From the European Biopharma team here at Jefferies. It is a pleasure to be joined today by Mike from Sanofi. We are going to talk a little bit about the research side of things, the drugs, and get into some depth about that. It is a pleasure to have you here. I am going to hand straight over to you and a little bit of introduction about yourself and your role within Sanofi.
Sure. Thanks, Ben, for having me. Really delighted to be here. Mike Quigley, I joined Sanofi, had the pleasure of doing so about eight months ago as Global Head of Research and Chief Scientific Officer. I have been delighted about what I've seen over the last eight months in the context of the breadth and depth of not only our pipeline—we'll talk a bit about that today—of what's out there in the development space, but also what's coming up out of our research pipeline, both organically and inorganically. Also the depth and breadth of our talent, the bilingual nature of AI—we might touch on that today—but also the deep sort of roots in immunologic sort of processes, pathways, and how they broadly apply for our focuses today in immunologic diseases, but more broadly thinking about adjacencies in spaces like neurodegeneration, ophthalmology, oncology, and the like.
Really delighted to be here, looking forward to the conversation.
Awesome. Let's kick it off. You said, yeah, I think you've been here as part of the organization about eight months now. What are you finding most impressive about the setup, and where do you see opportunity to improve and leverage?
Yeah, I think if I reflect on the last eight months, I hit on a little bit in the intro, but my background as an immunologist, I've sort of developed drugs across immunology, oncology, neurodegeneration, and ophthalmology. I say that purposefully because there's a thread of not just immunology, but immunoscience. That's really the benefit of the evolution of Sanofi and our R&D sort of strategy is really understanding the broad applicability of immunoscience across therapeutic areas. I'd say that coupled with our sort of true embracing of artificial intelligence and the enablement that brings not only in the early space and the context of research, but more efficient drug discovery and also development as we think about sort of clinical execution, development, decision-making, and the like.
I think the decision-making as that last part of the answer is really a key focus for us, not only in the research sort of organization and how we can better improve decision-making and sort of rethink how you view return on investment in the context of a research portfolio, but also as we have a growing, for instance, immunology pipeline and our development organization, how we think about thoughtful trade-offs, for instance, in moving assets from phase two to phase three and how we can sort of improve that decision-making in the context of our growing pipeline. All areas that are both a strength and area for continued growth within Sanofi.
Yeah. Before we delve a little bit further into the pipeline, I do want to ask about AI. I realize it's been a little bit of a buzzword over the past few years, but Sanofi touched on it in 2023 at the R&D Day, talking about over 90 novel targets have been identified, seven progressed into research within the prior 12 months to that. How central is AI in developing the clinical portfolio at Sanofi? As a result, what is its clinical utility within the organization?
Yeah, thanks, Ben, for the question. Maybe it's not incorrect to say that over 90% of every single program we run through our research portfolio is enabled by AI. Most of our competitors will have likely comparable numbers as we think about sort of traditional drug discovery and optimization of lead molecules. It's part and parcel to what many are doing today. We're doing the same thing. I think where we're really looking to elevate and use AI in the research organization, for instance, is capitalizing on the ability to synthesize and sort of propose the next set of experiments. I can take in an upskilling fashion a bachelor-level scientist in any one of our labs and turn them, with the use of AI, to be able to synthesize all the external data and internal data and propose the next set of experiments.
They sort of overnight, if you will, become sort of PhD-level scientists. That is enabling. It does not replace them, of course, from a robot perspective, but enables not only the improvement in the science that we do, but the decision-making. That is on the research side. That is here today, and we will continue to sort of improve that. Part of your question hit on the clinical development organization, and I will not pull it out now, but we have an app for that. AI is really in real time sort of enabling us to understand from a manufacturing supply perspective where that is moving globally from a recruitment perspective, each individual trial site, whether they are ahead of or under schedule.
We will propose, at least for conversation, sort of considerations for decisions to make to optimize not only delivering on our sort of manufacturing capabilities, but also our clinical development programs. That is really going to continue to accelerate our entire development pipeline going forward.
Yeah, very interesting. I want to talk a little bit about immunology and inflammation, given it's obviously a focus area for Sanofi. Before we actually dig into some specific assets, are there any that you'd particularly highlight that you think on a research basis are particularly interesting based on their mechanism?
Good question. Maybe I'll start with a bit of a half step back to frame for everyone here and online what the Sanofi I&I strategy is writ large within R&D. I would clarify it into sort of four main distinct pillars. One is the goal of increasing efficacy ceilings in the context of the therapeutic and subtherapeutic areas we're interested in. That's largely in our portfolio, both organically and some recent deals we've announced in the sort of bi and multi-specific space. I'm sure we'll talk about some of them, and I'll hit on them in our current pipeline. That's the first pillar. The second pillar I would frame is pre-biologic oral approaches. I would add to that sort of all oral combination strategies, both for type 1-17 diseases and for type 2 diseases.
We'll come back, and I'm sure I can touch on some recent deals in that space and evolution in our development pipeline there. The third pillar I would put into long-acting or durable responses for patients. That's really the heart of all of it. That's not only long-acting from an exposure perspective, but from a sustained, for instance, pharmacodynamic and efficacy maintenance. I'd reference, for instance, amlitelimab there. Clearly, the observation we have of sustained pharmacodynamics and off-treatment maintenance of clinical activity we see with that asset, probably based on the biology, which we might come back to in terms of where that sits as an apex node. The fourth pillar is a bit newer for us, but I think incredibly promising.
I'll come back and answer your question on assets, which is really around immune reset, tissue homeostasis, and long-term remission. I'd reference maybe some activity we've had in this space around deep B-cell depletion in the context and the notion of that leading to reset and long-term durable remission in areas like lupus, scleroderma, and myositis. As you look at our pipeline, you should be able to clearly map across that strategy all of the assets we have internally today and we're prosecuting, as well as those that we might bring into the portfolio to complement what we have internally.
Along those sort of four, what I would highlight and sort of early, depending on how you clarify it, sort of pre-proof of concept, clearly on the sort of efficacy ceiling and the bi-multi-specific approach, we have Linsecamig and Brevecamig, TSLP IL-13 bispecific, and TNF alpha OX40 ligand bispecific, respectively, using our nanobody platform. As we're going to talk about the sort of oral strategies, we may or may not come back to it. We have obviously our Bell and TinFib, small molecule TNF R1 selective inhibitor, as well as recent announcements in the context analogous situation in type 2 diseases with STAT6 now coming into the portfolio. Then I referenced maybe the CD20 myeloid engager in the context of deep disease remission that we've added to the portfolio recently. Again, all consistent with the overarching strategy for immunology going forward at Sanofi.
That's very clear. Look, let's touch on really briefly the IL-33 itepekimab. I feel like we have to, following the results of ARFI12 in former smokers with COPD. What is the potential reasoning behind that result that we saw in ARFI12, whereby, just as a reminder for everyone, it failed to show statistical benefit for reduction of exacerbations? Which are the mechanisms beyond IL-33 that could perhaps show a clinical utility in COPD?
Yeah, thanks, Ben, for the question. Not much more to add, but just for everyone's benefit in the context, as you pointed out, between ARFI1 and ARFI2 and COPD with itepekimab. What I will say and can comment on, well-conducted study. The disease and demographics were consistent across the two studies. As we indicated, the PK looked good and as expected across the two studies between ARFI1 and ARFI2. ARFI1 actually, consistent with the phase two data, seemed to sort of read out as expected, and ARFI2 maybe did not do that. What we are doing, as articulated, is obviously working quite closely with our partners at Regeneron to pour through that data to run through a series of hypotheses that we have.
You will hear more from us when we have a decision and the next step forward for both Itepekimab and the path forward. What we have in hand is a commitment to COPD and the clear unmet need there. You referenced other, or the question referenced other assets. I already referenced Linsecamig. In that case, TSLP IL-13 is promising biology and clearly implicated not only from Dupixent and the activity in COPD, but also some data we saw last year at ATS on the ability for TSLP to impact the disease. We think, for instance, in that case, Linsecamig is well positioned in the context of combining both TSLP and IL-13 for the treatment of COPD.
Yeah, so we look forward to those results. I guess we'll then start looking a little bit more forward. The next asset I think we get a lot of questions on is the OX40L amlitelimab, with the lead indication for this being atopic dermatitis. What do you think differentiates amlitelimab as an antibody that blocks the OX40 ligand versus, let's say, Amgen's OX40 that has already shown some phase three results?
We're incredibly excited about sort of the breadth of ability for amlitelimab and sort of the ability for OX40 ligand biology more broadly. You asked sort of on the biology basis to compare and contrast the receptor versus the ligand. What I'd say, OX40 ligand, the target of amlitelimab, expressed on antigen-presenting cells, predominantly expressed in inflammatory sites as opposed to more broadly and peripherally. From a mechanism of action perspective, we're a blocking approach, not a depleting approach. That blockade, following that blockade, regulatory T cells are preserved. We don't think that's the case if you adopt a depletion mechanism based on OX40-based depletion. We also preserve sort of central and effector memory T cells, incredibly important for dealing with reintroduction of latent viral infections or new infections, for instance, nasopharyngitis and the like, relying in heavy part on those cells.
Again, those are preserved in the context of OX40 ligand blocking mechanism. The last thing I'd say, the sort of observations we have is that we do not see, following OX40 ligand blockade with Amlitelimab, any evidence of immune activation that sort of mirrors something like a cytokine release syndrome. We do not observe fever and chills in the context of that approach. That might not always be the case if you adopt a sort of a depletion mechanism, for instance.
That makes sense. I guess the first quarter update suggested that we could get early results a little bit earlier than anticipated after the trials are recruited relatively rapidly. How would you define success for a drug like this? What is the profile that you're targeting as part of the research?
Yeah, it's a good question. What I'll first start to say is a testament to the Sanofi Development Organization. We talked a little bit about the enablement of AI, but I think writ large, the ability to execute that size of a global study ahead of time, as we indicated, or in accelerated fashion. I think how I would position Amlitelimab in atopic dermatitis is obviously a unique mechanism of action. We believe, as I just articulated, it's an upstream sort of apical node within sort of core T cell biology. It's important for not only type 2 diseases, but also type 1 and type 17 more broadly. Clearly, what we see is a long-term durable or sustained response, both pharmacodynamically and obviously from the phase two data set, even in an off-treatment sort of situation, continued clinical responses.
With that in mind, from a positioning perspective, I not only see the durability as added value within the atopic dermatitis landscape, but also the dosing paradigm. As everyone will be aware, that Q4 and Q12 week dosing paradigm, we think adding sort of convenience for patients, regardless of which one sort of plays out in the context of phase three studies.
Yeah, that's clear. I guess there's a lot of other indications that it's also being assessed in. I think we've got asthma, systemic sclerosis, celiac disease, HS, alopecia. Is there any of those that you particularly pull out that you think has the strongest earliest stage data for the role of OX40 in the disease? Because we're obviously looking here to establish Amlitelimab potentially as a pipeline and a product as what tends to be referenced.
Yeah, thanks, Ben. If I looked at the sort of the gradations of where we have and the data we have in hand, I would point first to the asthma data set in the context of phase two A and how clearly we think that that's we're still sort of going through the phase three design and the options there. We think that's compelling and differentiated in the context of not only eosinophils, but the neutrophil sort of intersection in context of bringing benefit to those subpopulations in the context of asthma, alopecia areata, obviously a disease continued on that need there, T cells implicated in that disease pathogenesis. That data set for amlitelimab will read out later this year. We have celiac next year.
I'll move to the other end of the spectrum and maybe double down on some of the conversation we had earlier around decision making. That would be in hidradenitis suppurativa. From an intra-portfolio perspective, as our immunology pipeline grows, we need to be thoughtful, data-driven in the context of decisions and moving assets from phase two to phase three. I think an example of that decision is comparing and contrasting Brevecamig. We talked a little bit about that already and amlitelimab. As we looked at the data in HS between the two, we've decided to move forward Brevecamig in HS and not amli.
I think as we think about the gradations of not only the sort of the data that supports Amly moving forward, we're also sort of making decisions around not moving forward when we have in an intra-portfolio fashion something that appears to be more meaningful for patients in the context of, in that case, HS.
That makes sense. I was going to ask a little bit more on that HS move forward there with the nanobody. What underscores the confidence to move that forward is the phase three go-to candidate?
It's really that 2A data set and the activity, although it be a small study, the activity we saw there really gives us confidence that that has a differentiated profile. From an efficacy perspective in HS, it's a crowded space, but we think even with that data in hand, we'll be competitive with Brevecamig moving forward. That gave us the confidence to pursue it.
That's very clear. Look, another nanobody technology, I believe, is this Linsecamig that we touched on before. I'd be interested to hear about what makes you believe that this asset could potentially raise the bar for efficacy with patients with severe to high-risk asthma.
Yeah, I think maybe a couple of comments on the nanobody platform in general, and then we're moving into Linsecamig. I think what you'll see from us today and going forward behind Brevecamig and Linsecamig is really capitalizing on the exquisite sort of ability of the nanobody platform to really tailor in a lot of the biologies, both in cis and trans, so in the same cell type, two cell types from a blocking versus an agonism mechanism, a lot of sort of novelty in the mechanism of action. Linsecamig is a beautiful molecule in how it was designed. There's two binding parts for both TSLP and IL-13. And they were designed in a way that sort of really drives to high avidity mediated blockade. So they bind different regions of the respective cytokines.
Really what that manifests in in our mind, and you're asking about the sort of asthma sort of situation, clearly compared to what we've seen out there with single agent blockade of TSLP or IL-13, the data we have so far in asthma shows clear superiority in the context of the combination in Linsecamig of blocking both TSLP and IL-13 sort of simultaneously. We think that that's not only applicable in asthma or, again, I referenced it earlier, likely COPD in the context of some of the precedent out there on the monotherapy arms, if you will.
If we stick within the INI portfolio, then another one I want to ask about is the IRAK4 degrader that we've not actually spoken to, I don't think so far. What underscores the confidence that this could be a meaningful asset in the indications that it's being studied in? How could it be positioned in the increasingly competitive atopic dermatitis treatment paradigm as a result of that?
Yeah, it's a good question and an interesting asset. IRAK4 biology is incredibly intriguing, sort of downstream of TLR signaling, IL-1 signaling. It's distinct from some of the other things we're pursuing within our own portfolio and maybe more broadly in the field. IRAK4 clearly has a scaffolding function on top of the kinase activity. We believe both are important and particularly supported by the preclinical data sets in that space. Therefore, the ability to approach it via degrader makes a lot of sense. What I'll say in the context of the clinical development plan is we think that the biology is quite interesting and it's likely broadly applicable even outside of where we're studying it currently.
I would, in concert with our partners in that case, Chimera, expect to hear more from us on the plans for IRAK4 going forward from a development path perspective.
That makes sense. Is there anything you can share at the moment? Because obviously there is interest in other gastrointestinal, skin, rheumatic, autoimmune disorders when we look at the IRAK4 pathway. Is there anything that potentially could be of interest to you going forward in that development plan?
Yeah, I'd say what was on the table, I won't comment, just we'll do it in partnership with Chimera as appropriate. Our subtherapeutic areas that underpin the strategy that I laid out for everyone earlier, clearly respiratory and dermatologic indications important for our current portfolio and our growing portfolio going forward, growing efforts in gastroenterology behind Duvakitug and some of the bispecifics that we partnered on earlier this year. Then selected approaches in rheumatology, I referenced sort of deep B cell depletion as one example. We may or may not come back to TNF-R1 in that case as well.
Yeah, for sure. Look, your partner Chimera also has a STAT6 degrader. Interestingly, I think earlier, was it this week or last, you opted into a STAT6 degrader from Nurix, the collaboration there. What drove the decision for that opt-in and what underscores your confidence in that mechanism?
Yeah, I think from a company that stands as arguably the leader in type 2 diseases, STAT6 is an incredibly important target for us and for the field more broadly. I think the earlier news this week that we rolled out with our partners in Nurix is to internalize a development candidate, a degrader against STAT6, an important target for us, as I just mentioned. I think key for us is it frames back to my sort of overarching strategy, a component of that, meaning the oral combination approaches, much like the TH117, where a potential backbone there would be a TNF-R1 small molecule inhibitor. For type 2 diseases, you could argue that the analogous situation exists for a STAT6 inhibitor and/or degrader. I think it's even more the data we saw earlier this week from another party sort of further increased our interest there.
I think we look forward to moving that forward as fast as possible.
Very clear. Let's stay on partnerships and acquisitions of external assets here. I want to talk a little bit about the Vigil Neurosciences deal. It's obviously a clinical stage biotech focusing on developing drugs for neurodegenerative diseases. You gain access to an oral small molecule TREM2 agonist. Could you talk to us a little bit about the rationale of what this is and how exciting you find that mechanism?
Sure, absolutely. Part of what I laid out at the beginning starts to thread this immunoscience sort of aspect of our R&D strategy within Sanofi. It's no different as we talk about Vigil. We have clear sort of core capabilities and expertise in immunologic nodes. We have clear capabilities and expertise in neuroinflammation from our success in the context of multiple sclerosis and our efforts with tolebrutinib and frexalimab. We have sort of an evolution in particular in the Alzheimer's space based on blood-based and imaging biomarkers that now make sort of early trial designs even more tractable. All of those, coupled with an investment we did in Vigil that gave us a right of first negotiation around that small molecule TREM2 agonist, came together in a situation where we made the decision it was the right time to internalize and prosecute our own.
I'd say TREM2 as a target is something the hardest decision we do in research is target selection and credentialing. We've done that for TREM2. It's a genetically validated target within, for instance, Alzheimer's disease in this case. We believe the small molecule agonist has the right exposure within the CNS to agonize TREM2 in the microglia and carry out the functionality in the context of promotion of plaque removal, for instance, and some of the other sort of anti-inflammatory aspects that it takes. For all of those reasons, we have both an effort within the Vigil small molecule agonist for TREM2 and a growing effort and interest in neurodegeneration more broadly within Sanofi research and development.
Yeah, that's clear. I guess if we then think about kind of your platform approach, are there any areas of the pipeline or research organization that you think could benefit from external acquisitions or enhancing the platform that way, particularly thinking around perhaps the clinical presence in gene therapy or editing? Is that somewhere of particular interest for you on the research side?
No, I'll come back to the gene editing. We certainly have efforts there that I'll comment on. Maybe more broadly to take a step back around acquisitions. Obviously, we announced one earlier this week in the context of Blueprint Medicines. And what I would do is I'd frame that again, consistent with the immunology strategy and where we are from a subtherapeutic area. First of all, I say credit to the colleagues at Blueprint for now bringing a medicine to patients that did not have one in the context of mastocytosis. Obviously, we believe that we could be an ideal partner to really accelerate Ayvakit and that medicine to even more patients. Mastocytosis obviously manifests in the gut, in the skin, and outside of the bone marrow as well, or on top of the bone marrow.
Our call points as we think about the subtherapeutic areas that we're interested in for our own pipeline really sort of affords that intersection and accelerating that. As we think about acquisitions or M&A, you should think about the core capabilities and strengths we have internally, not only from an R&D, but in that case, perhaps from a commercial perspective to really accelerate medicines to patients, obviously the ultimate goal for all of us. I'd view that as sort of an area you'll see continued efforts from us in analogous spaces. I referenced in the context of the growing interest in gastroenterology, a series of bispecifics we brought in earlier this year in the context of UC and Crohn's disease and TL1A bispecifics for Alpha-4, Beta-7, and IL-23P19. Again, consistent, you should see some consistency aligned to our strategy.
Now, Ben, you asked about genetic medicines and platforms in general. We're sitting on some real strengths at Sanofi around sort of small molecule medicinal chemistry, the nanobody platform we talked about, as well as traditional biologics. We also have had for the last sort of four or five years a growing effort internally and through some acquisitions, including, for instance, the Tidal acquisition and lipid nanoparticles efforts around both viral and non-viral genetic editing and gene medicine. We continue to have those efforts. You'll see from us coming out of our internal pipeline into the clinic efforts in both the viral and non-viral space broadly in areas such as rare disease, in neuroimmunology and oncology, as well as ophthalmology. Some RA in the clinic, for instance, in ophthalmology with a wet AMD program that started earlier this year.
You'll see more from us in the sort of genetic medicine space.
Very clear. I guess if we stick a little bit on partnerships. Again, when we think about Duvakitug, the anti-TL1A, you obviously got this as part of a deal with Tever. We have seen other pharmas enter the space for significant upfront. What do you see about this medicine that differentiates it from the other TL1As, especially thinking that a couple of them are ahead? How excited are you about the development program of this?
Very excited with our partners at Tever to sort of continue to prosecute Duvakitug. I think the phase two data would speak for itself with respect to both the UC and Crohn's data set meeting all of the endpoints, showing the clear dose response in those data sets, giving a lot of confidence. Mechanistically, you asked a little bit about perhaps the distinction between Duvakitug and the mechanism of action and some of the other assets out there. You're likely aware, but in case you're not, Duvakitug binds TL1A in a fashion that allows a DCR3 or the decoy receptor, which is a negative regulator of the pathway, to continue to bind while preventing DR3, the pro-inflammatory signaling, to occur. There is a mechanistic rationale why you might be sort of superior in the context of the MOA.
We will see whether or not that continues to play out in the data sets as we prosecute further development in phase three for Duvakitug.
That makes sense. We step away from INI just during the last few minutes. I want to touch on Frexalimab, so the CD40L antibody. What is your level of confidence around this asset when you consider there is a pretty high bar set by anti-CD20s in the indication? Any color around that?
Yeah, thanks, Ben. Maybe I'd say CD40 ligand biology analogous to what we've already discussed with Amlitelimab in the context of that T-B cell interaction and sort of an apex node. Clearly, Frexalimab in the context of multiple sclerosis providing a non-depletion mechanism, a novel mechanism of action in the context of the apex node. We'll see how that plays out from a durability perspective. We believe that's the right sort of target in a non-depletion, both to compete, I'd say, with B cell depletion, but also to complement for patients in the context of the armamentarium to treat multiple sclerosis.
Very clear. I guess we've spoken about a lot of assets, broad array there. Is there anything that we haven't spoken about yet, even in the very early pipeline, that potentially is things to watch in the future that may not potentially be a late-stage driver now, but something that could emerge and be very interesting for you?
Yeah, thanks for the question. I sort of already hit on a few things, which is the hardest decision we make in the context of research is target selection, target credentialing. Anything that is sort of burgeoning in the research organization is three to five years to the clinic. What you'll see from us at Sanofi is an increased quality and sustained output in our first in human pipeline going forward. A lot of what you'll see in the next few years is a bolus of bispecifics coming into our pipeline in the early clinical development space. That is really buoyed by our ability to credential targets using AI. A lot of the reverse translation and back translation form we're learning in our INI development programs, starting with the patient first. They are all credentialed.
We look forward to sort of moving those forward across all our subtherapeutic areas. Those should be showing up in the clinic in the 2026- 2028 timeframe. That is exciting. I referenced the sort of effort in broadening the context of neurodegeneration and ophthalmology. You will continue to see that and realize our continued ambition in rare diseases as well.
Very clear. That takes us to about time. I want to thank you so much for joining me on stage and chatting through this. Very interesting, very exciting times. Thank you all for joining. If you have any questions, please do feel free to reach out to myself or the team at Sanofi. Enjoy the rest of the conference.
Thanks, Ben. Thanks, Roman.