Biogen Inc. (BIIB) Earnings Call Transcript & Summary

All right. Good afternoon, everybody. Welcome back. We are lucky enough for our next session to have Chris Henderson, who is the Head of Research at a little company called Biogen. And Chris, you've been in this new role now since March, but you have been in this organization for almost 6 years.

So maybe you could just give us just a sense of behind the scenes at Biogen, talk about the general strategy of R&D there, your research capabilities, the R&D mantra, how maybe you're even different from a few other organizations, just quickly just set the stage?

Yes, I think that's a really good way to start, actually, because I think our main mantra is what separates us from other companies. And that's a strong focus on neuroscience. And this is just a huge unmet need going forward for the coming century. And we feel it's the right time to be taking this island. And this focus has got really lots of advantages for us in R&D, actually. I mean, first of all, it allows us to go deep in each disease. And so if we've got the in-depth notes that allows us not to case over the purpose, we've shown that how valuable this is, for instance, in the past in multiple sclerosis and SMA. But for something like I hope we'll talk about a bit later, ALS, just having a first trial in that disease teaches us so much about expanding that the depth is important. So I think there's another thing about focus on neuroscience, which is the strong interconnection between the [ general ] disease areas. So some target, in fact, we will be working on a target like [indiscernible] as it has implications both for Parkinson's disease, obviously, but for rarer diseases like MSA. Really good example, I think, is the work we've done in biomarkers and especially biomarker disease progression. So one thing we've talked about a lot, and I think have made a lot of progress on using newer filament levels in serum and CSF to measure ongoing neuronal damage and neurodegeneration. And there what we learned from MS, what we learned from ALS, which is some of the most advanced areas and SMA where we've shown a drug responsive effect really now impacts every program we take going forward and should allow us, we hope, to take earlier decisions on some programs. Yes. I think the interconnections we have too is across modalities. So obviously, you know about ASO, SPINRAZA and what we've learned for that is really helping us expand the pipeline for ASOs across the whole disease spectrum in neuroscience. And I think today is talking about R&D environment research, but I'd like to say that from the very beginning, when we're thinking about a new disease or a group of diseases, we do think about the commercial impacts because there are so many potential synergistic adjacencies. If you want to take on a bunch of diseases and they have -- they're being treated by the clinical, same clinical endpoint, the same commercial point of start and the same people looking at the patient, then we can help more patients with less upfront investment per disease. So we -- I think one other strength that we have, so all the different modalities available to us now, especially with the new focus on gene therapy. So we can follow the biology and that's really the mantra that comes down from Michel Vounatsos, every time he talks about research, which is to follow the time. And we can use that both to drive our internal research operation, which, I think, is reasonably well-respected, but also to drive some of the fantastic partnerships with [indiscernible]. So on that basis, I think we've built a pipeline in neuroscience that we are really pleased about. We've added 15 clinical programs since the beginning of 2017. We've got 6 assets in Phase III, 12 in Phase II and 10 in Phase I. And just as importantly, we've got a whole series of preclinical assets that are yet more novel, and we think, yet, more groundbreaking. So this focus on neuroscience allows us as a reasonable-sized company, we think, to have the most impact.

It's interesting. I don't think Biogen gets much credit for its pipeline. It's viewed as [indiscernible], very high risk, high-reward type of projects. What's your thoughts on that view? I mean, do you agree with it? What -- so you're taking to mitigate risk with steps -- what steps to lower the risk of the portfolio, if that's the goal?

Yes. Well, honestly, I do agree with that point of view. Seeing from the inside, up closely, high visibility assets are important for Biogen. They're important to patients, but we look very much with a portfolio in mind as what's coming through. And so you talk about high-risk and high-reward but the -- it is the reward that drives it. But we're driven by the patient needs. These are dreadful diseases, they are more and more abundant. And we feel that we can -- we are well positioned to deliver on those needs. Overall, we feel the risk may be decreasing into the risky area, but it may be going down. We've got treatments now for diseases that were unthinkable before in terms of therapeutics like the ones we have for SMA, for instance. I've talked about the biomarkers. We've got much better human genetics and so on. So the risk is decreasing. And I'd say, as far as risk reward goes, whatever the conversations about drug prices, something that's really innovative, that really makes a change to patients live, it's going to be painful. And we are not indicating the me-too project -- product. So -- but you're right, still about this. And we think about it very deeply. And then I try to think about it concretely actually and just at the research level. And we've taken a whole series of steps to reduce the risk. And I'd say the single most important one is that more and more, we're taking what we call a human-first approach to drug discovery. So obviously, using genetically validated targets, and we'll come back to some of those probably. But just using all the evidence we get from human to human pathology, from other drug trial outcomes, from natural history studies, there's an -- actually other clinical trials. So we think we're going forward with much better targets than we ever had. And as a result, we're attracting, I think, some of the best people. This is a place to do neuroscience, if you're keen on -- you have a great neuroscience and you're keen on applying your knowledge to making drugs for people. And the biomarkers, I think, are a major effort on reducing risk. They should allow us not only to choose better target, but to terminate trial earlier, if really things are not going the way we think they are. And they were allowing us to select patients better for the trials. And I think Biogen can really claim to have lead the way there. Going back to the [indiscernible] drug, we won't be talking about much today, but the inclusion of amyloid PET as an inclusion price here and there, which is just a really important step forward to the field, I think. And I'm pretty sure we'd be talking about the opicinumab drug that you know very well. And the imaging data to look for white matter integrity there, another way of focusing on outcomes. And just last but not least, I think. We agree with everyone. We need to have more digital readouts. And that includes things that are happening in the real world, it also includes improving the sensitivity of clinical tests performed by clinicians in hospitals. And where we've got quite a lot going on for Parkinson's disease, for instance, in the last case. But we're really pleased to have some things that go well beyond R&D, the applications that's called Aby and Cleo and Neurodiem. And there are ways for patients to -- independent of the drugs they're on, by the way, and whether it's the Biogen drug, to receive curated information that helps them respond, helps them know what they need to do, and recently, it's been really valuable in providing them with MS-specific insight about COVID, for instance. So yes, there is a risk. It would be stupid to say not, but the reward is top grade and [the need is still ] great. And we're trying to think of everywhere of improving the risk benefit ratio.

When you think about whether -- in neurology you think about the risk spectrum, right, from highest to lowest risk and maybe Alzheimer's is the highest in -- and I don't know, maybe we'll pick another CNS area like epilepsy that might be lower risk just because there are so many proven areas that have worked. Do you try to have drugs across that spectrum? Or are you really saying, we need to hit the high unmet need areas. And unfortunately, those just tend to be high risk. And the way we derisk them is what you just went through, biomarkers, target engagement and things like that.

I think, overall, what you say is correct, but I don't think you're implying that there's no unmet need in epilepsy, there certainly is.

Well, you know what I mean? Lower versus higher, I meant.

I think it's -- we don't want to have only high-risk programs. If there's a place where we can make a significant impact based on our modalities, based on our biology, based on our insights into the disease, we'll do it. We just don't want to make a me-too impact. So we don't deliberately choose all areas of a high risk, and we want to find lower risk areas. And I think maybe we'll come back to this later if we're going into ALS, sporadic ALS is a high-risk area. It's been a high-risk area for as long as I've been working, which is a long time. And yet now by going into the monogenetic familial genetic forms, they clearly are lower risk. But they are not no risk, they're lower risk. And I think we're seeing the first spines of that being a great approach, actually. So I wouldn't want you to go away with the idea that we deliberately choose risk because there's nothing there. But if we choose only areas where there's lots of drugs available, then we're going to need to, and that's not Biogen.

I want to talk about approaches to Alzheimer's that go beyond AMI alone. What's your view of tau? We just had a panel with 2 physicians who spoke about tau. We had AC Immune, CEO, go through a little tutorial on tau for everybody and their approach. Talk about Biogen's view of tau, the different approaches and what you're doing.

Yes. I mean, we think tau is a critical target right there, and we've got 3 clinical stage programs and another one coming. And we've also got preclinical program and -- that we're using multiple modalities to go after it. I mean it's striking but as opposed to APP, most of the evidence for tau comes from examination of postmortem brains. And we think, it's so striking that the facial distribution of the tangle, which are the aggregates of tau, that's a characteristic of AD. The density and the facial distribution really correlate quite well with the various diseases. And as I think you know quite well, in other diseases with tau aggregates [indiscernible]. Actually, the place where you find those in the brain correlates really quite well with the specific clinical phenotypes. So there's a real set of strong basis implying that tau is a driver of these and in particular, of AD. I mean, we should just all be open with the fact there is one big unknown, we simply do not know which ones of tau drive disease, and we won't until there's a successful clinical trial. So the only way of getting around that is to attack tau from multiple angles, and that's what we're doing. And so as you know well, I think, we have multiple antibodies, but they're mainly targeting extracellular tau and should help to prevent tau spreading. And -- but we also recognize that a lot of tau is inside cells and that maybe those antibodies won't affect that. We think that the extracellular tau, which is increasing AD, and maybe we'll come back to that is really important. But we're -- that's why we're also developing with Ionis. And as you said, [indiscernible] basics at the moment, which should go to all the potential measures of tau pathology. And these trials are the way we're going to better understand Alzheimer's disease and better help patients.

Well, I mean, it's interesting, like is tau more important than Abeta? Are they equally as important? Do we need a combination of the 2 to kind of get there?

Yes, I wish I asked -- we knew the answer to that. And I'm asking your question says...

Don't worry. We're going to hold you to this for the next 5 years. So don't worry.

Don't worry. So will my bosses. No. I mean, we just need to develop a greater understanding of Alzheimer's biology, I think. And until we do, we're looking at isolated data points. But there's obviously quite a bit of evidence out there that the 2 mechanisms are linked. And so mouse models using transgenic mice has expressed the amyloid. They suggest that you also need to have tau there, if you're going to see the toxicity of the amyloids peptides. So those are mice though, that's not the same. I mean what's striking is that in Asia, you do see the increase in the tau and the phosphate tau in the CSF. And in both the EMERGE and ENGAGE trials, we got a reduction in those, circulating tau levels and even a dose proportional response in the EMERGE. So -- and other similar data have been seen in other AD trials. So that's the gist, I think, in humans. And -- so I think one of the strong rationales going after tau is that the aggregate that appear later in AD patients can do the amyloid. And these correspond quite closely to the onset of some of their cognitive and other symptoms. So there's a feeling that the tau therapy may be able to target patients slightly more advanced. Once again, that needs to be proven by trials, but that's what we're testing very actively. So you asked about combination. I mean, if as current wisdom would have it, APP is the initiator of disease or Abeta is an initiator and tau is the executioner, then -- so both stopping new fires and putting up existing ones would seem to make sense to explore for mild to moderate Abeta. Honestly, before we do that, we need to learn a lot more about the individual agents and drive from how they work.

Right, right. Well, if you could talk about 092, which is your antibody. Maybe you could talk about that and how it works and what kind of data do you have so far that gets you excited? And what do we expect? And...

Yes. I mean, I think what the data, that really excites us is the degree to which it will suppress the levels of unbound tau in the CSF. And so this is an antibody data and goes against an internal epitope, and that epitope is found in both in the of full-length versions of the protein that can aggregate and also these fragment of tau internal fragments that are thought to induce excited toxicity by overstimulating neurons. So we have to pace one data from the BIIB092, a trial in PSP. High dose, single dose in human volunteers and all multiple IV infusions. And in all cases, we saw a very significant decrease in levels of the unbound tau, going up to 96% at the highest dose and the longest time point. So this is obviously true for asking the right question. And we believe that asking that question in Alzheimer's is important now. And so we believe we can lower tau. We now need to know what that will do for patients.

You feel like the anti-tau mechanism is more validated for Alzheimer's than the PSP? We've seen you and another company have problems in PSP with this approach.

Yes. Honestly, I do, and I would just said that even before the news of the PSP trial. Because I mean, I think it's important to remember that AD and PSP are really quite different diseases, I mean, different regions of the brain affected and the tau tangles are in different places. And actually the molecular forms of tau that are observed in the brain are quite different between the 3R and the 4R. So that's already a way of saying we might expect quite different results. I've already said that the fragments of tau are specifically elevated in Alzheimer's, but not in PSP or any of the tauopathies. And as we look at the trial, what we did in PSP and what we're planning to do in Alzheimer's, the PSP patients were mostly further along in the disease course, you might call it moderate disease, whereas we're hoping to go in MCI and mild data with Alzheimer's. So -- and last but not least we -- kind of in Alzheimer's, we've got the potential to benefit from patient selection using the tau biomarkers. And the current tau PET prices don't recognize the PSP aggregate. So none of that is a guarantee of success, but I think the arguments are stronger and what the PSP gets us is a very strong tool to ask the question.

We all hope that, that is true very much. Let's switch gears to neuromuscular. That's -- and an area of focus for your career, even before you joined Biogen, right? So we've all watched the SMA space, we have 2 products. There's going to be a third. But if you just kind of move away from SMA, what are some of the most exciting places in the field right now? What are you excited about?

So yes, I think I have to say the single thing I'm most excited about is our new ASO called tofersen. This form of ASO that's caused by mutations in the SOD1 gene. This is a relatively rare form of the disease, and we'll maybe come back to that. But it -- this ASO really enables the selected reduction in levels of SOD1, its dose dependent, and it's reversible. I mean there's a beautiful set of preclinical data actually that show that. So if I were to say where this plays a role in Biogen's pipeline, it's highly visible up and down the company actually. I'd say our first deliberate step to build an ASO portfolio that will support adults living with newer degenerative disease. So that's sort of a big claim for a fairly rare subset of ALS patients, but we saw, as I think you've seen, some very helpful signs in the small group of patients in Phase I. There's an ongoing Phase III BALANCE study, and we need to wait for that before affirming anything more. But this would just have a lot of impact across the field. I mean, obviously, first and foremost, if it works out, it will have impact on these patients, some of whom have the most rapidly progressive forms of ALS. And many of you on the call know that this is a really bad thing to have. I think more generally, it -- if it pans out, it will dispel the idea, which I'm thinking, too negative, but treating patients with over clinical science is inevitably too late, treating earlier may be better. But I think if we rule out the possibilities of treating patients who are already sick, that will get you narrower, and our first data seem to suggest that's not the case for SOD1. We -- plenty of people say to us, but ASOs were validated with SPINRAZA, and of course, they were in wonderful ways. But that was an ASO for correct splicing rather than reducing gene level, and it was used in children. And so if the SOD1 data continue as we've seen, we will have a way of reducing gene expression in adult patients and using an RNA -- RNase H mechanism. I think that would be a big breakthrough across the board for us. And to be fair, that seems to be the data coming out of the Huntington ASO trial that Roche is conducting with Ionis. So I think it's a really good time for ASOs in adults. Just overall I've been working on ALS much longer than [indiscernible] public webcast. But this will create the first significant crack in the glass ceiling for people affected by all forms of ALS. So I'm really excited by that, and it couldn't have happened, I don't think, without a sustained commitment from Biogen. Honestly, the reason that I'm here, I have a very happy academic career at Colombia, was just the way that Biogen has been so upfront about this from the beginning. We have -- about 7 years ago, we had a failed trial with a small molecules that's called dexpramipexole, that was in the EMPOWER trial. And immediately afterwards, George Scangos who was the CEO at the time, got ahead and said, "of course, we're not stopping. We're out to help patients, and we don't have to expect to have successes all the time." And Michel Vounatsos and the Board have just really been equally hardened supporters of this approach and recognizing that you need to go step wise. And so this has really allowed us to build an explicit multiyear strategy. And actually one thing that George Scangos also said is that was an old-fashioned trial, referring back to the EMPOWER trial, we're never going to do one like that again.

Old fashion meeting. What I would...

Meaning, we didn't know the target. We didn't have a biomarker. We didn't have it. So on a -- I get told off I recite too many of those. But as a result, honestly, ALS trials are just really entering a completely different era, once [indiscernible] into the last 30 years. So we have much better target, much better preclinical data. Biomarkers that are really informative. We've got patient stratification and we've refined outcome measures. And when we understand the disease a lot better. And so I really think those are all needed, we're going to take the measure of the ALS challenge and the tofersen is just the first for the series from Biogen, it recognizes what we're trying to do there.

Yes. And I mean, obviously, SOD1 ALS is just a small piece of ALS. I mean you've got a pipeline that moves into the other forms, right? I mean -- so how do we go after the big population of it?

So I think we continue our very conscious strategy to build up to them. So we -- calling SOD1, we already have a publicly announced trial from more of a frequent form of genetic ALS caused by the C9orf72 drain and which can also provide some links of frontotemporal dementia. That's about 5% to 10% of the cases. But we've recognized from the beginning that we also want to help patients with a sporadic disease. And there will never be a single target for that. And so there'll never be a perfect preclinical model by definition, and otherwise, it wouldn't be sporadic. So what we really need to do, and I think we've succeeded in doing, to some extent, is to maximize the quality and the quantity of the human and preclinical rationale we have. And we need to think about diminishing the cost and duration of the proof-of-biology and proof-of-concept trial because in an era like this, it's inevitable, there will be failures, but the rewards would be so high. So I've also shared with you actually for the first time today, in more detail, a program that we -- I believe, or we believe is the best example of a target that bridges the genetic and sporadic forms of ALS. And this target is called ATXN2, A-T-X-N-2, if abbreviated. And it's first known because long nucleotide expansion repeats in the gene causes a disease called SCA2 or spinocerebellar ataxia type 2, which is a movement [indiscernible], and it's one we're actually interested in, like other SCAs. But it was more recently when a series of beautiful biologic back at Berlin, actually not done in Biogen, it was discovered that medium length expansions in this gene are strongly associated with an increased risk for ALS. And it's been shown that actually patients with these medium length extensions, also have a more aggressive forms of ALS. And so that's one genetic link, but also every single sporadic that has been examined, has got problems with the way ATXN2 is localized in cells and especially in the neurons that are affected. So it's probably the best example we can hope for to target with prioritization in sporadic ALS, that's not to say 100% probability of success, but lots and lots of good data. And so we'll soon be announcing, we hope, with -- in collaboration with Ionis, the Phase I trial of an ASO to reduce ATAXN2 levels as well. And there's a build-up to that, we've really confirmed and extended some of the published preclinical data, which shows a protective effect of ASO in multiple mouse models. And the human genetic data about the more rapidly progressing form should allow us a very helpful patient stratification. So -- and this -- now we're going to sporadic ALS but this trial too will learn just so much from what we've gained from the SOD1 and the C9 trial. So that's the target that's been in the literature, that we are starting to talk about more. We have talked already about another approach to sporadic ALS and the drug we call BIIB100. And lots and lots of convergent biology around ALS from different model systems and from human pathological material. So just there's a common defect that affects the way molecules are taken from the cytoplasm to the niches of the cell and back. And there are lots of mechanisms for recycling to occur. But this small molecule, which inhibits a protein called XP01, has shown benefits in multiple models, and it's right on spot for that particular biology. And so it's currently in Phase I trial for ALS. So this will be our way of knowing the degree to which the biology is important to ALS. So I'm very excited about that program so...

What about SPINRAZA, what are you doing as far as life cycle strategies initiatives?

Yes. I mean, honestly, SPINRAZA is such an amazing drug, and I would say that have a different work at Biogen. It's just sort of changed the [ effect of ] all we do. And we believe we've established a foundation of care in SMA, but and we've got long-term safety data and the long-term efficacy dataset. We can talk a bit more like about [indiscernible], but we've never said SPINRAZA is a cure. We recognize, there are ways of enhancing its impact for patients. We don't think that any of the drugs out there at the moment are a cure, it's wonderful situation to be in. But we should still look for a further improvement. The first we're doing for SPINRAZA is that using PKPD data from one of our studies, which is called ENDURE, they certainly suggest that any individual with a higher level of the drug in CSF will achieve greater improvements in some of the clinical endpoints. And so we wanted to make sure, first of all, it was safe to increase doses, which we think it is. And so the DEVOTE study is being started and using a 28-mig dose instead of a 12 mig. And we hope that this will show these higher doses are even more efficacious. And we're testing them across a wide range of SMA patients from infantile to later on platform. And in terms of following up on SPINRAZA itself, we -- I think we've taken a look at the data, a really exciting data. I think we just released on our longest -- on the longest study of presymptomatic patients with SMA called NURTURE and that was presented at the Cure SMA meeting just recently. And so this works with patients who've had up to 4.8 years of continuous stream of SPINRAZA. 100% of them are alive, none required permanent ventilation, 96% are now able to walk with assistance. And these are patients with SMA copy numbers that was predicted a much more severe clinical outcome. And so we're extending that study to take it up to 8 years of age. But even then, we believe, obviously, especially in terms of patient convenience, that can be scope for improvement. So we're collaborating with Ionis to think about new ASO candidates that may have greater duration, for instance. We've announced a strategic collaboration with SkyHawk to develop a small medical spicing modifier. And we hope that we'll be able to develop a small molecule that has the same effect without some of the dose-limiting toxicities that might otherwise be seen. And obviously, we're working very hard on how to administer ASO. This is important for SMA, it's important for every disease we're going into, in terms of devices and others, and we are actually working on that with partners.

Let's flip gears to Parkinson's disease modifying therapy? Can we get one?

I hope so. It's a huge news. I mean, in some ways, that kind of feels under the undoubted success of the [indiscernible] therapies, which are wonderful symptomatic therapists, but we need to have disease modifying. That does not low the ongoing down -- ongoing neurodegeneration [indiscernible]. So we're looking at wholesale as a target here, but the foremost for us and obviously for others is alpha-synuclein, there's such strong genetic evidence linking new alpha-synuclein to PD both in terms of patients with -- due to patient's interpretation of the gene and others who have -- from the [indiscernible] study, showing a risk. And so we are back into the moment, and I'll come back to other ways of doing it on an antibody. Once again, that's in Phase II trials and should have an interim readout later this year. And the specifics of this antibody, it certainly goes after the aggregated forms with synuclein because one is like trial, we don't honestly know which are the toxic forms. But here, there are lots of arguments for thinking about the aggregates of a formulated budget themselves and so on, are going to be the culprit. And when you look at the CSF or PD patients, for instance, there's a lot of alpha-synuclein there that's in a normal form. And really any of the subject that in this misfolded form that is targeted by our antibody. But we believe that it's by targeting that form that we'll change the trajectory. And though we just published a very nice, I think, preclinical studies -- set of preclinical studies, showing the efficacy of this in terms of model. So that's the first thing we're going after. But here as at in tau, it's predicated on the hypothesis of spreading of alpha-synuclein and the role of extracellular. I would argue that for alpha-synuclein, it's even stronger that hypothesis based on preclinical data and some of the pathological data. But once again, we are developing an antisense oligonucleotide that will be mechanism blind that if we can safely lower the levels of alpha-synuclein, which we believe, we believe we can reach the relevant regions of brain. And the -- then that will be -- allow us to just ask whether alpha-syn is important. And maybe there's a world in which it's more effective than the antibody because it's targeting mechanism that are not affected by the antibody, but it may be that the antibody will be equally effective and more convenient. And so that's why we're derisking by taking both approaches.

Yes, there's like 7 or 8 different companies that are going after alpha-synuclein. I mean can you even differentiate what everybody is doing?

Well, yes. I mean, some are further ahead than others for start. And there are different forms of alpha-synuclein, recognized by the different antibodies. And so I hope that we've chosen the right one. But this is the type of question that will only be resolved by experiments in humans, the clinical trials. We are working very hard as well to improve our repertoire of biomarkers and clinical endpoints that can allow us to see changes faster than before. And as I alluded to some of the work we're doing in digital studies to make some of the behavioral endpoints with the pass at the clinical scales, even more robust and even more accessible. So I think we'll move forward on this. And it's the trial that will tell us. We just have to find ways of doing this in the most effective way possible.

Yes. I mean, I don't know anybody else who's also got the antisense and the monoclonal kind of right, the 2 approaches. Everyone's got to pick their...

No. No, I thought you were just referring to the antibodies. I believe that's a real strength.

Yes.

We will know a lot more about alpha-synuclein as the target at the end of -- both -- well, during both of these trials.

Yes. And when do we know? When is the data coming? I just don't remember.

The -- for the -- there should be an interim analysis at the end of the placebo-controlled phase during the coming months for the BIIB054. For -- the ASO is behind so we don't have data for that.

Right. Okay. Very good. Neuro repair. It's very interesting. We obviously wrote that recent report on opicinumab. I mean, like anti-lingo, I mean, fascinating. I mean I looked at all of the data, you look at the post-hoc analysis, I mean, it makes sense. So I don't know, give us -- what's coming? First of all, explain to everybody why you're so confident here in the post-hoc analysis for this drug?

Maybe I will start with the complement, not because that's a especially difficult question. But I felt I learned a lot about this by reading your paper, Marc. So I thought it's really well balanced. So yes, I mean, you say, why are we so confident? I think we just realized that as we go to a new area, we're going to have to learn from successes and failures. And not to -- I'm coming back to opicinumab, but just to take neurorepair. I mean it's got to be one of the more exciting areas in neuroscience at the moment in terms of targets and so on. But anything applied to the clinic is just scratching the surplus. So like any new field, we're going to find targets that work. We need to have other biomarkers and so on. So we're really excited about this readout, which also should be coming in 2020. But -- and there's reason for that. You refer to the imaging that -- we think that learning from the SYNERGY study, we can use imaging to identify a subset of patients, where the criteria makes sense, where you've got white matter where the [indiscernible] is still intact. Without that, it will be hopeless to remyelinate. And the -- overall, the structure has integrity. And one reason maybe for the lack of effect in SYNERGY was that there wasn't -- the information wasn't sufficiently presented because we just had AVONEX there. So as you know, well, we've got 3 different disease-modifying therapy groups now, the [indiscernible], we've got TECFIDERA and we've got TYSABRI. And so that hypothesis, I think, will be well tested by this trial. And the -- we're using this overall response store, which has got several advantages, I think, it was analyzing SYNERGY. But I think it's real advantage is that it integrates both improvement and worsening and disability over time, whereas the primary composite endpoint that we used in SYNERGY was really about improvement only. So it may not work and that's really -- I'm only speculating the hope for anything before seeing the data. And I sadly haven't seen those. But I think some of the things we'll be looking at will include the specific patient profiles. The drug regimes they have been on. We need to look at these endpoints in a different way they read out in the patients. We need to know that the imaging evidence we have from each of them. And one thing I think it's important to say is that AFFINITY is testing formally for improvements in baseline this ability, which will be a wonderful outcome. But we and now our advisers think that we could show an effect on flowing progression, that would also be great. So we're obviously looking carefully at the data for that but...

Are we getting this data soon? I mean previously, we thought it was going to be sometime mid-year into third quarter, but I don't know, is COVID causing a delay or...

There's probably a slight delay, and I will refer you to the team for a precise communication on that, but not massive delay.

Okay. Good. And 061, which is another approach to -- I mean, besides to oral, what else makes this different approach?

Well, I'll say, I'm quite excited about that one. Also in preclinical models, it shows very nice effects on remyelination and it does depend on [ unknown ] forms and we deliberately not disclose the mechanism of this. And honestly, the reason for that is that we think it's catch into a whole set of pathways that could be really important, and it could lead us to develop other drugs that are related to those. But I think the oral is not insignificant either. It just shows that when we want to go after a particular disease, or in this case, a therapeutic outcome, which is remyelination, we do go deep enough to decrease the risk and to learn more about the biology at the time. So I'm sure that we'll gradually share more about BIIB061, but it's clearly the thing from the lingo mechanism.

Yes. Is that something we're going to learn more about, you think, this year? Or we might have to wait till next year?

About the mechanism?

Yes. Is that this year?

I wouldn't like to promise that for this year, you'd know more about the mechanism. We're still [indiscernible] in depth ourselves, and we haven't [indiscernible] communication strategy. So...

There's another company...

And honestly, that's not the basis of all conservative, I don't think. It's just trying to be rigorous about the time. When -- you can summon an up a mechanism overnight, if you like, but we like to share mechanism where they are deeply demonstrated. And we put myself behind.

And this [indiscernible] W approach that's another company's approach to repairing myelin. Do you have any comment on that? Does that make sense to you?

Yes. I mean, I think I'm not going to comment on anyone's clinical trials, especially for the quite early ones. But I mean, I just say, especially the progressive aspects of MS, the field as a whole needs to broaden and deepen the base of target. It's been so dominated by some of the immune approaches, focusing in a very exciting [indiscernible]. But think of the impact, we need more targets in a lead market pieces. So I think endogenous retroviruses, and it's always an interesting theory. They be linked obviously to inflammations ALS. In the past, it's been difficult to prove some viral hypotheses, but these might be the right one. But we are actually trying to go much deeper, well, not -- in addition to that, we're going to look at other target. And particularly on the highlights how much we're trying to use human genetics. Initially, human genetics was a great reinforce of the immune-related mechanisms in MS. But as people started diving deeper. I think there are big clues there for helping with the progressive disability. And so we want to have that human data on the target, that let's us take the risk to move those forward and really have a game-changing therapy for that aspect of the disease.

Yes, yes. Last topic I would ask about is gene-targeted therapies. You have this relationship with Ionis. Obviously, you delivered one major success already. You got other programs in the pipeline. You now have to deal with this Sangamo Therapeutics for gene therapy and AAV gene therapy. Is there overlap with these modalities? Like how do we think about these? Is there an advantage to one against the other?

Yes. I mean, I think it's a very good question, actually, because they're both going after many cases [indiscernible] but -- and so that you could call that the overlap. But I actually think there's a lot less interference than some people might say quickly. And for the foreseeable future, those 2 modalities are going to exist in common, and that's good for patients. Both of these fields, even ASOs actually are still at an early stage compared to something like small molecules in the CNS. And we've got a lot to learn about the relative benefits and risks. And both fields are evolving very rapidly at the technological level and obviously gene therapy no less than ASOs. And if we're not involved in both of those, we just won't be able to best make physicians to help patient. But so I just think it's important to remember that there are objective differences. And so I think everyone would accept now that ASOs and AAV, which are the most common gene therapy vectors, just reach different classes of cells in the brain. The impact of that is going to vary from disease to disease, that could be decisive in the favor of ASOs for one disease looking to for [indiscernible] as a whole. And same is still emerging, but the same is going to be true for some aspects of safety from reversibility, probably manufacturing and patient convenience, which I'll refer to. So I just really think that we should be going through the thinking of patients needs, thinking of the target. And having these 2 approaches will just be enrichment of the immunotherapy for the moment.

Yes. And then maybe just lastly, in conclusion, I'll kind of open it up for you. Anything in the pipeline that we didn't talk about that you specifically kind of want to highlight or anything you may be moving into, you want to talk about?

Yes. By the way, there's lots of things in the pipeline we haven't talked about, and that's what makes it so exciting to be [indiscernible], to be quite honest. And we are dedicated to building a multi-franchise portfolio. And I think we can call and SMA core businesses now. But obviously. It has not it takes your attention that we're interested in the Alzheimer's field and ALS, but we've got other emerging growth areas, including ophthalmology and lupus in some of the genetic and [indiscernible]. So we've got following the Lifestar acquisition, we've got 2 late-stage ophthalmology assets in the clinic. And BIIB059 BDCA2 antibody is -- has shown some very promising result in the cutaneous lupus. And so those are broadening. And I mean, if I can take 2 minutes just to sum up this conversation, which has been great. Thanks. We do acknowledge it's difficult. It's a neuroscience field, but we're just so deeply motivated by what's happened in the past for us with MS and with SMA. I think we can claim to develop life-changing therapies there. And that's just a source of the such great motivation and pride. And yet there are so many diseases still waiting for something similar -- of similar impact. And so if we keep the focus on neuroscience, we really believe that we hope that it can foster much deeper know-how. We can get better targets. We've talked about that quite a lot today. We can be agile in where we expand into neighboring areas and synergies and medium-term goal, we find a way of doing clinical trials faster and cheaper, so that we can get drugs to patients sooner, but with the same degree of assurance of safety and efficacy. So I think the current state of our pipeline shows how active we've been and how we've been able to accelerate over the last few years. And with this very explicit approach we've taken now to risk management. I think that we should further strengthen the [indiscernible] for each asset, either in the pipeline now, the ones to come. So we feel very upbeat.

Well, thank you very much for joining us. Good luck with everything that you're working on. And if the other side of the house needs your help to get ado over the goal line, I'm sure you'll help them out just in case, right? If they need something?

I certainly will.

Thank you very much. Take care.

Thank you, Marc.

Yes.