All right, good afternoon, everyone. Welcome back to day three of our inaugural Healthcare Innovation Conference. My name is Eddie Hickman. I'm one of the biotech analysts here at Guggenheim, and I'm joined this session by ARS Pharma. And I have a few members of the management team with me on stage: CEO Rich Lowenthal and CCO Eric Karas. Rich, Eric, thank you for being here today.
Thank you.
Maybe just to start, could you maybe just give a short overview of the company, the history, and then sort of highlight what some of your core capabilities are?
Yeah, so ARS Pharmaceuticals was founded about eight years ago. The group that founded it really had a lot of experience in nasal spray products. We actually were the group that got Narcan approved. And Eric came later. He was actually at Adapt Pharma when Narcan got approved and launched Narcan, helped commercialize Narcan nasal. And then we also worked on a product called Valtoco, which is a nasal spray for emergency use epilepsy for treatment of acute repetitive seizures, and several other products in that space. And so we were familiar at that time and working with a company in San Diego called Aegis, which had a nasal absorption technology, which was quite unique. And epinephrine does not get absorbed intranasally really at all in aqueous solutions. You need either very strong chemicals or solvents to destroy the mucosal membrane to get penetration.
So the technology that we acquired at the time, which is Intravail, it's a very benign compound, no pain, no irritation, that creates little basically pores through the mucosal membrane. So it makes it more permeable, but almost instantaneous. So it doesn't carry the drug. It just affects the nasal mucosa. And that's really how we started ARS Pharmaceuticals. We licensed the use of Intravail for epinephrine. And then, of course, we founded the company internally for a couple of years. And then we had an angel investor come in, Pratik Shah. And then once we did our proof of principle studies and showed this technology was going to work and really give us injection-like absorption with epinephrine, we then went out and did more of a traditional funding.
The first round was just Deerfield Management because we didn't want to raise too much money, and they didn't want to put in too little. So they took the entire $20 million funding. And then we did a $55 million funding led by SR One, RA Capital Management, and then Baker Bros. Advisors. And Deerfield Management put in a portion to that as well. And then merged with Silverback Therapeutics, a company called Silverback Therapeutics, an oncology company that raised an enormous amount of money and then failed in their first phase one trial. So we did a reverse merger, which was a good deal at the time for us. We got about $250 million out of the reverse merger. And that brought in some other board members, OrbiMed primarily, and some other big investors that came with the Silverback Therapeutics side. And then, obviously, we were in pretty good cash position.
And then we announced on Monday, ALK announced over the weekend, believe it or not, actually close to midnight on Saturday, they announced in Denmark, which is a little odd, but that's their rules because that's about when we signed the actual agreement. And we got another cash infusion, actually showed up in our bank today of $145 million from the license agreement with ALK, which we think is a really positive outcome of our negotiations with several companies in Europe over the rights to neffy.
Great. No, thanks for that background. Lots going on. And obviously, you've taken the company to where it is now, which is having an approved product. It was approved earlier this year, neffy, the first needle-free treatment for Type I allergic reactions. Before we get into some of the metrics you provided this morning on your earnings call, can you maybe just set the stage for what the allergy market currently looks like, dominated by these auto- injectors, and sort of what the key challenges your commercial team is going to have in sort of penetrating that market?
Yeah, so currently in the United States alone, so just talking about the U.S., the market is a little more than $1 billion net sales for generic auto-injectors, primarily. Some of it's AUVI-Q, the one still innovator type product out there that has higher pricing is AUVI-Q, but most of the market is generic EpiPen products, but it's a little bit north of $1 billion. And the way we see the market is that there's about 40 million people in the United States that have this disease. Of those, about 20 million have more severe disease. They're generally visiting a doctor. They're generally being treated or they've had anaphylaxis in the last three years. So we know those are active patients. And that's what we see as the real opportunity is around 20 million. Of those, about 3.2 million have prescriptions today for epinephrine.
And there's about 6.5 million, so the 3.2 million + 3.3 million that have been given a prescription, but 3.3 million don't fill it. So they don't want the auto injector mostly. So they avoid filling the prescription. So those are generally that 6.5 million are generally actively treated by allergists and pediatricians who are more well-educated and they have higher utilization of epinephrine. And that's why the 6.5 million visiting that population pretty much all have had prescriptions. Whether they fill them or not is a different question. So the way we see it is that there's really those three buckets. There's the 3.2 million that have an auto- injector today. About 80% of them don't carry or use the auto- injector. They have a prescription, but they won't really use it.
So those are what we call the switchers that we believe a large percentage of those will switch to a nasal epinephrine neffy. Of the 3.3 million that have been given a prescription, so they know they need something, they've been told by their doctor, but they either didn't fill the initial prescription or didn't renew it. We believe a large percentage of those will also come back to the market because now they have an easier to carry, easy to use version or option. And then, also of very, very big interest is the 13.5 million people that are visiting mostly other doctors. Very few of these are visiting allergists. And they have no prescription. They've never been given a prescription. But they've been diagnosed or they've had anaphylaxis. They've shown up in emergency rooms just in the last three years. So we know that they're patients in need.
That's a different population that we're going to target differently through CME programs, through direct-to-consumer advertising, and through a public service announcement campaign that will start up very soon with one of the largest advocacy groups in the world who are basically managing it and we're sponsoring it. It will be a public service announcement campaign to try to expand that reach.
Got it. So it's easy to understand why somebody might prefer not having a needle. But is the opposite true? Are all of these patients potentially eligible for you? Or is there a population that wouldn't want to switch or is not eligible for the?
I think they're all eligible. They're all potential people that will switch to nasal. We know with Narcan, it was about 95% eventually switched. But there's always an initial period of time where people are going to say, well, is this going to work the same? It's new. Do I want to switch? And for those people that are, let's say, the 20% that are better users, they carry their auto injector and they're willing to use it, then they may be more hesitant to switch because it's okay, I don't mind injecting myself. If you're one of the ones that are terrified to inject yourself and won't do it or won't carry it, don't bother, I think those are easier to switch. They're low-hanging fruit, whatever you want to say. They have no barrier to switching because they have nothing they're willing to use.
But over time, as people get more experience and see that it works just as well as injection, and in fact, it may in reality work better than injection, and the reason is if you're hesitant to inject and you wait to inject and you're more willing to use the nasal, the sooner you administer epinephrine, all the data, all the literature shows less chance of a second dose being needed, less chance of biphasic reactions, much better clinical outcomes. The hazard ratios for being hospitalized, for death are dramatically different if you take it sooner than if you wait too long, and so the fact that you take away the hesitancy and maybe the stigma of pulling out an auto-injector in the middle of a restaurant, right? People won't do that. But will they be willing to say, okay, now I'm just dealing with neffy, which is I pull this out of my pocket and I had it in there with my phone. I had my phone and the neffy in one pocket.
Both fit in.
You pull out the neffy and you basically just have a small sprayer. For people to be able to do that in public and just pull that out and put it in their nose and fire it in public is a much, much easier kind of thing psychologically for people to do than pull out an auto- injector, activate it, and fire it into their leg.
Are the instructions the same as if they gave themselves an auto- injector where they're technically supposed to go visit an emergency room? Is everything the same?
No, actually, let me mention that. Actually on that point, no. The instructions up to that point are very similar. Administer as soon as symptoms are occurring, give a first dose, wait. Auto-injector labeling says wait five to 15 minutes. The FDA wanted to modify that in our labeling to say wait at least five minutes and then give a second dose if needed. The reason is that they told us that some people wouldn't give a second dose after 15 minutes. And that's not what they mean by that. You can give a dose anytime after. They just don't want you to give a dose too close to the risk of overdose. The FDA has always been more worried about too much epinephrine.
So you want to wait at least five minutes to make sure you need that second dose, right? Because 90% of people don't. 90% of people respond to single dose. Now, with regards to hospitalization, that's a dramatic change because the old labeling for auto-injectors says basically, “in conjunction with use of this product, seek emergency medical help,” and it was old legacy language that came from way back when EpiPen got approved, and the two mistakes in that language that FDA didn't realize until recently is one, in conjunction with use, people interpreted that as the reason I have to go to the emergency room is because I use epinephrine, and they wouldn't use epinephrine because they thought they had to go to the emergency room if they use it, and that's wrong.
And then, too, it was an absolute go to the emergency room every time. Okay? But you got to remember, 90% of people respond to a single dose and the event's over. So if you go to the emergency room, what do you do in the emergency room? You sit there, wait for somebody to come look at you and say, go home, right? You're fine. The new guidelines, so COVID kind of helped this because during COVID, nobody went to the emergency room and everybody was fine. We had no deaths, zero, from people not going to the emergency room. So the docs also realized that was a mistake. And the guidelines at the end of 2023 were changed. But our labeling now reflects that. So our labeling says, totally separate, take epinephrine, take neffy as soon as symptoms occur.
Totally independent of that, seek emergency help if needed for further treatment of your anaphylactic episode if the event doesn't resolve. So now it's a very different message, meaning take your neffy immediately. If the event resolves, you're fine. Maybe contact your doctor, but you don't need to go to the emergency room. If the event's continuing, then you go to the emergency room, but you're going to the emergency room really to treat your anaphylaxis. So now it's really clear that that's the reason you're going to the emergency room is because your anaphylactic event is still continuing.
Presumably at that point, you've tried the second dose as well.
Right. And it does say to take your second dose immediately and then seek emergency medical help at that point because you do want to take your second dose right away. But then you don't have a third dose. So in theory, that's the time you may want to think about activating emergency help and going and getting emergency help just in case.
Gotcha.
And this really bodes well for us too because we know from our market research and we see it in the literature is that patients with needle injectors, they're waiting 10- 15 minutes and a lot of them aren't even injecting. So when we actually did our market research and we showed the patients our device, they said they would use it in half the time or they'd use it right away. So it helps from the hospitalization standpoint, but it's also better outcomes and what physicians want and what patients need. And then just one other point to build on what Rich was saying too in terms of not only penetrating the current market of converting that because most of those patients, again, aren't prepared. They're not carrying. They're not administering. They're not using it correctly.
There's another 3.3 million patients that have been given a prescription over the last couple of years. A third of them have filled it, but they haven't refilled. And the other two-thirds have just not filled the prescription. When we talk to these patients in market research and the physicians tell us this as well, the three major reasons why they didn't fill their auto injector, size, needle, and portability. And we address all of those. So there's a tremendous opportunity not only to convert the market, but to grow the market too.
Yeah. I want you to just briefly talk about, because you did 505(b)(2), so the bioequivalence, but can you talk a little bit about the differentiation more in terms of the stability and shelf life as well? Because I know that's a key differentiator as well in addition to it being sort of equal in terms of its PK.
Yeah, yeah. So within PK, so injection products are highly variable. Okay? So they're all over the place with regards to the PK. But what the objective of our development program in conjunction with talking to both FDA and European Medicines Agency, because we did it at the same time, so we got approval from FDA on August 9th and August 29th from the European Medicines Agency. So basically simultaneous. And the idea was that they wanted us to be greater than IM needle and syringe injections. So we're always efficacious. There's no question we're going to be better under any circumstances, even under nasal allergen challenge, meaning we induce a severe allergic reaction, nasal rhinitis. So they wanted, even under severe conditions, they wanted to make sure neffy was going to be better than injection, but not more than EpiPen.
Because if we're more than EpiPen, which is usually the highest exposure of any of the auto-injectors, the concern was it's not necessary to be that high for efficacy, but there's a concern always about safety with epinephrine that too much epinephrine can cause cardiovascular responses that are too extreme. And so we want some cardiovascular response, but you don't want too much, right? So they said if you're more than EpiPen, we don't know the safety. Because you're testing this in a clinic, we don't know real-world safety in a real population having anaphylaxis. So you can't be more than EpiPen. And that was kind of the guidance for PK. Interestingly though, on the pharmacodynamic response, neffy tends to work better than injection.
Probably the same as we say it's very similar to EpiPen, but much better than IM needle and syringe, which is kind of the gold standard used in hospitals and emergency rooms and emergency medical units. The pharmacodynamic response is faster and much more sustained than with an IM needle and syringe. That's actually a positive to most doctors. They see that and they're like, wow, you know I have a person that could be hypotensive. I need their blood pressure up. neffy's getting their blood pressure up eight or 10 mm systolic blood pressure for a really good period of time. That makes the doctors feel good because they know that's the issue. If you're a teenager or adult and you die from this disease, you normally die from hypotensive crisis. Younger children don't tend to have hypotension as much, but they get angioedema.
They tend to die from the angioedema, so they really want to see that response. neffy tends to do better at that, and then the other differentiation points, obviously no needle, much smaller, easy to carry. We obviously promote you should carry two. Of course, that's what our labeling says. So we provide this. You got to order this separately online. It doesn't come in a box, but you can get it online. Just order it. And the nice carry case has the instructions in here. So you have a little reminder instructions on how to use it and a QR code. It's much more stable than auto-injectors. So typically auto-injectors are 18 months- 20 months stability. Some are a little shorter. I think one's a little longer, 22 months maybe. neffy's 30 months expiry.
And also at high temperature, we've tested it that one of the big problems with the auto-injectors is if you expose them to high temperature, they degrade really fast. And so if you left it in your car in the summer, it's a problem. We knew that from focus groups early on. So we actually anticipated this formulation is going to be much more stable, but we actually put it for three months at 122 degrees Fahrenheit, 50 degrees Celsius for three months. And it's still past specs. So release specs. So that's what FDA would expect. So we do have an excursion in our label where EpiPen says that it can tolerate temperatures up to 86 degrees Fahrenheit. Our label says excursions up to 122 degrees Fahrenheit are acceptable. Now, we don't want people to store it at that temperature.
So we don't want to promote storing it in your oven or anything. But nonetheless, it should be stored at room temperature like any drug. But if you left it in your car, you could have really good reassurance that there's nothing wrong with the medicine, that it's still stable and effective.
I want to make sure we have time to get to some of the updates from this morning. Can you maybe just walk us through how the launch is going so far? Maybe sort of in that, sort of talk about the different channels that patients can get drug from and sort of how your revenue is generated that way.
Going extremely well. If you look at our internal projections, we're on track in terms of our ex- factory sales and prescriptions on a weekly basis, so our field team just started about a month ago, so they've been in the field calling on the top volume allergists, high decile physicians, and we're making really strong progress. To date, we've called on about 6,000 physicians. We have about 1,700 that have prescribed, which is very strong, and then we also have a program called neffy Experience, which we talked about and you're probably familiar with, but we have about 1,100 allergists that have enrolled in that program, and basically what we're providing is courtesy packs, so it's three units, six doses for allergists to use in their food challenge clinics, and the reason why we're doing this is we want them to have firsthand experience with the product.
So when they're prescribing it to a patient, a parent, and they get the question, well, hey, does this work as well? Have you seen it work? They can say in their own clinical practice they have. So that program is really off to a great start with, like I said, about 1,100 physicians enrolled in it in just about four weeks. We are also doing quite a bit from a payer perspective as well. The early discussions that we've had with the PBMs, the major insurers, have been very, very strong. They see the value proposition with this product. They understand some of the challenges that Rich mentioned around needle anxiety, needle-related issues, safety, hesitation, the impact that that has to the healthcare system. And they see the value of our product with a longer shelf life, with temperature excursions.
We are on track to hit 60% covered lives at six months. And we're on track to get to 80% at one year. But in the interim, we do have a program called neffy Connect through BlinkRx. And this is where a doctor can submit a prescription electronically. It goes into the system. And they're able to help the doctor's office with anything around the formulary exception or prior authorization. That's typical, as you know, in the first couple of months of a brand new product and a launch. But we're seeing really good numbers. When 10 prescriptions go in, 10 orders go in, three or four are being covered with no additional paperwork. And then when a doctor's office submits a prior authorization, we're seeing a success rate of about 50%. So that's very good.
Strategically, this is why we set it up, is we wanted to make it easier for doctors to get this to their patients and easy for patients to get. We have a copay program for commercially insured patients that buys the copay down for a majority of them down to $25. We also offer a cash price of $199. We also have a patient assistance program for patients that are uninsured or there's economic issues. Things are going extremely well. There's a lot more going on with CME, peer-to-peer education, conference presence. We're very pleased with it.
Yeah, no, it sounds like weeks.
And just to add one more point to that. So just to put in context our kind of pricing plan, generic auto-injectors. So if you go to get a generic EpiPen, the average copay is $40. Okay? And if you don't have insurance or you're in a high deductible plan, the average cash pay price is $200. So what we did is we wanted to match the price for the cash pay. And then we actually do better at the copay. So when people go get neffy, there's going to be zero cost barrier to switching. It's really all about, do I want the needle or not? And we didn't want to have any cost barrier. So once we get on formulary, we think there will be very little resistance from a cost perspective.
Somebody who's highly motivated, just get it now.
Yeah, yeah, yeah, exactly.
Are you finding the sort of third-party tracking like IQVIA accurate so far on the launch? And is that something that you think will get more or less accurate as it goes on?
Yeah, I can explain that. So overall, I would say like 95%, 99% accurate. In the first couple of weeks, there were one pharmacy chain that wasn't tracking. That's been fixed now. So as of the last three to four weeks, it's been tracking. So there's a couple about 100, 150 prescriptions that weren't captured that'll be put into the data. But IQVIA captures everything at the retail setting. If anybody goes through GoodRx at the retail setting, they're capturing that. Also, the BlinkRx commercial prescriptions are being captured. What's not is if they go through the BlinkRx program and it's cash, that doesn't show up in the IQVIA data.
BlinkRx. You also have, you're submitting an sNDA for the one milligram dose.
Right, right. So that's been submitted.
Submitted, sorry. So what's your sort of timeline on that approval? And do you expect an inflection there?
Yeah, yeah. So FDA, so that's around 15% of the market, correct? Roughly 15% of the market is 15-30 kilogram children. It's been accepted by FDA. They've given it priority review. And PDUFA dates March 6. They may approve it sooner. It's not that common that FDA approves things sooner, but they've had that study report for over a year in the IND. We didn't submit it to the NDA because they didn't want to complicate the final approval of the 2 mg . But they were very adamant that the one milligram had to be a post-approval requirement, a legal requirement. We have to file it within a certain timeframe because they're worried about off-label use. So they're worried about parents getting the 2 mg and using it for a 15-kilogram kid. And they'd like to get the 1 mg out there. So we expect it to be approved very quickly. And they gave us priority review. So they're really on top of it.
Yeah. And obviously, you're launching in Europe now with that new licensing partnership. And then you have a program in CSU. If you want to spend 30 seconds just to.
Yeah, yeah, sure. So we're also very focused on taking what is very well known to work in chronic spontaneous urticaria. And I'll explain in a minute exactly what we're doing with it. But epinephrine is very well known to work. But nobody wanted to use an auto injector for that. So now with a simple nasal spray, we believe that it will be very effective. And what we're doing really is treating what's called an acute flare or an exacerbation. So this is not a chronic therapy. This is going to be an acute therapy. But if you're on antihistamine therapy or you're on Xolair, those patients are still having frequent flare-ups of the urticaria, which can be very itchy, irritating hives, and even angioedema, which people don't want to go out when their lips are swollen up and things.
Epinephrine is exceptionally effective at reversing all that and stopping it, and we think that as an acute therapy for the flares, so people on chronic therapy are ready, but you're having flares that a lower dose, it won't be neffy. It will be a different brand because it will be a lower dose because we can get the effect with a much lower dose than we need for food allergy. That we think it will be an exceptionally effective therapy, and it happens in minutes. You get statistically significant improvement in itch in five minutes rather than waiting hours for a steroid to kick in, and we think it would be a very, very effective way of managing that.
From a pharmacoeconomic perspective, if you think about it, or from safety, so either way, if I'm on antihistamine therapy, which is costing me a couple hundred dollars a year for antihistamine therapy, and I'm going to step up to Xolair at $70,000 or some of the new biologics at even a higher price. The reason I'm stepping up is because I'm having these flares every six weeks. The doctor's saying, I'm not well controlled. I'm going to go to Xolair and see if that works better. To keep them on antihistamine therapy is an amazing advantage if they can manage that flare with a nasal dose of epinephrine. The other side of it is if you're on Xolair and you're having these flares, they move you to cyclosporine, which is a huge safety issue, a huge safety risk.
If you can manage it, you manage those flares with a simple spray of epinephrine and don't have to go to cyclosporine, that's a huge safety advantage to keep you off cyclosporine. We think it's a good approach.
Yeah, we'll keep an eye on those results when they come.