Todd Brady: Good morning, Catherine. Both vehicle and drug improved vision from baseline. The improvement in the drug arm, the Reproxalap arm, was statistically significantly greater than that of vehicle. I think that speaks to a couple of phenomena. One is dry eye patients are inflamed. There is edema or swelling in the cornea, which affects visual acuity. As we’re treating these patients either with vehicle or drug, we would expect that inflammation to improve. What’s remarkable is, again, if you go back to other 12-month safety trials in dry disease, it’s never been shown that either drug or vehicle can improve visual acuity. And I think in this case, the improvement of visual acuity speaks to the activity of our drug product that is the drug itself, Reproxalap plus the vehicle, in calming down the eye and potentially reducing that edema and improving inflammation broadly that facilitates an improvement in visual acuity.
Most of these patients, by design, in enrollment, Catherine, have normal acuity. In other words, if patients have best corrected visual acuity, I think, it’s more than 2100 or worse than 2100, they are not enrolled for obvious reasons. So, to see any change, any improvement in visual acuity in a group of patients that are essentially normal, I think it’s quite remarkable. As I mentioned in response to another question, as we age over 12 months, you would expect to see visual acuity worsen slightly, particularly in the age group that is characteristic of dry disease, which is, on average, in your 60s. So, all in all, I think these findings are quite remarkable. It’s not something you would see with massively visually impaired populations. But here, any improvement, I think, speaks to the activity of the drug and, frankly, there’s little that’s more clinically relevant in ocular disease than acuity.
We have eyeballs to see, and if we see a little bit better, I think that speaks volumes for the activity of drug.
Catherine Novack: Got it. Thank you. That’s very helpful. And then, one last question. I’m wondering if you can talk about the rationale for RASP modulators in geographic atrophy. We know that inflammation, oxidative stress, et cetera, have been implicated AMD, but at this point, most of the therapeutic approaches have focused on the complement cascade. So, what led to the initiation of the study? And what do you think is differentiating about your approach?
Todd Brady: Well, I could talk about this one for an hour. We’re particularly excited about geographic atrophy and dry AMD broadly as it relates to RASP modulation. It could be that we look backwards in time, decades from now and are somewhat embarrassed that we tried to treat a complicated inflammatory disease by targeting a single aspect of the complement cascade. RASP modulation is entirely different. As I mentioned in my prepared comments, the idea of RAS modulation is to influence a broad group of proteins and, said in another way, reduce inflammation from a variety of different fronts simultaneously, and that’s exactly how RASP behave. They are broadly pro-inflammatory. They affect many different proteins, not just a single aspect of the complement cascade.
That’s part one of why we’re excited about RASP modulation in geographic atrophy. Part two is characteristic of dry AMD and GA and related diseases such as Stargardt disease is the accumulation of undigestible metabolites or macromolecules that build up in the back of the eye. These are the so-called drusen, which are comprised of a compound or group of compounds called lipofuscin, which are directly derived from RASP. So, RASP are not only pro-inflammatory in GA, but they also lead to the accumulation of these macromolecules, which the retina is not capable of getting rid of. And what happens is this accumulation of indigestible metabolites over time that lead to lipofuscin and drusen. So, we have two mechanisms with RASP modulation, a broad anti-inflammatory approach, and I think, it’s very clear that GA and dry MD and Stargardt are related inflammation, but also the prevention of the formation of these metabolites that buildup in the back of the eye as we age.
