Study Result

Aug 25, 2020

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. As a reminder, this call is being recorded. Joining me on the call today is Doctor. Pete Salzman, Chief Executive Officer of Imaduvant. 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 the potential efficacy and safety of Immunovance product candidate and Immunovance 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 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 refuse to remain in advance 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 Doctor. Pete Salzman. Thank you, Doctor. Salzman. 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-fourteen oh 1 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 IIa 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 6 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 6 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 3 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 auto antibodies to a known antigen, we believe it is 1 of the ideal indications for IMVT-fourteen oh 1 from a biological perspective. In 85% of patients, auto antibodies bind the acetylcholine receptor or ACHR. Note that we didn't include MuSK other Phase 2 trial designs in MG. Moving on to Slide 5, you see that our study design included a 6 week blinded treatment period with weekly dosing. Other recent anti FcRn trials have generally used an 8 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 3 40 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 6 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 5 placebo patients. On Slide 6, you see the baseline characteristics for participants in the trial. These baseline values are very much in line with recent Phase 2 and Phase 3 studies of other anti FcRn agents in MG. In fact, our population was very much in the middle of the moderate to severe range with 60% characterized as Class III MGSA 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 7, in line with our prior results, IMVT-fourteen oh 1 was observed to be generally well tolerated with no Grade 3 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 3 40 milligram arm and a 26% reduction observed in the 6 80 milligram arm. All albumin reductions were asymptomatic. On Slide 8, you see that mean reductions were in line with our prior Phase 1 results in healthy volunteers. The average IGG reduction from baseline following weekly injections of 3 40 milligrams was 59% and the average IgG reduction from baseline following 6 weekly injections of 6 80 milligrams was 76%. Reduction in IgG was the primary endpoint for the study and these reductions comparing treatment with placebo were highly statistically significant. And now Slide 9, these are beautiful graphs. MG ADL hits statistical significance in a pre specified analysis, examining the mean change in MG ADL at the end of the 6 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 6 week treatment period and increased over time, achieving nearly 4 points by week 6. In terms of MG ADL responders, defined as participants achieving an improvement of 2 or more points on the MG ADL at week 6, We observed a response rate of 6 out of 10 in the pooled treatment group and 1 out of 5 in the placebo group. The percentage of responders was similar across the 2 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 end 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 10 or by selecting the best performing items from both patient recorded and physician led assessments. It is comprised of 10 functional domains, 3 ocular, 3 vulvar, 1 respiratory, 1 neck and 2 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 3 scales are currently important, here we're showing mean improvement in each scale at the end of 6 weeks. This is also called mean change from baseline. Changes are shown for both placebo and for 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 8 points was seen in the pooled treatment group and this was quite significant with a P value of 0.00 6. Slide 12 is another really exciting slide. At ImmuneVant, 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 minimum threshold for a clinically meaningful change. For example, a change of 2 points is considered clinically meaningful in MG ADL. We wanted to evaluate 1401 with a higher threshold of 6 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 4 1401 treated 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. Mean Improvement on the MG ADL at 6 weeks and a highly statistically significant 8 pointmeanimprovement 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 1 and Phase 2 results for IMVT-fourteen oh 1, 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. Finally, 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 2a data shared today and then starting our Phase 3 trial in the first half of 20 21. Our thyroid eye disease Phase 2b trial remains on track and we expect to share results in the first half of 20 21. 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 WAYHA trial in warm autoimmune hemolytic anemia, we now expect results from the high dose cohort in the Q1 of 2021. Finally, I want to use this opportunity to share with you that we are expecting to announce 3 new indications over the next 12 months. We see tremendous potential for 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 and A. Thank Our first question is from Brian I guess maybe I know it's early after these data and you still have to have a discussion with the FDA about Phase III plans. But I mean, should we just kind of expect I mean, we've seen some Phase IIIs in the space. Should we just kind of like expect standard maybe like argenx like Phase 3 study here? Or is there anything kind of unique that you guys are thinking about in terms of Phase 3 clinical trial design? And then just on the Allebn side of things, I know in MOMENTA study they saw a rebound after cessation of drug. Did you guys see the same things here? Hey, Brian, thanks for those questions. So first of all, with regard to our Phase 3 trial design, I want to make 3 points. First of all, I'm very excited by the profile of both doses. Secondly, we plan to take the 6 80 forward and 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. And of course, we'll and that's the third point that we'll be discussing those with the FDA. And after we have those discussions, then we'll release some specifics. But I'm excited about our Phase III design. I think it's going to have some unique aspects enabled by the 2 doses and by the fact that we're in the clinic with a subcutaneous injection. And to your second question in terms of albumin, so the data that we're discussing today that we have locked is only through the 1st 6 weeks and patients were treated if they were in the treatment arm for that entire 6 weeks. So I don't have the data to answer that question today. Thanks and 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? Hey, thanks, Thomas. So the consistency was tight, similar to what we saw in our Phase 1 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 much wider range of IgG reduction, correlation between IGT reduction and clinical scales that I think is well validated. We only have at this point 6 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. Got it. Validated for the class. Got it. Got it. And then I guess I know obviously the extension portion of the study is still ongoing here. But 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 2a ASCENDO study? Yes, absolutely. Thanks for the question. The 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 2A data from the thyroid eye disease, we do have 1 data point that's required to be done in a live lab and we're waiting for that to be finalized or if they've had some delays due to COVID in terms of running that final analysis. So once we have that, then we'll have the entire data package from the 2A-ten trial and we'll get that information out. With regard to this trial, as I showed in the trial overview, there are these 3 periods and the open label extension and the follow-up period off treatment, those are still ongoing. So we need the patients to get through those phases and then, collate all the data before we can present that. And again, we'll target standard medical meeting within neurology for that information. Got it. Got it. All right, great. Thanks, guys. Appreciate you taking the questions. Congrats on the data. Thanks, Thomas. Our next question is from Stan Slutsky with Leysi Capital. Please proceed. Hey, thanks for the questions and congrats on update. I guess first off, just given the data from 1401 and then other FcRn inhibitors at this point, Be great to hear your take on where you see these likely to be used in the treatment paradigm as well as what you're hearing from physicians? Thanks, Sam. It's funny, classically the treatment paradigm for many conditions and myasthenia is often listed as by lines of therapy as if they're sort of independent milestones, 1st line, 2nd line, 3rd line, 4th line. I think in reality for a lot of these chronic autoimmune conditions, patients cycle around between steroids and the broad spectrum older immuno suppressant 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. So 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 like much more likely to achieve that on a product like 1401 than on those older therapies. So that's where I see them being used more upfront over time. Of course, at that launch, they're going to be used in patients who have failed other therapies. But over time, I think patients are going to want to use them early in their therapy. Okay. And then, obviously, not every patient is 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. But for the non responders, are you seeing any kind of continued improvement there? Is there potential for additional response as you think over time, but just kind of hear about the kinetics of their response? Right. So again, with only 6 weeks of data, it's a little bit hard to answer that with a lot of certainty. But absolutely, at the group level, what you pointed out is very true, which is we see a trend to increasing response over time. And I think that actually makes a lot of sense. When patients begin therapy, they've obviously had auto antibodies binding, in this case, their acetylcholine receptor for quite some time. And 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. So I think you'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. So I think that 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. And then lastly too, just for the open label extension and then follow-up here, just remind me kind of 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? And that's 1 question. Sure. Thanks for that question, Sam. So the open label extension has a dosing regimen of 3 40 milligrams every other week. That's, 1st 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, but it will enhance our pharmacodynamics models and that will be helpful across anything we would study. And then 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. But honestly, I think the much, much, much more important questions are going to be answered in Phase 3. Look, we know that 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 5 in placebo, we saw a statistically significant response and a strong rate of responders and deep responders. So 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 3 trial for that. 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 characterize 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 1 way or the other sort of and 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. So myasthenia is a chronic condition and patients with chronic immunology autoimmune diseases, again, they don't want to feel normal just for 6 or 8 weeks. They want to feel normal for ideally the rest of their life, right? So that's the first point. And secondly, in terms of the biology of myasthenia, I don't see any evidence that anti XTRN therapy puts patients into remission. You remove the offending pathogenic IgG and they approve. And then when therapy is withdrawn, the pathogenic IgG comes back and the symptoms return. So 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. So that's what patients need. Now we have a subcutaneous injection in clinical development. So that's a dosage form that is really well aligned with the patient needs because it can be given chronically. So, I agree with you that chronic dosing is the way to go and it really starts with the patient needs. Great. And congratulations on the data. And then just maybe 1 quick follow-up, and I'm sorry if I missed it. Do you plan to I know there weren't any MuSK patients in the Phase 2 in this data set. Do you anticipate enrolling any MuSK patients in the Phase 3? Yes. 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 3 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 II trials, most of which did not have MUS patients. But MUS patients will very likely be in our Phase 3 program. Okay, great. Congrats on the data again. Thanks. Our next question is from Gopolo Amusa with Chardan. Please proceed. Hi, Gopolo Amusa from Chardan. Thanks for taking my call and congrats on STAT SIC which is untreated patients. I have 2 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? And the second is, just wanted to understand whether the announcement that you will have 3 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, Bola. So I think in terms of the first question, creating value in immunology starts with having an asset that strongly meets 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 and our plan is to bring this product to market. And so 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. So that's the first point. And I guess the answer to the second question actually relates to that as well. So I think from the in terms of the timing of announcing our 3 new indications, absolutely, we're bolstered by this data. It's very exciting. But 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. And for 1401, we've now seen proof of concept in 2 indications. So, it kind of all comes together. I mean, this is an exciting class and we're very excited about our assets. So, 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, Bola. Our next question is from Danielle Brill with Raymond James. Please proceed. Hi, guys. Good morning. Congrats on the data and thanks for the question. Just a quick 1 from me. Since you mentioned that you're moving forward with a 6 80 milligram dose, is it safe to assume that you saw a higher percentage of deep responses in MG ADL in this arm? Or is this a decision that was already made before you even had the data generated? Great question, Danielle. So 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. And so I think that's 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. So 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 arm. So there's a lot to be excited about with both doses in this data set. Understood. Thanks so much and congrats on the data. Thank you, Danielle. Our next question is from Robin Kalynskevicius with Truist Securities. Please proceed. Great. Thank you, guys. Congrats on the data. I was just thinking outside the box, now that we have data from 3 companies, data looks somewhat similar. And how do you think about now that you have all the information, right, that you know your drug is proponent, it can be given subcu in a very convenient way. How do you think about what is most important for designing Phase 3 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 classes may be de risked. So how do you think about that going forward? And then my other question was more sort of point of like, do you think the speed of enrollment for the WAHA trial is how is the ad going? You said you're now going to have data in the Q1. Is there some impact from COVID? Are you seeing like more accelerated enrollments now that we're going to 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, Robin, for those 2 questions. They're good ones. So with regard to designing the Phase 3 trial, I think, as I said, we're going to do that based on where we think we can deliver the greatest patient need. But that said, I think we have 2 really nice levers that we can use creatively to design a tremendous protocol and finalize that in discussion with the FDA. And those 2 levers are that we have the 2 doses and that both doses can be given as a subcutaneous injection. So that allows us flexibility across a range of disease severity and allows us to chronically dose patients easily. So we're going to maximize the use of those 2 levers to design a Phase 3 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 Q1 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 just it's on track for the Q1, which I think is a pretty good accomplishment given everything that's happened over the last 3 to 4 months. And 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 that many patients recur. And so 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, but splenectomy has fallen out of favor for a lot of different reasons. And 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. So 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 a potential for a really large effect size. So that's what we're hoping for in warm autoimmune hemolytic anemia. And I think if we see that, that's going to be a very, very exciting indication. Great. Thank you. Thank you, Rob. We have reached the end of our question and session. I would like to turn the conference back over to Doctor. Salzman 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've shared today and really, really excited about the potential for 1401 more broadly, not only in the 3 indications we're currently studying, but in the 3 indications we expect to announce over the next 12 months. So 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.