Immunovant, Inc.

Good morning. My name is Melissa, and I will serve as your conference call operator. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this call is being recorded. Joining me on the call today will be Dr. Pete Saltzman, Chief Executive Officer of Immune Event. Before we begin, I would like to remind everyone that today's conference call will include certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, among other things, statements regarding Immunovet's plan to initiate two Phase III clinical trials for beta-climate in TED in the second half of calendar year 2022 with an expected top-line data readout in the first half of calendar year 2025, and it's planned to initiate a Phase III clinical trial in MG by the end of June 2022, with an expected readout in the second half of calendar year 2024. ImmuneVance plans to develop Betaclimab across a broad range of autoimmune indications, the potential efficacy and safety of ImmuneVance product and candidate, Immunovant's expectations regarding the timing, design, and results of its clinical trials, including the timing of future data readouts and the announcement of additional indications, and whether, if approved, beta-climab will be successfully distributed, marketed, and commercialized. All forward-looking statements are based on estimates and assumptions by Immunovant's management that, although Immunovant believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Immune Event expected. For more information, investors are encouraged to review Immune Event's annual report on Form 10-K for the year ended March 31, 2022, filed with the SEC on June 8, 2022, and Immune Event's subsequent filings with the SEC. Any forward-looking statements speaks only as of the date on which it was made. An immune event undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Now I'd like to turn the call over to Dr. Pete Saltzman. Thank you. Dr. Saltzman, please go ahead.

Thank you, Melissa, and thanks to everyone for joining the call today. I'm very excited to share that Immunivant recently achieved alignment with the FDA Division of Ophthalmology to move forward with a pivotal program in thyroid eye disease, or TED. This is a big milestone for Immunivant, and we now plan to initiate two placebo-controlled Phase III trials for TED in the second half of 2022. We expect to have top-line data for these trials in the first half of 2025. TED is the second pivotal program we have announced for betopimab and represents a first-in-class program with an exciting market opportunity. As we heard from physicians and as we discussed at our R&D day this past March, there has been a paradigm shift in the treatment of TET. As many of you know, the FDA approved tepratumumab in January of 2020, which is now the only FDA-approved treatment option for thyroid eye disease. When new medications are approved for a disease with high unmet need and a historical lack of innovation, then some patients who are already under the care of a physician can rapidly gain access to the new medication. In addition, these types of approvals raise awareness of the disease among other patients who may not yet be under the care of a physician or specialist. The growing patient awareness also impacts physician decision-making and the market expands. We've seen this unfold in thyroid eye disease. The market opportunity continues to grow as the awareness of the disease continues to expand, and we believe this will be the case for quite a while. similar to the steady market growth experienced in other immunology markets after the first big innovation. At the same time, the TED market has some very unique features. The disease itself is heterogeneous and therefore lends itself to complementary mechanisms of action. Fixed duration of dosing, specified in the FDA labels for TED, also supports the development of new and complementary mechanisms of action. The net result is what we believe to be an exciting opportunity for patients and for Botoclimate. Today I will introduce our TED Phase III clinical design and focus on the important points of differentiation for metoclomab in thyroid eye disease. I'll start by reviewing some of the fundamental biology for how metoclomab may work in TED and why we believe that TSH receptor autoantibodies are key drivers of Graves' hyperthyroidism and of TED. In the top row of the figure, anti-TSH receptor autoantibodies circulate in the body and bind to the TSH receptors. In the rightmost figure, the autoantibody is binding to a TSH receptor in the thyroid gland. This activates the thyroid follicle, increasing cellular metabolism and the release of thyroid-related hormone. Of course, this is not the end of the story since TSH receptor antibodies can circulate in the blood and bind to other target cells that also express the TSH receptor. In the middle figure, the autoantibodies are shown binding to the TSH receptor in the periorbital space where they activate orbital fibroblasts. This leads to proliferation of the periorbital tissue and differentiation of these fibroblasts. In the absence of the topramab, anti-TSHR antibodies are recycled back into the blood by the FC receptor and endothelial cells. They remain present to recirculate and reengage receptors throughout the body. Note that beside the TSH receptor, the insulin growth factor 1 receptor, shown on this slide in blue, and adjacent to the TSH receptor, also plays a role in the pathophysiology of the disease. Once an autoantibody binds the TSH receptor, there is crosstalk between the TSH and the IGF-1 receptors, and the engagement of both receptors leads to activation of intracellular pathways linked to the clinical signs and symptoms of TED. So this crosstalk between the TSH receptor and the IGF-1 receptor appears to be crucial to the pathophysiology of the disease. As most of you likely know, butoclumab reduces circulating IgG by binding to the FC receptor and inhibiting FCRN-mediated recycling of IgG that normally takes place in endothelial cells. I'll review some data later in the presentation regarding betoclomab's observed impact on anti-TSHR antibodies in TED patients from a prior study. Although preptosis is a prominent and important feature of thyroid eye disease, TED is actually a heterogeneous condition. Indeed, patients experience a variety of symptoms. This slide includes pictures of two different people with thyroid eye disease that together provide an example of how TED can vary patient to patient. Both people in these photos have proptosis, but the degree of inflammatory changes differs between them. The patient in the top panel has much more eyelid edema and conjunctival redness than the patient in the bottom panel. The symptom heterogeneity is common in TED. We also found that even with treatment, Patients with active TED report making substantial lifestyle modifications. Based on our market research, 80% of participants reported making moderate or major lifestyle modifications despite ongoing systemic therapy to which they were responding. The patients we surveyed were between 30 and 60 years old, reflecting a prime working age range consistent with the TED population. In fact, the impact on work life was highlighted as particularly challenging as participants reported difficulty working on electronic devices, difficulty driving, and challenges engaging in social situations. When we asked participants to rank their most important treatment goal, there was not a single top treatment goal shared across the patient population. Rather, the most important goal varied patient to patient. While improving proptosis by two millimeters or more is clinically significant and very important, there are symptoms other than proptosis that can be an even higher priority for certain patients. We believe it's possible that medications with different mechanisms of action will address different symptoms in different ways and can therefore be complementary in the treatment paradigm. As I mentioned in my opening comments, Tepratumumab has made a meaningful impact on the treatment of TED since its launch in early 2020. The launch has probably improved diagnosis rates in TED and has certainly reframed the urgency to treat compared to the historic watch and wait approach that was frequently applied. This sort of post-launch market development is common for a disease that hasn't had any innovation in a long time. In addition to this favorable market growth, which we expect to continue, the TED market also has some unique features centered around the fixed duration of dosing specified in the FDA labels. Fixed duration of dosing is uncommon in immunology, but common in ophthalmology. In fact, we believe that FDA labels for TED will continue to specify a dosing duration defined by the length of the controlled period of the clinical trial. This is important because the dosing duration specified in the label may be insufficient for many patients. As noted here in the OPTIC 48-week off-treatment follow-up period, 44% of TPEZA patients who were preptosis responders at week 24 in OPTIC were not preptosis responders at week 72, highlighting an opportunity for additional treatment. We believe this opportunity is ideally suited for a new mechanism of action, not only because reimbursement is often strictly limited to the frequency and duration specified in the FDA label, but also because TED is a heterogeneous disease that is likely amenable to complementary mechanisms of action, Such complementary treatment in series will, of course, be longer, and so a simple subcutaneous route of information, of administration, becomes even more important, at least for one of the medications.

So what is the bottom line?