Roivant Sciences Study result

Please go ahead. Good morning, and thanks for joining today's call to review the CLARITY phase III results.

I'm Stephanie Lee with Roivant. Presenting today, we have Matt Gline, CEO of Roivant. For those dialing in via conference call, you can find the slides being presented today, as well as the press release announcing these updates on our IR website at www.investor.roivant.com. We'll also be providing the current slide numbers as we present them to you all along. I'd like to remind you that we will be making certain forward-looking statements during today's presentation. We strongly encourage you to review the information that we have filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties. With that, I'll turn it over to Steph.

Thank you, Steph. Thank you everybody for joining this morning on short notice. We really appreciate it. It's obviously an exciting moment to get together. I'm going to do a little bit of frame-up here, then I'm going to take you through what are some obviously really exciting data that we're putting out this morning. Starting on slide 3, just as a reminder, this was from our Investor Day last year. By the way, we're announcing today that we're doing another Investor Day in December of this year. We'll come back to more of that in a moment. But it's the middle or early innings of a really busy period for us.

We're excited about continuing to add green check marks to this slide such as it is as we advance multiple among these programs, but just wanted to highlight lots more to come, including LPP, CS, other representative indications, and well beyond. Just a tremendously exciting moment. As a reminder on slide 4, our overall hypothesis around Brepo was always that we could find a constellation of diseases where there was a sort of orphan prevalence with a large unmet need with pathobiology specifically aligned to the unique mechanism of Brepo, and where we thought we could make a big difference. I think DM was obviously the first proof point for that, and now LISRAYA is out in the market. By the way, one comment. We're not going to be talking today about the LISRAYA launch.

We are excited to do that on our Q3 on November 9th with our quarterly earnings. Today we are focused on the NIU data. With NIU, we have added another leg to that stool such as it is, another proof point which hopefully will become a commercial product here that we can deliver this kind of transformative data and these high morbidity indications. There is a lot of need. On slide 5, NIU is a high morbidity indication. It is the third leading cause of blindness in the U.S. There is not a lot that works here. The only really approved non-steroid therapy is Humira. Both in the clinical data as well if you look at the claims data, it looks like half of NIU patients on Humira either fail or worsen while they are on the drug.

There is a high unmet need, and you can wind up in addition to blindness, obviously wind up with pain, with redness, with distorted vision, with floaters, headaches, fatigue, just a really tough disease. It is a fairly prevalent disease as well. Obviously, many of these patients have front-of-the-eye inflammation. Even among patients with back-of-the-eye or all-over inflammation, there are somewhere between 70,000 and 190,000 of those patients from a variety of different etiologies. It is just an indication with a huge amount of unmet need in the world. One highlight on slide 6, and we are going to talk much more about the marketplace for NIU, how it is evolving, how we see the patient numbers, et cetera, on our Investor Day in December.

In the meantime, just as a reminder, we are in a moment of evolution for the treatment of NIU across a couple of different axes. First, over time, more and more of these patients are getting treated by uveitis specialists, often at uveitis referral centers. These are docs with either a specific uveitis fellowship under their belt or they are double-boarded or whatever. These are docs who are really specific to treating these patients and who are highly comfortable with systemic therapy. Often they have a general medicine training as well and away from these community retina docs who are more procedure-based in their approach.

Part of that is coming with an increasing understanding that this systemic, this local sawtooth flare and treat cycle, which the localized therapy and high-dose steroids lends itself to, is just not good for patients or their eyes. There is a goal to get much more stable, long-term, properly controlled disease. Bluntly, given the quality of data we are putting out today, Brepo could not have come at a better moment for that transition. We are excited to talk more about that. I think as you speak, especially these uveitis specialists in your own research, you will hear something similar reflected back to you from the field. With that I am going to get into data. Ben Zimmer from Private Events on the call, too.

I am going to present the data, but he will be available for Q&A as we get into it. Look, on slide 8, before we get to the headline, just a reminder, we chose NIU on a pretty directed thesis that it is understood that a number of the key pathogenic cytokines involved in NIU, IL-23, interferon gamma, IL-12, IL-6, all of these are signaled by either JAK1 or TYK2, and that Brepo will therefore get us good inhibition across this whole inflammatory cascade. That was the hope. Obviously, the NEPTUNE phase II data was highly suggestive, albeit with small n.

I think, look, the headline here, and we will get into it now on slide 9, is I would say largely, we recapitulated the really, really exciting data that we had seen in NEPTUNE in phase II in much larger n, and we introduced a placebo arm that looked comparable to what the placebo arm in other studies, including the Humira study, showed. Just a really great outcome. We got the largest efficacy benefit ever seen for a non-steroidal therapy. Our time to treatment failure was the primary endpoint here, was over 48 weeks. It was a 48-week study. We will go into the study design. More than half of the patients had not yet failed by the end of the study, so the median time to treatment failure was in some sense indeterminant or not reached by 48 weeks versus about 12 weeks.

12 weeks in one of the studies and 13 weeks in the other study, with obviously a really great P value. We met the primary endpoint and every secondary endpoint in each study on a separate basis as well as on a pooled basis. We had over 60% of patients got to steroid-free quiescence. That is a steroid-free quiet eye at the end of the study, which is really a key treatment goal for physicians. It is something that docs are really working towards. It was consistent across all subgroups. We had statistically and clinically meaningful improvement in vision-related endpoints, structural and functional benefits, including on fluorescein angiography. Really great resolution of macular edema. We will talk more about that. Just a phenomenal outcome. A safety profile, which we will go into, but which is well-tolerated and entirely consistent with everything you would expect, both from our own prior data and from the JAK inhibitor class and other JAK inhibitors.

On slide 10, as a reminder of the study design here. This was an event-based study. It was a 48-week treatment period. CLARITY-1 and CLARITY-2 were identical studies. You can see all the ends on the slide. The way these studies work is you start out with a very high-dose burst of steroids, 60 milligrams starting for 2 weeks, and then you taper. As a reminder, we had, I think, the most aggressive steroid taper, certainly in any big NIU study. We were tapering over 6 weeks as these patients were fully tapered by week 8.

Our data is particularly exciting in the context of having achieved it, even against the backdrop of a more aggressive taper than in the other studies for approved drugs. That is sort of the design of the study. Then these patients, once they failed treatment along a variety of different axes, they were then taken out of the study and put into an open-label extension. Or a long-term extension, I should say. So that is the design of the trial. This was a representative NIU population on slide 11. Good range of patients, good disease severity. Notably, about a third of the patients across the studies were exposed to prior TNF. That is really nice to have that data set, and we will talk more about what it looked like in that group specifically.