Back to School Summit from Citi. My name is Geoff Meacham. I am the Senior Biopharma Analyst here. We are thrilled today to have Vor Biopharma. We have Jean-Paul Kress here, CEO. Welcome. Thanks for joining. We have the broader team as well. Maybe most of the companies will just give a bit of an opening remarks just for a few minutes, and then we will get right into it.
Sure. Well, thank you, Geoff, and glad to be here and to tell you about our progress. Does it work?
Yeah.
I am here with my team. They will pipe in and answer questions with me. Vor is a company focusing on B-cell-mediated autoimmune diseases. It has in-licensed our main asset a year ago around June 2025. It is called Telitacicept. It is a BAFF-APRIL inhibitor, which has the ability to tackle the upstream of the B-cell lineage. There is a big unmet need with that, and it basically modulates the B-cell development, production, and survival and inhibits the production of pathogenic autoantibodies. It has been approved in six indications in China. That is very important. There is a wealth of data out there in several autoimmune diseases, and we have chosen in the West, in the U.S., and elsewhere to develop Teli in myasthenia gravis and Sjögren's disease to start with. Since we licensed the asset a year ago, we have made tremendous progress.
You probably saw the announcement yesterday that we completed the enrollment of our phase III trial in myasthenia gravis. It is a huge achievement for a company of our kind, especially we took over a trial which was not doing very well at the time, and it is now doing very well. Jeremy will talk about it further. We believe that we have a fantastic opportunity in MG. We are always hearing from the physicians that there is a big unmet critical need there. They need therapies with a deeper clinical efficacy, but even more so, a durable clinical efficacy. That is what lacking with the current therapies. We believe Telitacicept has everything here.
As a matter of fact, I'll draw your attention to AANEM in a couple of weeks, where we'll present very compelling and exciting data on an endpoint, which is probably the come to Jesus endpoint in MG, which is called minimal symptom expression, which is basically achieving less than one in MG ADL for patients, basically asymptomatics. There we will show that we have a deep but even more important durable effect on patients achieving MSE. That's for MG, but we also saw that we announced yesterday that we have the intention to start ocular myasthenia gravis phase III in the first half of 2027. We believe it's a perfect adjacency. It's logical. It's not busy.
There are only two products approved, and there is also a high unmet medical need, and we can help patients earlier in their disease journey and modify the disease because we act on the upstream and help those patients. We can achieve more than $1 billion in this indication. MG is our beachhead indication, multi-billion dollar potential, now complemented by OMG. Again, shows our confidence in our ability to execute in our results as well with this second myasthenia gravis indication. I'll finish by saying that we also have Sjögren's disease. We have a phase III. We started de novo, I think, late last year. Jeremy? March, actually. So March. We are enrolling very well, above expectations. Shows the two things again, our ability to execute, but also the interest from the space in a white space.
Yeah.
There is no product approved. We have the potential of achieving multi-billion dollars in this indication. We'll talk about it more. It's probably a market which at start should be more than $10 billion, but could be more because all these large indications and tabletop number AD, there is always a potential to treat patients better and earlier.
Yeah. Let me follow up on that, Jean-Paul. So that when you think about the Teli and the BAFF-APRIL mechanism, there are a lot of drugs out there. There are a lot of opportunities, but talk about how you view Teli's differentiation from a mechanism standpoint versus the Vertex's virus of the world or Atsuko. Maybe give us some context for the differentiation and how you see the market.
Sure. That is probably a great question for Jeremy.
First, we will start differentiating BAFF-APRIL from APRIL. I think IgAN has taught us that in IgAN specifically, there is not a lot added from BAFF to APRIL. Sibeprenlimab, povetacicept, Atacicept, Telitacicept all have roughly similar levels of Gd-IgA1 reduction, proteinuria reduction across when dosed appropriately for IgAN. That led to the argument that we are not sure what BAFF is adding. That is the exception, not the rule. In a disease where you are targeting the autoantigen, which is Gd-IgA1, they are produced by mucosal plasma cells. APRIL inhibition is very effective at reducing mucosal plasma cell generation of Gd-IgA1. Therefore, APRIL alone tends to be similarly effective to BAFF-APRIL in IgAN. That is not the case for any of the other autoimmune diseases we are going to talk about, where you have to address the autoreactive B cell that is making the pathogenic antibody, not the pathogenic antigen.
Even once we get there is differentiation within BAFF-APRIL inhibitors, some of which have a higher potency for BAFF, some of which have a higher potency for APRIL. Think of it like the bispecific antibody. If you do not get the stoichiometry correct, you will end up either overdosing or underdosing in different disease indications with the wrong molecule. Telitacicept specifically has a 2-to-1 BAFF to APRIL mechanism. It is the most TACI-like native TACI. That may be lucky, may be by design, but the 2-to-1 gives the opportunity to dose to APRIL and overdose on BAFF, which is absolutely acceptable and safe. BENLYSTA taught us, belimumab, that 1 mg per kg, 10 mg per kg, relatively similar efficacy, maybe a little improvement, but no increased safety liability when you 10X the dose of BAFF.
APRIL going from even 80 to 240 in the povetacicept phase II studies of IgAN showed that there was clearly a dose-dependent increase in the incidence of hypogammaglobulinemia. At the end of the day, the goal has to be dosing to APRIL, because APRIL is the one that you need to maximize without going over, and if you do that with a drug that is APRIL heavy, you will underdose BAFF. Whereas with a drug like Telitacicept, by dosing to APRIL, in some situations, we may slightly over target BAFF, but that is acceptable. In other places, in other patients with different heterogeneous drivers, hitting that level of BAFF is critical to modulating that upstream mechanism of B-cell inhibition.
Okay. That's really, really helpful. Thank you for that. Let's talk about it before we get into tele development. Talk about the business model with having data, having substantial body of work done in China, and maybe what are the nuances with predictability as you develop in U.S. and Western Europe?
Well, that's the question, right?
Yeah.
We are not the only ones to ask this question or try to answer this question. We are probably the only ones in that advance in autoimmune diseases. You have proxies in oncology and some other TAs, but probably we are the one on the forefront for the autoimmune space. We're very happy with that and proud with that. Well, again, we have a series or a wealth of data coming from China, from early stage to late stage, from mechanistic, which is very important, to late stage as well. Many phase III approvals there. It's not a coincidence. I think the product works, and the product is safe. Otherwise, more than 10,000 patients have been dosed with this product, we would have known it would have a signal. It's a huge advantage compared to other products in this space.
Now, the next question is by how much are we going to differentiate? There are nuances here that we can talk about. We know that in China, you have probably less heterogeneity that we will face with our clinical program like any other company in the world. Different countries, different size, different patient cultures, origins, and everything involves heterogeneity. That's one thing that companies have been struggling all over the place in immunology and beyond, especially on the placebo level. That's probably your question. Yeah, we'll probably see the placebo effect creeping, but we're very confident in our active arm, and we've done everything in our trial.
When we inherited the trial, which started by RemeGen U.S., if you might say, what they had in the U.S., we optimized the study and tried to make sure that we were maximizing the active arm effect because we hear all the time from the KOLs that it's not only the separation from placebo. UPLIZNA from Amgen has a separation from placebo of 1.9.
20.
in the MG area. We have in our China study, close to 4.6. We have 4.6 probably not, but what counts, and UPLIZNA has been approved, and the launch is doing very well, so it's a great proxy. We do not need the separation we've seen in China, and we probably have a strong active arm. I will finish by that. What is very important is what I said earlier, it's a durability. Here we separate from many products, especially the FcRn.
Yep. Okay. That's helpful. Let's get into Telitacicept development, and congrats on finishing the MG study. Maybe help us with what investments you guys did to get the enrollment across the goal line, and then remind us just the approximate timelines of when you think that we will get some top-line data.
Sure.
Jeremy?
Yeah. I think the key thing is that enrollment's always a hockey stick, and it's when you can create that inflection in enrollment. The things we did were really several fold. One is Dallan and his field team really engaged with the KOLs. RemeGen was a China company. They were not aware of some of the KOL networks that were critical to access. Some of them enrolled patients, but really they created an enthusiasm and excitement around the mechanism throughout the MG community, which really got sites and investigators excited about enrolling in our study. Many of these sites are enrolling multiple studies simultaneously, and they ultimately have to choose which drug they will then prosecute, they will then offer to patients. We saw a great uptick in the use of Telitacicept from those sites. The other thing that we did was really making ourselves the sponsor of choice.
We got into the sites. We made it easy for them. Sometimes when you have a CRO, it's not so easy to access the CRO. They have my phone number, the CMO. They have the phone number of the study director. They have the study director of my head of ClinOps and the clinical lead for, and the ClinOps lead for the study. By making it easy for sites, you make it easy for them to enroll patient fail? Is there anything we need to correct systematically in our study? Is there anything we can do to re-screen this patient because this screen failure was a temporary setback that's going to be transient? At the end of the day, it brought us in not just on time, but ahead of time.
I think it really shows the ability to take a company from zero operational presence to a high-performing operational presence in less than a year.
That gave us the confidence for the next chapter. When we saw that couple of, we didn't know at the beginning. Then with the weeks, the months, we got our confidence boosted, and we decided to go on ocular MG.
Great. Yeah, absolutely.
Sorry. You asked the second question, which was the timing of data.
Yeah.
Obviously the 24-week clock starts with the last patient dosed. We anticipate we'll have data lock, and then we'll be able to have top-line data. We're still guiding towards the first half of 2027. Obviously, this brings it more proximal in the first half of 2027 than we had anticipated.
Yeah.
Let's maybe frame that data update that we could expect in first half 2027. Maybe given the trial design, what should we look for?
The key messages are going to be the way we benchmark, which is still the delta for the MG-ADL. All other studies have asked that question, and when you look at comparators, everybody says, "What's the delta on the MG-ADL?" Again, we highly anticipate that our placebo will be higher than observed in China, consistent with all the other global placebos that we've seen. That's the population they enrolled. That's the population re-enrolled. We've done some things to mitigate the placebo, but it will be higher. We anticipate that placebo will go up. We anticipate the active arm will similarly go up, leaving us a relatively preserved delta that approaches, if not duplicates, the delta we saw in China. That's the MG-ADL delta. But the other two pieces which we're really excited to be able to communicate are the breadth of response and the durability.
Now, at 24 weeks, durability may not be easily reported and may have to come through a subsequent report, but the breadth of response we will be able to show. For instance, early on, the approvals for MG were based on a two-point improvement in MG-ADL, and efgartigimod, when approved, had a roughly 67% rate of two points improvement, which is considered maybe the minimal clinically important difference. We have raised that to three points. We will report that. And we will also be able to report higher levels, such as a change of five or six, which starts to become a very meaningful number, and that is the breadth of response.
When we show that and you compare it to what has been seen with other mechanisms, we hope to be able to additionally show not just a greater depth of response, but a wider breadth of response in terms of the probability that if you give a patient Telitacicept, they will have a clinically meaningful response.
Right. Then, I guess, looking at safety and tolerability, what should we expect there-
Yeah.
in myasthenia gravis?
So obviously, there's a significant amount of preexisting data across China, so we don't expect any real surprises. We've obviously seen the data to point, and again, it looks consistent with what we've seen for Telitacicept. Rates across the historic Telitacicept program showed a small increased rate of minor infections, urinary tract infections, upper respiratory tract infections, but notably no increased imbalance in serious infections leading to hospitalization, infections leading to death, or opportunistic infections, and we think that's probably the message we'll hopefully be able to continue to tell six months from now.
Just on the MG market, what would you say by the time you guys have the data and are launched, how do you guys view maybe the bigger pockets of unmet need?
Yeah. Well, again, currently it's around $3 billion in the U.S. It's supposed to top $10 billion in the U.S. by the end of the decade, so it's growing fast with the arrival of new products. The space was owned by the FcRn until now, and before that it was just complement inhibitors. So there has been phases of innovation. There is no doubt that the FcRn completely transformed the space, but it's a very downstream mechanism. We hear all the time from the physicians that it's like mopping the floor with the faucet still open. We close the faucet, or at least we modulate the faucet. So that's very important, and there is an unmet need because the durability that Jeremy alluded to is probably the result of this mode of action. Commercially, it will follow.
We believe that the market is hungry for this unmet medical need addressing, and we believe that products will be rewarded if they provide the right clinical profile. The proxy is probably UPLIZNA. It's a CD19. It was reserved to heme malignancies, as you know, and it's more carpet bombing on the B cells. It doesn't really address the modulation that we speak about, and it doesn't address actually the antibodies production itself. Really only address killing the B cells upstairs, I might say. So despite that doing well, for us it's great because it shows the appetite. And we've done market research and could talk about that, but we hear constantly that from the KOLs and the physicians. Now, it will take commercial muscles, obviously, and we have the team for that preparing. We have a great medical affairs team, many people coming from great competitors.
These guys know usually. They know the KOLs, so they know when a product is good, and we have already a team engaging. Which for a biotech usually not the most easy thing, but we have been able to assemble that very early.
Maybe just frame the development into ocular MG. Just give us some context for that. Is that a different segment of an unmet population? Maybe what are the decisions that went into that?
Yeah, I'll just start at a high level, and Jeremy will explain further. I think the decision was made, as I said, when we felt confident enough in our ability to execute and the appetite from the space for our product. It's a very logical choice, and there was also some de-risking from other products, some data, and filing and approval, which clears the space here. It's an adjacency. Jeremy, do you want to explain it?
Yeah. There's obviously the operational opportunity. We have now engaged with a wide range of sites, wide range of key opinion leaders and investigators. Operationally, it's a logical time to move into this adjacent indication of ocular MG. A lot of the same sites, a lot of the same KOLs, a lot of the same investigators, and a lot of the same pathways. We've already had that optimized, so we can continue leveraging that momentum. But also, as Jean-Paul mentioned, it's an open space, right? There may be one entrant soon, which would be argenx, potentially UCB behind them. That's still the FcRn, which don't really modulate the disease pathogenesis upstream. And what we know about ocular MG is that 80% of ocular MG progresses to generalized MG.
This gives us, at least potentially, the opportunity to intervene with a disease, an immunobiology-modifying drug, which could then potentially prevent that progression. So back to the sink analogy, before the water seeps through the floor and starts destroying your insulation. I think that's kind of the goal with getting into ocular MG. Then the other point is, in addition to whatever Dallan tells me, a $1 billion market, and I go, "That's a great market," but it also increases that halo around MG because now providers don't have to make that decision or justify their decision to give Telitacicept based on a preponderance of ocular symptoms.
The payers have put a limitation, right or wrong, they put a limitation saying, "Oh, this is ocular, not generalized, therefore, we're not paying for it unless you show a study where you demonstrate that your drug specifically affects ocular." So by giving that to the community and giving it to the payers, we open up the aperture for all MG patients who someone might want to prescribe Telitacicept. I think argenx has done us a huge favor developing the outcome measures, which are reliable. Also, I think there's an increased teaching that it's not just mild MG. There's a lot of morbidity. If you think about a disease like TED, thyroid eye disease, it's double vision, blurry vision, but a very serious condition.
Ocular MG is the difference between driving and not driving, using a computer and going to work and not using a computer and going to work, being able to do the activities of daily living that you count on, and we want to be able to get those patients back to that status.
Maybe one more from me on MG, but could you talk a little bit about looking at broader MG, just discussions with regulators, how that's going as you're approaching later-stage development or in later-stage development?
Yeah. We cannot say too much, but we've been doing all the steps necessary with the FDA and the European Medicines Agency, by the way. Everything starts and ends with the data, so we're focusing on a very strong outcome with our data. We finished recruitment, but now the phase of data quality, data collection is starting, and it's very important. We don't rest on the level of enrollment only. That will be paramount. But we have all the activities and the work streams in place and the expertise internally and externally to compile the BLA, which is now our number one priority for MG, and it includes, obviously, manufacturing, quality, et cetera. We are in a good shape, but it's going to be a lot of work, as always.
Let's switch gears to Sjögren's. Maybe just give us a quick couple liners on the pathophysiology of the disease, obviously a huge unmet need. Then you guys obviously dosed your first patient earlier this year. Talk a little bit about how you tend to really leverage the BAFF/APRIL mechanism in this disease.
Yeah. It's a beautiful modality for Sjögren's.
Yeah. Sjögren's is really a prototypic B-cell-driven autoimmune disease, and it has, I like to think of, just two components. There's an antibody-dependent component whereby antibodies drive pathology. They target antigens. They make immune complexes. They cause inflammation. There's also an antibody-independent component to Sjögren's, which is the hyperactive B cell. These hyperactive B cells, some of them make antibodies, but others don't make any antibodies. They're literally having an antibody-independent pathology whereby they make cytokines and drive tissue inflammation. They activate T cells through co-stimulation to make cytokines to cause tissue damage. The damage in Sjögren's is really a B-cell-centric disease but involves multiple B-cell mechanisms. And the nice thing about Telitacicept is it sits squarely in the middle of that pathology. It affects the upstream B cells, which are making cytokines and causing co-stimulation.
It also affects the downstream plasmablast and plasma cells that are making pathologic antibodies. If you think about the mechanisms currently being evaluated in Sjögren's, there's things like FcRns, which drop antibodies but don't affect upstream B cells. There's things like BAFF receptor targeting, like ianalumab, which affect upstream B cells but don't particularly affect the downstream antibody production. By covering both sides of that pathologic spectrum of hyperactive B cells, we think that really is a key to being able to demonstrate a stepwise increase in the level of efficacy. That level of efficacy is critical because I'm going to be honest, the outcome measures in Sjögren's are still pretty crappy. Because of that, they have a lot of heterogeneity and variability in how they are interpreted, and that creates a challenge in getting positive studies. The way to get around that is twofold.
One is well-designed studies, well-trained investigators, and very clear protocols. We do that. Beyond that, it's about having a drug with a large enough effect size to overcome the heterogeneity in the background population to show an effect size that beats out that variability and that heterogeneity that has limited the effect size of some of the recent studies.
We are fortunate to have started our trial now in this era, while others have started a few years ago. Actually, many years ago, several years ago. They experienced the hardcore of what Jeremy described in the difficulty and the heterogeneity, and the challenges with the evaluation scales, which are not used in clinical. Now we have a much better trained bench of investigators that we can select, that we have selected, and are better equipped to deliver on results. The timing is very good.
There's regulatory clarity on the, was it the ESSDAI scale?
Yeah.
Talk about the challenges of that even, given multiple organs that are in place.
Yeah, that's the heterogeneity.
How many domains?
That's the heterogeneity. There's multiple domains, but most of it's driven by a relatively smaller subsegment of the domain. If you look across the phase III China study, and you look across the phase III ianalumab study, and the phase II nipocalimab studies that have reported out domain-specific improvement, it tends to go across the musculoskeletal, skin, glandular, lymphadenopathy, and biologic domains. We drive all of those because of our mechanism. Because our mechanism is so strong at each of those domains, we feel confident that we'll be able to show, in a typical population with those manifestations, the ability to change and improve those symptoms. I think that's really the opportunity. The other thing is the ESSPRI, which is the symptomatic scale, which no one's been able to win on, because again, it has a very narrow dynamic range.
The only way to win on the ESSPRI is to have such an effective drug that it overcomes that background heterogeneity and that background variability. We think that a drug like ours that affects so many parts of the potential pathology driving fatigue, dryness, and pain, has the ability to overcome that heterogeneity. If you look at the phase III China study, the only phase III study ever to be positive for ESSPRI with Telitacicept.
Great. I guess as your phase III is ongoing, we talked a little bit about efficacy here, but maybe could you comment on some safety and tolerability expectations and I guess how that would work in Sjögren's?
Yeah. Safety obviously is going to be consistent with the safety we've seen previously. We're not anticipating any new signals from Sjögren's versus what they've seen in Sjögren's elsewhere. Tolerability, there's always the issue of weekly injections. Some people will not like weekly injections. Most people will tolerate it just fine. We've put in place a lot of really good trainings, so the patients who choose to self-administer at home learn how to self-administer at home well. The China studies had incredibly low rates of discontinuation. They required patients to come to the clinic every week. We're giving patients the optionality to be trained and go home, and we have to optimize that to make sure patients who take that drug home with them know how to give themselves the injections and are comfortable coming back for retraining if they're finding it uncomfortable.
Right. You talked about KOL commentary around myasthenia gravis, but maybe given the unmet need in Sjögren's as well, could you comment on what you're hearing from KOLs in these?
Sure. Maybe Dallan can answer this question.
Yeah. We have been very excited about the KOL reception and Jeremy, as he said, has designed a great study in consultation with the KOLs and the early enrollment is far exceeding our initial expectations. I think there is a really good understanding of the mechanism from the KOLs and particularly some of those KOLs looking at the risk factors for developing lymphoma. There has been a lot of work around APRIL and BAFF, and APRIL being the highest predictor of developing lymphoma. It is early days in terms of our KOL engagement in Sjögren's versus MG, but the reception is really positive both in the U.S., in Europe, especially in France, where there is a lot of-
Yep.
good research being done.
It is a complete coincidence. The other thing I would say is that we have the opportunity to mold the space here much more than in MG, although we think we will transform the field in MG. In Sjögren's, there is an appetite from emerging KOLs because it is a new disease, so that is always great. Remember RA in AbbVie days or Abbott days at the time, or Amgen and these kind of things. So you can really partner with them at an earlier stage in their career or in their journey, and that is why we see so much accolade from the space, and that is very encouraging. We have to enroll 250 patients for our phase III. I will not say numbers yet, but we are well advanced in our early phase and especially on U.S. patients, which was the opposite for the MG trial.
We had to work a lot to correct things from the beginning. Here, it is really going well.
What are the lessons learned from a risk context from Sjögren's in China or any other geography based on where you guys. Also, how you perceive the landscape?
You mean clinical development-wise?
Yeah.
Yeah.
Well, great.
Obviously what we've seen is twofold. One is the placebo effect, and the placebo in the one phase III study that's been positive was incredibly high, and that limited the effect size. It's hard to know exactly what drove that placebo effect, but a lot of it is investigator training. Having investigators who early on in that study at baseline didn't have the same experience they had 52 weeks later at the end of the study probably resulted in some regression from a high baseline to a lower final score. We adjust for that by, again, as Jean-Paul mentioned leveraging those already very experienced investigators. We're very grateful to Novartis for having trained several hundred investigative sites in the ESSDAI, and we were able to leverage them to overcome some of that precision liability that is inherent to the scoring system.
I think that's really the key risk there. The other, obviously, is the heterogeneity of the disease, and that just is, again, is overcome simply by really having a mechanism that addresses the breadth of heterogeneous mechanisms driving the pathology, but also the heterogeneous mechanisms driving the different components of the pathology, the arthritis, the skin rash, the lymph node enlargement, the glandular enlargement.
I would just add that the bar, the regulatory bar, we don't know yet, but we'll know soon with Novartis, obviously. With unmet medical need in this disease, I would assume that the bar would be quite lower than it would be in the future, but so that also helps for the potentiality of having some room in our results. We think we'll do better than Novartis with our asset in our trial, but you don't need a separation of 5 points on the SDAI to be approved.
Yeah.
By the way, Novartis was negative on the ESSPRI, failed this endpoint, and the delta versus placebo is very limited on the SDAI. Despite that, this product will most likely be approved.
Yeah.
You okay on Sjögren's? Should we move on to other indications?
Yeah.
Yeah. Just talk a little bit about how you balance the data from RemeGen in China for Tai'ai, and maybe what your thought process is as you move to other indications. You could take this into IgAN or a number of other indications, but maybe how does the-
Yeah.
the probability of success sort of inform that?
We have been very diligent. We have worked on indication selection, which starts with clinical development, the science first, can the disease be addressed by the modality, and there are a lot of diseases which can. Then there are the nuances in the mechanism and the modality. Jeremy spoke about APRIL versus BAFF or BAFF versus APRIL. There are some nuances that we are applying on the selection and the ranking. Then there is a commercial relevance and competitive edge we could get. It would not make sense to start to study in RA, although it is approved in RA in China. Those are the kind of things. We have in mind a couple of other indications, but I just remind you that we already have two and soon three phase III studies.
One which is soon to be complete, but Sjögren's will still run for, it's a 48 weeks study, so it's going to be longer. OMG will be probably 24 weeks. We have our hands full, but we are ready to start when and if it makes sense. Probably at the declaration of results for our gMG study, we'll probably be in a good place to decide what we do next. Because if we have a great outcome, for instance, we'll be probably capital-wise in a very good situation, and then we can decide on what we unfold. All these parts are in flux, but we're ready to act as soon as we have the catalyst.
Okay. Well, with that, thank you, guys. Appreciate the time.
Thank you very much.
Appreciate that.
Thank you.
Appreciate it.