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

Good morning. My name is Melissa, and I will serve as your conference call operator. [Operator Instructions] As a reminder, this conference is being recorded. 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 12, 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 IIb 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 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.

[Operator Instructions] Our first question comes from the line of Robyn Karnauskas with Truist Securities.

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 seen any -- have you tested -- so you're not measured in other trials, but do you know, are you aware of other trials by other competitors that all have looked at cholesterol? Any data points would be helpful. And third would be is there any other data point that would help us feel more comfortable that this is only focused on TED. Like is there anything related to thyroid levels or hormone levels that might correlate with cholesterol?

Thanks, Robyn. Those are really good questions. I appreciate them. So 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. And you asked about other anti-FcRn programs. A literature review that we conducted didn't reveal any reports of cholesterol from other clinical trials, so I'm not aware of any data in that regard. And then in terms of...

A quick follow-up...

And then in terms of -- yes, go ahead, Robyn.

Just one quick question on that. So as a follow-up: With the dose levels you use, can you just remind us of the albumin reduction [ also for ] doses in other studies just so we're aware of that, if there turns out to be a correlation that could explain the dose effects?

Right, yes. Thank you for that. So for the 680-milligram dose in the Phase I trial and in the myasthenia gravis trial, we saw reductions in albumin of 25% to 30%. That's the average for the group. And in the 340-milligram dosage arm in the Phase I trial as well as in the myasthenia trial, we saw reductions in the 15%- to 20%-range group average mean change from baseline.

Okay.

And so the other question you asked was, I think, whether there is a rationale for variability across indications. So 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. So that trial's, it 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. So 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 the 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. So you mentioned WAHA. What could be the time line for getting more color? Or can we even get it? Since you said you've halted that trial's data on cholesterol from your WAHA study that's been ongoing just to give you some insight with -- 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.

Yes, great question. So 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. And we will -- we're modifying our monitoring program for those patients, which will include measuring cholesterol. So 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, so stay tuned for that.

Our next question comes from the line of Derek Archila with Stifel.

Great. So just two from us. So I think in the literature antithyroid treatments have shown similar transient increases in LDL, so maybe you can discuss whether again is this an on-target effect of 1401, again removing those antibodies that are stimulating the thyroid. And then also I think you mentioned, Pete, that these T3 and T4 levels correlate to LDL increases, so just curious again. Did you measure those in this study?

Yes, great questions, Derek. So first of all, with regard to whether -- let's -- I'll even generalize your question as 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 show -- as we mentioned in the press release, the increase in LDL was larger in the higher dose than in the lower dose and that's consistent with that as well. And we do note a decrease in not only pathogenic IgG -- sorry, not only total IgG but pathogenic IgG in our thyroid eye disease patients when treated with 1401. That's not surprising, right? So you're lowering the auto antibody. And the TSH receptor is also involved in cholesterol metabolism. So I mentioned the T3, T4, but there could be impacts via the auto antibodies that are being modulated as well. So a lot going on that we need to sort out. You asked, Derek, about whether we measured T3, T4 and TSH. Absolutely, we measure 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. So those data aren't yet analyzed, but they will be soon.

Our next question comes from the line of Brian Skorney with Baird.

I guess, just kind of wanted to get your thoughts on reimplementing dosing if you think it's safe. I know you sort of point to the ability for statins [ to sort of ] reduce LDL levels by a similar amount. Would you think that the best path forward here would be to start re-dosing, co-administration with statins? And have you thought about something that might be more useful like a PCSK9 antibody which might have a greater magnitude of effect here?

Yes, thanks for the question, Brian. Certainly I can envision a lot of modifications that we can make to the protocol that would allow us to optimize benefit-risk for patients in the trial. And 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. So 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.

Our next question comes from the line of Colin Bristow with UBS.

Just can you speak to anything regarding the distribution of the LDL, cholesterol increases; how that looked across patients? Whether -- were there significant outliers driving the quoted average? And 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. And 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?

Great. Thanks for those questions, Colin. So 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 are -- 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. So in terms of your second question, with regard to trends over time, that's the trend 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 the -- 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, so you can't really -- even they, I think, will -- won't be able to do a full analysis of the data until such time as they unblind it when it's completed. And then 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 a follow-up. Did you -- with regard to the time trends. Do you -- was there any data to get a sense that you were hitting a plateau in terms of the 40% to 55% increases? Or could this be, in extended dosing, we see just from the curve you'd expect levels to continue to rise?

Right. I don't -- we don't really have curves because we just have 3 data points. So we measured at baseline, at week 12 and week 20. So that's I'm not able to provide that level of granularity at this point.

Our next question comes from the line of Yatin Suneja with Guggenheim Partners.

Just a couple for 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? Then I have 2 more follow-ups.

I don't have the answer to that yet.

Okay. With regard to the cholesterol increase, right: So they are transient because, I think, it seems like they -- these levels come back to baseline at week 20. That's correct, right? And then if that's true, maybe conceptually talk about the modifications you could make. Could you actually pursue a chronic intermittent therapy? Is that even viable where a disease is driven by continuous production of auto antibodies?

Right, yes. I think I don't want to speculate on any specific changes because we're -- we still have a lot to learn, including collecting better time course data, to the points that I was discussing with Colin, but 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. And we look forward to doing that.

Got it. And then final question. So it seems like you have unblinded the data on 40 patients, so when can we hear -- or when 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?

Yes, great question. So over the last little bit here, we've just been working furiously to understand the safety data. And we haven't unblinded the efficacy, so 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, but we haven't yet made a decision about whether to unblind the efficacy database, so stay tuned.

Our next question comes from the line of Thomas Smith with SVB Leerink.

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? And can you describe what happened to their LDL levels during the study?

Yes. Thanks, Tom. So in terms of baseline values, there wasn't any special screening parameters with regard to cholesterol, so you have sort of a distribution that you might expect in the general population. It's a wide distribution of baseline levels, and there were some patients on statins. We're just kind of collecting that element of various concomitant medications, but 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. And then were there any patients randomized to the lower-dose 255-milligram arm? And if so, did you see a similar signal here?