive Officer of Immunovant. Before we begin, I would like to remind everyone that today's conference call will include certain 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 products candidate and Immunovant's 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 and uncertainties, assumptions, known and unknown, which would cause actual results to differ materially from those indicated or anticipated. For more information, investors are encouraged to review Immunovant's most recent quarterly report, Form 10-Q filed with the SEC on August 12, 2020. Now I would like to turn the call over to Dr. Pete Salzmann. Thank you, Dr. Salzmann. You may begin.
Thank you, Sherry. I'd like to start off by saying how thrilled we are about the positive clinical results we are announcing today in myasthenia gravis. As the only anti-FcRn therapy in clinical development for myasthenia gravis as a subcutaneous injection, we believe IMVT-1401 has the potential to be life-changing for patients, and we couldn't be happier with the outcome of this randomized, double-blind, placebo-controlled phase II-A trial. In this study, we observed an encouraging safety and tolerability profile, and we observed strong IgG reduction, both consistent with prior studies. In addition, we are reporting statistically significant improvements in clinical efficacy measures, MG-ADL and MGC, observed at six weeks. This was likely driven by the high rate of participants in the treatment arms who experienced a deep clinical response.
For those of you who are following us closely, you will note that this trial had a target enrollment of 21 patients, and prior to March, the trial was on track to hit that number with a Q2 readout. Based on the strong validation of the anti-FcRn mechanism in MG provided by other programs, we decided to unblind the trial with 15 patients having completed the six-week treatment phase. Ultimately, the decision to unblind the trial at 15 patients came down to our confidence in 1401 and our desire to accelerate our phase III pivotal program. Before jumping further into the data, it may be helpful to provide a brief overview of MG, a serious autoimmune condition with a prevalence of about 66,000 patients in the United States alone. There is a bimodal distribution of patients, with younger patients more commonly female and older patients more commonly male.
MG is characterized by weakness of voluntary muscles, including ocular, facial, oropharyngeal, limb, and respiratory muscles. Given that MG is driven by autoantibodies to a known antigen, we believe it is one of the ideal indications for IMVT-1401 from a biological perspective. In 85% of patients, autoantibodies bind the acetylcholine receptor, or AChR. Note that we didn't include MuSK antibody patients in this phase II-A trial, consistent with most other phase II trial designs in MG. Moving on to slide five, you see that our study design included a six-week blinded treatment period with weekly dosing. Other recent anti-FcRn trials have generally used an eight-week blinded treatment period with variable dosing throughout the period. The key inclusion criteria for our trial were designed to enroll a population very similar to other anti-FcRn trials.
Note also that we still have patients completing the open-label extension and follow-up periods, which will allow us to observe the durability of response and the pharmacodynamic effect of 340 milligrams administered every other week. Though we don't yet have that data available, we look forward to sharing it along with the complete study results at a future medical meeting and ultimately in a peer-reviewed journal. On the following slides, I will review the results from the six-week treatment phase of this trial. I would also like to mention that our pre-specified statistical analysis plan called for pooling the treatment arms with regard to efficacy scales so that we could compare 10 treated patients to five placebo patients. On slide six, you see the baseline characteristics for participants in the trial.
These baseline values are very much in line with recent phase II and phase III studies of other anti-FcRn agents in MG. Our population was very much in the middle of the moderate to severe range, with 60% characterized as Class 3 MGFA in both groups. Baseline QMG, MG-ADL, and MGC values were balanced. Recall that we had an inclusion criteria on QMG only. Some other trials have used an MG-ADL inclusion threshold, and some have used cutoffs for both scales. Nevertheless, all trials are similar on the mean baseline values in the primary MG scale. As I mentioned in the disease overview, MG tends to affect younger women and older men, and you can therefore see age and gender tracking together. It's important to note that disease severity and response to treatment have not been reported to vary by age or gender among anti-AChR positive patients.
At the bottom of the slide, you see that patients in each arm were also balanced with regard to background therapies. Turning to slide seven, in line with our prior results, IMVT-1401 was observed to be generally well-tolerated with no grade three treatment emergent adverse events, no withdrawals due to adverse events, and no imbalances in specific AEs. Reductions in albumin were also consistent with prior studies, with a 16% reduction observed in the 340 milligram arm and a 26% reduction observed in the 680 milligram arm. All albumin reductions were asymptomatic. On slide eight, you see that mean reductions in serum IgG levels were in line with our prior phase I results in healthy volunteers. The average IgG reduction from baseline following six weekly injections of 340 milligrams was 59%, and the average IgG reduction from baseline following six weekly injections of 680 milligrams was 76%.
Now slide nine. These are beautiful graphs. MG-ADL hit statistical significance in a pre-specified analysis examining the mean change in MG-ADL at the end of the six-week treatment period, comparing the combined 1401 treatment arms to placebo. The P value for this comparison was 0.029. A reduction in MG-ADL began early in the six-week treatment period and increased over time, achieving nearly four points by week six. In terms of MG-ADL responders, defined as participants achieving an improvement of two or more points on the MG-ADL at week six, we observed a response rate of 6/ 10 in the pooled treatment group and one out of five in the placebo group. The percentage of responders was similar across the two doses.
Before diving into additional clinical efficacy results, I want to take a minute to discuss the myasthenia gravis composite, or MGC. In recent trials, MG-ADL and QMG have received greater attention. MG-ADL is a patient-reported outcome and will remain very important as it is currently the preferred regulatory endpoint in the U.S. QMG is a physician assessment often used to complement MG-ADL. It has a couple of limitations that may reduce its importance over time. MGC, on the other hand, is likely to become more prominent. It was developed by selecting the best-performing items from both patient-reported and physician-led assessments. It is comprised of 10 functional domains, three ocular, three bulbar, one respiratory, one neck, and two limb items. For the MGC score, the individual items are weighted based on importance to patients and physicians so as to accurately reflect what is most clinically meaningful. Turning to slide 11.
As all three scales are currently important, here we're showing mean improvement in each scale at the end of six weeks. This is also called mean change from baseline. Changes are shown for both placebo and for the pooled treatment group. For MG-ADL, a reduction of 3.8 points was seen in the treatment group, and that was statistically significant as previously noted. For QMG, a reduction of 3.9 points was seen in the treatment group with a P value of 0.068 compared to placebo. Finally, on the MGC scale, a reduction of eight points was seen in the pooled treatment group, and this was quite significant with a P value of 0.006. Slide 12 is another really exciting slide. At Immunovant, our vision is to enable normal lives for patients with autoimmune diseases.
Getting back to normal requires a very strong clinical response, a response larger than the minimum threshold for a clinically meaningful change. For example, a change of two points is considered clinically meaningful in MG-ADL. We wanted to evaluate 1401 with a higher threshold of six points. Setting the bar this high, we saw 40% of treated patients and 0% of placebo patients achieve a deep response on MG-ADL. These same four 1401-treated patients achieved a deep response on MGC, defined as a 10-point improvement, since the MGC has a broader range. No placebo patients achieved a deep response on this scale. In summary, based on the top-line results, we observed a statistically significant 3.8 point mean improvement on the MG-ADL at six weeks and a highly statistically significant eight-point mean improvement on the MGC. Results that were driven by a deep responder rate of 40% on both scales.
On the safety and tolerability side, our results were consistent with prior phase I and phase II results for IMVT-1401, namely no severe adverse events, no withdrawals due to adverse events, and a rate of mild to moderate adverse events that was well-balanced with placebo. Turning to slide 14. We previously shared that we would update our clinical trial guidance in Q3, which I will do now. With regard to MG, we anticipate meeting with the FDA to review the phase II-A data shared today and then starting our phase III trial in the first half of 2021. Our thyroid eye disease phase II-B trial remains on track, and we expect to share results in the first half of 2021.
This guidance remains unchanged as the trial is benefiting from European sites that have come back online faster following the Q2 pandemic shutdown that impacted many sites globally for new patient enrollment in clinical trials. For our ASCEND-WAIHA trials in warm autoimmune hemolytic anemia, we now expect results from the high-dose cohort in the first quarter of 2021. Finally, I want to use this opportunity to share with you that we are expecting to announce three new indications over the next 12 months. We see tremendous potential for IMVT-1401 to enable normal lives for patients with autoimmune diseases, and we are therefore excited to significantly expand our portfolio of indications. With that, I'll ask the operator to open the call for Q&A.
Thank you. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would 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. Our first question is from Brian Skorney with Baird. Please proceed.
Hey, good morning, guys, and congrats on the data. It looks really clean. I know it's early after these data, and you still have to have a discussion with the FDA about phase III plans, but should we just expect, we've seen some phase III in the space. Should we just expect a standard maybe like argenx-like phase III study here? Or is there anything unique that you guys are thinking about in terms of phase III clinical trial design? Just on the albumin side of things, I know in Momenta's study, they saw a rebound after cessation of drug. Did you guys see the same things here?
Hey, Brian. Thanks for those questions. First of all, with regard to our phase III trial design, I want to make three points. First of all, I'm very excited by the profile of both doses. Secondly, we plan to take the 680 forward, thought leaders with whom we've been consulting have some really interesting ideas for optimizing our protocol. I'm not going to share all those today. That's the third point, that we'll be discussing those with the FDA, after we have those discussions, then we'll release some specifics. I'm excited about our phase III design. I think it's going to have some unique aspects enabled by the two doses and by the fact that we're in the clinic with a subcutaneous injection.
To your second question, in terms of albumin, the data that we're discussing today that we have locked is only through the first six weeks, and patients were treated, if they were in the treatment arm, for that entire six weeks. I don't have the data to answer that question today.
Thanks, congrats again.
Thank you.
Our next question is from Thomas Smith with SVB Leerink . Please proceed.
Hey, guys. Good morning. Thanks for taking the questions and congrats on the top-line data. First, can you just talk a little bit about the consistency of the IgG reductions you observed in the patients in the study, and then how closely those seem to correlate with the clinical improvements on MG-ADL or QMG?
Thanks, Thomas. The consistency was tight, similar to what we saw in our phase I study in healthy volunteers. Generally, it's a little bit tighter in the 680 arm, but the reduction in IgG is pretty consistent by dose. In terms of the correlation between IgG reduction and response to clinical scales, obviously in the Momenta trial, where they had a much wider range of doses and therefore a much wider range of IgG reduction, they were able to show that correlation between IgG reduction and clinical scales that I think is well-validated. We only have, at this point, six weeks of data and with a narrower range of IgG reduction. I can't answer the question today whether we saw that in our trial or not, but I would certainly expect that, and I think that's validated for the class.
Got it. I guess I know obviously the extension portion of the study is still ongoing here, can you just talk, I guess, about your preliminary plans to present some of the detailed data from this study and maybe any update on plans to present detailed data from the phase II-A ASCEND-GO study?
Yeah, absolutely. Thanks for those questions. All of the live medical conferences being shut down and only some of them changing to virtual has certainly reduced the number of conferences to present this kind of data. With regard to the phase II-A data from the thyroid eye disease, we do have one data point that's required to be done in a live lab, and we're waiting for that to be finalized. They've had some delays due to COVID in terms of running that final analysis. Once we have that, then we'll have the entire data package from the phase II-A TED trial, and we'll get that information out. With regard to this trial, as I showed in the trial overview, there are these three periods, and the open label extension and the follow-up off treatment, those are still ongoing.
We need the patients to get through those phases and then collate all the data before we can present that. Again, we'll target a standard medical meeting within neurology for that information.
Got it. All right, great. Thanks, guys. I appreciate you taking the questions. Congrats on the data.
Thanks, Thomas.
Our next question is from Stan Plotkin with Lakeside Capital. Please proceed.
Hey, thanks for the questions and congrats on the update. I guess first off, just given the data from 1401 and then other FcRn inhibitors at this point, it'd be great just to hear your take on where you see these likely be used in the treatment paradigm as well as what you're hearing from physicians
Thanks, Stan. It's funny, classically, the treatment paradigm for many conditions and myasthenia is often listed by lines of therapy as if they're independent milestones, first line, second line, third line, fourth line. I think in reality, for a lot of these chronic autoimmune conditions, patients cycle around between steroids and the broad-spectrum older immunosuppressant therapies. Neither of which achieve a very strong outcome from an efficacy standpoint in most patients, and most of which have a lot of tolerability issues. I think as newer agents and anti-FcRns in particular that are showing it preliminarily, I think a really nice benefit-risk come to the market. I think they're going to move to the front of the line. Patients want to feel normal.
That's what we hear when we talk to patients individually or in market research, and I think they're much more likely to achieve that on a product like 1401 than on those older therapies. That's where I see them being used, more upfront over time. Of course, at launch, they're going to be used in patients who have failed other therapies. Over time, I think patients are going to want to use them early in their therapy.
Okay. Obviously not every patient's going to respond to every treatment. Just looking at your MG-ADL curves, it looks like obviously it's improving up to week 35, kind of plateauing. For the non-responders, are you seeing any kind of continued improvement there? Is there potential for additional responses, you think, over time? I'd love to just hear about the kinetics of their response.
Right. Again, with only six weeks of data, it's a little bit hard to answer that with a lot of certainty. Absolutely, at the group level, what you pointed out is very true, which is we see a trend to increasing response over time. I think that actually makes a lot of sense. When patients begin therapy, they've obviously had autoantibodies binding, in this case, their acetylcholine receptor for quite some time. It's going to take a little time for patients who have higher antibody titers, and particularly probably to not only clear those antibodies, but then have the inflammation at the neuromuscular junction resolve, and then they have to make new acetylcholine receptors at the cellular level before their muscle function is going to return. I think we're going to see some variability in time course.
That's not something that's going to happen in every patient quickly. You do see in some patients a rapid response, which is tremendous, but other patients probably are going to take a little bit longer. I think that's likely to be the case with longer trials, that you see those patients who don't respond initially responding over time.
Okay, great. Lastly, too, just for the open-label extension and then follow-up periods, remind me what the goal is in terms of that portion of the study and then for the follow-up? Are patients still being monitored for response or what are you looking at there as well? That's the last question.
Sure. Thanks for that question, Stan. The open-label extension has a dosing regimen of 340 milligrams every other week. That's first and foremost a pharmacodynamic trial to really expand our understanding of our pharmacodynamic profile, which could be useful for any condition. It's not really so specific to myasthenia, this particular regimen of every other week. It will enhance our pharmacodynamics models, and that'll be helpful across anything we would study. The follow-up period off treatment, that is designed to see what happens to things like albumin and IgG and clinical response once patients are off treatment, asking questions like durability of response and things like that. Honestly, I think the much, much, much more important questions are going to be answered in phase III. Look, I think we know that anti-FcRn works in MG.
That's why we decided to unblind this trial with 15 patients and even in this study with 10 patients in the treatment arm and five in placebo, we saw a statistically significant response and a strong rate of responders and deep responders. We know it works. Now it's a matter of plotting out how do patients best benefit over time, and you really need the phase III trial for that.
Got it. Thanks, and congrats again.
Thanks, Stan.
Our next question is from Douglas Tsao with H.C. Wainwright. Please proceed.
Hi, good morning. Thanks for taking the questions. Obviously we've seen sort of some different paradigms being looked at in MG in terms of sort of the continuous dosing or as argenx sort of characterized the sort of customized individualized dosing. Just given your subcutaneous presentation, which obviously makes it very easy for patients to dose, do you sort of have a bias one way or the other sort of in particular sort of towards the more regular dosing, which seems to sort of offer simplicity?
Hey, thanks for that question, Douglas. I absolutely have a bias, and it's driven by the patient needs. Myasthenia is a chronic condition, and patients with chronic immunology, autoimmune diseases, again, they don't want to feel normal just for six or eight weeks. They want to feel normal for ideally the rest of their life, right? That's the first point. Secondly, in terms of the biology of myasthenia, I don't see any evidence that anti-FcRn therapy puts patients into remission. You remove the offending pathogenic IgG, and they improve, and then when therapy is withdrawn, the pathogenic IgG comes back, and the symptoms return. Starting with what patients need, I think patients need a safe and effective way to chronically suppress their pathogenic IgG and therefore a safe and effective way to deliver a sustained clinical response. That's what patients need.
Now, we have a subcutaneous injection in clinical development. That's a dosage form that is really well-aligned with the patient needs because it can be given chronically. I agree with you that chronic dosing is the way to go. It really starts with the patient needs.
Great, and congratulations on the data. Just maybe one quick follow-up, and I'm sorry if I missed it. I know there weren't any MuSK patients in this data set. Do you anticipate enrolling any MuSK patients in the phase III?
Yeah, no, thanks for that question, Douglas. You didn't miss it. I didn't say it before. We do anticipate that. We haven't finalized our phase III trial, but I think that's a really important subset of patients with myasthenia. We did not include them in this trial, primarily because it was a smaller phase II trial, and we wanted to have maximum ability to compare to other trials within the anti-FcRn space, the phase III trials, most of which did not have MuSK patients. MuSK patients will very likely be in our phase III program.
Okay, great. Congrats on the data again.
Thanks.
Our next question is from Gbola Amusa with Chardan. Please proceed.
Hi, Gbola Amusa from Chardan. Thanks for taking my call and congrats on stat sig, which is 10 treated patients. I have two big-picture questions. First is on the recent acquisition in the space, just given that for context. Can you update us on how you think about whether or not a company sale is among the many long or short-term scenarios for management to return value to shareholders? The second is, just wanted to understand whether the announcement that you will have three new indications was informed by the data you just presented. Was it a coincidence or did it give you the confidence to pursue new indications?
Thanks, Gbola. I think, in terms of the first question, creating value in immunology starts with having an asset that strongly meets a patient need. I think that's the absolute most important thing, and we have that. I'm confident that we can create a lot of value. We've shown an ability to, even as a small company, execute clinical trials effectively, and we'll continue to do that going forward. Our plan is to bring this product to market. I'm super excited about that, and I don't have any hesitation with our strategy, which is to develop into a fully functioning commercial and development biotech organization. That's the first point. I guess, the answer to the second question actually relates to that as well. I think in terms of the timing of announcing our three new indications, absolutely, we're bolstered by this data.
It's very exciting. To be honest, we've been working on what those indications might be for quite a while. Over the course of this year, we've just seen multiple consistent data readouts validating the potential of the anti-FcRn class across a wide variety of indications. For 1401, we've now seen proof of concept in two indications. It kind of all comes together. This is an exciting class, and we're very excited about our assets. We're ready now to make the commitment to broaden our portfolio of indications, and I'm really excited about that.
Great. Thanks.
Thank you, Gbola.
Our next question is from Danielle Brill with Raymond James. Please proceed.
Hey, guys. Good morning. Congrats on the data, and thanks for the question. Just a quick one from me. Since you mentioned that you're moving forward with a 680 milligram dose, is it safe to assume that you saw a higher percentage of deep responses in MG-ADL in this arm, or was this a decision that was already made before you even had the data generated?
Great question, Danielle. I think the most important data point to answer that question is the statistically significant relationship between IgG reduction and clinical response across different scales that Momenta demonstrated in a trial that was really nicely designed to show that because they had a lot of different doses, therefore a broad range of IgG reduction. I think we know that stronger IgG reduction leads to stronger clinical response, which is not surprising to me at all in a population that has varied degrees of baseline severity. I think that's the most important thing. With regard to our responder rate, I mentioned that those were similar, the 60% response we saw in the pooled treatment group. We actually saw that same response rate in both the 340 and the 680 arms.
There's a lot to be excited about with both doses in this data set.
Understood. Thanks so much. Congrats on the data.
Thank you, Danielle.
As a reminder to star one on your telephone keypad if you would like to ask a question. Our next question is from Robyn Karnauskas with Truist Securities. Please proceed.
Great. Thank you, guys, and congrats on the data. I was just thinking outside the box. Now that we have data from three companies.
Data looks somewhat similar. Now that you have all the information, that you know your drug is potent, can be given sub-Q in a very convenient way, how do you think about what is most important for designing phase III so that you look differentiated from a commercial standpoint? I know it's kind of a weird question because I know you're focused on efficacy and making sure you get the drug approved, but the class is maybe direct. How do you think about that going forward? My other question was more to the point of, do you think the speed of enrollment for the WAIHA trial, how is that going? You said you're now going to have data in the first quarter. Is there some impact from COVID? Are you seeing more accelerated enrollment now that we're going through the back half of the year?
Just color on timing of these trials, and if you think they'll start to speed up over time. Thank you.
Thanks, Robyn, for those two questions. They're good ones. With regard to designing the phase III trial, I think, as I said, we're going to do that based on where we think we can deliver the greatest patient need. That said, I think we have two really nice levers that we can use creatively to design a tremendous protocol and finalize that in discussion with the FDA. Those two levers are that we have the two doses, and that both doses can be given as a subcutaneous injection. That allows us flexibility across a range of disease severity and allows us to chronically dose patients easily. We're going to maximize the use of those two levers to design a phase III protocol that I think is going to be really exciting for a wide range of patients with myasthenia.
In terms of warm autoimmune hemolytic anemia, you're right that guidance moved from the second half of this year into the first quarter of next year. That trial is enrolling. We have patients who are dosed and COVID is impacting that trial to some extent, but it's on track for the first quarter, which I think is a pretty good accomplishment given everything that's happened over the last three to four months. Most importantly, I'm really excited about the potential clinical benefit in warm autoimmune hemolytic anemia as well, because thinking about the treatment paradigm there, you're looking also at primarily high-dose steroids, which work, but when they're tapered, because you can't treat patients long term with high doses of steroids, then many patients recur.
They end up in this zone where they're on a moderate dose of prednisone, and they still maybe need occasional transfusions, and they're still not back to normal from the standpoint of their hemoglobin and therefore, in terms of how they feel. The only therapy that's really, really effective in getting patients back to a very close to normal hemoglobin reliably is splenectomy. Splenectomy has fallen out of favor for a lot of different reasons. We see splenectomy as kind of a potential analogy to treatment with an anti-FcRn therapy because the spleen basically removes the red blood cells that are covered with pathogenic IgG.
If we can get the pathogenic IgG off the red blood cells with the anti-FcRn therapy via 1401, then that might be like a monoclonal antibody treatment that's very similar to splenectomy and therefore has the potential for a really large effect size. That's what we're hoping for in warm autoimmune hemolytic anemia , and I think if we see that's going to be a very, very exciting indication.
Great. Thank you.
Thank you, Robyn.
We have reached the end of our question and answer session. I would like to turn the conference back over to Dr. Salzmann for closing remarks.
Thanks, Sherry. I'm just going to briefly say that, again, we're just very, very excited about the results that I shared today and really, really excited about the potential for 1401 more broadly. Not only in the three indications we're currently studying, but in the three indications we expect to announce over the next 12 months. A lot of exciting things going on and with that, I will close the call. Thanks, Sherry.
Thank you. This does conclude today's conference. You may disconnect your lines at this time and have a pleasant day.