Okay, good morning, everybody. Thanks for joining day two of Barclays Global Healthcare Conference here in Miami. My name is Emily Field. I lead the European Equity Research team covering European pharmaceuticals out of London. And we're pleased to be joined today by the leaders of Sanofi's immunology team, Shaju Backer, who is the global head of the immunology branch, and Naimish Patel, who heads development for immunology and inflammation. So as we were just getting started here, we thought maybe a good place to start was the big cutaneous therapeutics conference over the weekend, AAD. So I don't know if maybe that would be a good place to start 'cause I know you guys presented a lot of data there, and then we can get into Q&A.
Sure. Naimish, would you like to kick off with the amlitelimab data we presented at AAD?
Yeah, thank you. Absolutely. Emily, thanks for inviting us. It's great to be here today and talk about the pipeline. So Sergey and I just returned from San Diego, where the American Academy of Dermatology Conference was, and we presented our data on amlitelimab, the part two of our phase 2b study. So we presented the part 1 data back at EADV in Berlin in the fall, and that was the first 24-week period of that study where we had four doses compared to placebo in patients with atopic dermatitis to severe atopic dermatitis. And what we showed in the part one data, week 24, at the highest dose, there was a response compared to an IGA 0/1 response of almost 50%, at week 24, which is as good as any biologic, during that time span. So very, very, interesting data.
And we also had some data around biomarkers showing effect on both type two and non-type two biomarkers, suggesting an effect on amlitelimab of amlitelimab on both type two and non-type two pathways in a different type of patient population that probably the anti-IL-13s alone get. And this data that we shared at AAD was part two of that study. So in part two, we took the patients who were responders in part one at week 24 and randomized them to either continue their dosing at Q4 weeks that they did in part one, or withdrawal of therapy. And we followed them for an additional out to week 52. So their last dose of drug was at week 20, and they had 32 weeks follow-up after that.
And what we were able to show is that if you include the data from the patients who took topical steroids, somewhere between 70%-80%, depending on the dose, had a sustained response in terms of IGA 0/1 or EASI-75 at week 52. And this is really very interesting and very novel data. No compound in atopic dermatitis has shown this. Essentially, patients, despite even not having detectable levels of drug for the last 8-10 weeks of that withdrawal period, still had a sustained response in terms of efficacy. And if you looked at their same biomarkers, the ones I mentioned, the non-type two and type two biomarkers, they also stayed at similar levels as to when they were actually taking drug as well.
This really has started the conversation among the experts in this field about true remission in atopic dermatitis, a very new concept where patients have long-term sustained and deep disease control. This is somewhat, but very consistent with the mechanism of action of amlitelimab, where it blocks OX40 ligand, which is a key step in promoting T effector and T memory cell function, as well as inhibiting T regulatory cells. So if you block that, you decrease the level of memory cells, T effector cells, and increase the function of regulatory cells, really rebalancing immune response in a sustained way that's even present beyond the exposure of the drug. This is really interesting data and very novel data in the atopic dermatitis field.
So at R&D Day, Emily, as you know, we, that's when we first announced we are taking this asset to Q12 weekly dosing. So this was our confirmation that, you know, we can or this asset, this product can carry through from a durability standpoint. In addition to the amlitelimab data we presented, we also showcased our entire pipeline. You know, as we started doing that more often at these major conferences, the feedback was phenomenal. We had a couple of experts telling us, you know, this is an exciting time to be working with Sanofi. You have a phenomenal pipeline. You're leading with science. The number of trials you're rolling out, you know, from a dermatology standpoint alone, as you know, we have multiple assets in AD, HS, PN. So yeah, the journey is just beginning.
Yeah, great. Certainly out of R&D day, I thought that was one of the most exciting components that we learned about amlitelimab was the Q12 week dosing. Maybe just from a commercial perspective, I believe in the phase two, you are also in Q4 weeks. In that EUR 5 billion peak sales target, you know, are you getting to sort of the higher assumptions? Is that really hoping to get that Q12 week dosing, or do you think this could still be competitive Q4 weeks?
I'll let Naimish answer the question on the dosing regimen, and I'll come back to the commercial question.
Yes, it's a great question. One, I would say, would point out that also, even with for the Q4 dosing arm in phase three, there's an induction study and a maintenance study. In the maintenance, all the patients will roll over into a maintenance study where they will also switch to Q12, after 24 weeks of Q4. So we still anticipate, even if, if for some reason Q12, that outset doesn't work, that patients still will be able to switch over. So long-term, it is really Q12 dosing for, regardless of regimen. We think that the data that we have accrued, both in terms of modeling data shown at R&D day plus the new data, as Shaju mentioned, in terms of sustained response, really, at least, will allow us to do Q12 and hopefully also actually, the Q12 from the outset will also show equivalent efficacy.
So from a commercial standpoint, Emily, to your question, Q12 will be a big differentiator for sure. But more importantly, I think, you know, we need to come back. It's the efficacy. It's the safety, durability. That will carry the most weight of the commercial positioning. And Q12, the convenience factor comes in. And, you know, you can draw parallels from risankizumab in psoriasis if you look at, you know, coming in much later and what that they've been able to accomplish in the psoriasis space. For your $5 billion-plus peak sales forecast, we announced six different programs with this asset. So that includes AD, and asthma phase will be reading out in quarter four this year. And from there, you know, we have multiple programs in systemic sclerosis, in alopecia, in HS, and I'm missing one.
Celiac disease.
Celiac disease. Thank you. That is the high unmet need disease. We are very excited about that, you know, that there's currently there are no treatment options available for celiac disease.
Yeah. And one I know this was covered at R&D day, but it's still a question that we get. And you brought up, you know, type two and non-type two. Obviously, for AD and asthma, phenomenal data for Dupixent in type two-driven disease. So should we think about amlitelimab as the opportunity really being in the non-type two, or do you think that it will have an opportunity across the whole broad spectrum of patients?
So if you look at the biomarker data that we shared at EADV, that you saw a very potent effect on blood levels of IL-13, blood eosinophils, and TARC, so your classic type two biomarker. So it does cover that. And atopic dermatitis, I would say, all patients generally have a facet of type two inflammation. It's just that some patients have a mixture of type two and non-type two. And it tends to be the patients who have more longstanding atopic dermatitis with really older lesions, some pediatric patients, Asian patients, and also patients of dark skin, African American patients. And so we anticipate that there's probably a different patient profile that might respond better to amlitelimab than versus an anti-IL-13.
We don't anticipate requiring any type of diagnostic looking at biomarkers, but it's more clinically, and we're doing studies within special populations, both within our randomized control trials, but also within our long-term trials to show efficacy within these different subpopulations, especially populations with dark skin is also a very important area because we think maybe those patients might have a slightly different profile. And those sort of things could help guide physicians on choosing one for the other, in the clinic, in the real world.
Right. And we can't have a Sanofi immunology discussion without talking about Dupixent. So and we were just that you helpfully just reminded me that the PDUFA for COPD is 27th here in the U.S. So, a lot of excitement in the investment community about the potential for this launch. You know, how are you thinking about launch preparations, what the slope of this curve could be like? Because it does seem like the feedback from KOLs is they can't wait for this approval.
Yeah. We are very excited about this launch as well. You know, it's a high I know you COPD, you almost have to think like oncology. It's a third leading cause of death. It's unlike any other immunological diseases in that sense. From a launch preparation standpoint, one, Dupixent, the pulmonologists are familiar with the assets, from their utilization in the asthma treatment for asthma treatment. Having said that, the type two signature in COPD is actually a unique phenomenon in the sense that community pulmonologists are still trying to get their head around the data. For example, when we presented the data at ATS last year, the first question was, "Surely you must have had some asthma-like exacerbations in there." But the fact is, FDA had asked us to make that an exclusion criteria, to be very clear on the patient profiles.
We believe there is a bit of education that needs to be done. Of course, you will see the tertiary centers, the academic centers adopting very quickly because they are many of them would have taken part in the trials, very familiar with the data. But it will take a bit longer for the community pulmonologists to come around.
Yeah. And then in COPD, there obviously will be a number of readouts of another IL-5 towards the end of this year, we're expecting, and then your own IL-33, itepekimab, next year. So maybe first question on, I know that there's different patient segmentation between where dupilumab could be effective in COPD and itepekimab. So how should we think about what we should look for for that data for next year on itepekimab?
I'll give you a sense of the patient numbers, and I'll hand over to Naimish to talk about the profiles of the drugs. So from a patient population standpoint, there are 1 million GOLD E biologic eligible patients in the United States alone. Of that, 36% of them will have EOS over 300. That's our estimate. So roughly 350,000 patients will be eligible for Dupixent at launch. Then itepekimab, which we hope to be indicated for prior smokers. With itepekimab and Dupixent, we hope to reach 80% of the GOLD E biologic eligible patient population. Now, that 350,000, if you include EU5, that's 500,000, half a million, by the way, just for Dupixent alone. And then with itepekimab, we want to reach the 80% of the GOLD E biologic population. Naimish, on the profiles and the IL-5s.
Sure. My, my favorite topic. So, maybe going back to Dupixent and the data, Dupixent blocks IL-4, IL-13, which are two key steps in the initiation and propagation of type two inflammation. The IL-5 drugs are fairly specific in getting eosinophils, but they're not as broad in covering type two inflammation. And we have seen within asthma a difference in the outcomes that you can see where, especially with regard to lung function, the IL-5s don't really affect lung function as nearly as much as Dupixent, probably because the IL-13 component, especially in dupilumab, is very important for controlling airway mucus and airway inflammation, and it's probably responsible for the effect that we see in terms of lung function improvement.
This translated very well to what we saw in COPD with dupilumab, where all the patients in both trials in NOTUS and BOHRUS saw significant reductions in exacerbations, 30%-35%, which is significantly greater than what has been seen with the anti-IL-5s, which is in the range of 15%-19%. And then also the improvement in lung function, 100-150 mL. None of the IL-5s have really shown any significant changes in lung function. And this is very impacting, impactful in these patient populations because they're already on triple therapy, maximal inhaled therapy, and still having symptoms and exacerbations. And this also translated to improvement in symptoms and quality of life in these patients where many physicians thought that was not even possible in this severe population.
So that is now, I think, the gold standard for what we think is now possible in COPD. We hope and a lot of the key experts have told us that this will really open up the entire field of COPD because now people see that this is possible to do with the right agent. So we anticipate the IL-5s reading out, but we don't think that we'll see what we've seen with Dupixent. Now, so going towards Dupixent, covers the patients with a screening 300 eosinophils, 300 or greater, but it will have the patients with less than 300 eosinophils. So itepekimab, our anti-IL-33, is the only anti-IL-33 class drug that's shown in a moderate-sized COPD trial of about 350 patients, reduction in exacerbations of greater than 40% in former smokers.
This was regardless of baseline eosinophil count. High and low eosinophils both responded. So we think this is truly a different type of drug than dupilumab. IL-33 is fairly upstream in the initiation of inflammation and involves both the type two and non-type two pathways. We think that's probably responsible for what the efficacy we saw in the low eosinophil COPD in the former smokers. And Sergey mentioned there's some overlap with smokers with high eosinophils, I mean, excuse me, former smokers with high eosinophils for both drugs. But then the former smokers with low eosinophils are not covered by any of the IL-5 or IL-13 agents. So recently, we've announced that we're on track to finish recruitment of both studies, the phase three studies for itepekimab this year with a readout in 2025.
And we've also seen some data from tozorakimab, the AstraZeneca anti-IL-33. They failed their primary endpoint in a recent asthma trial. And they also shared some PK data suggesting their exposure was a little low from what they had planned. And so they added a third COPD study with a more frequent dosing regimen. So there's some evidence there that maybe the dose that they chose for the first three phase three might not be the right dose, and they've added a third study. And they also announced that all three studies now, the readout will be post-2025. So there it looks like they're delayed. And probably similar to what we experienced as well, it's been so hard to recruit COPD studies coming off the COVID epidemic. So it's not completely surprising. We did start first, and we looks like we will finish first.
And for the first-in-class, hopefully best-in-class as well.
Yeah. There's certainly going to be a lot of readouts next year. But maybe sticking with exciting data from ATS last year, lunsekimig, which I believe, lead indication asthma. Really exciting data last year. You know, we do have TSLPs approved, a recent deal for a longer-acting TSLP. So maybe could you just help us understand why this bispecific approach could be so differentiated?
Sure. So, maybe I can talk about lunsekimig again, or if you want to talk about what we think of these long-acting biologics. So what we saw with anti-TSLP tezepelumab in asthma, they've gotten the indication for all of asthma, not just eosinophilic asthma. But if you really dive down into their data, most of the effect seems to be in the high Type two population, both in terms of exacerbation reduction, and lung function. If you take truly non-Type two patients, the patients that are low in eosinophils and low in FeNO, the other Type two biomarker, there's not much of a response in those patients. So it's probably more of a Type two agent.
But what we did observe is that if you compare similar patient populations, the other interesting thing about their phase three study is that they recruited patients with two or more exacerbations at baseline, where the Dupixent studies only had one or more. And doing that actually selects for a more intrinsically type two population because those are the patients at risk for more exacerbation. So if you compared a similar population - we published this in for the Dupixent studies, two or more - you see Dupixent has a better exacerbation reduction and better lung function improvement in the same type of population. And you could also compare the OCS-sparing studies of the two, Dupixent successful with tezepelumab, whereas not suggesting Dupixent is a better type two drug.
And so when we designed lunsekimig, we thought adding IL-13 and anti-IL-13 would enhance that part that we see that it's not as competitive or anti just TSLP alone. And TSLP, as a cytokine, works very upstream as an initiator of type two inflammation. And IL-13 is very downstream, causing the tissue damage we see in type two inflammation of the airways. And combining those, we saw in preclinical models potential for synergy. And so we did a phase one study of lunsekimig. This past year, we reported ATS looking at FeNO, which is a biomarker of airways inflammation. And we showed that after a single dose in a mild to moderate asthma population, we'd reduce FeNO by greater than 40 parts per billion.
And so if you compared that to single-agent studies of either anti-TSLP or anti-IL-13 alone, those generally have an effect of 10-15 parts per billion reduction in FeNO. Well, we're talking about greater than 40. So true synergy where one + one equals three or maybe even four and adding these together. So we're really optimistic that this will potentially be the best biologic in asthma and also adding, spreading to additional disease. We announced that we're going into milder forms of asthma with that drug, into CRS with NP with that drug, and eventually COPD as well and atopic dermatitis.
So yeah, it is an exciting asset, as Naimish mentioned. For us, the ambition is, you know, the launch timing of this is towards closer to 2030, all program running in parallel, fingers crossed. That gives us the ability to really raise the efficacy ceiling and continue our leadership in the phase three space with asthma, of course, and then exploring it in COPD, then further taking it to AD once we have more proof of concept data in hand. But the more exciting part about this nanobody platform, we also have an OX40 Ligand TNF nanobody, which we announced. We have HS data reading out in quarter four this year. So with that, we will have now three assets. There is an approved asset company that we acquired in Belgium, Cablivi, for blood disorders.
So in Phase three getting on to itepekimab, we have the data in hand in asthma. And with the OX40 Ligand TNF with HS, we have three Nanobody coming out of this platform. So we are now looking forward to having this platform, delivering a pipeline of molecules for us with the unique this unique ability to combine proven mechanisms and really raise the efficacy ceiling. So we're very excited about this platform in its entirety.
Great. Yeah. And, you know, one asset R&D day where I think, obviously, the company's very excited, but maybe the investment community is still a little bit skeptical of the oral anti-TNF. And I believe we're going to do data this year. But could you just remind us of particularly why you're excited about this from a clinical perspective, obviously, with the biologic cell going biosimilar here in the U.S. now?
Yeah. So I, I will try to address the positioning, and I think it's important. Naimish talks about why we think this will be a differentiated molecule. So I'll start with that. We believe this will be a differentiated molecule. First of all, it is a TNF R1 signaling inhibitor. It's not an oral Humira. So we want that to be very clear. So our first step will be we are having internal discussion with our regulatory team to engage with the regulators to have that dialogue. How do we deal with the two mechanisms? One is the MAB, and this one is a different mechanism. That is important from a micro standpoint, as you know. The other reason we're excited about is the efficacy.
You know, we hope our TPP is and Naimish will describe why we think we can have a differentiated efficacy, from a mechanistic standpoint, but also safety. The safety from our Listeria and Bullspray clinical models, we're not seeing any infections. If we can replicate that in the clinical trials, we have a completely differentiated molecule that hopefully will have TNF-like or better efficacy and, no black box warning. And having that safe orals, that is our player here. In, dermatology space, as you know, you've seen Otezla coming in, creating that, a prebiologic gateway medicine, with orals. And we see that opportunity wherever TNF has gone. So this could have the potential to be a prebiologic in rheumatoid arthritis, for example, in the rheumatology space, in the dermatology space, and especially IBD where TNFs still are considered in many ways the gold standard.
On top of that, we talked about this being a core backbone of combination therapies. So we're exploring other oral combinations also, looking at fixed-dose combinations with which we can raise the efficacy ceiling once again, similar to the nanobody platform we're doing with MAB. With that, I'll hand over to Naimish describing mechanistically why we think this will be differentiated.
Absolutely. I see the clock beeping. So I'll be quick.
So many questions.
No, great discussion. So we're expecting the readout for Thrice to be H1 2025 in order, and the mechanism is unique in that it binds the soluble trimers of TNF and prevents their binding to TNF R1, which does not inhibit the interaction between membrane-bound TNF and TNF R2. And so we think that unique mechanism will provide improved safety, as Sergey mentioned, and also potential for improved long-term efficacy. Improved safety because TNF R2 seems to be important for protecting from excessive inflammation and increasing T regulatory cell activity, as well. And so in preclinical models, we're able to show with our compound that it actually preserves response to a Listeria bacterial infection model compared to the biologic and actually prevents mice from dying from Listeria infection.
And also, we know that patients on biologic TNFs often lose response long-term due to the antidrug antibody formation. And this molecule, of course, because it's a small molecule, it's not something where antidrug antibodies play a role. And because of this T regulatory cell effect, it's an additional potential mechanism for long-term disease control. So for those reasons, we think potentially a really unique profile that's more effective and safer than TNF biologic.
Great. And unfortunately, we're at time. I have so many more questions because you have so much going on in the pipeline. But thank you guys so much for joining, and I hope everyone has a great day too here in Florida. Thank you.
Thank you, Emily.
Thank you.