Well, good morning everybody, and thank you so much for joining us for the 46th annual TD Cowen Healthcare Conference. I'm Yaron Werber from the Biotech team, and it's really a great pleasure to have with us today, Vor Biopharma and Jean-Paul Kress, the Chief Executive Officer. Telitacicept is a BAFF/APRIL inhibitor with really promising data in both phase III in gMG and Sjögren's. The gMG data is gonna come mid-year and first patient in for the phase III global Sjögren's study is gonna be by the end of the first half of this year. We've written extensively about both opportunities. gMG looks really promising based on the data, and we're equally to frankly even more excited about Sjögren's, which is frankly a big white space. Jean-Paul, thanks so much for joining us. We appreciate it.
We'll do a presentation and then Q&A.
Thank you, Yaron. Good morning, everyone. Very pleased to be here to update you. Oops. Presentation. Just trying to retrieve the slides. Very pleased to be here and to tell you about our progress at Vor Bio. Thank you. I'll be making forward-looking statements during this presentation. This is our disclosure slide. At Vor, our ambition is to significantly improve the standard of care in autoimmune disease. For doing that, in 2025, in June, we in-licensed one of the most exciting opportunities in autoimmune, a late-stage asset called telitacicept. Telitacicept comes from the China biotech innovation engine. It's RemeGen, our partner there, who has developed this asset in a series of late-stage trials that I'll talk about in a minute.
The great thing with t elitacicept is that it has a very uniquely designed and differentiated profile. It's a BAFF/APRIL inhibitor, as Yaron alluded to, which has the ability to tackle the upstream and the downstream of the B-cell lineage. With that, it remodulates the immune system without B-cell deep depression and unnecessary immune suppression. This elegant mechanism has applicability in a series of autoimmune diseases, and it's been very well characterized by in the RemeGen late stage clinical program in more than eight indications. There is an impressive list of phase three trials in the major autoimmune diseases and some at the forefront or in the white space like Sjögren's disease. We'll tell you more about that. It's clinically validated, which is extremely precious for us. It's also de-risked on the safety side because it's commercially available in China.
It has been administered to tens of thousands of patients there commercially in several indications. We have selected two indications for our global first trials. It's myasthenia gravis and Sjögren's disease. They are two very different diseases and opportunities, but they are both sizable and with unmet medical needs. We think we can compete very effectively and provide great advances in these indications and achieve blockbuster status in these indications, obviously. There is more than that, but we stay very diligent in our capital allocation. There is more than that with a series of autoimmune B-cell-mediated disorders. In theory, Telitacicept can cover most of them, if not all of them. We'll address that in time with the right discipline.
We have a healthy balance sheet with $450 million, which gives us the runway until mid 2028 and the means for our midterm catalysts, especially our global phase three. A great opportunity I'm going to tell you more about now. I should also say that we recentered the company completely mid 2025 around this asset with a brand new team of experts, great talents who have been executing on turbo boosting our phase three trials and preparing for the launch because the MG launch is not so far. Let me tell you more about the modality or the mechanism of action of telitacicept. BAFF and APRIL are two key cytokines in the B-cell lineage pathway. They are important for the development, the maturation, and the survival of B- cells.
By blocking BAFF and APRIL selectively, telitacicept inhibits the abnormal development of the hyperactivated B-cell clones, and it reduces the secretion of autoantibodies. By acting on BAFF and APRIL on the upstream and the downstreams, it basically remodulates the immune system without, again, deep B-cell suppression, which allows the immune system to function against pathogenic agents, for instance. This elegant mechanism or modality has a great applicability because you don't need to interrupt treatment time to time to help the system to restore. You can treat chronically and in a very reliable way on the long term. In these diseases, the patients need to be treated chronically and on a regular basis. That's very important. I mentioned the impressive clinical program, late stage program from RemeGen on telitacicept, and it's been obviously well characterized here with a very consistent and clinically meaningful efficacy profile.
Three commercial approvals there in systemic lupus first and then rheumatoid arthritis and most recently myasthenia gravis. Two more BLA submissions in late 2025 in Sjögren's disease and IgA nephropathy. It has achieved in at least three indications best-in-disease status with the phase III results. A very compelling set of data which give us a fantastic bearing point to select and carve our own global phase III trials at Vor. This is true for efficacy. The de-risking is also obvious for safety because tens of thousands of patients have been treated in China, either through the program or commercially. The safety profile is very consistent and manageable. There is no burdensome vaccination requirements like complement inhibitors. There is no signature B-cell depletion-associated serious adverse events like with depleters, the CD20s and others.
There is, in a consistent way, mostly mild to moderate adverse events observed in the clinical program and in the commercial endeavors. The safety profile is very important because it enables long-term treatment and chronic treatment in these diseases, which is actually one of the most important high unmet medical need in autoimmune disease. The ability to treat chronically without having to do drug holidays. This slide shows you the important and impressive list of clinical trials with telitacicept. There is a wealth of phase III data between RemeGen in China and ourselves globally now. You see we cover a large amount of autoimmune indications, and it gives the picture of a true pipeline in a product opportunity with obviously multi-billion dollars sales potential.
Again, a strong cash position which makes us, which puts us in a very good position to deliver on these opportunities. Now, let me tell you more about myasthenia gravis, which is our midterm opportunity. First and foremost, why did we select myasthenia gravis, our beachhead indication? For mainly two reasons. MG, despite the fact it sounds busy as a market, is a sizable market. It is forecasted to be in excess of $10 billion of sales in the U.S. only by the end of the decade. That's very much the case with most immunology or autoimmune indications. Remember that atopic dermatitis was forecasted to do only a few billion dollars of sales. DUPIXENT product is probably going to top EUR 25 billion at the end of the decade, and it's only one-third of the patients treated by biologics. Same in MG.
When the first FcRn was launched, nobody thought that it would be as important market at the end of the day. We have a lot of playground here to increase the sales in this market. Number two, there is still high unmet medical need in MG. The patients are treated by new agents, okay? These agents don't fulfill all the needs, which are mostly about the possibility to treat chronically with a holiday break with a better safety profile. It's true for complement inhibitors, it's true for FcRn. Our agent telitacicept ticks all the boxes here. The China phase III trial, which was communicated last year by our partner RemeGen, is extremely impressive in its results.
The MG- ADL primary endpoint placebo-adjusted results compared to the other agents on the market or being investigated show a very strong magnitude of improvement, -4.8 placebo-adjusted improvement here, which is almost double their agents at 24 weeks with a very consistent safety profile and very manageable. Importantly enough, what is true at 24 weeks is even more true on the longer run. If you look at the open label extension period, which is another 24 weeks in the China study, you can see that the MG- ADL score continues to improve, and the patients continue to feel better and be better and do better. Again, this duration of effect and efficacy is extremely important because it leads to disease modification, which is probably the main unmet medical need in myasthenia gravis.
On the right-hand side, you can see that around 87% of the patients achieve MG- ADL absolute score improvement of 6, which is best in disease definitely and very impressive. These results are a fantastic opportunity for us to replicate that in our global phase III trial. We have started and actually are enrolling at a good pace. You can see... Actually, I forgot to mention that in the phase III trial in China, it's an important differentiating point of telitacicept versus existing agents like the FcRns. There is no need for drug holidays or breaks because you might know that with FcRn, you knock down the IgG by such a magnitude that you need the system to recover time to time, otherwise the patients don't have immunity anymore.
You don't want to live with only 10% left of IgG to fight your COVID or other agents. That's why they have to stop and do a break and come back. During these breaks, beyond the fact that it's not convenient and obviously not very reliable, you expose your patients, especially in MG, to myasthenia gravis crisis, where you can have acute episodes with life-threatening events. That's not good. With telitacicept, because of the consistency of the treatment scheme and the mode of action, you don't need drug holidays. That's a key differentiating factor for us. I was going to tell you that our MG global phase III trial is enrolling very well.
It's a very similar 180 patients, very similar protocol than the China phase III trial, randomized between the active arm of `240 mg of telitacicept versus placebo and with an extension period. Here we have made some improvements in the protocol, learning from the China study, trying to improve it, especially in the duration of the OLE. We've made it from 24 weeks to 48 weeks, and even with the opportunity for the patients to stay longer, depending on the patients and the physician wish. We really want to see that as a long-term opportunity. We believe this duration of treatment and of effect is key to study, and that will add to our unique, differentiating profile.
We have guided for readouts of the top-line results of this study by the H1 of 2027. More to come. Great opportunity in MG. Well-studied indication, larger than thought, with a great differentiating opportunity. We'll keep you updated on our progress here midterm. Let's pivot to the next white space, as Yaron said. I like the expression. It's white space in the space that is probably the next frontier in autoimmune disease. This is an indication or a disease which affects more than 100,000 addressable patients in the U.S., so it's very large, and it's probably much larger than that. It's typically an underserved indication with no approved biologic modern treatments yet, which has underdiagnosed patients and is going to be larger than that.
The market will grow as with all these indications, pre-biologic going to biologic era. This is a much more complex disease than initially thought. It's usually traditionally mentioned as a dry eye, dry mouth disease affecting mostly female patients. It's actually multi-organ, multi parts of the bodies, joints, lungs, liver, skin with pain and fatigue, which are debilitating for the patients. They evolve in stages, and they end up with very debilitating late-stage disease with very importantly, the prognosis which can be very affected by the transformation into malignancies of these patients, and insignificant portion of them transform into B-cell lymphoma, DLBCL, which is a very different prognosis. That also underpin the fact that this disease is not only about purely just an IgG shutting down solution.
It would be way too simple, which actually it has a deep B-cell origin which you have to tackle in the upstream. You know, there are FcRn agents being investigated there, but we believe that our action, mode of action on the upstream has a very important relevance here. That's important to characterize the disease and spend a bit of time because it's new. People don't know it yet well. Even the physicians had to learn how to investigate this disease and study this disease and conduct the trials. It's very important, and we are at the perfect timing for our global phase III. First, let me tell you more about the incredibly impressive, excuse me, results from RemeGen.
At ACR last fall, they have presented their phase III on three patients randomized into two active dose of telitacicept and placebo, and they have shown incredibly stunning results on the two key endpoints, the physician endpoint, ESSDAI multidomain, and the patient endpoint symptom score, ESSPRI. Very important point in this study, these patients in China were clear of any background therapies. There was no steroids, no immunosuppressants. They were pure patients. What you see is what you get with this study. Pure patients and just the effect of telitacicept. It's the perfect proxy for us. We know that on the West, we will not be able to replicate that. We'll have to have patients with some background therapies, but we know how to control that.
We learned that. Here what you see is the effect of telitacicept, and you see the incredible achievement at the high dose of 160 mg, - 4.4 ESSDAI placebo-adjusted improvement and almost - 2 of ESSPRI, which is even more impressive on the symptoms. This shows you that it's true at 24 weeks, but it's also like for MG true in the longer run. At the end of the OLE period, you can see that the effect, the impact continues to improve, which shows the again, the potential of the duration of effect of the drug. Another way to look at it is, if you take the % of patients achieving a certain amount of reduction in the 2 scores.
90% of the patients report improvement on their symptoms on the right-hand side of the chart here. It's very important. Usually when the more than 1 point ESSPRI score is achieved, that's clinically meaningful. The results are clinically meaningful and statistically significant, and we are the only ones having been able to achieve that. Fantastic results. The KOLs actually are very impressed by that. If you want to put in perspective with other agents, you see on the right-hand side of the slide the phase twos available, the data available on the phase twos, us in dark blue and other modalities or products. You can see the magnitude of difference on the ESSDAI. On the left-hand side, only two agents have communicated or published phase three data.
It's us and a BAFF receptor inhibitor. You can see also the incredible separation of ESSDAI placebo-adjusted results, minus 3.8 for us, around 1 something for the others. There is a placebo component, as you might know, in this, but it shows that when the study is well run, the results can be absolutely amazing with telitacicept. On that point, we have turbo boosted the start of our global phase III trial in Sjögren's based on these remarkable results from our partner. We are in the position to announce that we will dose our first patient by the end of the first half. This trial will enroll 250 patients randomized between active arm of 160 mg of Teli versus placebo during 48 weeks, and we'll follow up for an extension period.
The endpoints will be ESSDAI, axSpA, and a series of more investigational endpoints, which are very important to characterize the disease because it's an evolving space. Again, the white space. There is also a need to accompany the stakeholders in this disease. I'm talking about the KOLs, the partnership, but also the regulators. The timing couldn't be more perfect because others are just ahead of us to kind of clean up the path for approval for this disease. Fantastic opportunity, and we talk about business here for a minute. Just MG and Sjögren's are multi-billion dollars opportunities for telitacicept. Sjögren's is very difficult to quantify right now because, again, it's a wide space. There are much more patients that we don't know yet.
With our probably best in disease profile, we ambition to be definitely multi-billion dollars with Sjögren's only. I'm not talking in this presentation about potential other indications as signified by RemeGen, many others, but we will be disciplined. We'll think about that with time. Keep in mind that the blockbuster pipeline, the product approach is very tangible with telitacicept. To conclude, we have once again one of the most exciting opportunities in autoimmune disease with de-risked asset on the clinical and the safety side. We have two great opportunities, one well underway like myasthenia gravis and one we're pioneering, but with an incredible set of assets in our hands here. They are both multi-billion dollars. The midterm catalyst will be top-line data for the phase III trial in MG in the first half of 2027.
The global phase III initiated for Sjögren's with the first patient dosed by the end of the first half, and the expansion opportunities that we work on in the next months and years with the right capital allocation discipline. Again, $450 million on the balance sheet, which puts us in a good position to fund our phase IIIs and the runway into mid of 2028. On that, thank you very much. Open for the Q&A session, please.
Thank you. Maybe, the first question would be, can you give us just an update? The myasthenia gravis, you'll have data in the first half next year. Enrollment will conclude first half this year, I assume. Maybe give us a little bit of a sense.
Yeah. We're trying to stay away from the granular dissection of the metrics on the patient enrollment and everything. It's a sport. It's an art, as you know, with different forces. It's going well. It's very competitive, but what we can say is that we will read out for the top line. You're in the ballpark.
Okay. For the phase III in Sjögren's, can you maybe give us a little bit of a sense on the ESSDAI? How are you thinking about powering it and kind of what are your assumptions on both arms?
Yes. Right. Remember that the China phase III trial studied two active doses, they needed more patients. They had 350 patients. We've done the modeling on the biostatistics for our own phase III, with 250 patients, we are well powered. We don't communicate on the numbers here, we are with knowing what we saw on the China data and the fact that we'll have our 160 mg dose studied versus placebo, two arms, we are well off. The thing is that the next question might be, do you need two or one studies? We believe that with all the data we have from China, including their phase III trial in Sjögren's, our...
We will have by then our global gMG trial. We are very confident that one study will be enough.
The secondary endpoint is ESSPRI. Would patients have symptomatic disease, or is this mostly in systemic patients? Would you also do a, later on, a symptomatic study?
That's actually a great question. We're thinking about the possibility of having other studies segmenting more the patients' population because the field will evolve in Sjögren's. ESSPRI is one of the secondary endpoints. We have others that we'll be looking at. We have been working very hard with the KOLs to try to improve from the learning from actually the BAFF receptor inhibitor, which has published their data at ACR last year. They had actually results that were very interesting to dissect, to try to understand why they had such a high placebo rate and stuff like that. We have optimized our protocol in all dimensions for that.
When we compared your data in China, I'm now moving to the RemeGen data in gMG, and we compared it to, let's say, Vyvgart. There is about data in about 27 patients or so that Zai Lab reported, and we looked at the placebo. The placebo, as you showed, did about 1.6, which is actually fairly typical of other Chinese studies. I think Vyvgart actually historically sort of, you know, there was a little discrepancy between U.S. and international. As you think about the global data that you will show, what would you expect to see on the control arm? To the extent that you can think about what decrement, if any, would you expect in your active? 'Cause I mean, you had to your point, almost a 4-point difference.
Yes.
You have plenty of room to go in both directions.
Yes. That's, that's the point. Actually, the plenty of room is the message here. We'll probably not have such a low placebo rate. China is usually with low placebo for several reasons. The patients are extremely compliant, I would say, and it's easier to do clinical studies there. But what we know is that we have the room to have a higher placebo rate because we know that our active arm works very well. So we're very confident we can still have best in disease. And we have modeled also our outcomes depending on a couple of scenarios here, and we feel very comfortable. Because it's, one is the magnitude of the results, but also remember that one of the key differentiating factor is the possibility to dose the product on a regular basis without drug holidays and with a compelling safety profile.
It's not just only on the pure efficacy. We were very confident of the efficacy side, but you also have to look at how the total package will deliver.
When we looked at UPLIZNA showed about a 1.8 point difference and continued to progress and get better, we know, with time between 24 and 48 weeks or 52 weeks. You have a broader activity in terms of the long lived plasma cells, and you have continuous therapy, to your point, whereas UPLIZNA is periodic. Does that mean that we can take the UPLIZNA data as sort of potentially a benchmark and that your data might be better with the caveats across trial differences?
Well, that's a very good point to try to make a comparison with the upstream's agent. I think the great thing with UPLIZNA is that they are opening. They are breaking the paradigm of the only IgG effect from and very downstream narrow flushing IgG from FcRn. You know, UPLIZNA is actually putting a bit of church in the middle of the village back, which is we have to tackle the upstream thing. Now that being said, they are a bit too much on the upstream because they deplete. This is where we come because we have the best of both worlds. We have the upstream and the downstream, and we don't deplete. UPLIZNA depletes like Rituximab depletes. It's carpet bombs. You know, I mean, the CD19, I was a CEO of MorphoSys. I launched tafasitamab. In what?
In DLBCL. It's only recently that the CD19s have been investigated in autoimmune. It's initially agents for Heme malignancies where you really want to blast, basically take away all your B- cells. I mean, I think we will differentiate with a more balanced profile and with the no carpet bombing approach and huge immune suppression, which is not always easy to manage. We welcome UPLIZNA to open the market to upstream's agents, which we are part of.