Okay. Hello everyone. Thanks for coming back for our Global Biopharma Conference with Leerink. My name is Roanna Ruiz. I'm one of the senior biotech analysts here at Leerink, and it's my pleasure to introduce the team of ARS Pharmaceuticals. I have the CEO and President, Rich Lowenthal, and also Eric Karas, Chief Commercial Officer. Thanks for being with us.
Thank you.
Thank you.
Great. Maybe I'll just dive right in with a bigger picture question just for any investors who want to refresh on the story. Could you just give us an overview of your intranasal epinephrine product, neffy, and how you plan to address core unmet need in the space?
Yeah. So neffy is a nasal spray, and we use the same nasal spray device. It's very well established. That's used by NARCAN and many other products that are now approved on the market. And it gives a very rapid absorption of epinephrine, which is similar to injection. And actually pharmacodynamic response, it's actually slightly better than injection. So that's the nature of neffy. It's very simple to carry. So it addresses a lot of the unmet medical needs in the community. It's simple to carry. There's no needles, so no pain. Our nasal spray is in a saline-based formulation, so it's just salt, water, and epinephrine and an absorption-enhancing agent, which is approved in several other products called Intravail. And that really gives injection-like absorption at relatively low doses. So we have a high bioavailability.
It replicates basically within the profile of other injection products that are known to be safe and efficacious. It replicates those injection products pretty well.
Got it. Great.
Then neffy will come. We want to make it convenient to carry. So this is how most people will use it in a pouch, two sprayers, because you may need a second dose twice. About 10% of people need a second dose with injection. So you have to have two doses. And then it would have an instruction card and a QR code to get a little video on how to use it if necessary.
Sounds good. You have a lot going on this year. Could you just walk us through some of the major catalysts and updates that investors should focus on?
Yeah. Well, we received a complete response letter from FDA. It was a little bit of a surprise. We had a very positive AdCom. FDA staff came up with one issue. We believe it may have been prompted by somebody else's data, not ours. But nonetheless, they wanted to; they changed their opinion on a study. They wanted us to do post-approval and wanted to see that pre-approval. So we've now completed that study. We announced the top-line results already publicly. So the next step for us is to respond to the FDA CRL letter. We believe we'll do that very early in the fourth quarter at the latest or second quarter, excuse me. Early April, let's say. We'll respond to FDA at the latest, and then we expect a response shortly after that.
No longer than six months, but they've kind of signaled that they'll try to do it much quicker than that.
Yeah. Got it. So you're preparing your response and resubmission of an NDA for neffy. Can you just talk about what are some of the remaining steps that might be left to do that, or is it relatively straightforward?
Yeah. Well, we've completed the study. We have the results. We believe the results will resolve FDA's concern that they've expressed. So it's just a matter of finishing the clinical study report and the other documentation for the submission.
Great. Sounds good.
There's only one other outstanding concern they raised, which was I think one of those things where they just threw it in as an additional issue. In August of last year, they issued a new guidance on nitrosamine testing. And so they asked us to just do that as well. And we've done that, and there's no nitrosamines detectable in neffy at all. So that resolves that concern as well.
Sounds good. Just digging in a little bit more, you recently disclosed data from the pre-approval study. Could you just give a couple of highlights of what you learned, what it reiterated for neffy's profile, and has it given you more confidence about neffy's future?
Yeah. Yeah. So what FDA was concerned about ultimately took a little while to get to exactly scientifically what they were concerned with. They were concerned that the second dose under rhinitis conditions, so under normal conditions, we've done once and twice dosing. Very dose proportional increase in absorption. Very good results with twice dosing. And dosing once in each nostril or twice in one nostril didn't make a difference with neffy under normal conditions. With rhinitis, the effect of severe rhinitis because we're really nasal allergen challenge is not typical rhinitis. We spray the antigen directly into somebody's nose who's allergic to it. They have an acute reaction. And so when you watch these people, they're not happy. Okay? Let's put it that way. They're sneezing, coughing. They're having runny nose, congestion, edema. So it's kind of a worst-case scenario to test a nasal spray.
We still got very good absorption. It was more rapid than under normal conditions. That's due to the edema. The mucosal membrane becomes more permeable. So you get a little more rapid absorption. But we got a little bit more rapid clearance because of the rhinorrhea, runny nose. FDA presented that to the AdCom. The AdCom had no real concern about the results because the allergists focused on the first 10 minutes. They know epinephrine works really within five to 15 minutes. And we were much higher than I am during that period, so they were fine with it. What FDA was worried about for some reason was the second dose may not be well absorbed. We didn't understand the scientific rationale behind that, but they nonetheless, at the end of the day, had something we're not aware of.
Some data that we're not aware of that's not our data that raised this concern. So they decided they wanted this study instead of a post-approval study to do twice dosing under rhinitis conditions under NAC conditions, they wanted to see a pre-approval. So fast forward, the results of our study that we released are that, first of all, twice dosing, whether you dose contralateral in the opposite nostrils or the same nostril, the second dose actually gets absorbed even better than the first. So you get actually a better absorption. And that was what we expected because epinephrine is a great cure for rhinitis. I mean, if you have rhinitis symptoms and you want to spray epinephrine in your nose, it actually works really remarkably well to reverse the edema, rhinorrhea, and even epistaxis if you're bleeding. It's really very effective.
Twice in one nostril was even better than once in each nostril. We think that's the local effect. So that's exactly what we're saying is that the reversal of the rhinitis may have worked on both sides, but certainly on the local side where it's been sprayed the first dose, it worked very well. The second dose was maybe even slightly more than under normal conditions. The second dose was really almost like there's no rhinitis. And that's what they wanted to know. I mean, they wanted to make sure, one, the second dose was well absorbed. Two, is there a difference under that nasal condition where we might want to label to dose twice in the same nostril? And that would mitigate any concerns. And pharmacodynamically, it really doesn't matter. From a pharmacodynamic response perspective, neffy is better than IM no matter how you dose it.
Whether you dose it once, once in each nostril, twice in one nostril, it's always better on the pharmacodynamic response compared to injection. So it's giving the blood pressure heart rate response very, very effectively. And then the only other thing to add to this that FDA didn't ask for, but now they've got it because we had it, is we published at QuadAI, and FDA is very aware of it. And we've sent data to FDA on two efficacy studies we've conducted. One required by the Japanese authorities was in anaphylaxis patients having a reaction. And this was what we call oral food challenge where we give them an oral antigen. And it's part of their normal testing. So it's not necessarily considered unethical because it's part of their normal treatment is that they're getting tested to see how sensitive they are to the antigen.
They get oral food challenge. Then Dr. Ebis awa, who was the professor that did the study in Japan, if the child had a reaction, which is about half, 50% of the kids would have a reaction, he'd treat them with neffy. Then the protocol was one shot of neffy. If there's a response, great. If there's no response, they would give an injection just because of ethical reasons. They wouldn't take a risk. 100% of the kids respond to a single dose of neffy. It was 100% and very few side effects. Then we also did a study in urticaria, which showed very rapid, immediate response to neffy and statistically significant differences even at five minutes from placebo.
The reason we did that is when we look at pharmacodynamics, we can measure alpha-1 and beta-1 response to epinephrine very, very well through heart rate and blood pressure response. We showed that's better than injection with neffy. Beta-2, which is a very important receptor that stabilizes mast cells, we couldn't show in a normal person. Urticaria is an inflammation of mast cells. You're looking at the beta-2 response in urticaria, and you see immediate response within minutes after dosing neffy. We think that helps complete the circle, complete the story about how neffy has as good or better effect than injection. That's why we did that study.
Got it. Great. So let's say everything works out. You file. You get FDA approval, getting ready to commercialize neffy. So how are you thinking about that launch and some of the preparations going into it?
Yeah. I'll let Eric talk about that.
Yeah. So when we think about the opportunity, clearly there's 20 million patients that are diagnosed with severe allergic reaction, but there's only 3.3 million patients that have treatment. That's a needle injector. That's the only option right now. And the challenge there is that we know that 80%-90% of those patients are either not carrying, they're not using, and they're really just not prepared in the event of an emergency. In addition, in that 20 million, there's another 3.2 million patients that were given a prescription over the last couple of years. It's expired, and they haven't refilled it or they didn't fill the prescription.
So as we think about to the question, when we think about launch, initially, that six million patients is a pretty significant opportunity for us not only to convert the market, but also really expand the patients that are coming in for treatment. What we've been focused on the last 12-24 months is obviously our market access strategy is critical. We've done a lot of work preparing for that. Right before our complete response letter in September, we met with eight to 10 payers to do clinical presentations, PBMs, insurers. So that's going to be really critical to make sure that we get access and affordability for patients. But we'll also have programs that help with copay support to buy the copay down to $25 for commercial patients and other programs too, like a cash price and patient assistance program.
That's really critical as we think about launching this. In addition, we want to make sure that we're building trust and confidence and adoption with physicians. We'll have a direct sales force. We'll be doing a lot of different types of education as well of physicians and really make sure that we're driving that early adoption with the allergists. Then what we'll also be able to do is making sure that we're educating patients. Not only building awareness of the product now as a solution being available, but also education too that if they're not prepared, they're not carrying epinephrine, this is now a product that can really fit into their lifestyle and give them, especially parents, we hear this all the time, peace of mind that their kid is going to carry this and they're going to be prepared in the event of an emergency.
So it's a multi-tiered kind of approach with obviously access, making sure we get physician adoption, and then driving that consumer awareness and action to ask for neffy as well.
Yeah. And just to add, just so you're aware, that $25 copay with commercial insurance or $199 cash pay, so that'd be the range of costs maximum. That's actually less than the auto injectors, than the generic auto injectors. The generic auto injectors are averaging about $40 copay with commercial insurance. And I think they're in the $200 or slightly higher than $200 cash pay price. So we would actually be priced in a relative there would be no price barrier to converting from an auto injector to neffy. It would be purely them wanting to switch from injection, which the vast majority of the population doesn't like the injection or won't use it.
Got it. So I want to dig in a little bit more. So thinking about the launch, what prescribers do you plan to target initially, and how much coverage could they enable in terms of allowing neffy to penetrate deeper into the total addressable market?
Yeah. So I'll let Eric.
Yeah. So we plan to launch with 95 representatives, obviously managers as well, so a little over 100. Our target audience is about 12,500 physicians. And these are all the allergists. They're also your high-decile prescribers, seven to 10. So the game plan is to make sure that we're having extra focus on the allergists in the initial first couple of months. We've also done some pretty interesting analysis too where we've looked at launches over the last five years in the allergy respiratory space. And we've overlapped those launches and the adoption with the physicians that we're going to be calling on. So we're able to identify physicians that are early adopters in other areas. And we'll make sure that we have extra focus on them to drive adoption and get utilization of this product.
So in addition to answer the question too, that 12,500 physicians will cover about 45% of the prescription market. It's interesting in all of those practices too that we're going to be going to, there's another 50,000 physicians that are co-located in the same practice. So if you count them as well, you're getting to about 55% of the market. And our reps will be trained to have a total kind of account office call. Obviously, we'll be calling on the high-volume prescribers, but within the office, we'll be driving that awareness and we'll be driving that education as well. So we're pretty excited about the opportunity.
And then also we'll have a virtual option for patients. And the other thing you have to recognize in this market especially, it's a very consumer-driven market.
The advocacy groups are very much behind a needle-free option because they know that's one of the major barriers to use of epinephrine and proper treatment. We also will be moving towards more direct to consumer, initially virtual targeting of consumers through social media and other online systems. Eventually, we've been talking even to large advocacy groups about public service announcements because there is a huge gap when you see three million people using auto injectors or have a prescription, not that they're using, only maybe 20%-25% of those people are actually using them, but three million have a prescription. There's 20 million people out there that have severe disease that really should be using epinephrine. There's a huge gap.
And the question is, how do we move towards that gap and bring more of those people that currently are not in the market today into the market to come and get a needle-free option like this that's easy to carry and easy to use? And we think that's really the big opportunity here. We're very confident that 60%-80% of this market will convert from auto injectors very quickly because those are the unhappy auto injector users that are just not carrying or using. But on top of that, you've got 17 million people that really should have epinephrine that those advocacy groups are going to target also, but don't like the current options or their doctors are not well educated in prescribing antihistamines instead of epinephrine.
How do we bring those people into the market and really expand this market well beyond the current $1 billion net that it is?
Yeah. You alluded to this a bit talking about the advocacy groups. I guess, could you just help frame how much of an impact is that in the space relative to other indications?
I think in this space, it's a tremendous impact. The advocacy groups are super well organized. There's 5 major ones, a few that are really huge, like FARE, Food Allergy Research & Education. They're very well organized, and they have huge outreach. They have huge databases of people that they can reach. And even the SnackSafely, who did a petition, got 46,000-48,000 signatures on a petition to FDA after they didn't approve neffy objecting. So that kind of advocacy to get that many people involved in signing a petition is pretty unusual. I mean, it really touches a large percentage of the population. Even those that don't have auto injectors, they have pretty good outreach. And as I said, we've started talking to them about even public service announcements, which advocacy groups as a nonprofit can do very cost-effectively.
When you have such a gap in the use of a product, it wouldn't be branded, of course, because it would be a public service announcement. If they do a public service announcement that is focused on getting people with this disease to get epinephrine and there are injection options and needle-free options, nasal spray option, they can say that, and we're the only nasal spray option. We think that would be very effective at helping to broaden this market out and get to the population.
Makes sense. So we were talking about U.S. for a bit. I just want to check in about Europe as well. So how's that going with neffy?
So unfortunately, we often think Europe is independent, but we were very close to approval in Europe. We had final day 180 comments, which did not have any major objections. Reports looked very clean. Went to CHMP. Unfortunately, right when we had to announce, given we're public, we had to announce that we got the CRL. Then what came back from CHMP was, "Nope, we want to see that study before we approve." So they paused everything in Europe. We think the results of our study will very much address anything for the Europeans, especially because they're not interested in PK as much. They're interested in the pharmacodynamic response because they look at that as a surrogate for efficacy. So we will respond to them in April as well. Their time frame is shorter than FDA's. So FDA has up to six months.
Now, they kind of signaled they will try to do it quicker, but they have up to six months. Europe has a maximum of 60 days to approve after we respond to the day 180. But we think this study will very much address their concern. I mean, the pharmacodynamic response was really much better than injection across the board. Even on the first dose, it was much better than injection.
Got it. In the final couple of minutes, I did want to ask about some of your QuadAI presentations that you recently had and your focus on urticaria. So could you give us a little bit of highlights?
Sure. Sure. So urticaria is a very interesting idea. Came from some of the older allergists that used to use epinephrine for a lot of different things. Urticaria for sure, severe bronchospasms, asthma. You came in back then, they gave you a shot of epinephrine. It worked spectacularly well. So we also did a study in asthma. We'll get into that today. But at least in urticaria, there's a very interesting gap in the market that we think neffy could address. It may not be called neffy because it may be a much lower dose. But in our study, we show very rapid, immediate response in refractory urticaria patients. But the real target there is going to be people who are on antihistamine therapy, who are relatively stable, but maybe having a flare, which is an exacerbation of the urticaria monthly or every other month, sometimes twice a month.
But they have these flare events. The flare event can be very, very upsetting, very irritating, even painful. It could go on for anywhere from hours to a couple of days. This is an exacerbation. There's something that caused this flare. A lot of times, it's an antigen. It could be temperature. It could be stress and sometimes unknown. But it causes this flare, exacerbation. Mast cells become unstable, and you have rash and hives and obviously all the symptoms that come along with that. Epinephrine is exceptionally effective. Within minutes, you get effect. Literally in 15 minutes, all symptoms were resolved in people that were refractory to antihistamine and XOLAIR.
So what we believe the gap is, is if we could treat those antihistamine patients or even Xolair patients because they get these exacerbations as well, even in the phase 3 Xolair studies, they went to the hospital three to four times a year because of these exacerbations. And when they go to the hospital, they're getting either IV steroids or IV antihistamine to try to control it. But you could treat this at home with a nasal spray very, very effectively. We did not see a difference in that indication between one and two milligrams. So we may even go even lower in dose. And it would then be a different product because we wouldn't want it mixed up with the treatment for anaphylaxis. But that market is a huge gap. And there's probably 300,000-400,000 patients with this issue out there.
They will use the product multiple times a year. They will use it many times a year where ideally, your food allergy patients are carrying it for insurance, right? They're not going to be using it that frequently. With urticaria, it could be a frequent use. We see the urticaria market as potentially as big as the food allergy market. Even though the patient population is smaller, they'll be using the product routinely. The price point would probably be fairly comparable. You can easily charge what we'll charge for anaphylaxis for urticaria. There's also one other aspect to this, which we didn't really think of. We treated these refractory patients in the clinic because we wanted to see the effect in the clinic with the doctor assessing and the patient assessing the effect.
We didn't think that was a real target population, but the doctors that did our study believed that these people will actually use this because these are people that have urticaria all the time. Even to get six hours of relief to go to a wedding or a birthday party, they would actually pay to use this product. So not necessarily our target population, but nonetheless, potentially an expansion population as well.
Nice. Sounds good. I think we're basically at time. Thanks again for coming out and talking about neffy with us.
Thank you.
Great.