All right. Hey, good morning, everyone. Welcome to Oppenheimer's 36th Annual Healthcare Life Sciences Conference. My name is Andreas Argyrides. I'm one of the senior biotech analysts at Oppenheimer, and today I have the pleasure to be joined by CEO of Aldeyra, Todd Brady. Aldeyra is a biotechnology company focused on developing pharmaceuticals that modulate protein systems to treat immune-mediated diseases. Product candidates include RASP modulators, ADX-248, ADX-246, and chemically related molecules for the treatment of systemic and retinal immune-mediated diseases. Late-stage product candidates include Reproxalap, a RASP modulator for the potential treatment of dry eye disease and allergic conjunctivitis, and ADX-2191, a novel formulation of intravitreal methotrexate for the potential treatment of primary vitreoretinal lymphoma and retinitis pigmentosa. Quite a mouthful. I tried to squeeze that in real quick.
Great to have you today here, Todd. You know, let's maybe we can start with Reproxalap for the treatment of dry eye disease. You guys are at a extended PDUFA date now of March 16th, which is just around the corner, believe it or not, right? What can you tell us about the extended PDUFA, and how are you feeling about the chances of approval?
Well, thanks, Andreas, for, first of all, the invitation, and I just want to remind you, this is why you get paid the big bucks, to say these long words, right? It's impressive.
The tongue twisters, yeah.
The tongue twisters. Yeah, first of all, great time to be talking because, as you mentioned, we're so close to this PDUFA date, which is March 16th. The lead product in our pipeline, which is, the first olive out of the bottle for RASP inhibitors, the novel target that we've been working on for many years now, it is approaching this decision date with the FDA for dry eye disease. You know, as you point out, we've had our fits and starts with the FDA. You know, we got a CRL back in 2023, and that was because one of our trials missed a co-primary endpoint. They said, "Repeat a trial." We did that. The trial worked. We resubmitted, I would say end of 2024.
Beginning of last year, we got another CRL saying, "Oh, there's a baseline imbalance," which I would just say is unique amongst CRLs. We've never seen a baseline imbalance CRL, principally because you control for that statistically. We immediately resubmitted because we had a backup trial. In fact, we had 2 backup trials ready to go, one of which was a positive, one of which was negative. We talked with the FDA. They said, "Submit the positive one. Don't submit the negative one, 'cause we have to review it, and it just doesn't make sense for anyone." You know, we had that in writing. We submitted the NDA, in December of last year, they said, "Oh, now you need to submit the negative one to cross the T's and dot the I's.
Those are the rules. We submitted. That's a major amendment. As you mentioned, PDUFA extension to March. There's our whole regulatory history. I used to have more hair before all that happened. Anyway, I think, if we take the FDA at its word, and we believe that this is a procedural matter of putting all the trials in the NDA, which are the rules. I mean, you can't cherry-pick your trials, so all the trials go in the NDA. That is a major amendment to put in another trial, that the results should be positive next month, for that reason. We'll see. You never know.
I think, like any government agency, the FDA works in mysterious ways sometimes. The only comment I'll make in response to your question. We don't provide day-to-day updates on FDA interactions, but the only comment I'll make is, it's been a quiet review, which is exactly what we wanted. We don't want major information requests during this review that seem benign, but turn out to be reasons for the FDA to reject your drug. You know, we don't want any more requests for major submissions, that sort of thing. I expect the FDA will meet the PDUFA date next month. Fingers crossed, it's positive.
Definitely. How do you see, assuming approval, how do you see reproxalap fitting in the dry eye treatment landscape?
Yeah, we were just talking about Tarsus before the call began. Good for patients and good for providers, there are so many more drugs you can give. The Tarsus drug isn't specifically for dry eye. We do have a group of new topical agents for ocular inflammatory disease, and I think that's good. I think that's good for everyone. In dry eye disease, specifically, we had an approval, I think, the middle of last year, which was the latest approval, a new agent that makes your eye feel cold. Like the cold gust of wind that makes you tear, and tearing is their endpoint on their label. We've had cyclosporine agents for a long time.
Restasis was the very first one out, I don't know, years ago, billion and a half drug at peak- billion dollar drug at peak. You know, since then, we've had a couple of other agents. We have, MIEBO, which is, in the United States, a scripted drug, but outside the United States, in many countries, an artificial tear. A couple of other semi-novel agents have come out. I think the key, though, to your question, is there's no drug that works in minutes. This is what you want. You come into the doctor's office, you have a hot eye, it's red, it's painful.
You don't want to hear, "Give this a few weeks to work," or in the case of Restasis, possibly, "Give this a month or two to work." What you want to hear is, "I'm going to put this in your eye, and you should feel better in 5 minutes. By the way, you're not going to look as bad as you do now with your red eye." Interestingly, patients care about how they feel, but they care more about how they look, particularly with topical agents, skin, eyes. I think that's very common. reproxalap has the potential to be the only drug with redness on the label. The only drug you can use chronically, not steroids, that you use chronically with redness on the label. I think that's meaningful to patients.
It's obviously meaningful to AbbVie, which is our partner in this development effort. AbbVie has an option on Reproxalap that expires 10 days after approval. I think with this rapid onset, the ability to control redness, those two things, particularly in combination, make for a differentiated asset in what has become a growing dry eye disease space.
I totally agree with you on that. I know a couple of people personally with dry eye, and those are two very important points. Hopefully for them and for other patients, you know, the FDA gives you guys the green light, and you can go out there and help them. Let's fingers crossed here. How are you thinking about the reproxalap in allergic conjunctivitis?
Thank you for asking. Many people gloss over allergic conjunctivitis. In theory, we're done with clinical testing for allergic conjunctivitis. We've run 2 phase III trials, which has, as of the other day, is 1 trial too many for the FDA these days, with their 1 trial rule. I can't wait to see how that plays out, by the way, broadly. I have a feeling that many divisions, including Ophthalmology, are going to find a way to request that second trial. Just FYI, 1 man's opinion on that. We've run 2 phase IIIs, both positive. They're in our corporate deck. Allergy is interesting relative to dry eye because they occur together in about half the patients. You have dryness and itching.
Pollen makes your eye drier, some of the agents that you use in dry eye may cause itching, it's a bad combination. You can write a steroid today for 2 weeks of therapy. That steroid might treat both of those things, after 2 weeks, you're on your own. You risk all kinds of steroid toxicity, so cataracts, glaucoma, what have you. Reproxalap has the potential, at least, to be the only drug approved for both conditions, dry eye and allergic conjunctivitis. I think the way to think about it is the dry eye approval, hopefully is next month. Subsequently, there would be a supplemental NDA or an SNDA for allergy. Potentially, that would be added to the label so that you would have both conditions.
That will be decidedly unique in the dry eye space. Take your activity in minutes, your control of redness, and then add to that the ability to, in theory, treat allergic conjunctivitis, then you have even more differentiation.
What are the terms for AbbVie on that indication? Do they have any? Yep, okay.
AbbVie optioned Reproxalap, so whatever indications Reproxalap is approved for, in theory, if they exercise the option, they could market. Our efforts with AbbVie since executing the option at the end of 2023 have been collaborative along all sorts of lines, not only just dry eye, but also allergy. It'll be interesting to see how, if AbbVie exercises and we enter into this co-promotion agreement, how soon the SNDA is filed. I think we need to talk to the FDA first, maybe have a pre-NDA meeting and discuss where allergy plays into the marketing of Reproxalap and so forth. Just to review the terms, because I always get asked about AbbVie, so they have 10 business days after approval to exercise.
If they exercise after approval, it's effectively $200 million upfront, $6 million of which has been paid already, so $194 million would come in. The terms of the agreement are, it's $100 million to exercise, it's $100 million if the drug is approved. That's how I get to $200 million, less the $6 million they've already paid. There are 2 other $100 million milestones. One's a sales milestone, one is a coverage milestone. Given that AbbVie is a superb commercial organization, I feel very confident about the second one. I mean, reimbursement is second nature to AbbVie and other large companies, so I'm not concerned there. Thereafter, it's a 60/40 split, 60 to AbbVie, 40 to Aldeyra in terms of the P&L.
Aldeyra is in charge of 40% of the cost to profitability, and afterwards would receive 40% of the profits. We have an annual cap on cost, given that we're a small company. I think for us and also for AbbVie, the deal is quite palatable. In a sense, AbbVie will be performing the commercial work, as you might imagine. As I tell people, on one day, they'll be paying 100% of infrastructure, and the next day they'll be paying 60% of the infrastructure after the opt-in occurs. I think from AbbVie's perspective, it could be quite lucrative.
Absolutely. I think you've got a good setup there. Let's turn quickly to the, just you have, you know, the pipeline. It's pretty diverse with a focus on large indication, but also two rare retinal inflammatory diseases. Can you talk about your foray into primary vitreoretinal lymphoma and the retinitis pigmentosa?
Right. I would say the next major milestone after allergic conjunctivitis. First is the PDUFA next month for dry eye. The next one would probably be, FDA willing, a submission in allergic conjunctivitis, and that would be a six-month review because it's an SNDA. After that is ocular lymphoma, or if you want to use the big words, Andreas, it's primary vitreoretinal lymphoma. I prefer ocular lymphoma, which unfortunately is a fatal disease. This is a disease that metastasizes to the brain. I think people forget, often the optic nerve comes right out of the brain, and so your retina is an extension of the optic nerve. When your retina, it has cancer, that cancer retrograde goes back into the brain, and patients don't live long after that.
Today, treated with compounded methotrexate, ADX-2191 is our own Orphan Drug-Designated formulation for ocular injection of methotrexate. That does not exist today, remarkably. The drug works, at least the compounded drug works in the literature. We have a one-trial agreement. I just want to say, we got this one trial agreement long before Marty Makary stepped into the FDA, or certainly around the time he came, long before this announcement came, and that is a single pivotal trial, where we compare frequent injections, that is twice weekly injections, of our drug versus monthly injections. Well, it's well-known in the literature, the more injections you give, the faster the cancer clears. That makes sense, given how methotrexate works.
I'm hoping to have data, if not end of this year, sometime the first part of next year, get that NDA submitted, and then these poor patients that have no approved drug today will then have an option in the marketplace. Andreas, I think you're on mute there.
I-
I'm good at reading lips, but I'm not that good. Yeah.
Eddie, you got. You were right. I just didn't want any feedback when you were speaking from my speakers here, but appreciate that. Looking at the rest of the pipeline, that covers atopic dermatitis to obesity, to CNS and dry AMD, I mean, it's a vast pipeline. It looks like ADX-248, an oral treatment for atopic dermatitis, is further along than the rest. What can you tell us about this program?
248 and 246 are the extension of the RASP modulator pipeline. Just to back up, RASP are a novel class of pharmaceutical targets that are small molecule mediators of inflammation. Sort of like, if you're an inflammation nerd, sort of like leukotrienes, except more toxic, I would say, broadly. Remarkably, no pharma company has initiated a concerted effort, to our knowledge, to target RASP. Reproxalap is the first. I would say a second cousin of Reproxalap, a better version of Reproxalap for oral administration is ADX-248. More potent, once-a-day administration. We're in the middle of phase I. In patients, the drug appears to be well-tolerated. We could definitely support a once-a-day dosing. For atopic dermatitis, that's important because I don't think the oral therapy space in atopic dermatitis has been worked out.
We're good at treating moderate to severe patients with injections, including Dupixent. That's all fine, but your nine-year-old kid with mild to moderate disease doesn't want to get injections. In fact, I would say most adults with mild to moderate disease don't want injections either. Dupixent isn't without its side effects. While I think we've done a good job with more severe disease, with IV or injectable formulations, I think we need to go oral, and that's where 248 would fit in. Hoping to start phase II once phase I ends, which I anticipate sort of middle of this year, phase II, back half of this year, data sometime next year.
Okay, great. Maybe just one last question here on the financial picture, and you did allude to some of the milestones you may get, but how are you looking from a financial perspective for the year, cash runway, et cetera?
We reported $75 million in cash as of the last quarter, which was the end of Q3. That covers about 2 years of runway, end of next year. That covers whatever emergency trials we might have to run for dry eye. I can't imagine what those would be, assuming another CRL. Dry eye trials are inexpensive, that's probably $10 million of the budget, just sitting there in reserve, pending the FDA's decision. ADX-248 for atopic dermatitis, ADX-246 for dry AMD, the early form of geographic atrophy we didn't talk about very much, that's another program that we're intending to support with the cash. You know, assuming an exercise from AbbVie, I think we'll be very well capitalized.
In fact, it's difficult for me to project runway post-AbbVie exercise at this point.
All right. Fantastic. I guess, you know, appreciate all the insights there. We'll look for a positive update on March 16th, and then we'll look forward to hopefully a launch thereafter. Appreciate.
Fingers crossed. That's right.
Yeah, fingers crossed. All right, with that, we'll conclude our fireside chat. Thanks for joining us today. I really appreciate it.
Thanks, everyone. Thanks, Andreas.