Zenas BioPharma, Inc. Common Stock Study update

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

Before we begin, I would 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, the timing of our regulatory submissions and clinical readouts, and our expectations for the market opportunity 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 this slide, along with risk factors described in our most recent annual report and quarterly report 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. Abby joined us a few weeks ago as our Director of Investor Relations, and I know she looks forward to meeting and interacting with all of you. Thank you all for joining us for our obexelimab IgG4-Related Disease Investor event today. We will walk through the unmet need within the current IgG4-RD treatment landscape, the commercial opportunity ahead of us, and how we are preparing to execute what we believe could be a transformational launch, both for patients living with this disease and for Zenas. We are also very pleased to have with us Dr. Guy Katz from the Division of Rheumatology, Inflammation, and Immunity at Mass General Hospital, who will share his perspective on IgG4-RD and the unmet patient needs, along with the INDIGO study results. Joe Farmer, our President and Chief Operating Officer, will then walk us through the market opportunity and our launch readiness in detail.

We will then open up the line for questions. While we are laser-focused on executing a successful obexelimab commercial launch, if approved, we feel that it is important to highlight how we are well-positioned regarding our overall rheumatology and neuroimmune pipeline, which spans multiple indications with recognized regulatory paths to approval and significant commercial potential. Of note, we are expecting top-line phase II results from the SUNSTONE study of obexelimab in SLE and pharmacokinetic, safety, and tolerability data for ZB021, our oral IL-17AA/AF inhibitor, both in the fourth quarter of this year. While we are very excited about the opportunities across our broader pipeline, our focus today is on IgG4-RD and the upcoming anticipated launch of obexelimab. We hope you will join us for a deeper dive into the SUNSTONE SLE study and our IL-17 inhibitor ZB021 at our R&D event later in October.

Zenas leadership and our overall team are deeply experienced across all aspects of drug development and commercialization. We are not a team learning what a drug launch looks like in real-time, rather a team that has seen where launches go right, and importantly, where they may quietly go wrong. We believe we have a validated launch playbook and are ready to execute. Before we get into the specifics of our launch planning, I want to spend a moment on what makes a successful rare disease launch. In our experience, the disciplined execution of a strong launch plan is what sets a company and a launch up for success. We build our plan around five interconnected components. First, recognize and refer sooner, shortening the path to diagnosis instead of waiting for IgG4-RD patients to find their own way to a specialist. Second, find every diagnosed patient through data-driven identification, not guesswork.

Third, earn physician conviction with evidence that is genuinely differentiated, not just differently marketed. Next, remove access friction so a written or inputted prescription can actually become a filled one. Finally, the link most companies under-invest in provides support that extends beyond the prescription, because a patient who starts therapy and quietly stops it months later isn't a launch success. This connected continuum is what can turn a good drug into a successful launch. We believe IgG4-RD represents a substantial market. Assuming approximately 50% of the currently diagnosed and managed patients are addressable and the benchmark price of the approved therapy for this indication, we estimate the U.S. market opportunity approaches $4 billion. We and others estimate there are 30,000 to 40,000 prevalent IgG4-RD cases in the U.S. today. Our analysis of claims data indicates approximately 25,000 patients are currently diagnosed and managed.

Of this population, we estimate that the flare frequency and/or the potential consequences of flares results in approximately 12,500 patients eligible for ongoing maintenance therapy, and that's the core of today's addressable opportunity. It is expected that diagnosis rates, awareness, and referral patterns will keep improving with the availability of approved therapies. We believe obexelimab can be positioned as the preferred first-line therapy for the majority of IgG4-RD patients, and this is supported by four key areas of potential differentiation. Efficacy and safety data that stand on their own, a mechanism that is genuinely different, the reversibility and flexibility to potentially pause around vaccination or intercurrent illness, which a B-cell depleting therapy cannot offer, and the convenience of at-home weekly dosing.

That combination is why, in our market research, approximately two-thirds of treating physicians told us they're extremely likely to prescribe obexelimab, and one-half indicating they would prescribe it first-line, and that is before any marketing or sales promotion. At launch, there will be two clear prescribing paths. The first is active flares, newly diagnosed patients presenting with a flare and previously diagnosed patients who are not currently receiving treatment and are flaring again. Both are moments when a physician is actively making a treatment decision. The second is active treatment, where patients are currently receiving a biologic and cycling back to their physician prior to scheduling their six-month infusion. Each of those visits is a moment where a physician will have the opportunity to introduce a new drug to patients, and we believe our profile gives them a compelling reason to potentially implement a switch.

That is the difference between hoping for adoption and intentionally impacting it. With that, I will now turn the call over to Dr. Katz, who is not only an expert in this disease but manages numerous patients living with IgG4-RD. Thank you, Dr. Katz, for joining us this morning and sharing your thoughts with investors on IgG4-RD and the unmet patient needs, along with the INDIGO study results.

Thank you very much, Lonnie. It is such a pleasure to be able to speak with you all today about IgG4-related disease. What we will do is we will discuss some overall concepts about how IgG4-related disease presents, how the diagnosis is made, and some key areas of unmet need. Then we will spend some time talking about the specifics of the INDIGO trial and the results. First, let us start with a next slide, please. First, let us start with a definition of the disease. IgG4-related disease is a systemic, chronic, and progressive immune-mediated disease. We think of it as a fibroinflammatory disease, meaning that there is a component of inflammation and a component of fibrosis or scar tissue deposition that results from the inflammation. This is a disease that can affect nearly any organ in the body. There are a few important exceptions, but almost every organ can be affected.

It is a chronic disease. The vast majority of patients will have active disease if they are not undergoing treatment. After they undergo treatment, the vast majority of patients will eventually relapse after treatment is discontinued. This is a disease that leads to very frequent irreversible fibrosis, organ damage, and is even associated with increased mortality. Some of the specific features that I would mention about it is typically multi-organ. The majority of patients have more than one organ involved, and some patients can have 5, 6, 7, 8, or even more organs than that. It is a relapsing disease, as we discussed. Most patients will have a relapse at some point after they come off treatment, and some patients might even relapse on treatment. Very importantly, there is a really substantial subclinical component to this disease, which we will discuss in more detail soon.

One of the ways that we come to the diagnosis is through histopathology. Biopsy is an important element of the diagnosis in many patients, not all patients. On this slide, you see the typical histopathologic features that we associate with IgG4-related disease, which are a dense infiltration with lymphocytes and plasma cells. Most of those plasma cells, or at least many of them, stain positive for IgG4. We see very frequent fibrosis or scar tissue, and in IgG4-related disease, it is very often in this typical store form pattern. Obliterative phlebitis is the third typical hallmark histologic feature that we see, where there is inflammation of the veins within the tissue that is severe enough that it obliterates the lumen or the inside portion of the vein. We often see elevated serum IgG4 concentrations, which is part of the reason that the disease is called what it is.

Imaging is an important part of how we make the diagnosis because we see very typical either enlargement or masses in the expected distribution, depending on the organs that are involved by the disease. As I mentioned before, this is typically a multi-organ disease, and almost every organ in the body can be affected. The figure on, I'm sorry, next slide. The figure on the left side of the screen demonstrates the multi-organ potential of the disease. You can see that there are certain organs that happen particularly commonly, and the most common manifestations are enlargement of the lacrimal glands, which are the tear glands, which are on the side of the eyes, as well as the major salivary glands, the submandibular glands, which are just under the jaw, and the parotid glands, which are just behind the jaw.