Biogen at Stifel 2025 Forum: Strategic Shifts in Neuroscience and Rare Diseases

On Tuesday, 18 March 2025, Biogen (NASDAQ: BIIB) participated in the Stifel 2025 Virtual CNS Forum, where the company outlined its strategic direction. The conference highlighted Biogen’s efforts to balance risk, emphasizing investments in neuroscience, immunology, and rare diseases. The discussion included both opportunities and challenges, reflecting Biogen’s cautious optimism.

Key Takeaways

• Biogen is focusing on Alzheimer’s, lupus, and rare diseases to drive future growth.
• Lecanemab, a key Alzheimer’s treatment, is expected to become more accessible with subcutaneous and blood-based biomarker advancements.
• Biogen’s lupus program is unique with two Phase 3 assets employing different mechanisms.
• Strategic acquisitions and collaborations, such as with Hi-Bio and Stoke Therapeutics, are enhancing the pipeline.
• The company is prioritizing late-stage assets for franchise development.

Financial Results

• Biogen expects Phase 3 starts for feldsartumab and Zoranavirsen in 2025.
• A PDUFA date is anticipated in August for subcutaneous maintenance, with FDA outcomes expected by mid-2026.
• SPINRAZA’s PDUFA date in the U.S. is set for September.

Operational Updates

Alzheimer’s (Lecanemab):

• Intravenous Lecanemab is approved, while subcutaneous maintenance is under review with a PDUFA date in August.
• Subcutaneous initiation filing is expected this year, with potential approval in early 2026.
• An intrathecal delivery study completed ahead of schedule in 2024.

Rare Disease (SPINRAZA):

• High-dose SPINRAZA filings are underway in both Europe and the U.S.
• SPINRAZA remains vital for spinal muscular atrophy patients.

Lupus (Dapirolizumab pegol and lefotilumab):

• Biogen is focusing on derisked late-stage assets, expanding into immunology and rare diseases.

Acquisitions/Collaborations:

• The acquisition of feldsartumab through Hi-Bio and collaboration with Stoke Therapeutics for Zoranavirsen are key strategic moves.

Future Outlook

Lecanemab:

• Subcutaneous formulations aim to ease healthcare system burdens.
• Blood-based biomarker approval in 2025 is expected to enhance uptake.
• Subcutaneous initiation is projected for 2026.

Tau Program (BIIB080):

• Phase 2 study results are anticipated in 2026, with a focus on tauopathies and Alzheimer’s disease.

Q&A Highlights

Zoranavirsen for Dravet Syndrome:

• Demonstrated an 85% reduction in anticonvulsant therapy, maintaining 75% durability at six months.

Lecanemab Uptake Challenges:

• Challenges include product-related issues and healthcare infrastructure limitations, with a promising outlook for blood-based biomarkers.

Lupus Program:

• Excitement surrounds the unique mechanisms of action in Biogen’s lupus treatments, with SLE results expected in 2026.

feldsartumab:

• Showed over 80% AMR resolution at week 24, with durability observed up to 24 months.

In conclusion, Biogen’s strategic focus on neuroscience and rare diseases, coupled with a robust pipeline and strategic partnerships, signals a promising path forward. Readers are encouraged to review the full transcript for more detailed insights.

Full transcript - Stifel 2025 Virtual CNS Forum:

Paul, Moderator: Great. Good morning, everybody.

Happy to be moderating my annual panel where Priya has to listen to me pepper her with questions for forty minutes or so with Priya Sinhau, head of development at Biogen. Thank you, Priya, for joining as always. I’m gonna kick it over to you to just make some opening remarks on Biogen and give us a snapshot of the development portfolio, and then we can do Q and A. So thanks again, and take it away.

Priya Sinhau, Head of Development, Biogen: Thank you, Paul. Thanks for having me. It’s always a pleasure to join you. So before we begin, I’d like to point out that we will be making that I will be making forward looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

I encourage you to consult the risk factors discussed in our SEC filings for additional detail. So really excited to be here, Paul. As you may know, you know that over the last two years, we’ve really focused on efforts to augment the pipeline. And the main goal has been rebalancing the risk profile and investing to win in key areas of expected future growth. So in 2024, I think we made a lot of progress in our pipeline where we’ve prioritized key programs, internal programs where we believe that we have the opportunity and potential to win such as Alzheimer’s, where we were able to amend our Phase II study, cilia, for Biberi and accelerate a potential proof of concept readout next year in 2026.

We also got a positive Phase three outcome with our DAPI Phase three trial. And then we also focused on external innovation. And, you know, we had one, M and A with Hi Bio and we have feldsartumab now in our portfolio, poised to have three phase three starts in 2025. And then in addition, we did the, you know, collaboration with Stokke Therapeutics and brought in access really to Zoranavirsen. And that’s very exciting because we have the ex U.

S. Region and also poised to start Phase three in 2025. We’ve also advanced Lekkembi. We continue to focus on SkyClaris Pediatrics, which is really the next, you know, very important milestone that we are ready to get going on as well as SPINRAZA high dose where we had a filing already in both Europe and The US. So very exciting year.

And I think as a result of this progress, we’ve been able to focus now our development efforts on a set of really high conviction high scientific conviction, mid to late stage assets. And if we’re successful, you know, we could set up franchises in very key areas like Alzheimer’s, lupus, as well as rare disease. And these, we believe, are really core areas of expertise and capabilities. So we are harnessing that low volume, high value, sort of portfolio here. So very excited.

Paul, Moderator: Yeah. Okay. Great. Well, we’re going to try to take time and go through each of the assets you mentioned and a couple of the key questions. But maybe one more forward looking question for you just in terms of the whole where is Biogen going.

And I guess there wouldn’t be a Biogen panel without the token business development question. But as it relates to sort of analyzing the tea leaves in your guys’ commentary about BD and what you just said, Priya, about shifting the risk profile of your portfolio, how do you think about Biogen’s positioning in neuroscience going forward? I think if we rewind, right, you guys had a lot of, you know, super cool science, but high risk programs like anti lingo, like the LARP2 program. And it feels like Chris now talks a lot more about rare disease and immunology as key areas. So just as it relates to CNS specifically, is this an area you think they’ll continue to build out and take on risk in?

Or is it an area where you feel like your portfolio is full and you’re trying to continue to shift elsewhere?

Priya Sinhau, Head of Development, Biogen: Yeah. It’s a great question. And I think overall, what I would offer are two two important thoughts here. One is that neuroscience continues to be a core capability. It’s an area we’ve succeeded in.

We’ve often broken the ceiling there. We’ll continue to invest and keep our capability in neuroscience, but we’ve diversified. So we’re not just going to go after high risk neuroscience programs that will be a decade to kind of get to proof of concept. We are balancing that with immunology and rare disease, both areas which we I also believe we have deep expertise. So with rare disease, you know, we’ve had one of the best launches in, you know, projects with SPINRAZA.

We’re continuing to build on that momentum and then we broaden SkyClaris. And you can see that we broaden SkyClaris where it’s rare but also neuroscience. So what the distinction here is, is being confident in the data, being confident that when we get to late stage, we’ve derisked and we have a significantly higher POS and a probability of technical and regulatory success and payer success than we have maybe in the past. That’s what I will offer is a key change. And then immunology, I think I would say that, you know, it’s really foundational.

With multiple sclerosis, everything that we’ve been doing, immunology has been in focus. We’re really the only company now with two different mechanisms of action, both in Phase III for lupus as well as, you know, systemic as well as cutaneous for litefelumab. So I think that’s how I would think about it. It’s not a departure. It’s a building around.

It’s a diversification.

Paul, Moderator: Yeah. Okay. Fair enough. As it relates to taking on risk, what gave you and your team conviction about executing the SCOPE deal before Phase three?

Priya Sinhau, Head of Development, Biogen: Yes. Excellent. So I think overall, you know, just stepping back, Dravet is, you know, a very serious disease, high unmet need, no disease modifying therapies. The other piece I think to keep in mind here is that these children are often cycling through four to seven anticonvulsant therapies. And they really, we know that from the evidence we’ve seen and we’ve kind of evaluated, we don’t believe these really impact what the decline is from a cognitive functional behavioral perspective as we’ve seen kind of, you know, in scales like Vineland-three.

So what we’re excited about with STOKE and with Zorro Vinersen is that we saw the data, although it’s a small subset, we saw that in this population that had the background of, you know, four to five anticonvulsant therapies, including fenfluramine, you know, fifty more than fifty percent of the patients were on background fenfluramine. We saw an eighty five percent reduction in anticonvulsant therapy and then out to six months, still durable with about seventy five percent. That itself is very powerful. Well, we didn’t just look at that. We looked at the natural history that also Stoke ran.

They they have a three year natural history dataset. And then we looked at what were the trends on behavior and cognition on the Vineland-three. And we believe that this product can actually impact that the developmental kind of milestones and the behavioral milestones that so important for Dravet’s. And then, of course, you know, it’s genetically, it’s grounded in genetic evidence. Right?

Because we know that eighty five percent of Dravet’s occurs due to a haploinsufficiency of the SC one gene. And that then results in the sodium channel NAV 1.1 reduction, which then leads to an impact on the inhibitory interneurons and the interplay causing seizures. So we think that there’s not only mechanism of action belief here, but there’s a potential data that we’ve seen in the early phase studies that set us up for Phase III. Now, of course, phase three studies, you do need to get regulator buy in. And that was the other important pivot and anchor for us that Stokke had already discussed their phase three program, had obtained agreement with regulators in The US, Europe and Japan on what the Phase three program would look like, how it would be powered.

So we had a lot of data going in. And it kind of goes back to your first question because I wanted to say that what’s changed is we are not it’s not like we wouldn’t take a risk. The question is how calculated can that risk be, and are we confident that we derisk some things that we would want to with POC? That’s the main distinction.

Paul, Moderator: So, I mean, this is a tremendously interesting program. And just as it relates to epilepsy more broadly being kind of going through, like, it’s not a shift because I don’t think it’s ever gonna be broadly like this, but like a subtle shift towards precision medicine. We felt like one of the key questions with this program and, you know, obviously, given the mode of administration, this would be a big commercial swing factor to the upside, right, if this is successful is the cognition piece. And I was curious, you know, how you think about this question and whether you can think this question is relevant. But if you were developing a drug for cognitive impairment in schizophrenia, right, you’d you’d be pursuing a population that is not acutely psychotic, right, because the FDA wants you to decouple cognitive benefit and benefit on psychosis.

As it relates to the STOKE asset, do you look at that data and think, you know, this impact on cognition is independent of seizure reduction? And then, I guess, as you think about getting, like, a label for this and a claim for this and marketing this, like, does does that matter? Like, how should we think about that?

Priya Sinhau, Head of Development, Biogen: Yeah. Another great question. I think it does matter. And I think it matters because we based on our current understanding and all the data that we’ve evaluated, I don’t think it’s been demonstrated that just simple seizure reduction will lead to that cognitive, improvement. We think there could be some effect, but we think you need to do be doing more, really in terms of the mechanism of disease.

So addressing mechanism of disease is going to be very critical. And that’s why we’re excited because this is not just anticonvulsant therapy. It’s actually going for more than eighty five percent of what we know as causative biology. Plus, mean, you know, just having that data isn’t enough because that’s what you know from disease understanding. But then we saw in the small dataset, granted it’s small and it’s open label, but I think we have great teams within Biogen, and we’re able to really dissect these datasets to see whether we have enough confidence that tips us over to know that could this have the potential if the phase three is designed correctly to have disease modifying therapy.

And that’s what gave us that confidence. So we’re not just looking for an anticonvulsive therapy. We are looking definitely, it has to have impact on seizure reduction, and we think that’ll be contributing to outcomes. But we think it needs to have a distinct disease modifying therapy, which we believe this product definitely has a potential.

Paul, Moderator: Yeah. Okay. Great.

Priya Sinhau, Head of Development, Biogen: All

Paul, Moderator: right. Let’s maybe just do hits around the whole pipeline. So on leucanumab subcu, can you remind us of just the general timelines there? And as it relates to subcu initiation, how has the program evolved over time as it relates to doing more dose work? And what would you say the target product profile is, specifically as it relates to ARIA and whether you can get to a lower rate of ARIA?

Priya Sinhau, Head of Development, Biogen: Yeah. So overall, I think, very excited about the intravenous Lecambi approval that we got just a couple of months ago because this was a big debate out there about whether this product has a dual action. Can we actually have a label enabling update on that? And I think that was an important milestone because Lekambi is really the only product now where we say where we know that if you remove plaque, obviously, if you remove amyloid, you that translates to clinical benefit, but that benefit can continue and be durable beyond plaque clearance. So I think that was a very important milestone for us.

The other is that, you know, we remain in review for subcutaneous maintenance, which I think is gonna be very important, and we will get an outcome and we have a PDUFA date in August year. And why is that important? Because this gives optionality to patients and prescribers, could potentially alleviate some of the stress in the health care system. But importantly, there’s going to be this bolus of patients who are gonna be completing their eighteen month therapy or or such where they have the plaque reduction and potentially they could transition if we assuming we get approval for the subcutaneous maintenance. Moving to subcutaneous initiation, what we’ve said is that we will file that at some point this year and we expect an outcome, a regulator, an FDA outcome, before the first half or within the first half of twenty twenty six.

We remain on track for that. Now the data, we try to be as driven by data, you know, in every program. So here, again, the data is driven us. Because we saw with the data that the three sixty milligrams IV twice a week will actually lead to a higher blood clearance and is much more than we potentially need. So the question here is, can we reduce that in some way to make it more optimized or reduce the initiation dose, which potentially could have an impact?

We think efficacy will be maintained, but it could have an impact on ARIA. Now ARIA, I think, you know, nobody’s fully understood it. And I think what’s important is two things. One is it has a window of susceptibility, especially for a product that’s not titrated. It happens early, and you can capture it with monitoring and most of it is asymptomatic and SERIES AREA really remains below the one percent mark, at least for licanumab, symptomatic less than two point eight percent.

We haven’t seen any differences with real world data with more than thousands of patients treated now. So that gives us confidence, one, that it’s kind of replicating what we saw in trials. Physicians are able to manage it, and it’s something that education really helps. Second is that if it’s lower, that’ll be a potential advantage, but we’re not there yet. So, you know, I think the data that we’re generating is to really look at can a more optimized dose be adequate in terms of efficacy.

And I think if it provides advantages in terms of ARIA, which we know with subcutaneous is more related to steady state, unlike the intravenous formulation. So we’ll see. But I think, overall, we believe ARIA continues to be manageable and is replicating filicanumab as we saw it in the clinical trials.

Paul, Moderator: Yeah. Okay. That that makes sense, Priya. You know, Chris, I’ve always appreciated his candor about this launch because I think he’s not he hasn’t tried to over simplify it. Right?

I mean, I think he’s been pretty open that this has just been such a complicated such a complicated launch and, like, there’s so many factors that play in. And I guess now, you know, where we are with leucanumab, how would you rank order the impediments to uptake? I would assume you told me if I’m wrong. I would assume subcu maintenance, you know, might have an incremental impact on uptake just because you have to be on a drug for so long. For subcu initiation, like, how much of a game changer is that?

Or is it still more about everything else, seeing a neurologist, the MRIs, etcetera?

Priya Sinhau, Head of Development, Biogen: Yes. I think you’re right. I think Chris has articulated that exactly right as well. It’s a multitude of factors. Some are related to the product, but a lot are related to the infrastructure and the fragmentation of dementia care in The United States really.

And I think that we believe there’s several catalysts. And to your point, I do think Saccharinius maintenance could be just incremental. But if we really see a blood based biomarker hitting the ground in terms of an IVDR in 2025, so, you know, FDA approved, that could really be quite important because I think the biggest hesitation, you know, neurologists have is that they have to go through so many steps to even confirm amyloid, right, before they can put a patient on drug. So I think that with the advent and sort of upswing that we see on digital cognitive tools, if IVDR comes along, like, I think the combination of that, the potential of optionality for patients with a subcutaneous formulation, all of this could be really powerful. And then if we can sort through some of those things and we come along with a subcutaneous initiation possibility in 2026, well, I think that could, you know, really be a very important but I think, yes, you’re right.

It’s gonna be a series of catalysts and continued education for prescribers.

Paul, Moderator: How would you how how would you think about the probability of success for a credible blood based biomarker coming to the market in the next one to two years?

Priya Sinhau, Head of Development, Biogen: I think it’s high. I think it’s high.

Paul, Moderator: Yeah. What should we be looking at? Do you wanna just help people? What should what are what should we be looking out for?

Priya Sinhau, Head of Development, Biogen: Yeah. So we know that Fuji Ray Bio is already in review, I think, well, as of September 24 in the public domain. And I think this is gonna be important because the one thing that people need to remember and prescribers are, you know, also need a lot more education on this is that there are lab developed tests, which are not FDA approved, and then there are IVDRs, which are, you know, potentially FDA approved. Fugitive Bio is definitely in review. There may be one or two more players who will get in there.

I think that’ll be good momentum to have. The difference is the sensitivity and the specificity. And this is important because this is a serious diagnosis, high unmet need, but a serious diagnosis with implications for both the patient, the caregivers, and the prescriber. And so I think that prescribers are looking for concordance with PET, amyloid, as well as CSF. So that’s gonna be important, which I think the specificity of an IVDR is poised to deliver.

That’s number one. Number two, it needs to get reimbursed, and I think IV having IVDR status is likely to potentially garner, I hope, reimbursement, which is really important. It’s not big dollars in the big picture. I think it’s just about getting the data right. And then finally, they need to scale up.

So I think that’s gonna take the entire infrastructure. But I do think that what next one or two years, this is likely. And I think it could be a game changer along with all the other momentum because on its own, a diagnostic test doesn’t mean much if you can’t do anything for the patient. Now with the advent of products like Lekambi, we believe the physician actually has something to offer. So there’ll be a lot of momentum, you know, in the future.

I think PCPs could be using the blood based biomarker, but, I think that might take a little bit of time. But things move fast when you get to this stage. There’s a tipping point.

Paul, Moderator: Yeah. Yeah. Okay. Very interesting. Let’s talk about the TAP program.

And I think the natural question and you guys have some data to address this, but the natural question for me for any of these intradheapally administered products, be it antisense oligonucleotides, RNA, gene therapy is you know, are you getting enough target engagement across the key areas of the brain? And, you know, I think it’s, like, complicated, but I think as we’ve tried to bridge from the early successes in spinal muscular atrophy to other diseases, right, like, the success rate has been very mixed. And again, it’s nuanced, but one of those is one of the reasons I think is biodistribution. And so to that point, can you just review for everybody the target engagement data you’ve generated and your level of conviction that you are reducing tau levels and the brain areas that matter in Alzheimer’s?

Priya Sinhau, Head of Development, Biogen: Sure. And I think there’s two two lines of evidence I’m gonna offer. One is preclinical data. And I think, you know, tau has been a long time focus for Alzheimer’s drug development. We know a lot of attempts have failed.

We ourselves have failed with BIIB ninety two or gostronumab, which was an antibody. And I think what we’ve learned from everything that we’ve done and evaluated is that you need to be able to knock down intracellular and extracellular top. And I think that’s the beauty of the ASO platform. That’s what it’s given us, the opportunity to knock that down. And when we looked at, really our preclinical models, we saw that we were getting sufficient exposure across the key brain regions.

And that really is the most direct evidence of target engagement for BIIB080. Now we’ve looked at BIP80’s effect on tau expression in brain tissue of mice, rats, nonhuman primates, and consistently, we’ve seen a robust reduction of the MAP MAPT mRNA or tau protein levels in brain regions where BIVID was detected. Now that’s not enough, right, so you’ve got to do the human experiment. And we converted that phase one study into a phase 1b study. We opted in early.

So this was our wholly owned now Biogen program where we saw effects on tau pathology and clinical outcomes. This was more than what we might have expected, right, which is more than just PK data. And I think what is most attractive about BIPEDI in terms of, you know, how do you kind of get to proof of concept and what gives you the confidence to continue to invest or invest to win as that’s the category the program’s in. And it’s the fact that we saw a confluence of the fluid biomarkers, tau PET, which we believe is very critical to observe.

Paul, Moderator: Can I can I clarify something with you? Have any of the antibodies that have failed shown an effect on tau PET to your knowledge?

Priya Sinhau, Head of Development, Biogen: Not to my knowledge. Not to my knowledge.

Paul, Moderator: Not to mine either.

Priya Sinhau, Head of Development, Biogen: Yeah. That’s the piece we’re always looking for. In fact, it’s become very simple for us to look at exciting programs, but we’re looking for that piece of data. Yeah. Yeah.

So that’s critical. And, also so I would say, unexpectedly, we saw an emergence of clinical outcomes that was very exciting. Granted, it’s a small dataset. It’s a mad study. But we saw that these were durable several weeks after drug, and that was another very exciting, piece of information.

So that’s the confluence that gives us excite you know, gives us the impetus to kind of keep going. So we looked at that data. Our CELIA study, which was our phase two study, was already ongoing. We went back. We reevaluated what was the power we needed for CELIA.

We actually cut that study in half. And, yes, like you, I was concerned about intrathecal delivery and acceptance, right, But you will be surprised to know the study enrolled very fast. We completed enrollment in 2024 ahead of our sort of expectations, I would say. So very exciting. And, you know, it’s anecdotal, but when I’ve talked to, investigators, they see that patients really wanna try it.

They really wanna try it. The the patient today is really well educated. This is also targeting MCI and mild. They have an understanding of, you know, the phase one data. They’ve seen the the information.

So I think they wanna give it a shot. And so it’s been very exciting. And, yeah, I’m I’m excited. We’ll get a readout in ’26.

Paul, Moderator: Yeah. No. I’m I’m very excited about that program too. Can you, maybe some of the other just biological questions that I think come up with tau. I mean, one is, you know, the right time to intervene or the right window for intervention.

So maybe you can comment a little bit on that when we think it plays a role in the disease. And then the second is just, you know, tau, if you just read about it, you know, at a base biology level. Right? I mean, it’s it’s evolutionarily conserved. It’s talked about an important cytoskeletal protein.

Like, how confident can we be that knocking it down is not gonna have some sort of safety down?

Priya Sinhau, Head of Development, Biogen: Yeah. We looked at this question very carefully, and I’ll I’ll offer a few points here. So first one is that the current understanding of the biology of tau is that there are lots of redundancies in the biological processes that tau participates in such that the the tau knockdown has an impact on the pathologic gain of function, but not on physiologic function. This has been published, and it I think it’s an important line of evidence. The other is that when we looked at animal models in mice, we looked at complete knockout of tau, and we saw that that’s tolerated and animals are viable.

So that’s like, you know, it’s it’s not a very high bar, but animals are viable. And multiple tau different tau knockout mouse lines have been generated and phenotypically characterized. In these lines, the complete tau knockout had normal development and cognition with a minor motor phenotype developing later in life. So, you know, potentially mitigating the safety concern that it would be a devastating outcome, right? So that’s one two pieces.

Now for humans, the way we’ve tackled this is we have had access to the UK Biobank samples, and our team, our translational medicines and translational sciences team did a lot of work on this question. And they saw that these, really, you know, genomic data that was available showed us that heterozygous loss of function of tau in humans is actually very likely tolerated and highly compatible with life. And that tells us that about a fifty percent reduction in tau may not be associated with gross neurological defects. So and we see that also in the data that we saw. Now in the BIIB080 trial, granted it’s a small trial and small number of patients, we have seen that we saw dose dependent and sustained reductions in tau, reducing it to about fifty percent in CSF and we have an acceptable safety profile.

So we think that this supports ongoing development. You can never be sure, so you need to continue to test it. And that, I think, is something that we are looking at very carefully in Phase two. But so far, all the lines of evidence tell us that this is really compatible. And and the other question you had is what’s the right time for intervention?

Well, as you know, I mean, everything we know about Alzheimer’s tells us that, you know, you’ve got amyloid buildup for years Right. Probably decades. And then you’ve got this penultimate sort of tau buildup.

Paul, Moderator: Yeah.

Priya Sinhau, Head of Development, Biogen: And and then you kind of had that tipping point few years later of getting into symptomatic zone. And so we are targeting that same population, the MCI and mild, but we continue to look at the spectrum and think about, are there other areas for intervention? With that but we’re being very systematic about what do we wanna first prove, and then what does that unlock? And in terms of development, because I think BIIB080 could be really powerful in so many other avenues. Right?

Primary tauopathies, potentially moderate AD, these are all areas we are exploring and we remain very focused on how do we accelerate once we get that confirmatory POC, which hopefully will have a readout. It will tell us we’ll learn a lot because we’ve got tau PET. We’ve we’ve got all these markers in the cilia study.

Paul, Moderator: Yeah. Yeah. Okay. Great. What are you what are you powered for from an effect size perspective?

And do you think the do you think the effect size for something like this given the IT administration has to be has to be bigger? How how do you think about the clinical hurdle?

Priya Sinhau, Head of Development, Biogen: Yeah. So I think one big thing to kind of keep in mind is, you know, we are looking at three doses and two dosing paradigms. We built this based off of the data that we had from Phase 1b. So that’s the number one thing. We’re thinking about burden and we’re thinking about adequate PKPD sort of exposure and all of that and biodistribution as you rightly pointed out.

And we saw durability of tau reduction. So that’s going to be important for us to nail. The other thing is, yes, we’re going to look for effects on fluid biomarkers. We’re going to look for tau PET. We’re going to look for clinical outcomes.

And we have the same primary endpoint, which is CDR summer boxes because we wanna anchor it on a validated registrational endpoint. Now obviously, we have a lot of other secondary and exploratory outcomes, so we’ll be looking to learn deeply. But we are anchoring this on what we know has evolved, you know, with, with the anti amyloid space. So we are anchoring it on CDR Summer boxes. What do we need to see?

I think it depends a little bit. I mean, we we believe we powered it to see an effect, but I think it depends because remember, DAO is not necessarily or we hope it’s not gonna be associated with ARIA. So what’s the benefit risk? How does that change? And I think a lot of these factors will be part of our overall framework as we think of developing a go no go framework for and a go no go means, you know, are we gonna go beyond AD?

Are we gonna do more other exploratory trials? What are we gonna do? Or are we gonna double down just in AD, mild AD, MCI? So I think all these things will matter. But overall, I think we’re powered on we believe we’re powered on CDR Summer Boxes and we’ve got a bunch of other things we’ll be learning.

We’ll be looking at Taupek very carefully. We believe it’s very critical and the fluid biomarkers.

Paul, Moderator: Yeah. Yeah. Okay. Last question here, and it’s really just on the oligo brain space in general. Do you have a view on the brain shuttle approaches?

You know, I think we’ve seen we’ve seen these approaches in the brain validated with, you know, antibodies, proteins, enzymes. And then in the muscle space, right, also with transferring, we’ve seen that oligos are a viable target you can deliver to the right part of the cell. And I I know there’s interest with this TAO target specifically with brain shuttle approaches, which, you know, again, super early, higher risk, but, you know, could be IV. Is is this something that Biogen has on its radar?

Priya Sinhau, Head of Development, Biogen: Very much. So Jane and her organization and we are partnering on this. We continue to believe that the brain shuttle delivery to the brain is a primary goal. So yes, the short answer is yes. This remains very exciting.

We’ve got a lot of work internally. We believe we’ve made headway and we have some real important areas that we think we’re making rapid progress. So, yes, continues to be very important, and we are continuing to work on it. It’s really the third pillar for us.

Paul, Moderator: Yeah. Okay. Okay. Alright. Let’s talk about lupus a bit.

So and then we can maybe talk about, Efelsa and IgA and the transplant space as well. But just as it relates to lupus, it’s interesting, right, because I feel like Biogen’s stock doesn’t get much credit for DAPI or lefotilumab. And I think the things that hold investors back, one is that in the DAPI Phase three, right, that the study was positive, but the P value was closed, right? So there’s a question on how much margin is there for the next study. Can we be confident in the reputability of it?

And then just the second question more broadly is that it’s weird. On the one hand, lupus feels like it’s this big unmet need. On the other hand, it feels like it’s a competitive space. Right? I mean, there’s a lot of stuff in development, and I think it’s hard for people to kind of figure out where you know, different assets fit in.

So I I realize that there’s multiple questions there, but it’d be great to kind of get your snapshot on, you know, both the clinical risk side and then just the positioning side as well for your two assets.

Priya Sinhau, Head of Development, Biogen: Yeah. You’re right. I mean, I think two points that you made, I’ll reiterate is very high unmet need, extremely high and lot of competition. Absolutely true. But I think that when you look when you step away from those two points, you realize that there have only been ever two products that have been approved.

It’s been a graveyard for trials. I think a lot of people did not expect DAPI to be positive. We believe that the broad mechanism was going to be impactful on the T and B cells. We understand the area really well. We’ve worked very closely with UCB on the partnership and we believe that the modality and the target are very important.

And so we were really delighted, normally with the primary endpoint, but, Paul, I wanna call your attention to the fact that fifty percent reduction in severe flares, steroid, sparing. I mean, these are the problems that these patients face every day and then really having that positive primary endpoint on Bikla, and this was a global trial. So I think that’s the other piece. Do I think that we have a good chance of it replicating? Yes.

We are working very hard before we actually, when we announced results within literally months, we were able to dose our first patient. So we were already behind the scenes very bullish on it. That should tell you because we didn’t lose any time in getting going on our second Phase three. Now the piece that I think we have appreciated over the past many years and we’ve called in a lot of patients, we have patients who advise us on trial design, you know, what matters to them as well as sort of, you know, we are on lot of private public consortia and such for lupus. What’s really become very clear is that only twenty percent of patients are treated today.

All modalities are important, very few biologics are available, and patients need more therapies. One of the key points that we’ve learned from our patient engagements is what patients tell each other, and they tell each other that this is heterogeneous. Your lupus is not my lupus. And so we actually keep this in mind, and that is why we’re so excited about GAPI attacking from a B anti cell perspective, high upstream mechanism, and then lidafilumab going up after the sort of BDCF2 type one interferon signature. So I think that’s what’s making us really excited.

And, you know, you see that now we’re in, we’re I think the only company the third product ever to have a phase three positive is DAPI. And then the only company with two programs with different mechanism of action in Phase three. It is competitive, but our teams are doing a fabulous job keeping us on track with enrollment and everything. And we’ll have a readout with SLE in 2026. You know, we we put that up at JPMorgan about the fact that we expect to read out in ’26.

Paul, Moderator: Yeah. Okay. Great. We only have a couple minutes left, so I just want to try to cover FELSA and anything else to close. But just as it relates to the high bio deal, there’s data in iGand, there’s work going on in AMR and PMN.

I think, again, like, we think about what holds investors back from describing value to these assets. I think I think people have a hard time understanding, like, in what area is this the best drug, right, or like the which indication is the flagship indication? How would you answer the question about where you’re most excited for this?

Priya Sinhau, Head of Development, Biogen: You know, I wanna say that it I actually am excited about all three, and I’ll tell you why. Because it’s rare to have the same product with an established mechanism of action with three POCs simultaneously. That’s what excited me personally a lot when we were doing the diligence. And I’ll just give you some snapshots of the data that was so compelling and really made me, an absolute believer. One is the anti CD38 and the specificity that FELSA has to protect sort of immune, you know, immune protection with going after the plasma cells that are releasing these auto antibodies.

And in the AMR data, this is like a serious situation. They’ve got often disease, designation. So they’ve got a lot of external validation, which is also very important and, you know, not to be, I think, minimized. I think it’s very important. And in phase two, they saw two things that I don’t think other products have shown.

One is nine doses over five months resulting in a greater than eighty percent AMR resolution by biopsy at week 24 and then twenty percent for placebo. And sixty seven percent of responders remained, resolved. That that fifty two weeks, that’s pretty compelling, you know, published in NEJM, as you know. IGAN is an important area because it is competitive, but this mechanism of action is unique. And I think that’s the other piece that this is the only product that offers you that UPCR sort of reduction, which we know leads to durable eGFR stabilization.

And importantly, you have durability out eighteen months after the last dose out of out till twenty four months. I mean, how important would that drug holiday could that drug holiday be for patients? I I that’d be pretty powerful. And then finally, with CNN. Yeah.

Paul, Moderator: Is that like the is that the counterpoint to, you know, when investors, I think, make a table of these drugs and they just compare a percent change in pertinent area? Like, this doesn’t rank at the top of the list. So is it more about the dosing holiday that got you comfortable with that or got you excited about this in IV?

Priya Sinhau, Head of Development, Biogen: Well, I think it’s both. So I think it’s 50% UPCR. 50% UPCR. That is important because I think they’re all in that range. These are small studies.

You know, the variability that could be there. We know it’s distinctive. Right? So we know it heralds the eGFR outcome. That’s one good thing.

I mean, you know, this is a wonderful space to be in because for once I find that, you know, the accelerated approval endpoints, surrogate endpoints are all established. So it’s exciting. Number two, the yes. The durability is pretty powerful, right? I mean, think about it.

And in the future, I think there’s also this potential of combinations and other things where we believe this is gonna be a unique mechanism. So I think it’s important. With PMN also poised to start phase three in ’25, and I think that we observed rapid partial and complete immunologic responses in both newly diagnosed and relapsed patients. And as you know, as well as people who were on immunosuppressive therapy, and as you know, PMN is the largest cause of nephrotic syndrome. I mean, this is really high on Metmy.

Paul, Moderator: Yeah. Yeah. Okay. I am just looking at, the couple questions that came in because we only have a minute left. You know, one asking for, and we’ll see what we get, Priya, but a comment on anything Sage, right?

And then just any updates on development work with SPINRAZA and then we can close.

Priya Sinhau, Head of Development, Biogen: Yeah. I think Sage, I will just say that Zerzuobi, I remain really excited. We see a lot of momentum in our launch in how patients and prescribers are responding to the option that XERZUBI offers women with PPD. So I think it’s really been a wonderful story, and we have so many stories I could spend in the next hour. So that’s what I’m going to comment on.

I think very excited. Teams continue to work very closely together on this launch, which we think is really important. On SPINRAZA high dose, very excited. We’ve submitted both in Europe and The U. S.

We’re working through, you know, we’ll soon be in that review period. We have a PDUFA date of September in The U. S, so we remain on track for that. We think this is going to be very important. I mean, I think that the data that we’ve seen is very compelling and I’ll draw us to the neurofilament data that we observed at day 64.

We think this is really, really important. And coupled with the data that we’ve generated from RESPOND, which is post gene therapy and all of that, we think SPINRAZA remains a cornerstone for spino muscular atrophy patients across all age groups. And so we are very excited about what this does for SPINRAZA.

Paul, Moderator: Great. Alright. Well, we’re one minute over. I’m really respectful of your time. Thank you, Priya.

This was an awesome discussion. I think we covered a lot of interesting stuff, so I appreciate you joining us.

Priya Sinhau, Head of Development, Biogen: Thank you for the great questions. Take care. Alright.

Paul, Moderator: You’re very welcome.

Priya Sinhau, Head of Development, Biogen: Bye.

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