Right. Good afternoon, everyone. Welcome to Oppenheimer's 36th Annual Healthcare Life Science Conference. My name is Andreas Argyrides. I'm one of the senior biotech analysts in Oppenheimer. Today I have the pleasure to be joined by Nasus CEO, Dan Teleman, and CFO, Eyal Rubin. Nasus is a clinical-stage pharmaceutical company developing a number of intranasal products, powder products, addressing acute medical conditions. NS002, Nasus's intranasal powder epinephrine product candidate, is being developed as a needle-free alternative to epinephrine auto-injectors for patients with anaphylaxis, using Nasus's proprietary powder-based intranasal technology designed for rapid and reliable drug delivery, leveraging the nasal cavity's rich vascular network for quick absorption. The PBI, powder-based intranasal technology, the PBI formulation uses uniform spherical powder particles for broad dispersion and potentially faster, higher absorption compared to liquid-based nasal products.
Great to have to have you with us today, Dan and Eyal. With that, I'll let you take it away with the presentation, and we'll have maybe some time at the end for some Q&A. Thanks.
Thanks, Andreas. Appreciate the invite to the OpCo conference, and thanks everyone for joining the presentation. Andreas gave a very nice overview of the company. We are based on a proprietary powder formulation or powder technology that is designed to enhance the intranasal absorption of various molecules. We are applying this powder technology across several molecules, several therapeutic areas, with the key focus being on our intranasal powder epinephrine for anaphylaxis as an alternative to EpiPen, where in several clinical studies, we demonstrated its superior performance in terms of absorption compared to EpiPen. This is our pipeline. We have a very robust pipeline, setting us up for long-term growth.
In addition to our epinephrine, which moves into a pivotal clinical study later this year, we have three additional products in development. The first one is ondansetron for chemotherapy-induced nausea and vomiting. This product is going to go into first in human in the second half of 2026. We have two additional products. The molecules have not been disclosed, but one is in the metabolic space, the other one is in the cardiovascular space, and again, those are moving towards clinical studies. By the end of 2026, we're going to have a very rich, broad pipeline of two or three products in the clinic, all leveraging the Powder Intranasal Technology. What makes this technology so unique? It has two key features. One is our ability to control or tightly control the particle size distribution.
We create particles that are five to 35 microns, which is the optimal size range for intranasal absorption. The other key feature, unique technology is the ability to create spherical particles. Taken together, the ability to control the particle size with the particle shape, creates a powder formulation that penetrates deeply into the nose, excuse me, gets into the deeper parts of the nose, where there's a much larger surface area for absorption, more vasculature beds, compared to the more traditional liquid intranasal formulation, which are heavier, more dense. They tend to concentrate in the lower part of the nose, where there's a smaller area of absorption, less vasculature beds, leading again to the powder formulation to have faster and higher absorption, which then translates into some potential clinical advantages of the powder formulation.
Epinephrine or anaphylaxis is our lead program. Obviously, everyone is familiar with anaphylaxis. Those are severe allergic reactions, could be fatal in about 1% of cases, and they progress very quickly. Between five to 15 minutes, anaphylactic reactions could lead to respiratory arrest or shock, with about 30% of the anaphylactic reactions actually occurring within three or five minutes. Getting epinephrine to patients, epinephrine being obviously the standard of care, getting epinephrine to patients as quickly as possible and having an epinephrine product that works as fast as possible, are key objectives for any new epinephrine product. I mentioned that EpiPen, and I'm sure everyone is familiar with EpiPen, this is the standard of care.
Despite this being the standard of care, despite every patient with anaphylaxis, history of anaphylaxis, or at risk of anaphylaxis, needing to carry an EpiPen, in reality, many patients do not carry the EpiPen, do not use the EpiPen. Many patients, caregiver, families, are needle phobic, are afraid of the needle. They delay the use of EpiPen because of this needle fear, and delaying the use of epinephrine has been shown to be associated with worse outcomes. Secondly, EpiPen is very large, it's very bulky, not easy to carry around. Again, many patients, particularly teenager kids, do not carry the EpiPen with them because of those reasons. Last but not least, EpiPen is a liquid formulation of epinephrine, therefore it has a very limited shelf life, needs to be replaced every 12 months or so.
In contrast, you see our product on the right. First off, obviously, it's a needle-free product, so avoiding the needle phobia, the needle fear of many patients. It's very small, very compact, very easy to carry, very easy to use. What is unique to our product is that because we use a powder formulation, a dry powder formulation, we have a very, very long shelf life, which means the patient doesn't have to be replacing the product constantly, doesn't have to be worried about the need to replace the product. Anaphylaxis is obviously a very large market opportunity, about two and a half billion dollars annually right now with epinephrine, growing double digits because of the rising incidence of allergy, expected to be four or five billion dollars in the next few years.
If we look at the U.S. specifically, about 20 million patients with severe Type I allergies that are at risk of anaphylaxis, yet only about a third of those patients actually have a prescription for EpiPen. Yet, even the patients that have a prescription for EpiPen, many of them do not carry the EpiPen with them, do not refill the product on a regular basis. There's also about 13, 14 million patients, about two-third, that do not have a prescription for an epinephrine product at all. Both of them represent significant market opportunities for what we call the needle-free epinephrine product, so epinephrine product that do not require an injection. In terms of our product, the NS-002, we completed several clinical studies to date.
We recently announced interim results from a very large, robust phase two study that looked at both single administration, repeat administration in subjects with allergic rhinitis, both under normal conditions and under nasal allergic challenge conditions. A very robust study. That paves the way to our pivotal study that will start in Q4 of this year, with data read out in Q1 of 2027, followed by an expected NDA submission by mid 2027. As you can see, a very rapid development timeline, very cost-effective, short, based on the 505 pathway. If we look at the competitive landscape, we just mentioned that anaphylaxis is a very large market, it's a growing market, and it's an expanding market that is shifting surely into the to needle-free epinephrine products.
Within this space, there's ARS Pharmaceuticals with their neffy product, which is a liquid intranasal formulation of epinephrine, has been approved about a year ago. You have Aquestive, with their sublingual formulation of epinephrine, and they recently received a CRL. You have Nasus with its powder intranasal formulation. You see there's a significant discrepancy in the market capitalization between ARS, Aquestive, and Nasus, yet we think we have the potential to be the best in class. If you look at the pharmacokinetic properties that essentially dominate or dictates the performance of the epinephrine products, we have the shortest Tmax. Tmax is the time to maximal concentration of epinephrine in the blood.
We want that time to be as short as possible, and as you can see clearly here, we have the shortest Tmax out of all products, injectable or non-injectable. Another very important pharmacokinetic property is the T100. This is the time to reach 100 picogram. 100 picogram of epinephrine is considered the minimal threshold of epinephrine to exert its hemodynamic effect, so the effect on heart. Again, you can clearly see that we have the shortest T100 out of all products, in a very significant way. Last but not least, the number or the % of patients that actually reach that 100 picogram level at early time points.
It's not just the average time, but actually how many patients get there at early time points, keeping in mind that about 30% of anaphylactic reactions occur within three or five minutes. You see the data, ARS, 18% at five minutes, EpiPen, 67 at five minutes, and Nasus, already 91% of patients or subjects achieving that threshold at very early time points. This is critically important to allergists. In a recent market research that we have conducted with allergists, speed of onset was by far the most important parameter for physicians. As you can see, almost 80% of responders cited onset of action as very important. When comparing between products, again, looking at different Tmaxes, obviously, the shortest Tmax was very important to physicians.
When asking about the proportion of patients or percent of patients that reached that 100 picogram threshold at early time points, again, that was extremely meaningful to physicians. Physicians understand the pharmacokinetic properties, they understand the importance of onset of action, and they would choose a product that has consistent performance and the shortest onset of action, because this is really life-saving. I mentioned the clinical study that we just completed and reported interim analysis a couple of weeks ago. This was a very robust study, 50 subjects, with allergic rhinitis, getting either a single dose or a repeat dose of the Nasus product with and without nasal allergic challenge.
The nasal allergic challenge essentially creates significant nasal congestion that is mimicking the early stages of an anaphylactic reactions, and we want to demonstrate that we have consistent absorption of the epinephrine despite the nasal congestion. Obviously, this was compared to either a single dose or a repeat dose of EpiPen. Broadly speaking, this phase two validated results from our previous clinical studies in terms of the PK and safety, further demonstrating the attributes of the powder formulation as having a faster and higher absorption compared to EpiPen. Specifically, we demonstrated a shorter Tmax and T100 compared to EpiPen. We showed that 91% of participants achieved that minimal threshold at 5 minutes, and close to 100% of patients already achieved that at 10 minutes.
Other pharmacokinetic properties like the Cmax and the total absorption were comparable to EpiPen. The pharmacodynamic effects, so this is the effect on blood pressure and heart rate, tracked really well with EpiPen and always within normal physiological limits. The product was well tolerated with no serious adverse events, no cardiovascular events, and most adverse events were local, self-resolving, and mild. If we look at some of the some of the data, this is the single dose result with and without nasal challenge. Without the nasal challenge, under normal conditions, this is the blue line. You can see that we have faster and higher absorption compared to EpiPen, and this is consistent across the entire time period. Overall superior performance to EpiPen.
Even with the nasal challenge, we still get faster and higher absorption initially, and then we always maintain a level of epinephrine that is above 200 picograms, reminding everyone that the minimal threshold is 100 picograms. Under normal conditions, under nasal challenge, we have excellent performance and consistent performance of our product. If we look at the specific parameters, the Cmax was slightly higher compared to EpiPen, but within the bioequivalence limits. Tmax, significantly shorter than EpiPen, and the time to reach the 100 picograms was also significantly shorter compared to EpiPen. We talked about the proportion of patients who reached a 100 picogram.
You see how quickly we get to the 100 picogram level with over 90% of subjects at pole minutes and close to 100% after seven and a half minutes. In terms of the pharmacodynamic response, we expect from any epinephrine product to have an increase in blood pressure, in the systolic blood pressure, and this is what we see here. We see a transient increase in blood pressure, but always within normal limits, reminding everyone that the normal limits for heart rate is 140 over 90, so we are always within the normal limits. No effect on the diastolic blood pressure. Epinephrine should not have an impact on diastolic blood pressure. The heart rate, again, we see a transient increase as we expect from epinephrine on the heart rate, which then normalizes.
We also looked at a repeat dose. Again, this is a regulatory requirement to test a repeat dose with and without a nasal challenge. In both situations, normal and nasal challenge, clearly see again that we have superior absorption compared to EpiPen. Faster absorption, higher absorption, and sustainable absorption, despite nasal challenge, at all time points. This is clearly very important to the FDA and what differentiates our product, again, from the competitors. Those are the pharmacokinetic properties. Again, very similar Cmax to EpiPen, similar Tmax with the repeat dose, and a much shorter T100 with the repeat dose. Again, with the pharmacodynamic response, we see an increase with normal conditions as well as the nasal challenge.
We see an increase in the systolic blood pressure, always within normal limits. Same for the nasal allergic challenge. No effect, again, on the diastolic blood pressure with and without challenge. A similar effect on heart rate, a transient increase in heart rate that normalizes over time, again, with and without a nasal allergic challenge. Overall, a very good pharmacodynamic response that tracks well with EpiPen and always within normal limits. In terms of safety, I mentioned earlier, no serious adverse events, no cardiovascular events, which again is very important. Most AEs were local in nature, self-resolving. Actually, we had more mild adverse events compared to EpiPen, where there were more systemic adverse events.
In terms of the local events, primarily runny nose, keep in mind, subjects in this study had allergic rhinitis, they have a runny nose to begin with, some very minimal administration site discomfort, and some nasal itching. In terms of systemic side effects, those are all associated with epinephrine, things like headache, nausea, this is expected and common with epinephrine. We had no vomiting with the single administration. The only vomiting that occurred was after a double dose with nasal allergic challenge. We have a very broad patent portfolio that covers both the powder technology that I talked about earlier, as well as the individual products that we develop, including the epinephrine. Those patents are granted and go to 2038 before any patent term extensions.
Just as a quick summary, we have our proprietary powder technology that is enhancing the intranasal absorption of different molecules. Our lead product, NS002, a needle-free, convenient, intranasal, powder epinephrine formulation, as an alternative to EpiPen. We've conducted multiple clinical studies, consistently demonstrating superior performance and absorption, compared to EpiPen. When we look at the broader, competitive landscape, we think we have the potential to be the best in class with a very consistent performance and the product with the fastest onset of action, which is critical for patients and physicians. We are expanding our pipeline. We are creating a robust pipeline with additional products that are moving into the clinic this year.
Strong IP protection, and with our recent PIPE financing, we are well positioned to execute on our development plan for epinephrine, get it to an NDA, and move our pipeline into clinical studies. With that, I'll stop. Thank you for everyone, and happy to take any questions.
Yep. Dan, give me one second here while I just scroll to see if we have any- I mean, well, in the meantime, let me turn my camera back on here as well. Just to get a sense of your sense of the market opportunity, obviously, neffy's on the market now. There was some good traction that they got in terms of market share from the auto-injector market. That seems to have, you know, stalled or plateaued or whatever, however you want to call it, just in the near term. We're all hoping for a, you know, acceleration this year. How are you seeing, one, from your conversations with the physician, allergists, how are you seeing the need for this product or the awareness that needs to be created?
You know, how soon, in essence, do you think that what we see as a disruptive opportunity for these non-needle alternatives to really make an impact on the market?
It's an excellent question. From our discussions and in our research, all the physicians are aware of neffy, and almost all of them have used neffy at least once, either in a food challenge or prescribed it to a patient. I think awareness is where it should be, and applaud ARS for getting the awareness out. I don't see an issue of awareness. I think physicians, again, because EpiPen has been the standard of care for so many years, because there is this perception that if you inject epinephrine, it would work better or faster, I think this is something that physicians just need to get more comfortable with, and feel comfortable using the needle-free epinephrine product.
I don't want to talk about the competition. I know that when we talk about our data, specifically the Nasus data, I think this resonates well with physicians because they see the performance is superior to EpiPen. I don't know if all other products, the needle-free can say this, but we consistently demonstrated that we are superior to EpiPen. We think that hesitation when it comes to our product is going to be reduced. Certainly, again, the work that ARS is doing with education, with reimbursement, with pricing, is going to help the entire market. I have no doubt that the market is going to ultimately shift to needle-free epinephrine. There's so many issues with the EpiPen auto-injector, again, that either delays the use or people are not using it at all.
I have no doubt that this is going to happen. It's just a matter of time, and I think we've seen it before in other therapeutic categories. With naloxone, with NARCAN, when NARCAN was introduced to the market, within five years, took 90% of the naloxone market from the auto-injectors. We've seen that with glucagon when BAQSIMI was introduced, again, as an intranasal product, took a significant market share with benzodiazepine for seizures. In many markets, when an intranasal product was introduced or a needle-free product was introduced, the market within five or six years, almost 80%, 90% of it transitioned. I have no doubt it's going to happen here. There's more reason it should happen with epinephrine.
I think it's just a matter of time and comfort level with physicians.
Just to add on that, I guess you would agree with the fact that more real-world data that's generated will help provide that comfort level so that they can make the switch. Outside of the preconceived efficacy notion here, everything else makes sense for a no-needle alternative, correct?
Agree with you completely.
Okay, great. Maybe, you know, we have a couple more minutes here. Just, can you give us a snapshot, a reminder, a snapshot of the financial picture here and how you, after your pivotal, in essence, to get to the market?
Sure. with the recent PIPE that we just executed, we're fully funded until the or throughout the NDA submission, which is planned, as Dan mentioned, the mid of 2027. That's, you know, obviously in parallel to the two other products that we're going to put into clinics in the third and the fourth quarter, ondansetron and the undisclosed metabolic and the drug also.
Okay, fantastic. All right, we look forward to further updates this year from you guys. I think, as you are, you're in the right space. Allergy is getting a lot more attention, and, you know, you are, you know, you guys, you amongst some of the others out there are leading the way here, and we look forward to future updates.
Thanks, Andreas, again, thanks, Oppenheimer, for the opportunity to present.
Absolutely. Thank you guys for presenting. We really appreciate it. With that.