Joining me on the call today 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 certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
These forward-looking statements include, for example, statements regarding potential efficacy and safety of Immunovant's product candidates and Immunovant's expectations regarding the timing, design, and results of its clinical trials, including the timing of future readouts and data readouts and the announcement of future indications. These forward-looking statements are not guarantees of future performance and are subject to risks 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 November 12th, 2020. Now I'd like to turn the call over to Dr. Pete Salzmann. Thank you. Please go ahead.
Thank you, Melissa. Good morning, everyone, and thank you for joining this call. As you will have seen in our press release, Immunovant is voluntarily pausing dosing in our clinical trials of IMVT-1401. We just recently became aware of a physiological signal consisting of elevated total cholesterol and LDL in IMVT-1401-treated patients in our thyroid eye disease phase II-B trial. We decided to pause dosing in our active clinical trials so that we could carefully review the data, so that we could notify regulators and investigators, and so that we could make modifications to the patient consent form as well as to the lipid monitoring and management parameters in our program. We are notifying regulators and investigators this morning, and we wanted to simultaneously inform investors to ensure transparency.
I should also note that Harbour BioMed is the license holder of IMVT-1401 in Greater China, and they have ongoing trials in myasthenia gravis and ITP. Harbour BioMed has informed Immunovant that based on a preliminary review of blinded data in their ongoing studies, similar increases in cholesterol have not been observed. In terms of next steps, we plan to meet with regulators to discuss the findings in our clinical trials. We will work with them to agree to modifications to the protocols, as I mentioned. After these discussions, we will be in a better position to provide guidance on timing for resuming dosing in our current trials, and we will be in a better position to provide timing guidance for the initiation of new trials.
We are committed to working expeditiously with regulators, and we remain excited about the potential for IMVT-1401 in our current indications and in new indications. With that, I will ask the operator to open the line for questions.
Thank you. At this time, we'll be conducting a question- and- answer session. If you'd 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'd like to remove your question from the queue, for participants using speaker equipment it may be necessary to pick up your handset before pressing the star key. One moment please while we pull up the questions. Thank you. Our first question comes from the line of Robyn Karnauskas with Truist Securities. Please proceed with your question.
Hi, thanks for taking my question. I guess first question is, do you have data looking at albumin reduction? Is there any correlation with albumin reduction and what you're seeing with the cholesterol increases? The second question is, in MG, in other trials, have you tested It says you've not measured in other trials, but are you aware if other trials by other competitors at all have looked at cholesterol? Any data points would be helpful. Third would be, is there any other data point that would help us feel more comfortable that this is only focused on TED? Is there anything related to thyroid levels or hormone levels that might correlate with cholesterol? Thank you.
Thanks, Robyn. Those are really good questions. I appreciate them. With regard to the correlation between the observed findings in cholesterol and LDL and other parameters such as albumin, we haven't had a chance to run those analyses yet, so I can't answer that question today. With regard to other trials, we have, as I mentioned, not previously measured cholesterol in the myasthenia gravis trial, nor in our phase I trial. You asked about other anti-FcRn programs. A literature review that we conducted didn't reveal any reports of cholesterol from other clinical trials. I'm not aware of any data in that regard.
Just a follow-up.
Yeah, go ahead, Robyn.
Just one quick question on that. As a follow-up, with the dose levels you use, can you just remind us of the albumin reduction of the different doses in other studies, just so we're aware of that, if there turns out to be a correlation that could explain the dose effect.
Right. Yes, thank you for that. For the 680 mg dose in the phase I trial and in the myasthenia gravis trial, we saw reductions in albumin of 25%-30%. That's the average for the group. In the 340 mg dosage arm in the phase I trial, as well as in the myasthenia trial, we saw reductions in the 15%-20% range, group average, mean change from baseline.
Okay.
The other question you asked was, I think, whether there is a rationale for variability across indications. We only have the data really from our thyroid eye disease trial. The warm autoimmune hemolytic anemia trial, the vast majority of patients who are enrolled in that trial have not yet reached week 12, and so I don't have cholesterol for the majority of the patients in the warm autoimmune hemolytic anemia trial. That trial doesn't really provide us insight into this question. From a theoretical standpoint, there is a correlation between T3, T4 levels and cholesterol via the LDL receptor. As T3, T4 goes down, the LDL receptor goes down, and that leads to an increase in LDL. There are a variety of other changes in hypo and hyperthyroid, but generally speaking, hypothyroidism is associated with elevated cholesterol and LDL, and hyperthyroid, the opposite.
I guess my last question would be, it'd probably be comforting to investors to know whether it's just TED or whether it's other indications as well. You've mentioned wAIHA. What could be the timeline for getting more color, or can you even get it, since you said you've halted that trial, data on the cholesterol from your wAIHA study that's been ongoing? Just to give you some insight, or even from MG, just some insight into whether or not it's only TED, or it could be other indications if this is actually a real effect.
Yeah, great question. For the patients whose dosing is paused in the thyroid eye disease trial and in the warm autoimmune hemolytic anemia trial, we will continue to follow them for sure. We're modifying our monitoring program for those patients, which will include measuring cholesterol. We will have cholesterol measurements from the patients in the warm autoimmune hemolytic anemia trial at a later date. We're also looking into whether we can run cholesterol tests on stored serum from our myasthenia gravis trial. Stay tuned for that.
Awesome. Thank you very much.
Thank you, Robyn.
Thank you. Our next question comes from the line of Derek Archila with Stifel. Please proceed with your question.
Great. Thanks for taking the questions and good morning, guys. Just two from us. I think in the literature, anti-thyroid treatments have shown similar transient increases in LDL. Maybe you can discuss whether, again, is this an on-target effect of IMVT-1401, again, removing those antibodies that are stimulating the thyroid. Also, I think you mentioned, Pete, that these T3 and T4 levels correlate to LDL increases. Just curious again, did you measure those in this study? Thanks.
Yeah, great questions, Derek. First of all, I'll even generalize your question. Do we believe this is an on-target effect? I think yes. This is a monoclonal antibody. It hits a target, and we see an effect as we mention in the press release, the increase in LDL was larger in the higher dose than in the lower dose. That's consistent with that as well. We do note a decrease in not only total IgG, but pathogenic IgG in our thyroid eye disease patients when treated with IMVT-1401. That's not surprising, right? You're lowering the autoantibody. The TSH receptor is also involved in cholesterol metabolism. I mentioned the T3, T4, but there could be impacts via the autoantibodies that are being modulated as well. A lot going on that we need to sort out.
You asked, Derek, about whether we measured T3, T4, TSH. Absolutely. We measured those things, partly because we want to ensure that patients remain as close to euthyroid as possible during the trial, but also to provide insights to learn from the trial. Those data aren't yet analyzed, but they will be soon.
Okay, great. Thanks.
Thank you. Our next question comes from Brian Skorney with Baird. Please proceed with your question.
Hey, good morning, guys. Thanks for taking the question. I guess just kind of wanted to get your thoughts on re-implementing dosing, if you think it's safe. I know you sort of point to the ability for statins to reduce LDL levels by a similar amount. Would you think that the best path forward here would be to start redosing co-administration with statins. Have you thought about something that might be more useful like a PCSK9 antibody which might have a greater magnitude of effect here?
Yeah, thanks for that question, Brian. Certainly, I can envision a lot of modifications that we could make to the protocol that would allow us to optimize benefit risk for patients in the trial. You mentioned a few, and I think there are others as well. The important thing is, as I mentioned in my prepared remarks as well as in the press release, is that we want to make any changes in full cooperation with regulators. We will propose some ideas to them, and then we will discuss those ideas with them and get their feedback and agree to any changes to the protocol before we reinitiate dosing.
Great. Thanks.
Yeah. Thanks for the question.
Thank you. Our next question comes in line of Colin Bristow with UBS. Please proceed with your question.
Hey, guys. Thanks for taking the question and appreciate doing this call so expeditiously. Just can you speak to anything regarding the distribution of the LDL cholesterol increases, how that looked across patients, were there significant outliers driving the quoted average? Do you have a sense or any sense of how this trended over time? Second question is just what do you make of the fact that these effects were not observed in the Chinese patients? Then just finally, I think you said you had stored samples in MG. Do you have the stored samples from the healthy volunteers as well? Thanks.
Great. Thanks for those questions, Colin. In terms of the distribution of values and whether it was driven by a small number of outliers, the median and mean values weren't that different. And so it's not driven by a small number of outliers. There is a wide distribution of values, so both at baseline as well as at 12 weeks and at 20 weeks for those patients for whom we have 20-week data, there's a wide distribution. But what you do see consistently across the doses and is that the value at week 12 is higher than the value at baseline and at week 20, as I mentioned in the press release, the values across the dosage arms are essentially back to baseline.
In terms of your second question with regard to trends over time, that's the trends that we observed over time, baseline to 12-week an increase, 12-week to 20-week, a return to baseline. In terms of the patients being studied by Harbour in their myasthenia gravis and ITP trials, I don't have more information than what I quoted. That's their trial and their data. It's also those trials are still blinded. You can't really, even they, I think, won't be able to do a full analysis of the data until such time as they unblind it when it's completed. With regard to data in healthy subjects, we do also anticipate that we'll be able to get stored serum from healthy subjects and run cholesterol tests on those samples as well.
We're still in the process of verifying that, but we'll be able to provide an update in the near future about that, Colin.
Just to follow up, with regard to the time trend, was there any data to get a sense that you were hitting a plateau, in terms of the 40%-65% increases? Could this be an extended dosing we see just from the curve you'd expect levels to continue to rise?
Right. We don't really have curves because we just have three data points. We measured at baseline at week 12 and week 20. I'm not able to provide that level of granularity at this point.
Got it. Thank you.
Yeah.
Thank you. Our next question comes from the line of Yatin Suneja with Guggenheim Partners. Please proceed with your question.
Good morning. Thank you for taking my question. Just a couple from me. Can you maybe remind us what literature suggests on IVIG, as it relates to its impact on cholesterol? Do we know if treatment with IVIG has or have any impact on cholesterol level? I have two more follow-ups.
I don't know the answer to that, Yatin.
Okay. With regard to the cholesterol increase, so they are transient because I think it seems like these levels come back to baseline at week 20. That's correct, right? If that's true, maybe conceptually talk about the modifications you could make. Could you actually pursue a chronic intermittent therapies that even viable where a disease is driven by continuous production of autoantibodies?
Right. Yeah, I think, I don't want to speculate on any specific changes because we still have a lot to learn, including collecting better time course data, to the points that I was discussing with Colin. The bottom line is the fact that you see an increase at 12 weeks and then a suggestion of a return to baseline by week 20, together with a few other factors, suggests to me that there are many ways probably to solve this challenge. We look forward to doing that.
Got it. Final question. It seems like you have unblinded the data on 40 patients. When can we hear, or when would you might be prepared to share us the efficacy or more clinical data? Will you do that or will you first sort of complete the full 77 patients that you have to enroll?
Yeah, great question. Over the last little bit here, we've just been working furiously to understand the safety data, and we haven't unblinded the efficacy. At this point, we haven't made a decision on that part. We've unblinded the safety database, and so we're in a position now to do those analyses that Robyn and others asked about. We haven't yet made a decision about whether to unblind the efficacy database. Stay tuned.
Got it. Thank you.
Thank you. Our next question comes from the line of Thomas Smith with SVB Leerink. Please proceed with your question.
Hey, guys. Good morning. Thanks for taking our questions. Can you provide any color on the baseline LDL levels for the patients in this TED study? Were there any patients on statins at baseline? Can you describe what happened to their LDL levels during the study?
Yeah. Thanks, Tom. In terms of baseline values, there wasn't any special screening parameters with regard to cholesterol. It's a wide distribution of baseline levels. There were some patients on statins. We're just collecting that element of various concomitant medications. At this point, we haven't had a chance to do the analysis of how their cholesterol did or didn't change relative to other patients in the trial.
Okay. Were there any patients randomized to the lower dose 255 mg arm? If so, did you see a similar signal here?
Right. There were. It's a smaller group. We left it out of the press release just because it was basically consistent and it was just going to be a lot of data, but I'll give you a data point. In the 255 mg dosage arm, the increase in cholesterol at 12 weeks was about 25%.
Okay. Appreciate that. Then, just one last question, I guess, because you've unblinded the safety data set. Apologies if I missed this earlier, but can you comment on, I guess, the level of albumin reduction that you've seen in this unblinded data set?
Right. I can't say because we haven't fully scrubbed those data. We were focused on the cholesterol data from a standpoint of getting all that scrubbed for this communication to regulators, investigators, and investors. We'll be taking a careful look at that and sharing that data when we have more complete data to share.
Okay. Appreciate that, Pete. If I could just sneak in one last question. Just, could you talk a little bit about?
Sure.
How you're planning to, I guess, analyze the patients that are currently enrolled as you're pausing dosing here, and how those patients will be treated in the study analysis plan?
Right. We're working those details out, but in terms of what data we'll collect, this is a study with weekly visits. We have an opportunity to monitor these patients closely. Our medical team has proposed a monitoring plan that we'll discuss with the FDA and other regulators around the world. We'll get agreement on that. That will certainly generate a variety of data points that we can then put into an analysis plan.
Okay. Got it. Thanks for taking the questions, guys. Appreciate it.
No problem.
Thank you. Our next question comes from the line of Danielle Brill with Raymond James. Please proceed with your question.
All right. Thank you for the question. I guess I have a follow-up on the Harbour BioMed studies. Is the dosing duration different in their MG and ITP studies? Do you know if they have 12-week data that they were able to analyze?
Right. Thanks for that question, Danielle. Their dosing is different and in some cases, they have every other week dosing and some cases every week, I believe. Because it's a blinded data set, we don't know which patients are in which group. They're all on either 680 mg or a placebo in the Harbour studies. They only have the one dose of their study.
Are they being dosed for 12-week durations?
They are.
Duration dosing different?
Right. They're longer. They do have dosing beyond eight weeks and it depends again, a little bit since it's an ongoing study. Some patients have just a few weeks of dosing and some have longer. They have patients who are being dosed longer.
Understood.
In that 12- week range.
I know this is very premature and you still need to scrub the data and do your analysis, but do you feel like this is related to TED specifically or do you think it may be tied to the formulation? What is your initial hypothesis as to what's going on here?
Yeah, great question. I don't think it's the formulation because there wouldn't be any reason, I don't think that excipients would cause this. I think it's a non-target effect based on the fact that we see a variation with the dose, with the highest dose having the greatest change and the lowest dose having the lowest change. We usually see these kind of things with a monoclonal antibody, it's a non-target effect. Which target exactly and what's the mechanism? That, we need to figure out, and we'll be doing a lot more work. Also the fact that we weren't able to find any other data with regard to published literature on cholesterol on anti-FcRn trials also puts us in a position where we're just at the beginning of forming hypotheses.
Got it. Thanks for the color.
Yeah, no problem.
Thank you. Our next question comes from the line of Sam Slutsky with LifeSci Capital. Please proceed with your question.
Hey, thanks for the questions. Couple from me. I guess first, in terms of LDL, do we know Momenta and all these other ones, have they measured it in their studies? Do we know?
I'm not sure, Sam. We haven't been able to find anything published, but I don't know whether they measured it or not.
Okay. In the case of Harbour, they were measuring cholesterol in their studies, though?
They are, yes.
In the sense that they were able to say that they're not. Okay. I guess in terms of TED specifically, since they have hyperthyroidism, which could be associated with low LDL, is it possible that the increases could be due to normalizing of thyroid function, maybe it's overshooting? What's your take on that since it's kind of specific to TED, the hyperthyroidism aspect?
Yeah, I think that's a plausible hypothesis and one we're definitely going to look into. The patients are not hyperthyroid at enrollment, they do have, obviously, the presence of thyroid-stimulating autoantibodies. Their hyperthyroidism is controlled in one way or another. There's a requirement that they be relatively euthyroid. They can't be more than 50% hyper or hypothyroid based on their TSH and T3 levels. There's some variability when they enter. As I mentioned earlier, we did collect TSH and T3 and T4 levels, and so we have a chance and opportunity to look for correlations there, which we'll be doing.
Got it. Okay, thanks.
No problem.
Thank you. Our next question comes from the line of Douglas Tsao with H.C. Wainwright. Please proceed with your question.
Hi, good morning. Thanks for taking the questions. Just curious if this was sort of the history of how this was identified, or this problem was identified in the course of the TED trial. I have another follow-up.
Yeah. The excursions in cholesterol was something that we just recently became aware of in our data set. When we became aware of it, we dug into it quickly and then made a decision to unblind the data set and presenting the information that we found to regulators and investigators today and as well as investors.
I keep the question is like, was there just some sort of standard review of cholesterol levels that sort of happened to be tripped? Was there some event with an individual patient that required you to sort of do this analysis?
Right. It was just a review. There was no events.
Okay.
I mentioned in the press release, we haven't had any serious cardiovascular events. You might say, well, have we had cardiovascular events? There have been cardiovascular events that are hypertension, palpitations, those kind of things. Even the lipid abnormalities themselves are actually a cardiovascular event. We've had that kind of thing, but we haven't had any serious cardiovascular events anywhere in our program. It wasn't that triggered it was just the lab abnormality was noted, and then we dug into it.
Okay. I think you said, or decided 25% increase, and I just want to clarify or confirm that is only specific to LDL levels, not total cholesterol.
Right. Exactly. The data that we shared in the press release was LDL, and the 25% figure for the 255 dose was a mean change at 12 weeks in LDL.
Okay. Okay, great. Thank you.
Yeah, thanks, Doug.
Thank you. Our next question comes from the line of Jason Gerberry with Bank of America. Please proceed with your question.
Oh, hey, good morning, guys. Thanks for taking my questions. Just have one. It was my understanding that IMVT-1401 and TED would be dosed for the bulk or the entirety of the active phase of TED to minimize the level of relapse that you see with teprotumumab. That could be one or two years, depending upon when the patient started their therapy. What I'm wondering is from the PR, it sounds like there's still, I guess, a theoretical risk that the LDL levels persist or worsen if you don't stop therapy at week 12. I'm just curious, what you'll be looking for going forward to consider this as a 12-week time limited course versus a longer duration therapy? From what I've heard this morning, it sounds like all those options are on the table, I just wanted to better understand that dynamic. Thank you.
Great question, Jason, and I agree with your conclusion of what you've heard. We need to understand the various parameters of cholesterol increase and return to baseline in the face of treatment with IMVT-1401, and then marry that up with the clinical situation that patients with thyroid eye disease face. We're going to do that now and look for ways to modify the protocol so that we can get back on track with regard to thyroid eye disease. We still see a lot of potential for thyroid eye disease as well as other future indications.
Okay. Thank you.
Thank you.
Thank you. Our next question is a follow-up from the line of Yatin Suneja with Guggenheim Partners. Please proceed with your question.
Hey, guys. Thank you for allowing a follow-up. Just a real quick one. I don't know if you already answered that, but can you remind us how many patients roughly have been dosed in China and for how long? Thanks.
Right. I don't have the exact figures there because that's Harbour's data. What they told me is they have a similar number of patients to what we have. We have 40 patients through 12 weeks, and they said their numbers were similar.
All right. Very helpful. Thank you.
Yeah.
Thank you. Ladies and gentlemen, this concludes our question and answer session. I'll turn the floor back to Dr. Salzmann for any final comments.
Thanks, Melissa, and thank you to everyone for joining today's call. I really appreciate all the questions, and we look forward to providing more information with our 10-Q in mid-February. As I mentioned, we are committed to working expeditiously with regulators, and we remain excited about the potential for IMVT-1401 in our current indications and in new indications. Thank you, everybody. Bye-bye.
Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.