Vor Biopharma Inc. Common Stock Stifel 2026 Virtual Immunology and Inflammation Forum

All right. Good morning, everyone. I'm Stephen Willey, one of the senior biotech analysts here at Stifel, and glad to have with us, as part of the next session, Vor Biopharma. We have Dallan Murray, who is the Chief Commercial Officer, and Jeremy Sokolove, who is the Chief Medical Officer. Thanks for joining us today, guys.

Thank you. Any opening remarks you'd like to make before we jump into Q&A?

Well, firstly, thanks for hosting us, Steve. We're very excited to be here. We're very excited to be in the position that we're in. It's just about a year since we've created this iteration of Vor 2.0. We've just recently announced the completion of our global phase III study, and we have exciting data coming up at AANEM that Jeremy can point to later. We believe we have best-in-disease data in our beachhead indication, which is one of the most exciting, dynamic, and rapidly growing markets out there, the MG market. Jeremy also has a global study running very well in children to date. Lots of progress in our first year, but even more opportunity looking forward to the future. Looking forward to the discussion.

Yeah, me too. Great. Maybe just broadly, you can talk a little bit about how you think about the mechanistic differentiation of telitacicept, specifically within myasthenia. I know when you look at the current treatment landscape, there are novel therapies that are targeting either upstream B-cell depletion or downstream circulating IgG. You are kind of the first to combine the two via BAFF and APRIL inhibition. How do you think this differentiation reveals itself in the China data that we have seen to date, and then potentially positions you for commercial success in what is obviously kind of an increasingly competitive marketplace?

Yeah, Steve, that is a great question. Telitacicept obviously is a dual BAFF/APRIL inhibitor, and as such, it covers that upstream and downstream targeting of the B-cell developmental pathway, autoantibody production, all the way back to early B-cell maturation. We think that, often we are asked, "Why would there be such a differential efficacy from your mechanism versus a downstream mechanism such as FcRn or an upstream mechanism such as the CD19?" The answer is exactly as you implied, which we think is that dual mechanism, and it is the ability to have that additive benefit where we first initially see relatively rapid improvement in acetylcholine receptor antibody reduction, and it is that initial effect that is very similar, not identical, to that seen with FcRn. All that time, we are remodulating the upstream B-cell repertoire, and that does two things.

One is it prevents repopulation of that autoreactive B-cell pool, such that we have really turned off the source of that autoreactive B-cell clone and autoantibody-producing plasma cell. Also, we think that the more we see, the more we are convinced there is an antibody-independent mechanism for B-cell-driven pathology in MG. We think that the evidence for that is really drawn by the success, reasonable success, of CD19 targeting. UPLIZNA has a very nice efficacy profile, relatively similar to the FcRns, and the complement inhibitors, but it has a very minimal reduction in immunoglobulin, 9% total immunoglobulin. We do not think there is a directly disproportional reduction in pathologic immunoglobulin. Thus, there must be another mechanism by which this B-cell modulation is resulting in that magnitude of efficacy.

We think that when we look at the curves for the two different mechanisms, FcRns tend to improve relatively rapidly, and then have a period of stability where you do not see further improvement, or you might see a wave pattern where patients actually do get worse between cycles and then get better, versus the CD19 upstream B-cell depletion mechanism, where you see slow but gradual improvement, which tends to further separate even between 18 to 24 and 24 to 48 weeks. If you look at those two patterns and you superimpose them, that is the pattern we see with telitacicept. We think what we are capturing is that early momentum and increased depth of the FcRn mechanism, and then similarly, the durability and continued remodulation of the B-cell response through the upstream B-cell targeting through the BAFF mechanism. We think it is that additive mechanism.

One investigator used a term, he said, "We're really looking for combination therapies in MG, and telitacicept may be the first combination therapy." Again, it's one drug, but it has that dual targeting mechanism.

Yeah. Steve, to your question of where it positions us in the market commercially, we think this dual mechanism will. It's all going to come down to the data, and we think it will allow us to come into the market with best-in-disease data. I think you can look to argenx in the market earlier, who came in in 2021 with a differentiated profile. If you can show differentiation on efficacy and/or safety, they're dominating the market now. While it's an orphan market, there's no one-time gene therapies. If there's a better profile of a drug coming in, the physician and patient community will move to that new option.

Mm-hmm. Maybe just another quick commercial question. I know that we've seen some recent literature that's been talking about the contribution of IgA and IgM antibodies to the pathology of MG. What are the commercial implications of these findings for Taly? Is this something that clinicians are looking for via serology at time of diagnosis, or is it just really you're an adequate FcRn responder, it might be due to this?

Yeah. Yeah, it's a great question, and Jeremy can talk to what's available diagnostically today. This data that's come out of Yale showing IgA and IgM, is resonating with the physicians because about a third of patients have these antibodies that are fixing acetylcholine, and that correlates with about a third rate of non-response to the FcRn's. There's not a commercially available assay to test this.

But I think that this advantage that we have, that we target IgG, but in addition, we target IgA and IgM, is a key advantage, and it speaks to the unique opportunity we have here. Even if you are on the conservative side, and you don't believe we're going to come in with best-in-disease data, we have a response rate that we think is driven by this broader immunoglobulin coverage, and 100% of patients are getting at least a 2-point or greater response on the MG-ADL, and that's unique and differentiated in the market. And we think this is what's driving that. So even if you're a little bit more conservative on the expectations of what our efficacy might be, this IgA and IgM coverage positions us very well for second-line use, even if we don't replicate the delta from China.

Even if we come in with a delta, we lose it entirely, that looks similar to the rest of the market, we have a $3 billion opportunity in second line that we can target. So that speaks to how de-risked the asset is. And the recent launch of UPLIZNA gives us even more conviction on this opportunity because the delta on MG-ADL was lower than what you see in the market.

Okay was low too. Yeah.