Hello, everyone. I'm James Stamos, representing my colleague, Farzin Haque, one of the biotech analysts here at Jefferies. It's my pleasure to introduce Jeremy Sokolove, Chief Medical Officer, and Dallan Murray, Chief Commercial Officer of Vor. This is a fireside chat format. Thank you for joining us today. To start off, Jeremy, could you kindly provide a quick overview of the company for those who are new to the story?
Sure. This is Vor 2.0. Vor 1.0 was a cell therapy company. It winded down in the 2024 to 2025 range, and through a collaboration of a consortium of investors led by RA Capital and others, Vor 2.0 was formed from that shell, with an asset called telitacicept. Telitacicept is licensed from RemeGen in China. It's a drug that's approved for rheumatoid arthritis, systemic lupus, as well as myasthenia gravis, and is now in registration for two additional indications in IgA nephropathy and Sjögren's disease. We've licensed global rights, taken over global development, and are now executing in two indications, primarily in myasthenia gravis, and more recently, we've initiated our phase III registrational study for Sjögren's disease.
Just to add on to that, we're in this unique position. We're less than a year into this new Vor 2.0, but as we sit here today, we're on the back half of this global phase III. We're going to have results first half of next year, an approval within the year following that, and as Jeremy said, we just started the Sjögren's trial, so an incredibly de-risked asset. It's the most extensively studied and the most advanced BAFF/APRIL globally, as Jeremy said, with multiple approvals in China, and incredibly de-risked because of the safety database that we have and the efficacy data that we have to support these launches.
Great, thanks. Let's start off with myasthenia gravis. In gMG, where AChR antibodies, predominantly IgG1, IgG3 are the primary drivers. Can you articulate the mechanistic advantage of dual BAFF/APRIL inhibition over selective IgG reduction via FcRn blockade?
There's two. One is actually even more simplistic, which is that although a large number of the anti-AChR antibodies are IgG, there's also IgA and IgM isotypes, which target that AChR receptor as well as MuSK, and those are not targeted by the FcRn receptors. FcRn very specifically inhibits the recycling of IgG, resulting in a lowering of IgG levels across the systemic circulation. That unabrogated IgA and IgM are critical for that subpopulation in that it would probably be associated with a significant amount of non-response, and we think that contributes to the increased breadth of response we see with telitacicept relative to FcRn. The other advantage, I think, is the durability. FcRn are great. They've really revolutionized the way we think about MG.
One of the challenges is that you treat with an FcRn inhibitor, you clear your IgG, and as fast as your body can remake IgG, that disease comes back. The cyclic nature of FcRn is challenging. Even when you don't do the cyclic nature of FcRn, you never really affect the underlying immunobiology of the disease. With a BAFF/APRIL mechanism, the APRIL side is rapidly decreasing the antibody-producing cells and dropping pathologic immunoglobulins. The BAFF side is also affecting upstream development and repopulation of those pathogenic B cells. That's really why we think there's a twofold opportunity, both to drop the pathologic immunoglobulins, but also to work upstream to really remodulate the immune repertoire so that we get that durability and continued improvement.
Our data's really interesting from China in that between week zero and 24, there's significant robust improvement, but the continued improvement from 24- 48 weeks is what really impresses the field, and we think that's that continued remodulation of the upstream B cells, which cannot repopulate the pathologic antibody-producing cell population.
Yeah, in the context, James, of the market as a whole, the biologic era kicked off in 2017. The market is $5 billion today. It's been growing at 60% per year. As Jeremy outlined, our mechanism is perfectly suited for where the market is going, and if you look at the emerging guidelines, that's towards upstream targeting and durability. We think we're perfectly positioned for what the unmet needs are today, where the market is going, and that's a good thing because the consensus projection for the market is that it's going to double in the next few years, and it's going to be a $10 billion market in the very near future.
Great. How is the global phase III trial in gMG enrolling, and what has been the feedback from site investigators on patient demand?
Yeah. Right now the enrollment's going quite well. We're on track or a little ahead right now. We brought on China. They're enrolling very nicely. They're going to be just about 8%-10% of the patients. We are also opening a couple of new geographies, which will contribute to our contribution. We opened about another eight U.S. sites. We are guiding towards last patient into the fall and top-line data in the first half of 2027. As far as the investigators, the feedback we're getting is very good. They say it looks like a lot of the other drugs in terms of tolerability. The one thing that, again, most of the investigators only have one to three patients in their cohort, but we are getting a lot of requests for an extended open label extension.
We have the first patients finishing the one and a half years from the initiation of the study when RemeGen started it several years ago. We have a lot of patients doing very well in that open-label extension, and the investigators really pushed us, and what we've done is an extended open-label extension, whereby patients who finish that one-year OLE can get continued access to the drug. We're really hearing them ask for that, and we've given it to them.
Great. How are you addressing potential differences between the Chinese trial population and the global population in terms of patient population differences, AChR positive versus broader subtypes, and background standard of care use?
I think MG is one place where there's a pretty good consistency between China and the U.S. in terms of underlying disease biology. I think that's one very positive translational confidence that we get for China to global. The background demographics are also quite similar. The patients in China had a slightly shorter disease duration, slightly younger age than some of the more global studies. Otherwise, the background rate of immunosuppressant use, steroids, was almost identical.
China does have a little more use of tacrolimus and azathioprine relative to globally, where there's a little more use of mycophenolate. Otherwise, the baseline MG-ADLs, the baseline QMG, and the baseline AChR and MuSK breakdown was pretty similar. We think it's pretty consistent. If you look at the one example of a MG study, which was initiated in China and then repeated globally, that's batoclimab. Batoclimab in China had a delta of two for their MG-ADL, and then when they ran a global study, the placebo went up, but they still had a delta of two. We think that we're looking at a very similar pattern that we anticipate globally.
It's also important to note that we're really on the leading edge of taking data from China and taking it to the global market. In less than a year, we've built an exceptional medical affairs team. We've got a standing U.S. and global advisory committee with the top KOLs in MG. We've got a med affairs team that really has expertise in this area. One of the things we're putting a big focus on is connecting the experts in the U.S. and outside of China globally with these Chinese investigators. We've established a scientific advisory board of top experts in the U.S. and China. Jeremy and I will be going to Shanghai in the next couple of weeks, and as we get the translation and the communication going, it's really going to facilitate Jeremy's efforts on the clinical side to translate the data.
Yeah. One thing I think is nice is this is a drug that's commercially available in China. It's getting rapid acceptance. The neurologists who treat MG are using this drug now across a range of immunologic autoimmune neurologic diseases because they like it so much. I think that communication from the Chinese investigators, Chinese clinicians, Chinese KOLs, will provide confidence to the global community as well.
Great. Can you talk about the powering assumptions in the China phase III telitacicept achieved a 4.8 point reduction versus placebo at 24-48 weeks. How much dilution of effect size are you anticipating in the global phase III and to be still considered differentiating for commercial uptake?
Yeah. I'll speak to the first part. We're not anticipating a huge drop, but we are powering for a huge drop. We're powering for a more conventional delta in the range of two. We want to make sure that if our MG-ADL delta does fall off, we still have an approvable drug because we think that the mechanism provides for opportunistic differentiation in terms of both breadth of response as well as the durability beyond just the depth of response. We are powering for that. We're dramatically overpowered for that Chinese delta, but we're well-powered for a more contemporary delta if we look more like the other drugs in the class. I'll let Dallan speak to the commercial.
Yeah. The MG-ADL is the gold standard gauge of efficacy in the market. It's natural that people hone in on that, and it's our splashiest piece of efficacy data because we're essentially double the competitive field in terms of that delta. We do expect to maintain an advantage there, but will it still be double? It certainly doesn't need to be, and we can actually lose that delta entirely and still win in the market because we really win in efficacy on three ways. That delta is one of them, and that's what we call the depth of efficacy. We also have two other efficacy advantages, one being the breadth of response. The current market leader was approved on a 67% of patients having a two-point or greater MG-ADL response. That's the label data.
For telitacicept, that's 100% of responders, that's a very important advantage, is the proportion of responders. We call that the breadth of response from an efficacy standpoint, that's absolutely going to continue. There's no risk really on that one at all. The third advantage is because we're targeting upstream and targeting B cells, is the durability. To that, on the global phase III, we have a full one-year open label extension after the 24-week placebo control portion. We expect to have great data longer term on durability. As I said earlier, that's where the market is moving, long-term sustained symptom control for MG. Even if we were to lose the delta entirely, which would be disappointing, we would still win on these other two components.
Just another follow-up question for the global phase III trial. Is it explicitly stratifying or evaluating efficacy in patients who are refractory to existing FcRn or complement inhibitors?
We are allowing patients who have exposure to FcRn and complement inhibitors. We do have a stratification. The numbers are relatively small. I think we're probably going to be in a sweet spot where we have just enough patients to be able to provide some empiric evidence that there's a response to FcRn inadequate responders with telitacicept, but not a large enough number that we think it'll affect our statistical evaluation overall of the population effect size.
Great. I guess let's move on to your Sjögren's trial strategy. The global phase III upstream Sjögren's trial dosed its first patient in late March, and target enrollment is 250 patients. What is your anticipated timeline for enrolling the study given multiple phase IIIs enrolling?
Yeah. We are looking at about a two-year enrolment timeline. That's both because of the competitive nature of the environment, but also because the population we're enrolling is a very specific Sjögren's population. We anticipate, obviously, there's a one-year study conduct. It'll be about just under three years to data is what we're anticipating. We'll have better guidance as we see the trajectory of the study enrollment. Right now, we're getting a lot of screening in the U.S. There's a lot of enthusiasm among U.S. investigators to get patients into this study. If we see that globally, we could have better news in the coming months.
For the ESSDAI training for Sjögren's investigators is notoriously challenging. It's a 12-domain, somewhat subjective scale. Can you elaborate on your site selection strategy, particularly in the context of investigator familiarity with ESSDAI and ESSPRI?
Yeah, definitely. We're actually very lucky that a number of Sjögren's studies have been conducted ahead of ours, including the two NEPTUNUS studies from Novartis. Novartis ran two very large studies, and in doing so, they had to bring a lot of sites on that didn't have a lot of Sjögren's experience. I think that might have been to their detriment in terms of their placebo effect, but it's to our advantage in terms of now having these well-trained sites who have a lot of experience with the ESSDAI.
The key to ESSDAI precision is repeated use of the ESSDAI tool, and I think that we've grabbed as many of those former Novartis sites as possible. People with experience with the nipocalimab J&J studies, people with the Horizon, now Amgen dazodalibep studies. We've taken investigators almost exclusively who have ESSDAI experience.
We've also trained or retrained all of them with the Sjögren's Foundation ESSDAI training tools, and ESSPRI training tools. We think that by selecting these sites with experience, not better investigators, just more experience with the tool, we'll be able to get better precision and reduce that placebo that was a challenge to the Novartis study.
What learnings from the Chinese study in terms of dose selection, patient stratification, et cetera, were implemented in the design of the global pivotal, and are there any notable differences compared to Novartis' ianalumab and J&J's nipocalimab, and argenx's efgartigimod?
Yeah, the main difference. China ran two great studies, RemeGen and China, for Sjögren's. The first study was a small phase II dose-ranging study where they looked at 240 mg and 160 mg. This was to ask the question, is there any advantage of the 240 mg over the approved 160 mg for lupus? The answer was no, 240 mg didn't improve on 160 mg. The phase III study was a much larger study and evaluated two doses, 160 mg and 80 mg, and showed that 160 mg was superior to 80 mg, but 80 mg still worked. In fact, 80 mg looked pretty similar to what other people have seen in their phase II Sjögren's studies. We think that really did a good job confirming the dose ranging.
There was a major difference in the China phase III Sjögren's study versus ianalumab, that was the use of background medications. In the China study, they weren't allowed to be on any background immunosuppressants other than hydroxychloroquine, and there could be no steroids. In the ianalumab study, 30%-40% of patients were on steroids and/or background immunosuppressants. That contributed to that placebo response or not isn't 100% clear. We're waiting to see the sub-analysis of the placebo in the patients who were or were not on background immunomodulators. We do have immunomodulators in our phase III study. For that reason, we anticipate we will not reproduce the very low placebo that was seen in China, but we don't need to.
Even if the placebo goes up to the average placebo of 2.5, our delta's still 2.5-3, which would be best in disease, and that assumes no increase in the active arm from that background therapy. We anticipate we'll see at least an increase, if not a directly proportional increase in the active arm maintaining that delta between placebo and active.
Yeah, if you'll indulge me for one second, I just want to sing Jeremy's praises. He came on board right around the time of the Novartis readout, and it was pretty impressive for me to watch. He immersed himself to find every lesson learned from that trial and incorporated that into the design of our phase III trial. We're grateful we've been able to learn from the Novartis experience, and Jeremy, as a rheumatologist, could really take those lessons quickly, adapt them, and apply them to our own trial design.
We're in a unique place where the field leader is really actually paving the way for us to do better. Dallan can speak more about the commercial opportunity of what Novartis is doing to help us. If nothing, we're grateful.
Great. Sjögren's disease is a highly heterogeneous disease with about 30%-40% of patients showing extraglandular organ involvement, skin, lung, kidney, joints. Are you stratifying for extraglandular disease?
All patients have extraglandular disease. Basically, this is a high ESSDAI population, so all patients have to have some component of disease outside the gland, so some systemic organ involvement. You can get points from the biologic score, but otherwise everyone will have joints, skin, lymph nodes, systemic symptoms, lung, kidney, something else. Everyone has systemic involvement.
We think this is the most compelling population to commercially pursue. It is estimated to be about 100,000 patients or so in the U.S., the high ESSDAI with the severe systemic organ involvement. The value proposition there is the strongest, and that allows us to lead the way in terms of this new era of biologics for Sjögren's patients.
Yeah. We're stratifying by ESSDAI greater than or less than 10, if that's important, but that's very similar to what other people have done. Everyone has extraglandular involvement.
Got it. In the China phase III trial, telitacicept achieved statistically significant improvement on both ESSDAI and ESSPRI. Placebo responses at 24 weeks were meaningfully lower than the benchmarks. Why is that? How are you addressing the potential for larger placebo responses to global phase III driven by partially subjective ESSDAI endpoint? I think you may have touched on it. Maybe if you want to elaborate a little bit more.
The ESSDAI is a little less subjective. The ESSDAI is physician-assessed, and the variability in the ESSDAI is really the precision of the investigator in reproducibly performing the assessments. Again, we overcome that by getting well-trained, well-experienced investigators. The ESSPRI is patient-reported, and there's a lot of subjectivity and variability. We think the most important thing there is that the systemic disease activity is driving that patient symptomatology. The better you can control the patient's systemic disease activity, the more likely you are to have better and more deep control of patient symptomatology. I think the failures in Sjögren's have often been from drugs that did work but didn't work well enough to overcome the heterogeneity and variability underlying the disease.
I think what you need to really win in Sjögren's is a drug that has a strong enough effect size across the heterogeneous population to overcome the inherent variability of the disease itself. I think ianalumab was the first one to do that, though they didn't do it with a lot of room to spare, shall we say. Their delta on ESSDAI was 1.1, which is below the minimal clinically important difference.
They did not see a difference in ESSPRI, I think that they've done a great contribution to the field, getting us to where we are now with our first positive phase III study. We think that by targeting upstream on the BAFF mechanism, downstream on the APRIL mechanism, we're able to really get that dual improvement across the heterogeneity of Sjögren's biology. That'll get us a larger delta, which is easier to overcome that heterogeneity and variability in the outcome measure.
Can you elaborate on the powering assumptions for the trial?
We're powering for a clinically and statistically significant outcome. The MCID for ESSDAI is about two to three . The MCID for ESSPRI is one. We're powering for that minimal clinically important difference, as well as the ability to target the key secondary endpoints.
Got it. Well, I guess you've already talked about this. Let's move on, I guess, to pricing, reimbursement, commercial strategy. With multiple FcRn inhibitors now approved, how do you envision the sequencing of telitacicept in the treatment paradigm? Do you see it as a first-line biologic, post-FcRn failure, or a complement alternative, specifically for gMG?
We certainly see it as a first-line biologic. This is not a one-time therapy. It's not one and done. If you've got a better superior efficacy profile, the physicians will prefer this first line. That said, we've got a really strong market leader with argenx, and the natural default position, if you look at the models out there, is we fit very nicely second line for the reasons that Jeremy outlined earlier. We address not only just IgG, but also IgA and IgM. 20%-30% of MG patients have IgA and IgM, and there's about a 20%-30% non-response to the FcRn. It's perfectly positioned if there's a non-response to the FcRn, who are driving the market right now, to go straight to telitacicept.
To put just that opportunity in context, in what will be a $10 billion market in the not too distant future, 30% gives us a total opportunity of $3 billion. That we get by default, and I think if we were satisfied with that, maybe we would stop there, but really, we want to become number one in the market. We want to go directly head-to-head against the FcRn, and we want to position ourselves for that first-line business. Of course, we know that argenx is going to have an ocular MG indication, seronegative indication. They're driving the market right now and will in the couple years leading up to our launch. Even if we never become the number one in that first-line business.
A real pathway to becoming number 1 in the market is dominating in that second line part of the market where we are going to be the default, and even getting modest share in the first line gets us to number 1. We think we've got the profile to really become the first-line agent of choice, but of course, we know that it's a competitive market, and we'll have to get the whole commercial strategy right, including our pricing market access strategy, and then go into a very competitive promotional market as well.
How are you thinking about pricing in the context of this increasingly crowded gMG market? Will you pursue parity pricing with FcRn inhibitors, which are about $400,000-$500,000 per year?
Well, we're a couple of years out, so we're not guiding on price yet. We have some time to do our research and be thorough about that. I think there's a couple of ways you could look at it. If we really were satisfied with that second-line business, you could potentially price it higher. If we really want to become the number one drug, you could. It's still very compelling to price it at parity with the FcRn. I think we are in a really nice position from a pricing standpoint with a lot of latitude and flexibility as we go into this, especially with regards to these first two indications. Because if you do even assume, for example, we go at parity with the FcRn, we're at about a 44% lower dose for Sjögren's.
It's 240 mg per week for MG, 160 mg per week for Sjögren's. We think that the parity pricing with FcRn in MG gets you to where the field thinks the pricing is going to land in Sjögren's as well. We've actually got a good pathway from a pricing standpoint for both of the first two indications. Of course, we're going to do rigorous pricing research. We're going to make sure we get it right to maximize the success in the short and long term in the U.S. and globally.
Got it. What are your assumptions around market penetration and peak sales for telitacicept in both gMG and Sjögren's?
Well, these are huge markets, right? These are $10 billion potential market for MG, and even larger than that for Sjögren's. Starting with MG, despite there being seven approved drugs today, there's just three modalities. There's FcRn, there's complement, and just the recently launched UPLIZNA, which is a CD19 B-cell depleter. As I said, we believe the profile warrants us becoming number one in the market. For us to be a multi-billion dollar brand, you don't even have to become number one. We're not guiding on revenue at this early stage, but we think both MG and Sjögren's represents multi-billion opportunities. Sjögren's, there's been a lot of discussion. Novartis just filed for ianalumab, and we see that as the biggest untapped large autoimmune market with a big unmet need. Ultimately, even a bigger market opportunity for Sjögren's.
There's going to be a lot of room for everybody. It's even further out than MG. As Jeremy said, we think we can beat the bar of efficacy of the first approved drug, what we think will be the first approved drug. We believe we have a path to the number one as well in Sjögren's. Again, you can be a very strong multi-billion dollar drug. There's plenty of room for everybody in this emerging global Sjögren's market.
Okay, we're about to close the session, just the last two final questions I'll pull together. What is your appetite for potentially in- licensing another asset for the pipeline? Can you remind us what your cash runway and key catalysts over the next six months are?
Yeah. In terms of we're always open. I think one thing that's notable about us, in less than a year, we've gone from, we say internally, zero to 100, which is we're already approaching 100 employees. We're attracting really the best and brightest in the industry because of the profile of the drug. People right now we're attracting have experience and established relationships in MG, also we're starting to hire the same from the rheumatology Sjögren's market. I'll let you answer the other.
We're well positioned to take on another asset in the sense of our development capabilities. We'd like something, if we did, that would be synergistic or with our current capabilities in telitacicept. We're opportunistic there. Right now, our focus is on delivery of the MG study, because that's really the value inflection for us in the short term. As far as our cash runway, we have about $490 million. That gives us cash runway through 2029. That includes the MG readout, MG filing, Sjögren's readout, and the money down we'll need for commercialization for MG. I think we're in a good position. We have enough money to do a small bit of elective activities, whether it be indication expansion or asset BD. Again, our focus is on delivery of the MG and Sjögren's studies.
Sure. Sorry, I had a frog in my throat there. Yeah. As we're always open on other indications, we are also ultra-focused on winning in MG and Sjögren's. That's our near-term focus. We're going to be responsible with our capital deployment in doing that.
Great.
Thank you.
Thank you so much for joining us today, Jeremy and Dallan.
Thanks, James.
Thanks, everyone. Appreciate it.
Thanks for having us.