Zenas BioPharma, Inc. Common Stock Investor update

Please go ahead. Thank you, and good morning, everyone.

Before we begin, I'd like to remind you that today's presentation contains forward-looking statements, including statements regarding the potential approval and commercial launch of obexelimab in IgG4-RD, our clinical development plans, the timing of potential clinical readouts and regulatory filings for obexelimab and ZB021, and our expectations for the market opportunities ahead of us. These statements involve risks and uncertainties that could cause actual results to differ materially from what we discuss today. I would encourage you to review the full disclaimer on the slide, along with the risk factors described in our most recent annual report and quarterly reports filed with the SEC for a complete discussion of those risks. I will now turn the call over to Lonnie Moulder, our founder, and CEO.

Thank you, Abby. Thank you all for joining us for today's R&D event, which follows the obexelimab IgG4-related disease commercial event we held last month. Today, we will focus on obexelimab, our investigational bifunctional monoclonal antibody targeting CD19 and FcγRIIb, and its potential opportunity in systemic lupus erythematosus or SLE, and on ZB021, our novel, potentially best-in-class oral IL-17AA/AF inhibitor. In addition to the clinical relevance of these programs, we will also review some of the underlying science and provide context in advance of the clinical data we expect to report from both programs later this quarter. I'll start by briefly discussing the overall Zenas pipeline and provide context for the SLE opportunity. Haley Laken, our Chief Scientific Officer, will describe the biomarker work associated with the phase IIb SunStone SLE trial.

Lisa von Moltke, our Head of R&D and Chief Medical Officer, will walk you through the SunStone SLE trial and outline what we intend to report. Haley will then present ZB021, our oral IL-17 inhibitor. We are also very pleased to have with us Dr. Joseph Merola, a board-certified dermatologist and rheumatologist, President of the Rheumatologic Dermatology Society, and a member of the Medical and Scientific Board of the Lupus Foundation of America. Dr. Merola will share his perspective on IL-17 as a target for the treatment of multiple diseases and the relevance of oral therapy. We will then take your questions before closing. As I mentioned, we discussed IgG4-RD, obexelimab, and our launch preparations in September, and we encourage you to access that event on our website for a detailed review of our commercialization plans.

While we are very focused on launch preparation and execution as we approach the May PDUFA date, we also feel it is important to highlight how we are well-positioned across our rheumatology and neuroimmune pipeline, which spans multiple indications with recognized regulatory paths to approval and significant commercial potential. We are expecting top-line phase II results from the SunStone study of obexelimab and SLE and pharmacokinetic safety and tolerability data for ZB021, our oral IL-17 inhibitor, later this quarter. Both of these datasets will inform us as we determine our program strategies and our capital allocation decisions in the near to medium term.

The SunStone trial is structured to provide us with information to design a phase III registration program in SLE, and for ZB021, achievement of target exposure levels with once-daily dosing, along with a favorable safety and tolerability profile, provides us with what we need to rapidly advance a potential blockbuster franchise. At Zenas, we are building rheumatology and neuroimmunology franchises. Priority number one, of course, is an approval and successful launch of obexelimab for IgG4-RD. The BLA is under review by the FDA with a PDUFA date of May 27, and we also recently submitted the obexelimab IgG4-RD marketing authorization application to the EMA. We will further discuss the SunStone phase IIa SLE trial today. We previously reported the highly successful phase II MoonStone trial of obexelimab in relapsing multiple sclerosis.

In progressive MS, we are advancing two large phase III global programs with orelabrutinib, a potentially best-in-class BTK inhibitor, PriMroSe for PPMS and Monarch for naSPMS. ZB021, our oral IL-17 inhibitor, which we will also review today, is rapidly advancing in the phase I SAD and MAD program, with clinical data expected this quarter. Our two earlier programs include ZB022, a brain-penetrant TYK2 inhibitor that fits into our neuroimmune franchise, and ZB014, an extended half-life molecule targeting CD19 and FcγRIIb with preclinical data indicating potential monthly dosing. We expect clinical data for both ZB022 and ZB014 in 2027. So over the remainder of this year and into 2027, important development milestones include the SunStone SLE and ZB021 clinical data this quarter, the obexelimab IgG4-RD PDUFA date in May, and initial clinical data from ZB022 and ZB014 in 2027.

Beginning with obexelimab, on September 29, we hosted our IgG4-RD investor event with Dr. Guy Katz from Mass General, who walked through the unmet need and the phase III INDIGO results. Since then, data were presented at the International IgG4-RD Symposium. First, data from the ongoing INDIGO open-label extension, or OLE. Remember, the randomized controlled portion of INDIGO was 12 months. Previously, we released six-month data from the OLE. These data from the OLE included the 12-month probability of remaining flare-free, which was 0.93 based upon investigator and adjudication committee flares requiring rescue therapy, and 0.87 based upon investigator-determined flares requiring rescue therapy. Additionally, glucocorticoid-associated toxicity results were presented. Obexelimab significantly reduced cumulative glucocorticoid toxicity versus control at week 52. The difference in the Glucocorticoid Toxicity Index cumulative worsening score was -11.4 with a P value of 0.021.

Finally, the vaccine study is where patients at select INDIGO clinical sites pause their obexelimab treatment, are administered a flu vaccine, a COVID vaccine, or both, wait 2 weeks, have titers measured that would indicate seroimmunity, and then restart obexelimab. Vaccination during the treatment-free window resulted in seroimmunity to influenza in 6 of the 7 participants, or 86%, and seroimmunity to COVID-19 in 4 of 4 participants, or 100%. We intend to add to this initial data set throughout the current flu season. Looking ahead, we will be at the American College of Rheumatology conference in November, where in addition to the vaccine data and GC toxicity data, the OLE data was accepted for poster presentation as a late breaker. Turning to orelabrutinib, a BTK inhibitor for progressive MS, as mentioned, we have 2 global phase III studies ongoing, PriMroSe in PPMS and Monarch in naSPMS.

There is significant need for new, effective therapies for progressive MS, and we are pleased to see how the BTKI category is evolving. Tolebrutinib is now approved in Europe for NR-SPMS. Fenebrutinib succeeded in a phase III PPMS study, and the NDA is now under review. Remibrutinib succeeded in a phase III RRMS program, and a phase III SPMS study is underway. Having just returned from the combined ACTRIMS and ECTRIMS meeting, MSToronto, KOLs and the broader MS community are very enthusiastic about the potential for BTK inhibitors to advance the management of patients living with progressive MS, and they recognize there are important differences across this class of agents. We believe the pharmacologic properties of orelabrutinib make it well-suited as an investigational agent for progressive MS. First of all, the kinase scan data demonstrate it is a very selective molecule.

It also has desirable pharmacokinetic profile and a low variability and once-daily administration. Because central compartment inflammation and the role of macrophages, microglia, and B cells are critical to this disease pathogenesis, brain penetration and potency at central targets are critically important. Orelabrutinib stands out with the greatest brain penetration IC90 ratio within the class. We also have very compelling clinical data in hand from the completed orelabrutinib global phase II RRMS trial. Not only strong week 12 and week 24 results, but 96 weeks of follow-up data, including disability progression and NfL data. No other BTK inhibitor is advancing in both naSPMS and PPMS. I'll now turn to obexelimab in SLE. SLE is a chronic autoimmune disease with unpredictable flares impacting joints, the skin, kidneys, and other vital organs, resulting in progressive organ damage. You can see the common manifestations on the slide.

It is a heterogeneous disease, and the driver of the disease varies across SLE patients. More than 80% of SLE patients are women who are diagnosed in their 30s and are patients facing decades of treatment. A significant opportunity remains for safe and effective therapies for long-term disease management. An underlying pathology is B-cell dysfunction, which results in the production of autoantibodies towards cellular and nuclear components. B-cell therapies have been proven effective in clinical trials, so we know B-cells are an important target. We evaluated and learned from prior SLE studies, including the previously reported obexelimab phase IIa study, and incorporated learnings from these trials into the SunStone trial. These include confirmatory central screening for patient enrollment, utilizing the latest guidelines for glucocorticoid tapering, and biomarker identification to potentially select for patients who are more responsive to a B-cell-targeted approach.

The SLE market in the U.S. consists of approximately 250,000 diagnosed cases. Excluding lupus nephritis, this is approximately 175,000 patients, with approximately 125,000 of those having moderate to severe SLE. Two biologics are approved for SLE today, and they generated approximately $2.5 billion in U.S. revenue in 2025. A minority of eligible patients are receiving a biologic, and we believe growth will be driven by the approval of improved therapies. With an estimated 125,000 addressable SLE patients in the U.S. alone, the overall market opportunity could exceed $8 billion. Illustratively, if 30% of this population is defined with our biomarker approach, which Haley will discuss, a focused market of over 35,000 patients could exist. With that, I'll now hand the call over to Haley, our Chief Scientific Officer, who will provide more context to the biomarker under development within the SunStone trial.