All right, good afternoon, everyone. I'm Stephen Worley, one of the Senior Biotech Analysts here at Stifel, and glad to have with us, I believe the last session of today's day one I&I Summit, Jean-Paul Kress, who is the CEO of Vor Bio. Jean-Paul, thanks for joining us.
Thanks, Stephen. Happy to be here.
Maybe we can just kind of dig right in here. Obviously a much different version of the prior Vor story that certainly I covered and other investors were perhaps familiar with. Maybe we can just kind of start off with a high-level introduction to the new Vor , the asset, the transaction, the team you've brought together, and maybe you can comment too, what specifically attracted you to the opportunity here.
Sure. You're right. It's a brand new Vor. We call it Vor 2.0, actually, as we rebuild the company around one of the most compelling late-stage assets in immunology, telitacicept. We licensed this asset from RemeGen, a China public biotech, late June. We got the global rights ex-China. It really comes to three reasons. Number one, the MOA, telitacicept, is a dual BAFF/APRIL inhibitor, which works both upstream and downstream of the B-cell lineage, which basically normalizes the immune system and provides durable efficacy and disease modification beyond symptom control, where most therapies currently fall short in autoimmune diseases, like FCRN antagonists, for instance. Number two, the data. We have an unparalleled amount of data. We are basically the most advanced BAFF/APRIL inhibitor in the world. We have more than 70,000 patients treated by the drug in China, around 3,000 in clinical trials, phase twos and phase threes. It's a proven three indications there, with two more PLAs being filed as we speak. As a whole, remarkable consistency of data across indications. Last but not least, the market opportunities are commensurate to the quality of the asset. We have in play myasthenia gravis and Sjögren’s disease, which are big, chronic, in some cases, underserved indications with high medical unmet needs. We think we are part of the solution here. We have the potential to fill a lot of gaps. We've built a world-class team of very experienced leaders to execute on this opportunity, which I believe is unique and rare. You asked me why I joined. That's why I joined.
Okay, great. I think I want to get into all of those things and obviously a bit more detail. So, telitacicept is, you know, one of many TACI domain variants in APRIL or BAFF targeting antibodies that are currently in clinical development. How is this drug either structurally or mechanistically different from these competitors? You know, how important do you think that differentiation may be from a competitive perspective?
You know, you said it, we are the most advanced of the three late-stage BAFF/APRIL inhibitors, for a couple of reasons I mentioned earlier. In terms of the biochemistry, which we always have to take with some reservation because the clinic prevails, we are the closest to the wild type TACI receptor, which basically is the receptor with the greatest affinity for the two targets we tackle, BAFF and APRIL cytokines. Being the closest to the wild type TACI receptor is a great proxy for optimal inhibition of BAFF and APRIL, the two cytokines which are acting upstream and downstream of the B-cell lineage differentiation and maturation. By tackling this BAFF and APRIL in a very optimal way, in a very natural way, because we're close to the wild type again, we think that we have a balanced, effective, and very safe therapy. It has been actually demonstrated on the PD of these diseases with a consistent efficacy on not only the immunoglobulin Gs, but also the IgA and the IgM, modulating those ones, and with B-cell normalization, which is very important because we don't want just to act on the autoantibodies. That's a very downstream thing. We also want to act on the upstream where we have a chance to normalize the pathogenic hyperactivated B cells or plasma cells, which are actually at the origin of those diseases. I would also comment on the fact that the opportunity is beyond the BAFF/APRIL class because we are talking about the possibility to favorably compare to other classes like the FCRN antagonists or complement inhibitors, just to quote those two classes.
Okay. Let's talk about myasthenia. This is the first indication you're targeting for global phase III development. I mean, obviously an increasingly crowded landscape here, right? A lot of different mechanisms with respect to variety. What would you highlight from the phase III trial that was conducted in China to suggest that dual inhibition of APRIL-BAFF via telitacicept offers something above and beyond what has been seen with the FCRN and the complement inhibitor class that you just spoke about?
Myasthenia gravis is a very important disease for any company in the autoimmune space. 90,000 patients just in the U.S. There are lots of symptomatic treatments, mostly all with safety limitations, like the complement inhibitors. The message here is that there is a high unmet medical need despite the number of therapies on the market and even with recent therapies like FCRN antagonists. What we hear from the KOLs and the patients is that they want more durable treatment with disease modification potential and not just one target with an effect which could be limited to, for instance, very downstream on and off modulation of the immunoglobulin Gs, which is clearly interesting, but not enough. As we know now, for example, there are other immunoglobulins involved in the disease, like IgA and IgM, in more than 20% of the patients. We need a more holistic approach with a more complete treatment like telitacicept, which acts on the downstream and the upstream of the B-cell lineage. If we turn to the data, the wealth of data that RemeGen and our partner in China have generated so far, there has been communication on the phase III trial last spring at a major conference where we showed unprecedented activity on the primary endpoint called MGADL, which is a symptomatic, very well-known scale, and the benefits are actually enduring well through the 24 weeks of the study. It's a fact that we'll actually present in a few weeks at a major rheumatology conference the results of the 48 weeks long-term prolongation of this study where we show that the curves continue to go down. That's probably the most important learning here with the product. We have an unparalleled way of enduring and helping the patient on the long term when current therapies fall short and have durability challenges. FCRN antagonists and complement inhibitors cannot do that. We will be, hopefully, the first therapy in MG that does not just manage symptoms, but it changes the trajectory of the disease in the long term.
Yeah, I think that's probably what I think in addition to just the magnitude of the benefit that you were showing, the fact that we were seeing MGADL and QMG still declining at week 24 really kind of caught my eye. It sounds like we're going to be getting that data in the next couple of weeks. I guess going back to some of your earlier comments, you would perhaps ascribe this continued trajectory in the improvement of these scoring systems to be related to the fact that you're getting this broader kind of isotype specific benefit that is beyond just the IgG class specifically.
We think so. The fact not to just act on a very on-and-off kind of, you turn the faucet, on-and-off on the very downstream on the immunoglobulins or the IgG, the fact that we act way beyond that in terms of regulating, normalizing the cells, the B cells, which are the onset or the origin of the disease in a normalizing way, in a tempering way. We think that this is the way to ensure this long-term effect. In fact, at AANEM on October 29, we should present this long-term 48 weeks data, which showed that telitacicept keeps going. We have the capacity to target the root cause of the disease and not only just, you know, help the patients in a temporary basis with some cycling that we see in current therapies.
Okay. The global phase III is currently enrolling patients. Maybe just, I guess, a couple of questions related to that. First off, can you just provide a little bit of color around how this works logistically with RemeGen in terms of just transitioning responsibilities and costs from them over to you? How does that work?
RemeGen started this trial about a year ago. The great thing is that we have been preparing for that since we looked at this deal in the spring of this year, and everything was done to construct the deal with that in mind. How can we ensure the least disruption possible in a transition? It's going very well. Execution on the transition is going very well. We're transferring contract CROs. The sites continue to expand, and it's a seamless one. As an example or illustration, our Chief Development Officer is actually the previous Chief Development Officer of RemeGen. We basically transitioned her with her team, so that's extremely helpful. It's going very well. In regard to duplication or replication of the China data, we get sometimes the question, does China data or China patient, can be replicated or are they similar in the Western world? First and foremost, it's very important to remind ourselves that China has incredibly improved in the execution of clinical trials over the last few years, as the whole biotech innovation has been booming there. It's just a few numbers, but it's important to think that this is happening as we speak. One third of the global pipeline in biotech and pharma right now comes from China, and about the same amount of products in the pipeline in the U.S. and in China, all stages from IMD to PLA or NDA, there are equivalents between the two countries. There is an incredible boom there, which is happening and with great quality. At the same time, the machine of execution, the machinery of execution there for clinical trial and regulatory approvals has been incredibly effective. We can leverage that because that's obviously everything we got or we're getting from China, and the learning we get from there is very replicable in the U.S. and can be leveraged. That's also part of the transition. Our global phase III trial in MG, which is planned for reading in the first half of 2027, is basically done in the spirit of leveraging the China innovation engine, but at the same time doing the best we can here, and it's going very well.
Okay. Yeah, I know the, I mean, obviously the translation of data generated in China into more Western populations has been a very popular topic for a lot of different investors here over the course of the last year or so. I guess within the world of oncology, right, I think we're trying to think about the translation of objective endpoints, like event-driven data, right, PFSOS. I guess maybe the question here is in a setting like this where maybe the endpoint is perhaps a little bit more subjective. You know, if you compare, I guess, the one-point reduction in the placebo arm that was seen in the China trial relative to just some of the more contemporaneous studies that have been conducted in the U.S. and MG, right, you tend to see a little bit of a higher placebo response. Would you expect that to manifest here as well?
You're referring to oncology news recently and it's probably for the U.S. Here, it's a very different thing. I mean, the patients are very similar, the care is similar, except there are less new products. I mean, there are less FCRN antagonists. We have their, you know, centers of excellence, which help to basically ensure the quality of the data. We've looked during our diligence in a very, very accurate way at the quality of the data, patient by patient. We're very confident that this trial is very strong. I'm talking about the RemeGen phase III MG trial. The best-in-class or disease result that you see with this phase III trial, where we have improvement on the primary endpoint of more than four points, placebo-adjusted, we think we can replicate that. That being said, we prepared for having a slightly higher placebo in a global study because you have different sites, different countries, different sensitivities or sensibilities around, you know, basically the symptoms. The way we know that some countries have higher placebo ratings, like the southern you go, the higher placebo is, for instance, the trend in every single indication in AI or autoimmune as well. We prepare for that. We have carved our study for making sure that we have, you know, enough room to show still best-in-disease results with our global study in myasthenia gravis.
Okay. Maybe we can shift gears to Sjögren’s. Obviously, an indication that's getting a lot more attention on the drug development front. RemeGen top line phase III success, I think just last month. I believe we're going to be seeing some of that phase III data presented next month. Maybe ahead of that, you can just kind of speak to the phase II results for telitacicept that are out there and why you think this drug could prove to be perhaps a best-in-class treatment option.
Sjögren is incredibly exciting for us and for the space because a lot is happening right now and very exciting news. Just a few words on the disease itself. It's a large autoimmune disease with around 300,000 patients in the U.S., only affecting female patients, mostly 90% of the patients. It's a debilitating disease, poorly characterized and underdiagnosed. There are a series of symptoms, basically lack of secretions, lack of tears, lack of saliva, pain, and fatigue, which are actually very life-altering. It doesn't stop here. It's a multi-organ disease which has some neighborish, some similarities with lupus in terms of physiopathology. It's mainly affecting the mucosal epidermal, or epitheliums, which is also important because it doesn't stop with the IgG. You have IgA involved in everything. That's why we think our modality, our mechanism of modulating and normalizing the B cells and tackling all types of immunoglobulins is very important. I'll also mention that the Sjögren patients have 15% - 20% are prone to developing heme malignancies like lymphoma, 15 x- 20 x more than the normal population. It's not just by controlling the downstream autoantibodies that you will help controlling that. You need to tackle the B cells as well upstream. The disease is then representing a huge opportunity, high unmet medical need, very untapped, very undeserved, and a huge business opportunity because of the number of patients, 300,000, 100,000 mostly addressable because they are moderate and severe with the new biologics. I wanted to characterize this disease, which is not so well known, but we will hear more and more about this disease because we and RemeGen have read our phase III trial, confirming the phase II data you alluded to, which are best in disease. We showed great results on the primary endpoint, which is called SDIE. It's a multi-component score of 12 domains and by the physician complex. We are actually best in disease versus other phase IIs from other modalities. Our phase III trial, I cannot talk about that in detail because it's under embargo from a major rheumatology conference for later in the year. Our phase III trial has shown very impressive disease results as well. Last but not least, I would say that there is a big pharma who has read phase III trials recently in the disease, which we think is great for the field because there is room for several products and they will be learning also for us from this company and their results. We think we have the best in disease results. It's a superb opportunity.
Okay. I'm guessing the big pharma you reference is Novartis. They announced the, I guess it was the top line disclosure for lenalumab, via the Neptunus program. I think it was last month, as you said. I would think that data probably gets presented fairly shortly as well. Would be curious if you can just maybe talk about what, if anything, of particular interest within that competitive data set you'll be looking for in terms of providing the framework of differentiation relative to telitacicept.
Two companies reading phase III results in a very undeserved disease population is remarkable. It should be, from what we understand, at the same conference. We'll have the results there. Two products reading their phase III. That's very exciting for all of us, the space. We will learn more from their results to inform us and our own program. Again, I see this as a large opportunity where there will be several products. It's obvious with more a couple of hundred thousand patients. There is actually a need for more one-on-one therapy, but we are so far the best in disease. I think this is a great advantage. We'll see, but we're very confident and there is room for several modalities or products.
Okay. I know that there's another competitor in the space who has a FCRN asset in phase III development currently. I guess we kind of talked about, you know, the FCRN antagonists versus the BAFF/APRIL antagonists in MG. Curious as to whether or not you think those differences maybe get amplified a little bit in the setting of Sjögren’s, just given that this is more of kind of a broadly symptomatic disease and some of those downstream effects you can have on some of the other IgG cytotypes. If you think that'll be more mechanistically meaningful in the setting of Sjögren’s than perhaps it may be in myasthenia.
I believe that our modality tackling the different points on the B-cell life cycle or pathway is extremely compelling, upstream, downstream, tackling the origin of the disease. Keeping in mind the fact that these patients are prone to transforming into heme malignancies, the consequence is also that for FCRN antagonists, which are good products and important therapies. By the way, I was leading a synthesis. I used to lead an FCRN company when I was CEO of SystImmune, so I know them pretty well. I believe they will probably fall short somehow mechanistically by just tackling one of the classes of the IgG, very downstream when this disease is probably more multifactorial, multi-components. We think about the IgGs and there are IgAs involved in this disease as well because we're talking about the mucosal epitheliums. We cannot really say before having seen the clinical data, but based on the phase II, we have actually more compelling data. We have a couple of points improvement, favorability compared to the other modalities, including FCRN antagonists.
How do you think about prioritizing these additional development opportunities for global development beyond myasthenia? I know that there was an IgA disclosure from RemeGen phase III, fairly recently as well. There are Chinese approvals for this drug in lupus and in rheumatoid arthritis. I guess how many of these do you want to pursue, and what does the current cash balance allow you to pursue?
Right. It's exactly the question. I mean, even a big pharma would ask the question. You have to be disciplined, but at the same time, you have to pursue the opportunities. We've chosen very clearly MG. We are actually enrolling in our global trial, as we discussed. We've chosen Sjögren’s, which is an obvious and very compelling opportunity. We have other possibilities. You mentioned IgAN. We might not want to do that immediately because other BAFF/APRIL have started IgAN or have data in IgAN. We have other possibilities. You can talk about the systemic lupus. We're thinking about it a lot. Number one, we are hyper-focused on MG right now and soon Sjögren’s. Large opportunities on their own. We have to be good stewards of capital. We'll balance all that. As soon as we deliver seriously on these first two diseases, we'll be in a position to probably expand thoughtfully. I strongly believe that discipline creates value here.
Okay. Maybe just in the last minute here,
You asked the question.
Can you just.
You asked the question on the cash balance.
Yes.
Yes, probably the near-term catalyst here. We have, basically, in terms of capital structure, $1.2 billion equity units fully diluted. As of June, we have $190 million in cash, which brings a runway into Q1 2027. I think that's important to mention that we are covered for going with the MG study. Obviously, we'll probably need to expand a little bit to all that. I think that we are really excited about the catalyst coming up. I encourage everyone to watch our MG long-term data, as we discussed, the 48 weeks data at AANEM, end of October. Sjögren’s, a major conference, at around the same time where we'll have our phase III data, super exciting. We are preparing for our global phase III data as we speak. We will also be presenting IgA data at a NEFRO conference pretty soon, phase III, from China, which show, again, that we have very consistent efficacy and safety results across the spectrum of autoimmune diseases. As a conclusion, just to close, I would say that we have this opportunity, very large opportunity. We're here to change the standard of care in some of these very important autoimmune diseases, thanks to our modality and our great profile. That's really the Vor Bio story right now.
All right. Very good closing statement. Lots to look forward to in the coming months.
Thanks, Stephen. Thank you for the time. I appreciate it. Thank you very much. Bye.
Thank you, everyone.