Vor Biopharma Inc. (VOR) Earnings Call Transcript & Summary

Back to School Summit from Citi. My name is Geoff Meacham. I'm a senior biopharma analyst here. We're thrilled today to have Vor Biopharma. We have Jean-Paul Kress here, CEO. So welcome. Thanks for joining. He's got the broader team as well. So maybe give us a little bit of a -- most of the companies just give a bit of an opening remarks just for a few minutes, and then we'd get right into it.

Sure. Well, thank you, Geoff, and glad to be here and to tell you what our progress at Vor. So I'm here with my team, and they will pipe in and answer questions with me. So 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's called telitacicept. It's a BAFF/APRIL inhibitor, which has the ability to tackle the upstream of the B-cell lineage. There's 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 6 indications in China. That's 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 Sjogren's disease to start with. Since we licensed the asset a year ago, we've made tremendous progress. You probably saw the announcement yesterday that we completed the enrollment of our Phase III trial in myasthenia gravis. It's 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's now doing very well. Jeremy will talk about it further. And 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's what's lacking with the current therapies. And we believe telitacicept has everything here. And 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 1 in MG-ADL for patients, basically asymptomatic. And there, we will show that we have a deep, but even more important, a durable effect on patients achieving MSE. So 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 easy. There are only 2 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. So MG is our beachhead indication, multibillion-dollar potential, now complemented by oMG. Again, shows our confidence in our ability to execute in our results as well with the second myasthenia gravis indication. And I'll finish by saying that we also have Sjogren's disease. We have a Phase III. We started de novo, I think, late last year, Jeremy? March, actually. So March. And we're enrolling very well, above expectations. Shows the 2 things again: our ability to execute, but also the interest from the space, in a white space. There is no product approved. We have the potential of achieving multibillion 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 [ gaps, remember, AD ], there is always a potential to treat patients better and earlier.

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 Vertexes, Veras of the world or Otsuka. Like talk about the -- maybe give us some context for the differentiation and how you see the market.

Sure. And probably a great question for Jeremy.

So first, we'll start differentiating BAFF/APRIL from APRIL. So I think IgAN has taught us that, in IgAN specifically, there's not a lot added from BAFF to APRIL. Sibeprenlimab, povetacicept, atacicept, telitacicept all have roughly similar levels of Gd-IgA reduction, proteinuria reduction across when dosed appropriately for IgAN. And so that led to the argument that we're not sure what BAFF is adding. That's the exception, not the rule. In a disease where you're targeting the autoantigen, which is Gd-IgA, they're produced by mucosal plasma cells. APRIL inhibition is very effective at reducing mucosal plasma cell generation of Gd-IgA. Therefore, APRIL alone tends to be similarly effective to BAFF/APRIL in IgAN. That's not the case for any of the other autoimmune diseases we're going to talk about where you have to address the autoreactive B-cell that's making the pathogenic antibody, not the pathogenic antigen. And even once we get there, there's differentiation within BAFF/APRIL inhibitors, some of which have a higher potency for BAFF, some of which have a higher potency for APRIL. And think of it like the bispecific antibody. If you don't get the stoichiometry correct, you'll end up either overdosing or underdosing in different disease indications with the wrong molecule. Telitacicept specifically has a 2:1 BAFF-to-APRIL mechanism. It's the most TACI-like native TACI. That may be lucky, may be by design. But the 2:1 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 mg to 240 mg in the povetacicept Phase II studies of IgAN, showed that there was clearly a dose-dependent increase in the incidence of hypogammaglobulinemia. So 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's APRIL-heavy, you will underdose BAFF. Whereas with a drug like telitacicept, by dosing to APRIL, we slightly -- in some situations, we may slightly over-target BAFF, but that's acceptable. And in other places and 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 a bit, before we get into teli development, talk about the business model with having data, having substantial body of work done in China. And maybe what are the nuances, what's predictability as you develop in U.S. and Western Europe?

Well, that's the question, right? And we are not the only ones to ask this question or try to answer this question. But we are probably the only ones that advance in autoimmune diseases. You have proxies in oncology and some other TAs, but probably we are the one on the forefront of the autoimmune space. So we're very happy with that and proud with that. But again, we have a series or a wealth of data coming from China, from early stage to late stage, of mechanistic, which is very important, to late stage as well, many Phase IIIs, approval there. So it's not a coincidence. I think so the product works, and the product is safe. Otherwise -- more than 10,000 patients have been dosed with this product, we would have known if we have a signal. So it's a huge advantage compared to other products in the 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, let's say, heterogeneity that we will face with our clinical program, like any other company in the world. I mean different countries, different sites, different patients, cultures, origins and everything, involves heterogeneity. So 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. So yes, we'll probably see the placebo effect increasing, 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., 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 in the MG-ADL. We have, in our China study, plus 4.6, right? So we have 4.6, but what counts -- and Uplizna has been approved and the launch is doing very well. So it's a great proxy. We don't need the separation we've seen in China, and we probably have a strong active arm. And I'll finish by that, what is very important is what I said earlier. It's the durability. And here, we separate from many products, especially the FcRns.

Yes. Okay. That's helpful. So let's get into teli development, and congrats on finishing the MG study. So maybe help us with kind of what investments you guys did to get the enrollment across the goal line. And then remind us just kind of the approximate time lines of when you think that we'll get some top line data.

Sure. Jeremy?

Yes. So I mean, I think the key thing is -- enrollment is 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 weren't 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. So 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 clin ops and the clinical lead -- and the clin ops lead for the study. And so by making it easy for sites, you make it easy [Technical Difficulty] fail, is there anything we need to correct systematically in our study? And is there anything we can do to rescreen this patient? Because the screen failure was a temporary setback that's going to be transient. And at the end of the day, it brought us in not just on time, but ahead of time. And I think it really shows the ability to take a company from 0 operational presence to a high-performing operational presence in less than a year.

And that gave us the confidence for the next chapter. I mean when we saw that a couple of -- I mean, we didn't know at the beginning. And then with the weeks and months, we got our confidence boosted, and we decided to go on ocular MG.

Great. Yes, absolutely.

Sorry, you asked a second question, which was the timing of data. So obviously, the 24-week clock starts with the last patient dosed. We anticipate we'll have data locked and then we'll be able to have top line data. We're still guiding towards the first half of '27. Obviously, this brings it more proximal in the first half of '27 than we had anticipated.

Let's maybe frame that data update that we could expect in first half '27. 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? So 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 we 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. So that's the MG-ADL delta. But the other 2 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'll be able to show. So for instance, early on, the approvals for MG were based on a 2-point improvement in MG-ADL, and efgartigimod, when approved, had a roughly 67% rate of 2 points improvement, which is considered maybe the minimal clinically important difference. We've raised that to 3 points. We'll report that. And we'll also be able to report higher levels such as a change of 5 or 6, which starts to become a very meaningful number. And that's the breadth of response. So when we show that and you compare it to what's 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.

Great. And then I guess, looking at safety and tolerability, what should we expect there on myasthenia gravis?

So obviously, there's a significant amount of preexisting data across the China. So we don't expect any real surprises. We've obviously seen the data 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, 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 6 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 the -- maybe the bigger pockets of unmet need?

Yes. 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 FcRns 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, I mean, 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's usually reserved -- 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, if I might say. So despite that, doing well. For us, it's great because it shows the appetite. And we've done market research that I 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 a team for that. They're preparing. We have a great medical affairs team, many people coming from great competitors. So 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 is 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. What is -- is that a different segment of an unmet population? Like maybe what are the decisions that went into that?

Yes, 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 derisking from other products, some data and filing and approval, which clears the space here. It's an adjacency. Jeremy, do you want to say something?

Yes. So there's obviously the operational opportunity. We have now engaged with a wide range of sites, wide range of key opinion leaders and investigators. So 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. So 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 FcRns, 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 and 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. So I think that's kind of the goal with getting into ocular MG. And then the other point is, in addition to whatever Dallan tells me, $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've 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 may be -- who someone might want to prescribe telitacicept. And I think argenx has done us a huge favor of developing the outcome measures, which are reliable. And 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 for 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?

Yes. Obviously, we cannot say too much, but we've been doing all the steps necessary with the FDA, and the EMA, by the way. We have -- everything starts and ends with the data. So we're focusing on a very strong outcome with our data. So we finished recruitment, but now the phase of data quality, data collection is starting, is very important. We don't base on the level of enrollment only. So 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, et cetera. So we are in a good shape, but it's going to be a lot of work, as always.