Sachin Jain here from the European team at Bank of America. My pleasure to kick off with the next company, which is Sanofi. We have Mike Quigley, Chief Scientific Officer. I think many of you may be less familiar with Mike, so I'd ask Mike to perhaps give a minute or so in background on himself, and then I'll get into questions. With that, Mike, over to you. Thanks for your time.
Thanks, Sachin, for having me, and good morning, everyone. A pleasure to be here. Mike Quigley, Chief Scientific Officer, Global Head of Research at Sanofi. I joined Sanofi coming up on about two years ago. Remit within the organization is everything from early discovery through handoff at phase I, both internal and external innovation. I came to Sanofi two years ago, and I'm sure we'll get into some of this today, with the goal of sustaining a high-quality output pipeline from the research organization in a way that's much more efficient and effective than has hopefully been done historically within the organization. I think even more important as we think about where Sanofi is going in the future, that stability and long-term output and durability thereof is going to be increasingly important.
Thank you very much. I'll kick off big picture, and then we'll drill into some of the later stages, which I'm going to be less close to, and then we'll do sort of circle back to research. The biggest picture question on everyone's mind is new CEO, new head of R&D, what's filtering down to you as the mandate and objectives? That's a super broad question. Take it as you will.
It is. I'll run with it. Belén in role, obviously, since April. Paul has joined us now three weeks ago as the head of R&D. I'd say starting with the CEO mandate, it's clear coming in that Belén had a purview enterprise-wide assessment around R&D, but also the group level, sort of where we are, where we should be going. Through that process, it's reaffirmed key core areas of focus going forward, I&I, rare diseases, and vaccines, and an ongoing effort around thinking through what additional spaces, both therapeutic areas and white spaces, if you will, that the company should move into based on our internal expertise, opportunity, strategic fit, et cetera. That effort's underway. You would've seen, obviously, in the context of Paul's remit coming in with Belén now, again, just three weeks ago.
Prior to his arrival, we made some critical decisions in our late-stage pipeline, terminating amlitelimab, itepekimab, and belantamab. What I would say is Paul, even three weeks in, is already leading the effort on an additional rigorous assessment of the late-stage development portfolio, the initial focus thereof. I would imagine Paul coming in, he's a rigorous scientist, experienced in broadly global organizations, late-stage development. That will be the immediate focus as we think about not only expanding into areas as I articulated, but making critical and rigorous decisions on our current pipeline going forward. I think the criticality of where we are within the organization, you should expect for us have, but even more so going forward, quicker decision-making, transparency, more of an underpromise, overdeliver mindset as we think about how we approach scientific excellence within Sanofi going forward.
To kind of just touch on the parallel piece. Does that mean we should expect more pruning of phase II, phase III as we enter the back end of this year, whether that be Q3 or full year?
What I'd say is the outcomes have not been determined. I think what we're going through and what Paul's driving is a deep assessment of two things in particular. I mentioned scientific rigor. I think an honest assessment of where we are from a risk-balanced portfolio. Historically, we've been first in class or best in class driven mantra. I think what you'll go into in our both the end of this year, but also in a future-looking statement where we're much clearer about articulating what the risks are in our programs and being measured in how we deploy capital for those programs. So whether or not there's a pruning or a reassessment of the relative capital allocation for some of these portfolio programs, I think that will play out, and obviously we'll announce more information when it becomes available.
I don't know whether this is correct, but I heard that pending Paul starting proof of concept or phase III starts were all put on hold. Is that still the case, or are you, is stuff flowing through?
What I would say is it is generally business as usual. Key strategic decisions around phase III starts. Obviously, the capital required for those were not necessarily put on hold, but they certainly were given the chance for Paul to weigh in. That is occurring as of last week for many of our programs that are in that mid to late-stage start. I think it is prudent as we think about not only new leaders coming in, but again back to that introduction of more rigor as we think about risk assessment and balance of our portfolio.
Okay. Investors are very squarely focused on what you are going to do externally to bolster pipeline, and we will hear that in due course. Just again, organizationally, I do not know whether this fits within your remit. Do you get involved in that sort of screening of targets you involve from a team perspective? What is the mandate? Just any color there.
Yeah. Happy to comment on that. I would say from a sort of BD perspective, R&D is front and center, the core of everything we do in BD. I think R&D helps assess with the broader group strategy around three key areas. Strategic fit, obviously scientific merit, and unmet need as we think about where any particular asset would be positioned, and then obviously potential financial return on that investment. Within the deep diligence that occurs, R&D diligence comes first. Once R&D has signed off on that scientific merit, the molecules, the development path, the unmet need, and making sure that we meet that TPP, target value proposition in the context of that asset then comes the commercial and financial sign-off. That has been the case, will continue to be the case, and that rigor, I would say, and relative risk assessment even being sharpened in the context of that approach.
How much time are you now spending on BD or your organization? How much time is Paul spending on that, and what areas have you been pushed to look at? Early, late therapy areas?
Yep
new therapy areas, just any sort of color would be very helpful.
Happy to. Yes. I referenced it already, the commitment from a strategic mandate perspective. Clearly I&I vaccines, rare. A focus in there, it is balancing our internal portfolio, where we are from an expertise perspective, where we can capitalize on our footprint, both from a commercial but working backwards from a development perspective, you can imagine that is all in scope. There, obviously, our internal portfolio is a bit hardier, for lack of a better term. It then becomes puzzle piece fitting and what makes sense and complementarity in nature. Those white space areas, I have a particular increased breadth in research. We have efforts in oncology, neurology, ophthalmology. You can start to sort of see that shape. You asked me how much time.
I will answer in the context of what I think a healthy research and early development portfolio consists of, and that is a nominally 50/50 split of internal versus external innovation. I think we should not kid ourselves that the innovation solely occurs within our own walls, but rather use the various levers we have to sample that external environment. Quite a bit of my time is spent. Paulo, obviously, not surprisingly, top of mind as we are thinking about what that development pipeline bolstering could look like as he is getting in to the organization.
I do not really understand how BD processes where I am going to be involved, but just how involved do you get in sort of even later stage assets and doing the sort of background, preclinical validation, whatever, and is that going up as well as your typical early-stage deals?
Both.
Okay.
I think back to the rigor and the quality. In late-stage opportunities, if you don't have a deep understanding of the mechanism, even as we think about market access, the differentiation that might go all the way back to the molecule behavior and hitting that TPP and TBP. I think all bias aside, research is actually very well positioned to really dig into those, and we do currently for anything we brought in. I reference even recent Blueprint deal as having the entire value chain on deck from a diligence perspective.
Can you just give me a sense of who the key people are within Sanofi now that would be at the table on BD from early, late, financial, commercial? Is that a new team? Is it the same team? How much has that changed?
Absolutely. Structurally, and I think it's a benefit, which is why I'm starting with that. BD now sits along with M&A under the CFO.
That's close connectivity, including ventures and Sanofi Ventures investments. All the various levers we have to expand our portfolio in one unit. That doesn't mean they're not in close collaboration as always with R&D. Actually, we've even strengthened through that sort of organizational move to make sure R&D, as I said earlier, is front and center in the context of those BD and more broad conversations. Key people, obviously, Paul coming in, head of R&D, signs off from the R&D perspective, just like François on the financials and depending on where it sits within our GBUs up through Manuela, for instance, in specialty. You do have some new players at the ExCom level, some same, some new.
I would say what we have done over the last two years is brought in, and will continue to do so, the right lens of expertise in our development TA heads. Those have largely all been new, certainly since I have joined, the vast majority of them. The same is true of the research organization. Many of my leaders are largely new over the last couple of years. They are bringing in that scientific rigor and expertise.
Is there any sense you can give of how much time that sort of BD ExCo is spending on early-stage stuff, which has been what Sanofi legacy has done? How much there is a renewed focus from your time and the BD ExCo, I will just frame it as that, are now screening this breadth of 15 to, I do not know, EUR 25 billion, EUR 30 billion deals, I think has been roughly referenced. Is there a shift? Are you being given a mandate of like, "We need to get X, Y, Z done by X, Y, Z time?" Just trying to get a sense of urgency and shift in focus.
Maybe twofold. One is we will never move simply because of time and sense of urgency. We will move for the right opportunity, the right assets, strategic fit, scientific unmet need, and it makes sense financially. So that is the guiding principle, regardless of any arbitrary, for lack of a better word, timeline. I think it is an honest assessment to say that if I were up here even a year to 18 months ago when I first joined, the focus was squarely on bolt-on phase I, phase II assets. You would have seen that in the deal flow that we brought about. I think fast-forward where we are today, there has obviously been some headwinds, some of which we came out of Q2 in terms of terminations in our late-stage development portfolio.
I think there is a healthy balance of looking at what could complement the sort of mid to late-stage development, not without or at the exception of any of the early stuff. I would say today we are certainly phase agnostic, as long as it fits both strategic sort of pillar with respect to therapeutic areas, but also the right scientific fit and the right financials for us.
But given the breadth has increased and slightly broader therapeutic focus, you sort of mentioned on neuro opths being added, do you have the expertise to do that? And is there any sort of particular area you're focused on initially?
That's a good question. I'd say I'd anchor back to the core areas in terms of initial focus and maybe just to draw the distinction you referenced with other therapeutic areas. Those are active efforts within research. I think to varying degrees you'll see early clinical development opportunities coming out of the internal pipeline. In the oncology, I'll reference a mid-stage PD-1/IL-15 asset, for instance. We'll have additional ones coming up in neurology. That's not a commitment per se to those therapeutic areas in earnest, but rather we will, as always, find strategic ways to assess and progress any promising medicines as they emerge. So just to draw the distinction between my research TAs and the three core development TAs I referenced-
Okay
I&I vaccines and rare. That being said, in terms of areas, I think the near-term opportunity is really those opportunities that are adjacent to the expertise we've built, in particular in the development and commercial organizations. So back to the rare franchises. Clearly, the expansion of that could be complementary to what we're doing internally. Same is true within the I&I diseases. Obviously, we're most prominent in the context of dupilumab, but more broadly in the dermatologic and respiratory space. I expand that to say that that's something we know what it looks like from a diligence perspective back to the rigor, and so those are areas that obviously as we constantly survey what might be an opportunity out there.
Okay. Spent a lot of time on BD, but there's a lot of investigators, so thank you for indulging me.
Absolutely.
I'm going to just shift on, which is slightly adjacent, but any comments you can make on how you're feeling with your Tarrytown colleagues? Is there anything going on? I know that Belén has referenced a conversation ongoing. There's been some hurdles. Just any perspective you can give there.
Sure. Happy to. Early conversations with our partners at Regeneron in terms of the alliance and what could, should go into the alliance to maximize the opportunity there, both within particularly dermatology, respiratory, maybe a slight opportunity to expand in gastroenterology in terms of where that DUPIXENT footprint resides. I'd say a prototypical asset that could be brought in from the Sanofi portfolio is lunsekimig. Obviously, TSLP, IL-13, nanobody, and respiratory diseases. It's not been decided that that will enter in, but that's the sort of flavor and the shape that we're coming in from the Sanofi portfolio under discussion. We'll continue to evolve those conversations and obviously, when decisions are made, communicate appropriately, on how best to maximize them.
Does revekimab sit within that debate as well?
To date, revekimab does not sit within that conversation. In particular, as we think about the evolution of TNF, OX40 ligands, so two distinct targets, and the prosecution within the Sanofi portfolio, in that case, into hidradenitis suppurativa.
Okay. How much time are you spending due diligencing the pipeline that Regeneron has talked to? Supemtek, the extended durations assets. Is that now being looked at as, from your perspective, would we want those to go into the alliance? I think there's still some confusion as to what is in or out of the alliance, particularly the IL-4 receptor debate.
Yeah, happy to expand. Again, ongoing conversations. We certainly, I would say the team collaboration is strong with respect to our partners at Regeneron and Sanofi. We are digging into the long-acting IL-13. As we think about complementing and maximizing the alliance, you have lunsekimig on the respiratory side, for instance, in that example, around COPD and asthma, and obviously the long-acting IL-13 monotherapy, IL-13 not playing out per se in the respiratory space, but obviously would have a role in the dermatology space. You can start to think about or see how we might shape, again, all ongoing active negotiations, but how we might shape the complementarity of those two assets, for example, in that. There's continuing, whether it's the Supemtek or anything else that they might have for ongoing, in terms of conversations.
Could you clarify for me then, is it still uncertain whether IL-4 receptor is in or out of the alliance? I know you say it's in, they say it's out. Shouldn't be that complicated. Is that still a topic of conversation?
It's all related to the ongoing negotiations and clarifications, I guess, more appropriately. What I would say, from our perspective is, what makes the most sense scientifically, we know the type 2 axis is incredibly important in type 2-driven diseases in respiratory and dermatology. For us, that's how we're framing maximizing that allowance and the types of assets that would be brought into it or could be brought into it.
Okay. That is very clear. The last question, is the discussion with your colleagues advanced enough yet to be collaboratively investigating external assets?
Certainly in scope.
Okay.
Absolutely. I think the internal ones obviously have more data at hand from either side to be able to dig into. There is always a possibility to bring in external assets into the collaboration.
Can I just check the timing of that? The assumption has been that you would probably need to fix the collaboration before you do something externally, but it sounds like they are parallel tracks, and it could all happen together. Is that fair or incorrect?
I think first things first is understanding, in the context of negotiations, the current assets at hand.
Yeah.
At the same time, I think it's prudent to understand what else could be brought in to maximize that alliance, both from a development perspective, but also a commercial integration perspective. I would just frame that respiratory, dermatology, and a bit of gastroenterology in terms of what might be in scope and makes the most sense as we shape that collective portfolio.
Okay. I was going to ask this as well. Gastro I hadn't really appreciated. Could you just touch on that?
Just the EoE indication.
Oh, that's it. Okay, fine. Sorry, one question on the side there. Feel free.
Hello? I just have a question. Several years ago, you acquired Translate Bio, which is an mRNA technology. You have a vaccine franchise, strong vaccine franchise. Why don't you launch neoantigens, individualized vaccine using mRNA in oncology? Thank you.
Certainly, I would broaden it back, so to your question, Translate, we're making use quite effectively of that platform broadly within the vaccines pharma collaboration internally at Sanofi. I'll reference, and you'll see it emerge in our early clinical development pipeline, in vivo CAR T efforts, using that platform combined with some other lipid nanoparticle platforms that we brought in, as well as our nanobody technology. So that's an example where we're maximizing that in the context of that pharma vaccine design. I think in the recent data, as we think about early stage II, stage III cancers, where a vaccine with a combination of checkpoint could make sense, I think that context and example is under a broader discussion that I referenced earlier as we think about what the right Therapeutic area, in particular in development and the commitment makes sense for Sanofi going forward.
It's not lost on us, in particular, the PD-1/IL-15 assets that we have in phase II could be complementary. So those discussions are active and ongoing, and obviously we'll communicate when we make decisions.
Any more? This might be a question more for Thomas. One of the questions I get is should we be expecting an update on these broad, or if you want to do it, on the strategy by year-end? There's been a debate of is there a CMD, is there not a CMD, where's the current thought process?
Thomas can complement. I think we're committed to an evolving communication as we make strategic decisions and prioritizations as opposed to a single snapshot in time. I think it's on us to make sure we communicate. I'd point to Q3 earnings in October as the next opportunity to give an update on the decisions we made and future-looking ambitions for the organization.
Okay. I think that's similar to what we sort of saw at 1Q, 2Q, where we sort of saw a couple of slides CEO. This is the evolution of thought process. We should expect something similar at 3Q rather than a big splash event, which has had mixed success with peers in recent days. Is that fair? Perfect. All right. I'm going to move on to perhaps an area closer to your expertise. Just interested as to in your two years that you've, 18 months you've been, what have you changed? And where do you think you're on the journey of improving the early-stage research and asset flow into development?
Yeah, happy to. Maybe a couple of reflections, and I think it should be consistent with what I've articulated in a go-forward fashion. Sanofi over the last eight or nine years as I came in and sort of looked at the dataset, it won't be a surprise to any of you, have had a lot of leadership changes, in particular R&D, heads of R&D. And with that comes a necessary reassessment of the strategy. The knock-on effect that has in the context of the cycle times that I operate under. Anything I start today in research doesn't show up to the clinic for on average 4+ years. The cycle time in a success scenario of anything we start shows up on the market in 14 years.
The knock-on effect of those heads of R&Ds and head of strategy changes have a significant impact on the perceived productivity of a research organization. My goal over the last two years is actually to create a more resilient research organization with the ultimate goal of sustained high-quality output over time. You will all have seen in our phase I pipeline the significant gap. The first in human starts over the last couple of years have been, quite honestly, abysmal. In N of one and N of three, you will start to see that build back and that is we have done some things internally. We have set up some collaborations and accelerated those starting this year in 2026 from a first in human start and continuing on in 2027 and 2028. That will be the first proof points.
The quality of those decisions and productivity is always a lagging indicator, so you will bear with me as we come through phase II transitions with the rigor that we already discussed. The last thing I would say is historically, Sanofi to an extent has been good at partnerships, particularly in the development stage assets. But from a research perspective, has had more of a non-event tier status, right? We have brought in Ablynx and platforms and those have proven fruit, but I have moved the organization to being much more nimble at making sure we can source effectively external innovation. You will start to see more of that in terms of announced partnerships coming up that are more platform-sized deals, meaning larger portions of a portfolio that make a lot of sense to prosecute with a partner, for instance. More to come, but I think that has been my focus.
The last thing I will say is decision making, whether it is AI enabled or just frank decision making, is probably where the most value gets destroyed in the research and early development space. That has been a big focus of ours and how we view our pipeline and how we make decisions. There is rigor included, but there is also timeliness of decisions and opportunity cost and dynamic capital allocation components of all of that that we have looked to significantly strengthen over the last two years.
Within the context, going back to BD, is the review from who is coming in that, yes, there has been a progression, but we actually need to bolster the R&D platform. Whatever M&A we look at is not only is this asset commercial, but also coming with a research platform.
In some cases, that is a lens depending on the opportunities we are looking at. Independently, with that same movement that we already referenced with respect to BD and M&A, our ventures arm and additional capital leverage that we have to bolster maybe early riskier stage investments are something that we have strengthened from a strategic lens perspective. We have had the corporate venture arm. I think that is a real asset within Sanofi. Others have it as well. But making sure we can understand areas of emerging biology that might not be ripe today, of course, and therefore we shouldn't take on internally, but a thoughtful risk assessment and in that case, investment for the longer term. We are doing both at the same time. It is a bit of everything everywhere all at once.
I think important to land that in a way that has an eye to future sustained output of a quality organization.
Okay. I might move in the last few minutes to just some asset questions, which is probably less close, but if perhaps you can touch on that. I am going to start with a really big picture question. You mentioned lunsekimig. I mentioned revekimab. One of the questions I get is it clear from the data we have seen that the bispecific mechanism is adding anything to single? One of the questions I get is revekimab HS data looks like the TNF. The lunsekimig data we have just seen at ERS doesn't look that different to the tezepelumab data. How would you contest that? If you are debating lunsekimig in the context of the alliance, there must be a view that it is differentiated, I guess. Just big picture
Sure. Let us talk about the second MEG and the phase II-B data, where to look at it, and what phase III could look like from that potential perspective. In that all-comer population, we will come back to the population versus the ITT that could roll into a phase III. Statistically significant achievement of endpoints associated with exacerbation in FEV1. I think in that context, because necessarily the phase II-B data set or patient population was broad, so one or more exacerbations, only 40% of those patients had high eosinophils. When you start to, in a predefined subset basis, start to look more at the ITT population, call it two or more exacerbations, for instance, you start to see more significantly meaningful improvement on those endpoints. Our HAR modeling would suggest that we should expect significant improvement across all three registrational endpoints in the context of a phase III.
That is the data set we have at hand in projecting forward in the context of that phase III, and in particular, the efficacy differentiation. I would say equally importantly, as we think about where IL-13 biology we think is playing a role in the context of asthma is small airway remodeling and mucus plugging. And I would point to the PROs where we think we see a significant improvement over standard of care that might be manifesting where that IL-13 biology will show up. And that is the sort of aggregate data that we have and confidence around why it is the TSLP and IL-13 combination that might be lending itself, and the relative regulatory endpoints were associated with that in a projected phase III approach.
Just to summarize, if we looked at the data in the correct subpopulation, you do think it is showing cross-trial superiority to Tezspire on exacerbations in some of the PROs.
It is tough to do cross-trial, as always.
Yeah
Of course. And we looked at 48 weeks, the Tesi study at 52 weeks, obviously DUPIXENT at 12 weeks with FEV. So different endpoints. I would caution against, as always, the cross-trial comparison. But I think we are confident, again, in that all-comers population, the data we saw there, and then the pre-specified subpopulation that would look closer to that phase III population.
And then similar question on HS. We've got the, I guess, phase IIb coming next year.
Correct. Obviously, that will be the data that we use to make the decision around the go to phase III. I think from the phase II-A data, the placebo-controlled HiSCR 50 going to 90 and the 30 to sort of 23% range placebo-controlled, I think gives us confidence in the context of, in that case, severe to moderate or moderate to severe patients, biologically naive. I think that will bear out if that continues into phase II-B. I think it, for us, the contribution of components of the OX40 ligand and durability, sustainability of T cell subset inhibition beyond just TNF sort of cytokine inhibition, seems to be playing out. The data will tell us in the context of the II-B.
So just for the IIb, what target profile would you need relative to what's becoming a crowded space to progress to phase III? Not only the IL-17s, but we've got the TL1As potentially there. You've got an asset there.
Correct.
BTKs, we'll see what they show. Just like what would you need to see?
There's still an efficacy ceiling in the context of the hidradenitis suppurativa scores. I'd look at hidradenitis suppurativa score, and I'd look at tunnels.
Okay.
At really where the unmet need is going within hidradenitis suppurativa. That's what we'll be looking in the context of the phase II-B and making the call on, to your point, differentiation and what that means for patients downstream.
Okay. Can I shift to perhaps some of the phase III assets? I know it's a bit less in your purview, but as an organization, do you want me to put it this way? Investors basically, I think, have given up on the phase III reads next year, whether that be frexalimab or riliprubart or PCV. Perhaps if you just couple of hits on each,
Sure
as to whether you still believe why, and I think in the case of frexalimab, there's been some changes in trial design or endpoints.
Maybe we'll start there.
Yeah.
With frexalimab, ongoing conversations globally with regulators, to adjust the primary readout, from superiority to non-inferiority.
Still ARR.
Still ARR as the primary. The rationale there is with an active teriflunomide sort of comparator, even with a superiority hypothesis, that activity sort of makes it difficult to power.
And so that's the rationale for the conversation. Equally importantly is the key secondary endpoint, which is disability progression. I would say from a Sanofi lens, those are the two data points, in particular disability progression, that we're using to judge the potential for frexalimab going forward. I think that's the key aspect. Why is that important? Frexalimab is a non-depleting CD40 ligand antibody, covers both adaptive immunity, inhibition thereof, driving a lot of those acute inflammatory aspects of the disease. The chronic smoldering inflammation, driving presumably in large part more disability progression, is more innate in nature. Frexalimab also inhibits that axis. So mechanistically, that's the reason why we're making sure that both the primary ARR as well as disability progression at six months are equally important as we weigh the promise of that drug.
Can I just check, because I haven't spent a lot of time on this. The target profile relative to CD20, or we've seen one, BTK, we'll see the second shortly. Is ARR comparable to CD20's and better progression? Is that the target profile?
Correct.
Can you just run over in phase II what gives you the confidence on that? Because some of the stuff we get back is this MRI data is super hard to extrapolate to one or both of those endpoints.
I think that's the data we have at hand.
Yeah
to sort of assess the disability progression. We are bolstered by the approach that we took with tolebrutinib, capitalizing on that in the context of disability progression. So that is the data at hand, but the six-month disability progression data set in the context of the ongoing study will be important for us as is.
How much better than CD20 do you think you need to be? If CD20 is a sort of I think Kesimpta has a study versus AUBAGIO, which is like 34%. Do you have in mind a target profile, or have you disclosed how the study is powered for what sort of CDP you are looking for?
We have not disclosed that.
Is there a target profile?
I think the critical would be, you need to at least meet that bar.
Okay
from an ARR perspective.
Yeah.
The benefit would be disability progression to patients.
Could you touch on infection risk? Because I think the non-CD20 mechanism of having better infection, which is also putative advantage, but the phase II had elevated infection.
I think we'll continue to play out with more patient years in terms of the infection risk and where that really looks different from a CD20. Obviously, that's part of the TPP and how we think about.
On a scale of 0 to 10, and investors are like at one or two, where are you on the excitement scale of frexalimab with the organization, not you?
I think we have no favorite children on the scale of 1 to 10. No, look, back to the rigor, in all honesty. I think we'll see the data at hand, and we'll make a call on frexalimab both in RMS, SPMS, obviously the following year, but more broadly including in transplant and the efforts we have with frexalimab there.
Okay. If I moved on to riliprubart, one failed study has driven investors to much more cautious on the second. They are different settings.
That's critical.
One could argue different biology, but I'm just interested in your thoughts.
Absolutely. Maybe including the conversation we had at Q2, but I'll just carry on from that. IDMC obviously reviewed importantly both MOBILIZE and VITALIZE. To your point, MOBILIZE are much more difficult to treat patient population, more heterogeneous, obviously refractory to IVIG. In that case, the IDMC recommended not on safety, no safety findings, but on futility, unlikely to meet the primary endpoint from an efficacy perspective. At the same time, they also reviewed both safety and efficacy of the VITALIZE study and recommended progressing forward. That's point one. We're still on track to read out in 2027. As we think about the VITALIZE study, these are now a more homogeneous patient population dependent on IVIG. 70% of those patients upon withdrawal will progress.
This now biologically and from a patient population perspective, I don't know that that gives us confidence, but at least that the IDMC assessment could tell us to go on.
Can you just touch on what the IDMC looks at when that second study having stopped the first? Is it a futility look? Is it a no-harm look? Is it this is going to get close to what our putative profile is? I am not quite sure how the IDMC process works.
It is really the safety first and foremost.
Okay
From a no harm. Subsequent to that, the futility analysis in that order.
Okay. The timing of that data is?
2027.
Okay. If I then moved on to, actually, I didn't list this initially, but FDOR where you've had to face the data. It was presented at a conference recently.
Correct.
Regulatory debates ongoing. My sense has been some sort of safety hurdle as to you have enough safety data to an accelerated file or not. Long-winded question, but where are you with the regulatory aspect of an accelerated file?
Yeah. With duvakitug alfa, obviously the Q3-week regimen hit all primary and secondary endpoints, in the context of that study compared to the Q4 week and then plasma-derived AAT. We are progressing with regulatory conversations with the assumption of accelerated approval and the assumption that we'll continue to track to the end of this year from a filing perspective. I think from the overall structure, that data would obviously be AAT level, sustained AAT levels compared to the Q-weekly plasma-derived standard of care. From our perspective, importantly, the open label extension rollover from that ElevAATe study, the phase II study that we presented, continues to generate safety data and efficacy data that will complement that conversation. And of course, we'll have a phase III study that will be dependent on the accelerated approval or be required under the accelerated approval if granted, and obviously for European filing.
All of that underway as we speak.
I might have missed this, but I thought the conversation was we are going to see how the regulatory conversation goes and update back end of the year. But if basically what you are saying, it sounds like it is more advanced, that you are comfortable enough to have that filing go in at the end of the year. Did I get that right?
We are having the conversations.
Oh, I see. Okay.
Yes. Just I guess what I am articulating is we are on track as we have communicated in the context of that conversation from the potential for an accelerated approval as well as what I referenced was just the open label extension adding additional safety to your earlier part of your question and efficacy, of course.
Is the gating factor correlation of the biomarker to endpoint or is the gating factor safety?
There has been no safety findings to date in the context of the phase II. It is really the correlation between biomarkers and clinical outcome and improvement.
Again, I am not as close to this, but the European U.S. regulators from history seem to have had a different view on that historically. Is that still the case?
Correct.
This is just U.S.
That is why the Phase III study will be required for a European filing.
Okay. I have had a number of questions on safety. From the detailed data, there was an imbalance in discontinuations and adverse events. So, perspective there.
For duvakitug, no significant permanent discontinuations based on adverse events. We did have some transient anti-drug antibodies. Only two were found to be non-neutralizing in two patients in the context of the study. Not material difference in the context of permanent discontinuations on FDOR compared to the Q-weekly plasma-derived AAT.
Okay. No real safety debate. Okay. I have been through the list of pipeline assets I get asked about most. Just what else would you have us focus on?
I think early days, maybe a few in particular, early days for the STAT6 programs. Obviously, those two are in partnership. We have two in the clinic now, an SH2 domain inhibitor with our partners at Recludix and a degrader with our partners at Nurix. Maybe I'd highlight upcoming ESMO data for our PD-1/IL-15 asset in solid tumors, colorectal and lung. The furthest along is colorectal data. We'll be presenting that data at ESMO. In particular, I'd point to CRC stratified with and without liver mets as potentially interesting in the context of there. Then I referenced maybe some other therapeutic areas earlier. We have two gene therapy programs in ophthalmology.
We have a program that's in phase II in neovascular AMD, and then a second gene therapy program also moving into phase II in geographic atrophy targeting two key nodes of the complement pathway as we think about that disease.
Okay. Back to the first asset you mentioned, I had it on my list. Are we expecting data for the STAT6 at some point by year end or early next year?
Both early programs. We have not guided to any material data release between now and 2028, which is how far we project out both phase I assets. They'll continue to present themselves at the merge.
No data for either for the foreseeable future?
Not today, but we will obviously update as that data becomes available.
Are those assets, just again, to pose a specific question, where do those assets sit relative to the collaboration?
Currently our partner Recludix is responsible for the early clinical development. We are responsible for the degrader development, clinical development, that is.
Okay. I think we're just on time. Are there any questions in the room before I wrap the session? Okay, Mike, thank you so much. We covered a lot of ground there.
Thank you very much.
It was very helpful. Thank you.