R&D Day 2021

Sep 28, 2021

Thanks, Paul. Appreciate the introduction. Thank you, Robin, for joining me today. You too. Thank you, Pete. I'm going to start out with a brief overview of our market and our asset, and then we'll get into our Q and A. I'll be making some forward looking statements, and I direct investors to this slide on our website. So our vision we're in immunology, and our vision is really to make a big, big difference for patients. We want to bring therapies to market that improve substantially on the standard of care. That's what our vision guides us towards. Our asset is a fully human monoclonal antibody Targeting FcRn. And by targeting and blocking the Fc receptor, we lower free floating IgG. Now I'm not showing data today in the interest of time, but the IgG reductions that we've reported are among the deepest of any of the anti FcRn assets. And we achieved those IgG reductions with a simple subcutaneous injection, whereas others achieve that with an intravenous infusion. Now this pharmacodynamic activity offers Many, many, many patients, the promise of disease symptom reduction. In fact, There are 15 indications listed on clintrials.gov across the anti FcRn program. That's a phenomenal number of active programs for a single mechanism of action. And we believe this is a multi double digit $1,000,000,000 market opportunity. Now within this set of diseases, there are some that are classic autoantibody conditions. And there are also others where Auto antibodies play a role even if they're not a pure auto antibody condition, and that's a little bit where the evolution of the market has gone recently. The indications also span therapeutic areas. And as you see from the blue diseases, which denote Where we have programs, we are currently in 3 therapeutic areas. Now I want to spend just a quick minute on myasthenia gravis because I think Highlights the patient unmet need that's present in many of these indications. Of course, patients with myasthenia gravis want reliable treatment options. Many of the treatment options today, which are more or less broad spectrum immunosuppressants or IBIG, are saddled with either a very, very, very long time until the treatment effect is known or side effects, which can be significant or both. IVIG, as an example, works well for many patients, but as a large volume intravenous infusion, is just challenging for many patients to take. The other thing about patients with myasthenia gravis is that they really want their disease to be controlled on a steady basis. So for those of you who follow the anti FcRn class, you know that argenx reported a successful Phase III trial. And that Phase III trial of their anti FcRn followed an IVIg treatment paradigm, meaning patients were treated for 4 weeks and then the responders waited until their disease relapsed, at which point they were treated with another 4 week cycle. Our market research shows that patients overwhelmingly with myasthenia gravis Prefer chronic therapy versus intermittent dosing. They associate intermittent dosing with flares. And those flares, in the case of myasthenia gravis, can be very severe. Can land patients in the hospital. So the concept of intermittent dosing doesn't resonate with patients, and this insight will guide our Phase redevelopment program. Finally, turning quickly to betoklamab or 1401's properties. This is an asset that started out right from the beginning with the patient in mind, and it was designed as a simple subcutaneous injection That provides a very easy route of administration for patients. And when you combine that feature with The broad therapeutic window, then you get the feature you see on the lower left hand side of the slide, which is the potential for a flexible dosing paradigm. This allows patients to adjust their level of IgG suppression over time without having to go off their medicine and go on their medicine. As we saw, that wasn't attractive. But adjusting the level of immunosuppression over time to meet the needs that they have is something that's very attractive to patients. So with that, Robin, I'll open up our dialogue, and I look forward to discussing these and many other topics. Great. Thanks, Pete. So Thinking about your second slide, I think, where you had all the 15 indications and thinking back about how FcRn initially were thought To take just a chunk of the IVIG pie, which is very large globally, and now some of those indications I never would have thought would have been up there. So maybe you could talk a little bit about How do you think the FCRN opportunity has evolved? How do you view the opportunity in the space? Yes, yes. So I think early on, like many mechanisms of action, it was hard for investors to of get their arms around what is the size of the opportunity. And the blocking FcRn lowers free floating IgG, as I mentioned. So the obvious indications were those that were classically autoantibody driven. So myasthenia gravis is a classic example, pemphigus vulgaris. And those were the indications that companies which had an anti FcRn went for What we've seen now is an evolution to indications where autoantibodies or Pathogenic IgG is playing a role, but there are other elements of the immune system that are also dysfunctional and really an evolution to a belief that Anti FcRn can play a role there as well. So that opens up you already had a lot of opportunity, maybe 250 ish 1,000 patients just in the U. S. Alone with the classic autoantibody conditions. When you open the range of possibilities up to those other indications, now you're really widening things. And so you've mentioned 15 indications there. I mean, what have you learned from some of the data that's been coming out on some of those indications already, like CIDP, as far as like the ability of FcRn to function when other things are wrong with your immune system, not just a bad antibody? Yes, yes. Well, I think what we've seen first and foremost is just a really consistent translation of the pharmacodynamic activity to a clinical impact across a wide range of the classic autoantibody conditions. And so that, I think, has given all of us who are working in this space a lot of confidence that lowering pathogenic IgG is going to be associated with the clinical improvement. There is also published literature on the role of the FcRn, The Fc receptor in prolonging the half life of immune complex. And so by blocking the Fc receptor, there's also a potential to lower that circulating immune complex. And many of these newly added indications are immune complex driven. When you have the IgG driven diseases and the immune complex driven diseases as a group, again, just a lot of opportunity in this market. That's good color. I don't think people think about that. They're still thinking about it the old way. So you're in the lead with the subcu version of an FcRn. Maybe talk a little bit about Your subcu versus the competition, you don't have to knock the competition, but where are you? Where do you think the competition will evolve In the subcu space? Yes. That's a great question. So formulation is not something to be taken for granted, even though It's not normally the primary point of differentiation within a lot of different categories. It's not a given that any biologic will be able to move from intravenous formulation, which is where most start, to a simple subcutaneous formulation. I like to say 1401 or betoklamab was born subcu. What do I mean by that? When the initial inventors of 1401 were selecting the lead antibody, they selected it not only for potency to the anti the FcRn receptor, but also for solubility. So when they had 20 or 30 antibodies to choose from, they made them all in small aliquots, which is very tedious, and determine which one was most soluble. So this solubility is engineered in. It's not just a luck that we have this advantage. And having that right from the beginning puts us out in front with regard to subcutaneous injection time lines, as you mentioned. We know that argenx had an in house subcutaneous injection format that they have deprioritized in favor of a co formulation with Halozyme. And that is a less proven modality. It's a good modality, for sure, it doesn't have the decades of experience that simple subcutaneous formulations have. And then, nivocalumab, another decent anti FcRn recently started a Phase III program with an with their intravenous formulation. So that's an action that I think is important So no sign of subcu there yet. And I think they were supposed to start a bridging study. I think that was the original plan. So Interesting point. I'll get back to it in a second. So for bintoclumab, am I saying this correctly? I practiced 7 times today. When will investors get clarity on what indications you will explore? You've given some hints on MG and like away as well as TED, but like when will we really learn the big picture? Yes. So this is an incredibly competitive market. Obviously, there's The standard of care is not very good for the vast majority of these indications, and the impact on patients' lives is high. So This is just an incredibly competitive, exciting market. Given that, I think we're, like most other companies, going to wait until we have all our ducks in a row to announce indications. We have an IND approved from the relevant FDA division, and we're sort of ready to go. Essentially, when it goes on clinicaltrials.gov is probably when it announced. With that said, we had prior to our clinical pause, had said that we would have 2 new indications announced by this last August, And we were on track to achieve that. So we had already done a lot of work, both in terms of understanding the science and figuring out how these trials would need to be structured to maximize chance of success. So we're feeling really good about the time lines that Matt shared earlier and that we've shared publicly that we'll announce 2 new indications by next August. So, Anir. And then talk a little bit about next I guess, next big event for you is clarity on your MG trial. You're going you've said you're going to meet with the FDA by the end of the year to get alignment around an MG trial design. Maybe comment on what you think The MG trial might look like given the profile and the patient market research that you've done? Yes. Those are great questions. So first of all, I think the alignment with the FDA, that's an important catalyst We will get alignment with the FDA by the end of this year. That's what we've said publicly, and we're well on track to achieve that milestone. And that's important not only because of the program specific design elements that we'll talk I'll address in a second, but also because of the other elements that are more applied to other indications as well, like our safety monitoring and CMC and all those other things that go into getting that green light. So that's a really important milestone for us and a catalyst for the end of the year. In terms of designing our Phase III clinical trial, so I mentioned that patients prefer chronic therapy versus intermittent therapy in MG patients and our market research. Just to kind of bring that to life a little bit, there was a patient that I met on an MG walk, And he ended up coming to speak to our team about what it was like to live with MG. And he'd had MG at the time he spoke to us a year or so ago for probably 15 years. Early in the course of his MG, he had, like many patients, been treated intermittently. So he had gotten disease control. And then he was feeling better, his physician took him off his MD medicines, and he was doing well for a while. And then one night at dinner, he actually in the morning, he said he, in retrospect, was feeling a little bit not so well. And at dinner, he basically his head collapsed. And one of the things that patients with MG can get is weakness of their neck muscles. And so his head he wasn't able to hold his head up, which made it difficult to breathe. And his daughter, who was a teenager, had to sort of help him Position his head so he could breathe and call the ambulance. It was extremely scary. So he doesn't ever want to have a flare again. And many patients have either experienced that firsthand or they've talked to other MG patients who've had that experience. And so this idea of Getting their disease under control and then maintaining control is really important. So those are the two elements that we're going to build into our Phase III program: getting the disease under control then maintaining the control. Now I'd like to say for Phase III programs in general, they have 2 goals really. 1 is to achieve approval, and that's a really important milestone. But the other is to provide data that differentiates the So but the other is to provide data that differentiates the product. When you're the very first asset in a category or for a disease, Then sometimes just getting approval alone can be differentiating. But for us, we will want to show the same type of improvement in MG ADL, which a commonly accepted endpoint by the FDA for primary efficacy to achieve approval. But then we also want to generate that data that will differentiate 1401 for physicians and patients. And that will come in the later periods of the trial where we'll show that with our goal is to show that With therapy that's adjusted to the level of immunosuppression that patients need, they can get the ideal level of control. They get just enough to maintain the efficacy, and they're able to adjust their dose over time. Maintenance phase. And then when you're dealing with the cholesterol questions, like how do you design a trial where you don't have people dropping out because they can't tolerate a statin, Like how do you design a trial where you don't have people dropping out because they can't tolerate a statin? Or how do you think about making investors comfortable with the design, not Just eliminating people who can't tolerate it as well, protecting yourself from that. Right. So there's a small number of patients with MG, who also have preexisting cardiac disease. And actually, interestingly, on the clinicaltrials dotgov description of the nippocalimab trial in MG, those patients who've had a recent cardiac event, I think, within 12 weeks or so, are excluded. So there's going to be a small number of patients for whom a medication like this may not be appropriate. But generally, patients The vast majority of short term changes in LDL, which we're likely to see, particularly with the higher doses, are something that their physician can monitor because LDL is a risk factor over the long term, not over the short term for cardiac disease. So in that short term phase where you're demonstrating primary efficacy, I don't think LDL management will be important for the vast majority of patients. During the long term phase, where we are titrating down the dose to maintain efficacy with sort of the least amount of immunosuppression that the patient needs, That will have a positive additional benefit of also lessening the impact on albumin and LDL since both of those are highly correlated with dose. And I'll throw this one in here. Can you remind us, I mean, Roivus has a lot of abilities for A lot of tech that they can use to accelerate clinical trials or keep them on track. Maybe highlight a little bit how you'll incorporate that into the MG trial. And do you think you can get the trial done quicker than, say, another FcRn in MG? Is that a possibility because you have more access to that tech look of it? Yes, yes. I think that absolutely, this is a key area in rare disease development to be extremely knowledgeable about any possible way to accelerate enrollment because time is money in a really big way for clinical trial development. So we have partnered with Royvant on some of those initiatives, even prelocovant, kind of when that work was just being it was a little bit more nascent. And there's really 2 categories that we spend a lot of time on. 1 is Site relationship management, really getting to know the sites. Each site is unique. Having enough sites so that you have, particularly in times like COVID, Geographic variability. Some sites are doing really well. Some are maybe struggling. That was apparent in COVID times. Having more variability geographically was really beneficial. And with that variability comes a need to understand what how does that site work. There's really not you know OneSite, you know OneSite. So I think that's where smaller companies with the model of ownership that Matt and Vivek both highlighted earlier, where People on our team are just 100% focused on making sure that 1401's programs are successful. They're highly motivated to get to know those sites and make sure that they're working with them effectively. So that doesn't replace data. That's a foundation. But it can really be accelerated by data because if you're getting the data faster in terms of a missed lab and In the prescreening phase or some you're noticing a pattern of something happening across a couple of different sites, that allows you then to take advantage of those relationships that you've built in a meaningful way. So the 2 work actually really well together. Great. And then thinking about Catalyst, there's a lot of short term investors out there. So I know the trial will be starting. It'll Hopefully, agree and align with the FDA on what the design should be. I think you've highlighted your Analyst Day coming up early next year. What do you see as the key Value drivers for Immunovant over the next 12 to 24 months. Yes, right, right. Well, as I mentioned earlier, just to restate it, Getting alignment with the FDA by the end of the year, I think that's a really important milestone for us. It allows all of the other great work that we're doing to be taken more seriously externally because we have now the green light on our lead pivotal program. So I think that's a big multiplier in everything we're doing. And then we've also said that right behind the MG program are the thyroid eye disease program and the warm autoimmune programs in terms of getting alignment with those relevant divisions and crafting what the next phase of study will look like in those two areas. And then the 2 new indications that we mentioned, so a lot of new activity that will be announced in the 1st part of the year. I think the new indications It won't be announced in Q1 with the R and D Day, but rather the focus will be on the protocol design for MG, thyroid eye disease, hormone autoimmune hemolytic anemia. How quick do you think you can get the trials up and running, say, for MG, once you get alignment, Given that you have these relationships with the sites, how quickly do you think you could get it going? Yes. We've said in the early part of 2022, and you know the various steps that you have to have is You have to have your protocol, once it's finalized after discussion with the FDA, you'd have to pull that through the CRO and IRBs and everything that. So that piece isn't really enabled by data, but we will benefit from having preexisting or previous trials in myasthenia. Last question. There was this perception after the TED data came out that TED was dead. I think we've all Talk to doctors, and we all don't believe TED is dead. TED is a real market opportunity for you. And a lot of doctors have told us that they Despite the cholesterol profile, there's a real need for a subcu drug, and there's some side effects with the current therapy. Maybe just comment real quickly on your view of the TED market. Help us feel better. Ted isn't dead. It's for you, for immunomat. Yes. I mean, so just very quickly, thyroid eye disease It's a really amazing opportunity because the patient need is so strong. We're seeing that the TEPASA uptake has been tremendous. And that's certainly partly due to the fact the strong efficacy that they've demonstrated. But it also just there's so much unmet need in thyroid eye disease. And across a wide variety of immunology indications, it's just never the case That one size fits all, that one medication sort of takes this huge amount of unmet need and takes it to 0. There are going to be different patients are different. So I think there's a lot of opportunity in thyroid eye disease. And although we haven't disclosed the extensive data that we do have from the trial that we had to stop prematurely, I have said that we saw strong hints of efficacy, maybe not at the level of TAPESA, but definitely separating, we think, from placebo. And so given the strong unmet need and the efficacy we're seeing, that gives us a lot of conviction that thyroiditis would be a good opportunity for Great. Well, thank you, Pete, for having me. Thank you.