Hi, everyone. Thank you for joining H.C. Wainwright's seventh annual Neuro Perspectives Expert Summit. My name is Natasha Ray. I'm an analyst on the corporate access team. H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 19 publishing senior analysts and over 650 companies covered across all sectors. If you would like more information, please visit our website at hcwco.com. As a reminder, please reference your online conference portal that provides your individual links to all your meetings and all company sessions. With that, I'd like to introduce Lonnie Moulder, CEO of Zenas BioPharma.
Thank you, Natasha. We're very grateful to H.C. Wainwright for including us in this conference. I'll be making some forward-looking statements and refer you to our SEC filings. I'll begin with our team. The reason I'll do this is because we're on the cusp of potential commercialization, and we have a substantial leadership team here at Zenas that has been involved in multiple successful drug development programs, BLA and NDA submissions, and ultimately, successful commercial products across the globe. We have a robust portfolio of product candidates that this team is advancing. I'll review each of these at a high level and dive in a bit more as we go through the presentation. There'll really be two parts to the presentation.
One will be our lead programs. The second will focus more on the neuro component of our pipeline, since this is a neuro emphasis meeting that we're participating in here. Let's begin with obexelimab. Obexelimab, as you may know, is a antibody that targets CD19 and FcγRIIb. It's in a broad development program. The IgG4-RD phase III program concluded successfully. We actually submitted our first BLA just a few weeks ago and anticipate launching in the first half of next year. The RMS, or Relapsing Multiple Sclerosis program, reported out the primary endpoint in the fall of last year, a highly successful trial with follow-up data that was reported earlier this year to confirm it. We have a lupus program ongoing that will report out in the fourth quarter of this year.
Orelabrutinib is a BTK inhibitor I'll discuss more and is the subject of two large phase III global trials, one in primary progressive MS, the other in non-active SPMS. Our earlier-stage programs, including ZB021, an oral IL-17A/F inhibitor that entered the clinic a few weeks ago, will report data year-end. ZB022, a brain-penetrant TYK2 inhibitor to round out our neuro portfolio. That will report data from the phase I program next year. Finally, ZB014, which is a half-life extended molecule, similar to obexelimab in that it targets CD19 and FcγRIIb and has the potential to be advanced in a number of indications. With obexelimab, obviously, we think we have a very novel approach here to treating I and I diseases.
This is through a potent inhibition of B lineage. CD19, as you know, is broadly expressed across B-cell lineage, FcγRIIb, or also known as CD32B, is the natural inhibitory pathway to shut down B-cell activity. That includes the proliferation, the production of antibodies, release of cytokines, the processing and presentation of antigen to T cells. Multifaceted and has shown itself to be quite effective and active in a variety of diseases. If we begin with the first disease that we are advancing obexelimab in, that is IgG4-Related Disease. Some people refer to this as a newer disease. It is an inflammatory disease that can lead to significant organ damage, fibrosis, and ultimately organ failure in cases. Most patients present with two to four organs involved.
I t affects probably upwards of 40,000 people in the U.S., similar in Europe, although today we know there are 20,000 people who are diagnosed and actively treated. The way to treat this disease, though, is evolving rapidly because historically, there wasn't much to be done other than courses of glucocorticoids that are effective but cannot be sustained over time, off-label use of an anti-CD20 antibody rituximab for B-cell depletion, most recently, a dru g approved last year, UPLIZNA. There are limitations, as you may know, to long-term B-cell depletion, as listed here, with some infection risk usually called out based on experiences that clinicians have had in the rheumatology setting using rituximab over the years, especially. Obexelimab was the subject of a large randomized Phase III trial, INDIGO.
In fact, the largest trial ever conducted in this disease. The results were reported out earlier this year, at last week's EULAR meeting, an oral presentation of the Phase III data occurred for the first time, along with the simultaneous publication of the data in "The New England Journal of Medicine." This trial is continuing as an open-label extension and will be reported in the open-label extension data in the second half of the year. These are the primary endpoint results. As you can see, 73% of the patients were protected from flare after the eight-week steroid tapering that occurs early. You see how the two arms separate and continue to separate. This is a highly effective agent. The four key secondary endpoints, all listed here, were also met in the trial .
I will just highlight the bottom right-hand corner, the cumulative glucocorticoid rescue dosing. It is really important to consider steroid-sparing therapies in this disease because steroids will still be used intermittently from time to time. There is an overall emphasis in rheumatology to spare patients from continual steroid exposure, and this highly statistically significant outcome is important. In addition, you may be aware that antibodies that are administered that are depleting antibodies, such as rituximab and UPLIZNA, are also associated with mandatory steroid dosing to prevent hypersensitivity, which is not the case with obexelimab. The drug performed very well in the trial also as it relates to safety. As you can see, similar overall number of adverse events, a lower number of serious adverse events or grade 3 events.
With these data, we view this drug as a drug that protects three-quarters of the patients. Because of its safety profile, could be a preferred first-line agent. I'll talk about some market research that indicates that. If you think about the patients from the demographics in the phase III study, over 40%, almost 50%, are 65 and older. Over a third have concurrent diseases that put them at great risk if they were being subjected to repeated B-cell depletion. There's a profile of patients that actually is the majority of patients with this disease that would be ideal for consideration with long-term maintenance therapy of obexelimab. It's also subcutaneously administered at home, which is preferred in rheumatology. The drug can be paused, and B-cell activity will return.
That may be important when handling vaccinations. All of this comes together, and I think it creates a really good commercial profile. We tested this commercial profile with a group of 80 physicians, two-thirds were rheumatologists. We asked them a variety of questions about what we deemed being product X that outlined the phase III INDIGO study results compared to the other biologics, the anti-CD20 and anti-CD19 antibodies. Clinicians saw or strongly agreed the value of a B-cell inhibitor compared to depletion. 51% agreed versus only 3% disagreed and preferred a depleter over an inhibitor. From a likelihood to prescribe, very highly likely in the future. Importantly, for first-line therapy, which agent would these clinicians choose? Based on the profile of product X, obexelimab, about 50%, with the remaining 50% divided between rituximab and UPLIZNA.
We also asked, "What if a patient flared on obexelimab? What would you do?" Most would add a very short course of steroids, which is not unusual in the rheumatology setting. Finally, we talked a bit about the ease of administration, weekly self-administered subcutaneous, and whether that was preferred or not. Physicians were about 50/50, where 50% were indifferent of subcutaneous weekly versus every six-month IV infusion. Over 40% strongly agreed that the subq weekly was preferred, with only 5% preferring every six-month IV. Patients also really value the ability to control their disease at home, with 75% of them preferring subcutaneous administration. With this profile, we think we have a really good commercial opportunity here in the U.S. alone, with potential outside of the U.S.
In the U.S., as I mentioned before, we know there are 20,000 patients who are diagnosed and treated today, and believe there's upwards of 40,000 out there, with many yet to be diagnosed. We typically look at this with about thinking about half the patients will receive long-term maintenance therapy, those who flare more often. 10,000 to 12,000 patients based on the current diagnosed population at the market pricing that exists today is a $3 billion market opportunity, where we believe we can be the market share first-line agent in this category. With the BLA file, we have a lot of internal activities underway for pre-commercialization. We have the leadership in place in Europe and in the U.S. Market access, medical science liaisons have been out there for several years.
Our field leadership is coming together and will be well prepared for a launch, as I said, in the first half of next year. Moving to the next potential indication of lupus, you may be aware of a phase IIa trial that was conducted with obexelimab in a less ideal IV formulation a number of years ago. Although the intent-to-treat outcome on the primary endpoint had an effect size of 17% over placebo, which puts it in the ballpark of the two marketed drugs, some of the more recent data from other drugs all hovering under or just over 20%. That was the IV regimen. If we look at those patients that had the optimized Ctrough, which is what the sub-Q provides, our new sub-Q regimen that we use in all our studies, the effect size almost doubled.
Importantly, an exploratory biomarker had an effect size of over 50%. This trial, which we call SunStone, is ongoing, has completed enrollment, and will report out in the fourth quarter of this year using, of course, the optimized sub-Q regimen. It's an all-comer trial, but we're evaluating all the patients for the presence of the biomarker, and we'll be reporting not only the overall data, but also the biomarker data in the fourth quarter. As we approach that, we'll provide more information on what that biomarker entails. Finally, from a rheumatology franchise standpoint, we're quite excited about the oral IL-17AA/AF inhibitor that we just moved into the clinic. As you know, IL-17 is a well-validated target across a variety of dermatologic and rheumatologic conditions, and the IL-17 antibodies have created a rather large market opportunity here.
This molecule, which is a true small molecule, has substantial potency based on its novel pharmacologic profile and how it actually binds and blocks the IL-17 binding to the receptor, and ultimately IL-17 signaling has been validated in a number of preclinical models. This is an example of the rat CIA model compared to an antibody. Importantly, as an oral molecule in this category, a challenge has been with some of these agents is the ADME profile. We have a molecule here that actually demonstrated 80% bioavailability in non-human primates. We look forward to bringing forw ard the SAD and MAD study results by year-end and the safety profile. I think with a validated target such as IL-17 demonstrating a ADME profile that is highly desirable and a safety profile.
I think those are really big clearing events as we move into next year in a psoriasis proof-of-concept study that we'll also report out next year. Let's move to the neuro component of the pipeline. I'll start with our BTK inhibitor, orelabrutinib. As you probably know, BTK inhibitors have demonstrated efficacy in multiple sclerosis and some now in large phase III trials. Why is that? Of course, targeting B cells, as one knows, in RRMS is highly effective. There are several anti-CD20 antibodies. We demonstrate it with obexelimab targeting CD19, high activity in RRMS. For progressive forms of MS, it's really important to get into the central compartment to not only impact B cells, the B cell-T cell axis, but other important cells that are relevant to progressive disease and are resident in the central compartment, including microglia and macrophages.
BTK is an important driver to all of the cells I just mentioned. The BTK category today, inhibitor category today consists of orelabrutinib, fenebrutinib, and remibrutinib, with tolebrutinib having not succeeded with the FDA, but I will mention that tolebrutinib has a positive CHMP recommendation and will be approved in Europe shortly. Across the progressive MS spectrum, only orelabrutinib is being developed in both primary progressive MS and non-active SPMS. Why we believe this is a best-in-class molecule goes back to its pharmacology. It's highly selective. You can see from the kinome scan the selectivity as compared to the other agents, with tolebrutinib having the greatest toxicity and the least selectivity here. It's covalent, dosed once a day, compared to fenebrutinib and remibrutinib that are twice a day at much higher doses.
It has strong CNS penetration, substantially more than remibrutinib and tolebrutinib, significant potency, much more potent than fenebrutinib. When looking at something we think is really important, the CNS concentration to IC90 ratio, it's multiples of the other agents. We think this molecule is ideally designed to excel in a progressive MS population. Orelabrutinib is a molecule that we licensed from InnoCare and is actually the second-most prescribed BTK inhibitor now in China for a variety of lymphoma and leukemia indications, and it's well-known in that community as the best-tolerated BTK inhibitor. Of course, a phase II trial was conducted with orelabrutinib. A classical RRMS trial, as depicted here, looking at doses. This was a global trial conducted by a U.S.-based CRO, and the top-line results are listed here.
You can see the selected phase III dose, 80 milligrams once a day, provided greater than 90% reduction in Gd-enhancing T1 lesions. The onset on the right was quick and sustained. Importantly, this agent was evaluated in this study up to 96 weeks. What we have here are select data from that 96-week endpoint where EDSS score was maintained. These patients would typically progress. Serum NfL dropped dramatically. SEL volume also. A drug that's been well-characterized and is now, as I mentioned earlier, the subject of two large phase III trials. These are both randomized, two to one, drug to placebo at the 80 milligram QD dose, with the PPMS study having a 12-week composite confirmed dis ability progression, or CDP endpoint, and the SPMS, na-SPMS trial, as agreed with the agencies, a 24-week CDP, with data being available in 2030.
Staying with the neuro franchise, we also have in our pipeline, moving into the clinic, which will have SAD/MAD results next year, is a brain-penetrant TYK2 inhibitor. We think having a CD19-directed therapy with ZB014, the long-acting obexelimab, a BTK inhibitor, and a brain-penetrant TYK2 inhibitor, we can creatively develop our portfolio to, in fact, include combination therapies over time for a variety of neurodegenerative diseases, with an emphasis on multiple sclerosis. Stay tuned on this TYK2 allosteric inhibitor , which we think rivals best-in-class. In summary, we have a lot occurring here at Zenas BioPharma, and in the near term, we'll have the filing of our acceptance of the filing of the BLA. We have two important medical conferences coming up, one being the International IgG4-RD Symposium.
Hundreds of KOLs across the globe will come together in Boston, and we'll have some data at that meeting. At ACR, we'll have some data. Look for both our vaccine sub-study data and our open-label extension data for those upcoming meetings. Of course, we have the SLE program, the SunStone study, reporting out in the fourth quarter, both th e overall and biomarker populations. Importantly, the ZB 021 IL-17A/F oral drug reporting out in the fourth quarter, the PK results and the safety results, as we then move into the psoriasis study. Next year, of course, we'll have, as we would hope, an approval and launch of obexelimab for IgG4-RD in the first half of the year, and other global approvals throughout the year, potentially, and potentially a start of the first SLE phase III trial.
As I mentioned before, for ZB 021, the IL-17A/F oral inhibitor, a psoriasis proof-of-concept study concluding and reporting out, along with the 022 and the 014 initial phase I data. All in all, a significant pipeline that we're advancing with many near-term and medium-term catalysts that we believe could drive value. Thank you for your attention, and we look forward to updating you as we progress.
Thank you, Lonnie, for leading a productive and informative presentation on behalf of Zenas BioPharma. We really appreciate the time that went into putting this together. We're very grateful for the team's participation in our summit this year.
Thank you, Natasha. Bye now.