Immunovant, Inc. (IMVT) Earnings Call Transcript & Summary

Good morning. My name is Sherry, and I will serve as your conference call operator. [Operator Instructions] As a reminder, this call is being recorded. Joining me on today's call will be Dr. Pete Salzmann, Chief Executive Officer of Immunovant. Before we begin, I would like to remind everyone that today's conference call will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not guarantees of future performance and are subject to various risks, 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 February 14, 2020. I would now like to turn the call over to Dr. Pete Salzmann. Thank you, Dr. Salzmann, you may begin.

Thank you, Sherry, for that introduction. I would like to start off by expressing how thrilled we are about the positive clinical results we are announcing today in thyroid eye disease. As the only subcutaneous therapy in clinical development for thyroid eye disease, we believe IMVT-1401 has the potential to be life-changing for patients, and we couldn't be happier with the outcome of this small proof-of-concept trial. Prior to seeing this data, we believed there was strong biologic plausibility for using an anti-FcRn agent in thyroid eye disease. Now with this data, we have the first clinical proof-of-concept using -- of an anti-FcRn agent in thyroid eye disease. For those of you who are following us closely, you will note that our press release described results for 7 patients. Although we initially planned to enroll 8 patients in ASCEND GO-1, the eighth patient enrolled in ASCEND GO-2 instead of ASCEND GO-1 at one of our 4 Canadian sites for this trial. All 4 of the Canadian sites are now converting to ASCEND GO-2 sites. I also want to note that following my discussion of the ASCEND GO-1 results, I will provide a brief update with respect to the COVID-19 pandemic. I will now turn your attention to Slide 9 of our deck -- Slide 5, excuse me. Before jumping into the data, I thought it would be helpful to provide a brief overview of thyroid eye disease, a serious autoimmune condition with an incidence of 15,000 to 20,000 patients per year in the United States alone. Also known as Graves' ophthalmopathy or Graves' orbitopathy, thyroid eye disease is characterized by a pronounced bulging of the eyes, known clinically as proptosis. Eye pain, double vision, known clinically as diplopia, and light sensitivity are also common. Thyroid eye disease isn't an ocular disorder per se, rather the tissue around the eye is particularly vulnerable to inflammation in patients with abnormal thyroid function due to stimulating auto antibodies. In ASCEND GO-1, we sought to minimize variability by restricting enrollment to thyroid eye disease patients who also have Graves' disease. For thyroid eye disease in the context of Graves', we believe that retro-orbital fibroblast activation occurs downstream of the stimulating -- stimulatory auto antibodies directed at the thyroid-stimulating hormone receptor and/or at the insulin-like growth factor receptor. On Slide 6, as you can see in the classic curve, first described by Francis Rundle in 1945, the disease has 2 phases: an active phase; and a static phase. During the active phase of the disease, the orbital tissue is inflamed, resulting in redness, swelling, eyelid retraction, orbital pain and general discomfort. Following the active phase, which often lasts a couple of years, the inflamed tissue gives way to fibrotic tissue. In the inactive fibrotic phase, patients are no longer responsive to medical therapy and are left with the long-term manifestations of the disease, including proptosis, diplopia and occasionally, strabismus, meaning patients cannot align their eyes in the same direction. Once a patient has reached this point, surgery is usually the only option. The best time to intervene to alter the natural history of the disease is during the active phase, as we've indicated here with the dark blue dotted line. In ASCEND GO-1, we included only patients in the active phase. Turning to Slide 8. Our Phase II program in thyroid eye disease consists of 2 trials. ASCEND GO-1, the results of which I will be reviewing today, is an open-label proof-of-concept study taking place in Canada. This study primarily uses our lower dose of 340 milligrams, supplemented by 2 680-milligram loading doses. The treatment duration in this study is short, just 6 weeks. Our larger Phase II program, which is already up and running, is testing 3 dosing regimens, including a higher-dose regimen of 680 milligrams delivered weekly by subcutaneous injection. This larger study has a 12-week treatment period. As I mentioned earlier, a planned eighth patient was enrolled in ASCEND GO-2 instead of ASCEND GO-1 based on the investigator's and patient's decision. Turning now to Slide 9. ASCEND GO-1 is the first trial of an anti-FcRn in thyroid eye disease. We had 2 major objectives for this trial: first, the study was designed to test the pharmacodynamic response to a loading dose regimen; second, the study was designed to examine the initial safety and efficacy of IMVT-1401 in thyroid eye disease. Patients were treated with 2 weekly 680-milligram loading doses, followed by 4 weekly 340-milligram maintenance doses for a total of 6 weeks of treatment. Further study protocol, all patients included were positive for antibodies directed at the thyroid-stimulating hormone receptor. To measure clinical improvement in thyroid eye disease, we used 3 scales. Proptosis is really the hallmark feature of this disease and can be measured using a device called an exophthalmometer, pictured here at the top of the slide. To measure double vision or diplopia, we used a standard clinical assessment called the Gorman diplopia scale. To capture improvements in other dimensions, such as pain, eyelid abnormalities and redness, we used the Clinical Activity Score, which is also a standard assessment conducted by a trained health care professional. One point is given for each of 7 abnormalities. Slide 11 is just to show you the baseline characteristics for the 7 patients in our study. Note that our patient sample was very similar to the patient populations that have been studied in other recent trials for novel agents to treat thyroid eye disease. In particular, the average CAS or CAS score and the average proptosis value are very similar to other studies. On Slide 12, we've provided a high-level summary of our clinical observations from the treatment phase of the study. Note that all patients have entered the follow-up phase, and we will be sharing much more data when the study is complete. 57% of patients improved by 2 or more points on the Clinical Activity Score or CAS. 43% of patients were CAS responders, defined as having achieved a CAS score of 0 or 1. 43% of patients were also proptosis responders, defined as improving 2 or more millimeters in proptosis in the study eye without significant deterioration in the fellow eye. At the bottom of the slide, you see that 6 patients had baseline diplopia, and 4 of these 6 patients with baseline diplopia saw an improvement. In addition, 2 of these patients achieved a status of no diplopia. I want to emphasize that we are very encouraged by the 43% proptosis response rate. The 3 proptosis responders were also CAS responders and all 3 showed improved diplopia. This consistent clinical effect across different parameters really speaks to a biological response. Turning to Slide 13. As a reminder, the primary end points of the study were safety and tolerability, change from baseline levels of anti-thyroid-stimulating hormone receptor antibodies, total IgG levels and IgG by subclass. Of these primary measures, the anti-TSHR antibodies and IgG subclass results are not yet available. We're looking forward to presenting those laboratory results at an upcoming medical meeting once the study is complete. What we do have available today to report is that the average reduction in total IgG levels was 65% from baseline to the end of treatment, right in line with where we had modeled it for the regimen used in this trial, indicating that thyroid eye disease patients responded similarly to healthy volunteers on this parameter. We are also pleased to report that the safety and tolerability profile we observed in ASCEND GO-1 was in line with our expectations from our Phase I study in 99 healthy volunteers. We saw no serious adverse events or SAEs, no withdrawals due to adverse events and no headaches were reported in this trial. All adverse events were mild or moderate. For albumin, we observed an average reduction of 24%. Albumin changes were asymptomatic in this trial as they were in Phase I. Finally, I wanted to use this opportunity to briefly address the global COVID-19 pandemic. Many clinical trial sites in North America and Europe have halted new enrollment in nononcology trials. At these same sites, visits are generally proceeding for patients who are already enrolled in the clinical trial. However, in certain cases, the key staff member or the principal investigator or the patient may not be able to go to the site, and this can interrupt the schedule of events in a trial. So what are we doing to ensure patient safety and to ensure trial quality? Several things. First, we are ensuring communication lines remain wide open between our sites and our staff. Our clinical operations team has a great depth of experience and is proving to be a valuable resource for our sites. Second, we are monitoring our trials very granularly. Our team understands where every patient is on the clinical trial journey. They know which visit is coming up, which tests are needed and what is going on in a particular geography. Third, we're staying abreast of evolving guidance from regulatory agencies that emphasizes patient safety, flexibility within certain guardrails and very good documentation. Finally, we are working with our partners to ensure we have backup services in place, working to get ahead of the need as much as we can. Understanding the situation is still fluid and subject to change. Our current estimates with respect to our programs are as follows. For the myasthenia gravis Phase IIa study, earlier this month, the trial was on track to easily hit our Q2 guidance based on actual enrollments, plus scheduled randomizations, plus patients in screening and prescreening, even accounting for some prescreen failures. However, based on the current environment, we now expect a Q3 2020 data readout. Warm autoimmune hemolytic anemia Phase IIa study. Results are currently still possible for the high-dose cohort by the end of 2020. We expect to have more clarity on the timing for this study by Q3 of this year. Thyroid eye disease Phase IIb study. Results are still possible in the first half of 2021. This study does have a meaningful number of European sites, which could prove challenging, depending on how the enrollment environment evolves there. However, I expect the positive results we're announcing today to be a tailwind. In other words, now that our Phase IIa initial results are available, we are hopeful we'll be able to reaccelerate enrollment once our sites in Europe and North America recover. We expect to have more clarity by Q3 of this year. To conclude my remarks on ASCEND GO-1, I just want to say again that we're absolutely thrilled with these results. Ophthalmologists are not generally equipped to deliver intravenous infusions, but we think a safe and effective subcutaneous therapy would fit their practice pattern as well. Of course, patients prefer convenience, too. Yesterday, we had only -- we had the only subcutaneous therapy in clinical development for thyroid eye disease. Today, we have that, plus a strong proof-of-concept across a range of important safety and efficacy parameters in thyroid eye disease. With that, I'll ask Sherry to open the call for Q&A.

[Operator Instructions] Our first question is from Gbola Amusa with Chardan.

It's Gbola Amusa. And congrats on the hit here with the top line. Just a quick question on clinical meaningfulness of the results with regards to CAS proptosis response and diplopia. Can you talk a little bit more about what these signals mean at least to patients? And then second is just does this go against natural history? We saw the Rundle's curve, et cetera, but for the duration of this study, do these results on those end points go against natural history?

Thanks, Gbola, for those questions. In terms of the clinical meaningfulness, patients experienced a tremendous amount of morbidity due to the pain in proptosis and also due to the double vision or diplopia. Double vision, in particular, I think is maybe under-recognized as a source of patient morbidity outside of the ophthalmology community. Ophthalmologists clearly recognize it, but when you're not able to remove double vision from your daily life, it just really impacts your ability to work, your ability to spend time with your family. It's probably one of the higher-impact symptoms from a quality-of-life perspective. Obviously, the proptosis is something that patients complain about from an appearance standpoint, but it can also impact the ability of -- or it can cause them to have an inability to close their eyelids, and that can cause drying of the eyes or even corneal abrasions if they scratch their eyes. So there's a lot of patient morbidity caused by the proptosis as well as the diplopia. Those 2 features are measured across the clinical scales. So obviously, the diplopia scale and proptosis directly measure those 2 features. But the Clinical Activity Score also includes 2 elements of pain and then a variety of elements of swelling and redness. So improvements across these clinical scales, I think, really correlates to tremendous improvement in the -- in how patients are feeling. And I think that's been validated by other agents in development for thyroid eye disease. In terms of the natural history of thyroid eye disease, I think it's a really interesting question whether the natural history will be altered or postponed. And what I mean by that, and I think this is getting at your question, Gbola, is whether when interventions during the active phase of treatment have an impact, does that mean that the Rundle's curve is shifted out to the right so that with withdrawal of therapy, there will be a return of the active phase? Or will the initial active phase be flattened and that chronic phase will occur at the same time period but with a lesser impact? Practically speaking, what that means is I think there's an open question with regard to whether patients will need a shorter term of therapy or a longer course of therapy in order to really achieve what they're looking for, which is a long-term result. The nice thing about having a medication that's available by subcutaneous infusion is it will allow us in our Phase III program to test that hypothesis and treat patients for a longer period of time and determine if that makes a bigger difference in terms of their long-term benefit.

Great. And just a really quick question on COVID-19. I know these are unprecedented times, but when you complete enrollment on future studies, might you put out a release showing that a trial was complete or to be determined?

Yes, I think that's to be determined. I think we'll see how things evolve over the next -- even the weeks or short months, and then we'll see where we're at.

Our next question is from Thomas Smith with SVB Leerink.

And congrats on the data. First, can you just give us a sense, either quantitatively or qualitatively, of how quickly you're seeing the proptosis responses observed in these patients?

Yes. Great question. So the -- for the patients who achieved a proptosis response, so they achieved that 2-millimeter or greater improvement, what we saw in those curves is essentially a steady improvement, so the curves just kind of keep going down. And it looked like at the end of treatment, they were still headed in the downward direction, which is not surprising because that's what's seen in other trials as well.

Okay. And then, I guess if you could just give us your thoughts about how you're thinking about dosing going forward. This is obviously a pretty unique dosing regimen, and you're using a different dosing regimen in the Phase IIb study. But can you just give us your thoughts on how you're thinking about dosing going forward?

Yes. For sure. So I think the Phase IIb program is closer to how we're thinking about dosing going forward. And what I mean by that is a straight dose during the treatment period. Obviously, that program also tests a higher-dose regimen. The IIa program is really closer to the lower-dose regimen. It does have 2 loading doses of 680 milligrams, which more quickly get the patient to the trough level. But the total IgG reduction was modeled to be very similar to what we saw in the 340 cohort and the multiple-ascending dose trial in healthy subjects, and that's, in fact, what we saw. Why did we do the loading dose regimen in this IIa trial? I think it was as much to learn more about our pharmacodynamic profile as a way to consider loading dose across a range of different indications. It wasn't so much specifically geared to provide insight into the treatment only of thyroid eye disease. So long story short, we're not going to make any changes to the IIb program. I think we want to see, in that program, if there's a difference in efficacy with longer therapy, which we expect, but also with a higher dose, the 680 compared to the 340. And I think that study will really be much more informative in terms of what is the appropriate long-term dosing regimen for patients with thyroid eye disease.

Right. Okay. And maybe just one last question. Just as you're looking through kind of the baseline characteristics for these patients, is there anything that jumps out as to why some patients may have responded better than others with 1401? Like were there any response trends in patients who didn't achieve clinical response?

Right. So in terms of the hard metrics of proptosis responder and Clinical Activity Score responder, meaning those patients who achieved either a 0 or 1 on Clinical Activity Score or 2 millimeters or more on proptosis, right, that's where we had a 43% response. However, the response on more leading indicators, such as an improvement of 2 or more points on the Clinical Activity Score, or for that matter, any improvement on the Clinical Activity Score, there were more patients who fell into that category of achieving some response but not meeting the hard end point. So we had 57% or 4 out of 7 who achieved a 2-point improvement on CAS, and actually 6 out of 7 achieved at least a 1-point improvement on the CAS. And each of those Clinical Activity Score metrics is a meaningful symptom to reduce. So I think based on all that, plus the natural history we've seen from other trials, we would expect that with longer duration of therapy, you're likely to see the number of patients and percentage of patients who hit those hard end points go up. In terms of being able to predict who responds and who doesn't, I think that's a very interesting question. We'll be very interested to see the results of the anti-thyroid-stimulating hormone receptor antibody titers and whether there's any correlation there. Of course, in a relatively small study like this, it's going to be somewhat hard to tease out the difference between responders and nonresponders, particularly because you clearly wouldn't expect anywhere close to 100% responders in a short study like this anyway.

Our next question is from Christopher Marai with Nomura Instinet.

And congrats on the data. I was wondering, first, if we could touch upon the IgG reductions. I was wondering, you saw mean at 65%. How does that compare to the trough level that you observed? And I have a follow-up.

Right. So just to -- that's a great question, Chris. Just to be clear, the mean is the mean at the end of treatment, which is the trough. So for these 7 patients, the mean change from baseline from treatment begin -- initiation to the end of treatment was a 65% reduction, which is what we expected for this particular dosing regimen based on pretrial pharmacodynamic models. Did I get your question correct, Chris?

Yes. I think so. I guess we were wondering if perhaps you saw lower levels at time points prior to the end of the study. But I suppose, how many data points do you have between baseline and the end of the study period?

Yes. So we have weekly values, and what you see again with that 680-milligram loading dose is you get faster to that sort of 60% to 65% reduction range than you would if you had given 340 milligrams the whole time based on models. And then that 340-milligram weekly dose maintains the 65% response. Again, recall from our multiple-ascending dose trial in healthy subjects in Phase I, we saw a 63% reduction from the 3 -- in the 340-milligram cohort. So that's essentially spot-on what we would have expected with the lower-dose regimen.

Okay. Great. Then just with respect to some of the clinical data, the diplopia, I was wondering if you could comment on how response was defined. I guess you presented that patients saw an improvement in it, but how did you define that improvement?

Yes. Great question. So we defined improvement as in as a change of one or more grade, and that's the same definition of response that has been used in other trials when they report an improvement in diplopia. So one grade or more change on the Gorman diplopia scale.

Great. And then with respect to the proptosis, the change -- the median change in millimeters, did you have that data? I don't recall if it was...

We haven't reported that yet. We're saving that for the more robust complete data package that we'll share at an upcoming medical meeting.

Excellent. Then just on safety, the albumin, you saw an expected reduction. I thought we saw that come back up in prior trials. Have you started to note that recover as well? And at what time point might you expect that to recover?

Right. So not everyone has gotten fully through the follow-up phase, and a few folks are relatively early in that follow-up phase. But there are 2 patients that have gotten all the way out to 18 weeks or close to it. And the curves in terms of the recovery of albumin were similar to what we saw in the Phase I trial. So you see a recovery in about 4 to 6 weeks after dosing has completed back to normal.

Great. And congrats on meeting your guidance.

Yes, thanks.

Our next question is from Sam Slutsky with LifeSci Capital.

And congrats on the update. Most of my questions were asked, but just looking forward to the Phase IIb readout, it would be great to get your take on expectations when using 680-mg dose consistently versus 340. And then if could you just remind us on any information out there that may support greater IgG reductions, leading to better efficacy.

Yes. Thanks, Sam. So I think the first question, there's really sort of 2 dimensions to that one, in terms of what we expect with the IIb trial. The first, as you pointed out, is we do have that higher-dose regimen in the IIb trial. We also have a longer duration of therapy. So I think we're going to be looking at what we see over this trial in more detail to try to create an estimate there. But the -- that 680-milligram cohort in the IIb trial is predicted certainly to have a deeper IgG reduction, and then that deeper IgG reduction will last longer. Why might that matter, and that gets to your second question, there are published -- there's published literature showing that the absolute titers of the anti-thyroid-stimulating hormone receptor antibodies, auto antibodies, correlates with clinical severity. And although we don't have complete information yet back on our own auto antibody titers from this trial, what I do know is that there was variability at baseline and in some cases, a pretty significant variability in the titers of those stimulating auto antibodies. So you might expect that patients who have a higher baseline absolute titer of anti-thyroid-stimulating hormone or auto antibodies are going to require a greater relative reduction in order to get them below whatever threshold you need to be below in order to see a clinical response. So that's, I think, the reason why there's likely to be a better response at the population level in the 680-milligram cohort versus a 340-milligram cohort.

Our next question is from Brian Skorney with Baird.

And congrats on the data. I guess maybe I missed it in your comments on the albumin reductions, but did you see a trough on treatment? Or was there a continuous decline over the course?

Right. The curves -- again, I don't have the full curves for everybody because some patients are just into that follow-up period. We wouldn't expect the albumin to continue to decrease, of course, in after therapy, but I don't have the complete curves. That said, the shape of the curves that we do have is pretty similar to what we saw in Phase I. You have a reduction over the first 3 weeks or so, then you have a flattening of the response, and then once therapy is withdrawn, then the albumin recovers.

Great. And then just big picture, I've been getting some questions just in terms of kind of COVID and the eventuality that hopefully we'll wind up with a vaccine here. Just general thoughts on the risks of IgG reductions and infectious risk and how that kind of impacts use of FcRns in the background of eventually us having a SARS-CoV-2 vaccine?

Yes. It's a great question, Brian. And obviously, it's really, really early days to provide any type of specific answer to that. I think there's a few fundamental elements of biology though that are important to consider. So whereas there's not much information available on the immune response to COVID, it's coming -- it's being published almost daily, but there's not that much out there. There is a fair amount of information published on the immune response to SARS, which is an RNA virus that's very similar to COVID. And what you see in terms of the immune response to SARS is that both the hyperimmune response that can be damaging as well as the positive immune response that confers a benefit longer-term is primarily a T-cell-based response for these respiratory RNA viruses and primarily actually a CD8, but both T-cells, CD4 and CD8, playing a role. Of course, there's some B-cell, T-cell cross-talk in maintaining that or creating that immune response. And then the memory is primarily through memory T-cells. There will be measurable circulating antibody titers that will probably be helpful in determining whether or not someone has immunity. But the memory -- the initial response and the memory response is probably if SARS is a good -- an analogous virus it's probably going to be more through T-cells. B-cell functionality is going to be important, and there's not evidence that anti-FcRn therapies impact B-cell functionality. And circulating free IgG may not be the primary contributor to that immunity long term, if -- again, if the SARS mechanism of immunity transfers to COVID. So a lot of unknowns, but I think there's reasons to be optimistic that anti-FcRn won't be a -- have a lot of interplay with COVID.

Our next question is from Robyn Karnauskas with SunTrust Robinson Humphrey.

And congrats. Like I know the mood is very dire out there, but it's great that you are hitting your time line. I guess my question, 2 of them, first, on the IgG reduction data, when will we, do you think, get that data and how will it be presented? Would it be in a format like this? And then second, compared to tepro, could you just give us some -- people are going to make the comparison, even though it's small study, small end, to tepro. Could you just put into context what you know about like the baseline characteristics of that study versus this study? And like also the other metrics beyond proptosis, like what the benefits were and what they weren't? I was looking through the data this morning, I was a little confused about how to assess it. Any help you can would be gratefully appreciated.

Yes. Thanks for those questions, Robyn. They're really good ones. So our initial plan was to present the detailed analysis at the May ATA meeting in New York. That meeting has been canceled, and it's not yet clear whether there will be a virtual component or not. So at the moment, we're looking -- we want to make sure that we get the data out in a robust fashion as soon as we can, but also in a good format. So we haven't made a final decision yet, given that, that May ATA meeting in New York has been canceled, where that will be. In terms of the comparison to the tepro trials, I think maybe some of the most important baseline characteristics are the average Clinical Activity Score and average proptosis of the patients entering the trial, since both of those speak to the activity and severity of the patients in the trial. And our average Clinical Activity Score was 5 and our average proptosis was about 23 millimeters. Those numbers are very similar to the baseline characteristics in both the IIb and the Phase III trial for tepro. If you look those up, they're really, really close. In terms of the clinical parameters, so I think it's important to look at all 3 of them. It's also, of course, important to note that cross-trial comparisons need to be done with caution. And as you're well aware, the teprotumumab trial had their primary end point in both of them at 24 weeks. They did report some 6 weeks data post talk, but again, their primary end point was at 24 weeks. All that said, if you look at what they reported in their IIb trial and their Phase III trial at week 6, you'll see that for Clinical Activity Score responders, so patients who achieved a 0 or 1, it was 21% in one of the trials and 22% in one of the -- in the Phase III trial. We had 43% on that dimension. Proptosis response was in the 50% range for both of us in 6 weeks. And then in terms of diplopia, they had about a 2/3 response at week 24. We're seeing that again with small numbers at week 6. So I think the efficacy that we have here compares very favorably, of course, with the caveat that this is a small sample.

Great. I appreciate that. And then one other question. When you think about disruption, and thank you for clarifying potential for that for MG, for TED versus MG, are there differences in where these trials are running or even the patients that might lead one to be less disruptive than the other? And are there any other challenges that you're facing as far as the clinical work that you're working on, getting enough reagents a bit preclinically as you move these drugs forward, there isn't an innovation gap approaching us in the future?

Yes. Thanks for those questions, Robyn. They're really good. I'll get the -- hit the second one first because that's real easy. We don't have any supply chain issues at the moment. We're -- we've -- our partners, Samsung and Catalent are doing a tremendous job, and we've been planning ahead fortunately there. And we have drug substance and drug product in supply, so no issues there. In terms of the differences between the impact on the myasthenia gravis trial and the impact on the IIb trial in thyroid eye disease, the difference there is really more based on where the trials are in their life cycle. So the myasthenia gravis trial was just about to finish up. In fact, we had a couple of people who -- 2 patients in Canada who were scheduled to have their baseline visit within the last 2 weeks when their institutions made a decision to not -- temporarily not enroll any new patients. So assuming that we get our clinical trial sites back up and running, and for myasthenia, those are in Canada and in the U.S., we've got a good pipeline of patients ready to go at a variety of sites. And there are other sites that are still enrolling, and so I just mentioned those 2 as an example. The same impact is happening for some sites in the thyroid eye disease trial, which, by the way, are in Canada, the U.S. and in Europe for the IIb. The difference in -- for the thyroid eye disease trials, we just have more time to put mitigation steps in place. That trial is still ramping up. There's still some site activations going on. And so we have -- there are things we can do now, I think, to be really well prepared for a fast restart in thyroid eye disease and potentially make up some time, whereas in the case of myasthenia, there's just not a runway to make up the time, which is why we're now guiding to Q3 for that trial.

Our next question is from Jason Gerberry with Bank of America.

Just wanted to confirm, did you guys just say that on CAS 0 to 1 at week 7, you were at 43% because I didn't see that number in the PR and I didn't want to confuse that with the proptosis responder rate? And then your just general thoughts on whether you would expect proptosis to improve over time, just based on the mechanism, just helping us bridge the gap in terms of the different durations of follow-up with this drug and tepro. And then lastly, just in terms of what is the FDA really focused on in terms of the laboratory safety data that you would be presenting at a future medical meeting, just to give us a sense of bridging the gap to a safe and easy patient self-administered therapy.

Great questions, Jason. So with regard to the CAS or Clinical Activity Score responders, you're correct that there were 43%, 3 out of 7 patients, who achieved a 0 or 1 score on the Clinical Activity Score. That's the same, actually, number, and it's actually the same patients who achieved a proptosis response defined as 2 millimeters or more improvement in their proptosis. So 43% for both of those metrics. In terms of proptosis improving more over time, I think that's very likely based on the natural history of the disease and also the natural history of treated disease from other trials with innovative therapies. The -- again, 6 weeks is a really short period of time. I would even get commonly questions leading up to today. Did we think that 6 weeks was enough to show any impact, given that you have to reduce the inflammation and then that inflammation has to regress, and then you have some shrinking of the tissue and then the proptosis goes down. So there's going to -- that's not something that happens in days. It's more a matter of weeks. And I would absolutely expect that with longer therapy, you're going to get more patients achieving a proptosis response. Again, that's what's been seen in other trials. In terms of what the FDA looks at, I think on the efficacy side, they've been very clear that proptosis responder rate is the preferred primary end point, that is the primary end point in our IIb trial. And clinicians, on the other hand, I think really appreciate the fact that this is a multi-faceted disease and that the Clinical Activity Score captures many elements of patient morbidity beyond just proptosis. Of course, diplopia, as I mentioned earlier on the call, is also really, really important. I think on the safety side, the FDA is going to look at the full range of a data package for any asset that's submitted. I think what we're really encouraged by in terms of our data to date is that all the adverse events that have been reported, both in our Phase I trial with healthy volunteers as well as in this trial, were just mild or moderate. We haven't had any SAEs. And although the FDA, I don't think, would be particularly concerned about headaches, patients certainly would be, and so we are really encouraged to see no headaches in this trial, which is consistent with the type of data we presented from Phase I as well.

There are no more questions in the queue. I would like to turn the conference back over to Dr. Salzmann for closing remarks.

Thank you very much. I'm just going to repeat briefly my concluding remarks and say that we're just absolutely thrilled with these results. I know that having spoken to a lot of ophthalmologists recently, they're very, very excited about the chance for patients finally to have some new therapies that impact the proptosis, the double vision and the swelling and redness of the eyes, and to be able to potentially deliver that benefit with a therapy that has the chance to be given as an at-home injection, I think, is really exciting. So we're really excited about these results, and I appreciate very much the engagement of everyone on this call. Thank you very much.

Thank you. This does conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.