Good afternoon. Welcome to Needham's 23rd Annual Healthcare Conference. I'm Serge Belanger, one of the healthcare analysts at Needham, and we're happy to have for our next session Optinose, a global, specialty pharma company focused on serving the needs of patients cared for by ENT and allergy specialists. We have the company's CEO, Ramy Mahmoud, with us, as well as the VP Business Development and Investor Relations, Jonathan Neely. I'll hand it over to Ramy, who's going to go over a quick slide presentation, and then we'll go to Q&A. For those listening online, you do have the option to submit questions in the portal that you're watching the presentation on. Alternatively, you can email them to me, and we'll ask them during the Q&A portion. That said, I'll hand it over to Ramy for the slide presentation. Great. Thank you, Serge, and thank you for inviting us to be here today. It's a pleasure to introduce folks to the company who may not be aware of Optinose. If we can advance the slide, please. Optinose is a commercial stage pharmaceutical company, and, as Serge said, we're focused on patients who are cared for in the ENT and allergy specialty space. We've developed our currently commercialized product, which is called XHANCE, with the intent of making it a new standard of care for chronic sinus diseases. There's about 30 million adults in the United States who are affected by chronic sinus disease. It's actually one of the top 3 diagnoses claimed in all of adult outpatient medicine. It's an extremely commonly diagnosed condition. XHANCE, our product, is the first and only FDA medicine that's ever been approved for the treatment of chronic sinusitis, which is also called chronic sinusitis without nasal polyps. We just received that approval a few weeks ago, and we're very excited about the enormous opportunity that that creates for us as we go forward. This new indication increases the total addressable market for the product by up to 10x, and it immediately leverages our existing commercial infrastructure, which we'll talk more about in a few minutes. Our current stable base of business of $71 million net revenue in 2023 will be meaningfully augmented by the opportunity in the new indication of chronic sinusitis. Next slide, please. So let me dive a little bit more into the potential associated with the new indication. Today, with the nasal polyps indication, or historically with the nasal polyp indication alone, the opportunity in the specialty space, which is where our commercial footprint is, was estimated at about 1 million patients. Of those 1 million, probably only about two-thirds, between 600,000 and 650,000 or so, were diagnosed at an office visit in any given year. So comparatively small population, when you put it up against chronic sinusitis, when you put chronic sinusitis on top of that, there's an estimated 3 million patients who are being both sort of presenting and also being diagnosed and treated by physicians in the current specialty space. So we expect a very big increase in the number of patients who are on label for us in the specialty space. On top of that, probably 70% of the total opportunity is in primary care. So there's up to about 10 million patients who are currently being diagnosed and treated with a diagnosis code in claims data for chronic sinusitis every year. Again, but 30% in the specialty space, 70% primary care. That 10 million patients is only a base, though. That's the number who are currently presenting. We believe there's an additional 20 million patients who know they have the disease, know they are suffering from the disease, but in any given year do not necessarily go in to see a doctor. We call them dissatisfied dropouts. And those patients, we believe, can be activated to seek care when they're presented with the opportunity. We've actually run a pilot 3-city test of direct-to-patient communication about our product using the product profile. We demonstrated an above-benchmark rate of activation of those patients to motivate them to go in and see a doctor and discuss the possibility of using XHANCE to treat their disease. So two-thirds of the opportunity could be activated on top of the 10 million. Next slide, please. A couple of little data points about the company. We talk about this as a launch, but this is technically an SNDA and line extension. So we have an existing infrastructure that we're building on. We're not creating from scratch. For example, 70% of lives in the United States are already in an insurance plan that covers our product, XHANCE. We've already filled about 1.5 million prescriptions for XHANCE with our previous nasal polyp niche indication. And we have a pretty high rate of prescriptions which are written, which are actually being filled, about 70% right now. We have 75 sales territories, and we intend to keep about 75 sales territories during the first period of launch here. One thing we did differently in the Q1, though, is that we realigned those sales territories to move away from nasal polyp potential and towards chronic sinusitis potential. So about 40% of the doctors called on by our reps are new targets based, again, on chronic sinusitis potential with the new indication. We've already communicated guidance that we expect about $220 of net revenue per prescription in 2024. That's higher than we had in 2023. And our 2023 net revenue was about $71 million. I will add one more thing that we did in the Q1 in preparation for this launch was to implement hub services. So we implemented hub services in January to support the CS launch. We think that's important because it improves the level of customer service, not just for patients, but also for physicians' offices when they're dealing with prior authorizations or other utilization management. And we think the presence of a hub service to support both doctors and patients will increase the overall approval and fill rates for the product as we go forward. Next slide, please. So a couple of quick words about the product and the disease area. The picture on the left there is XHANCE. The innovation is the device. There are 14 Orange Book-listed patents covering XHANCE, the last of which expires in 2036. Next slide, please. The reason the device is important is because it creates different biomechanics inside the body during use. And the consequence of different biomechanics will be a different pattern of drug deposition. Let me briefly walk you through what it does when you use the device. If you look at the upper left panel, you see that when you exhale against resistance into the device, it increases pressure in the back of the throat and elevates the soft palate. That isolates the nasal cavity from the oral cavity and lungs with an airtight seal. That airtight seal keeps what's in the nose in the nose. The exhaled breath at physiologic humidity and temperature is routed through the device. You introduce the aerosol medication into that airflow. As you'll see on the lower left panel, it enters one side of the nasal cavity. As it passes back into the nasal cavity, floating drug around above and behind various obstructing bony surfaces, it seeks an exit but can't exit through the usual path of least resistance into the throat because the soft palate is sealed. Therefore, it has to go all the way to the extreme posterior edge of the nasal septum, travel around behind the nasal septum, and actually exhaust the air through the opposite nostril, leaving the aerosol medication behind in the complex nasal labyrinth. So this pattern of delivery, which we refer to as bidirectional flow, is the opposite of what happens with a standard nasal spray. And it's one of three opposite characteristics that I'll highlight. The first is the closed palate with a standard delivery nasal spray. The palate is opened. Matter of fact, you force it open when you sniff because you're pulling air into your lungs. So it's the opposite of a standard nasal spray. The second is the positive pressure. The drug delivery is occurring under positive pressure, which tends to widen inflamed and narrow spaces as opposed to a standard nasal spray where you're sniffing, which creates Bernoulli's forces and tends to further narrow or even collapse inflamed narrow slit-like spaces. And the last, as I mentioned earlier, is the bidirectional flow. With a standard nasal spray, you get unidirectional flow as the drug and airflow passes from the nostril and is sniffed straight along the floor of the nasal cavity underneath the inferior turbinate bone and into the throat. So these three characteristics produce a different pattern of delivery. Go to the next slide, please. As illustrated on the right here, at the bottom right, you'll see radiolabeled drug delivered using a standard delivery nasal spray, and you'll see the hotspots for delivery are in the front of the nose, the nasal vestibule, nasal valve, front part of the nasal septum, and on the floor of the nose, underneath the inferior turbinate bone traveling back towards the throat. The upper right panel is the pattern of delivery that you see with an exhalation delivery system. You'll see that it's a meaningfully different pattern of deposition. You'll see there's actually less drug being delivered in the very front of the nose and on the floor of the nose. The drug instead is delivered broadly across surfaces in the upper and back parts of the nose. We believe that's important because you're targeting delivery to the area of the sinuses and the sinus drainage tracts, which is where inflammation creates symptoms in chronic sinusitis. Next slide, please. Let me tell you a little bit about the disease. Chronic sinusitis ends in an itis, but that's not because it's an infection. It's actually a chronic inflammatory disease, although it can be punctuated by infection because the chronic inflammation damages the normal protective mechanisms of the nose that prevent you from getting infected when you're exposed to environmental viruses or bacteria or even allergens. The chronic sinusitis is a common diagnosis, but it's not the same thing as allergies. If you have chronic sinusitis, you may also have allergies, just like anyone in the population may also have allergies. The rate of allergies is about the same in people who have chronic sinusitis as it is in everyone else. The chronic inflammation does what inflammation does in any part of the body: pain, redness, swelling, but it's happening now in these narrow slit-like spaces where the sinuses normally ventilate and drain. That produces symptoms. The 4 cardinal symptoms are congestion or obstruction, difficulty breathing through the nose, facial pain or pressure, rhinorrhea, which is drainage, postnasal drip, or anterior drainage, usually purulent rather than clear like you might get with allergies, and a loss of sense of smell or taste. The four cardinal symptoms are often accompanied by other symptoms, and prominent among the other symptoms are loss of sleep, constantly or frequently disturbed sleep, and persistent fatigue as a result of that, and recurrent sinus infections, which are often a reason for going in to visit a doctor. That can be as many as three or more times per year. It drives a lot of use of not just medical services, but also antibiotics. It's estimated that 70% of these patients receive antibiotics. Next slide, please. When I say it's very common disease, I really mean it's common. We estimate about $10 million annual office visits based on claims data. This is one of the top three diagnoses that is ever made by a doctor in adult outpatient medicine. Many of these patients actually undergo surgery. About 45% of patients diagnosed with CS are estimated to have undergone surgery at some point in time. The people who have surgery often have recurrent symptoms. Surgery is helpful in the disease, but symptoms either incompletely resolve or recur in many patients. Next slide, please. What do you do about this, and why is there an unmet need? Well, it is common to try to use standard delivery nasal steroids as anti-inflammatories to treat this chronic inflammatory process. The problem, though, is that every clinical trial that's been run with standard delivery nasal steroids has failed to show a statistically significant benefit. They simply don't work well. That's consistent with the published evidence that more than 80% of patients with chronic sinusitis are frustrated with the inadequacy of the symptom relief they get when they use standard delivery nasal steroid sprays. When you survey healthcare providers and ask why they think the products don't work well, they don't tell you it's because of a problem with the mechanism of action. Corticosteroids have a very broad spectrum effect on inflammation. They're used for many types of inflammatory diseases. What they tell you is that the problem is that you're not really getting up into the sinuses and sinus drainage tract regions with a standard delivery spray. And as a consequence, these topically acting drugs simply don't work well for treatment of this disease, unlike allergic rhinitis. Next slide, please. So what is standard of care in that context? So there's several things that doctors try to do, one of which, knowing that they're trying to get steroid up into the regions that we just talked about, is that they will use something called steroid irrigation or steroid rinses. That would be taking a liquid steroid that is poured sort of off label into squeeze bottles or other devices like Neti pots to be sort of rinsed or irrigated through the nasal cavity. There is some limited evidence suggesting that this may be helpful in patients who have already been operated on. But there's a great deal of uncertainty around both efficacy and safety of this approach. A lot of the drug ends up in the sink. Unknown amount stays in the body, unknown amount absorbed into the body. And it's highly dependent on this complex and time-consuming procedure where a patient, ideally twice a day, would have to be going through this entire process of trying to rinse this product through their nose. It's common for doctors to also use antibiotics or oral corticosteroids like prednisone. In both cases, though, the benefits are short-lived. As soon as you stop, there's ordinarily a recurrence of symptoms over time. These are difficult products, and there's a lot of side effects associated with staying on them on a prolonged basis. In the management of a chronic disease, these have some really serious drawbacks. Then surgery, as I referred to before, can be effective. It has its drawbacks also. It's an invasive procedure. It can be costly. It's common, actually, to continue to use medication after surgery. Matter of fact, the rate of use of medication after surgery is comparable to the rate of medication use before surgery because people continue to want increased benefit or they're treating recurrent symptoms. Next slide, please. What is it that doctors want when they're choosing a product for the treatment of this disease? Our market research suggests the top three drivers for a product are all related to the efficacy of the product. Number 1, doctors want a product that will reduce the core symptoms of the disease: the congestion, ability to breathe through the nose, the facial pain or pressure, and the persistent nasal discharge. Second, they want a product which is safe and well tolerated. We're talking about a chronic disease. Long-term treatment and safety and tolerability are important. And number 3, they would like to finally have for the first time a product which has been proven to be effective. So seeing data that shows that the product does, in fact, relieve symptoms, improve symptoms relative to placebo, is considered high priority for what doctors are looking for. And that's regardless of specialty, whether it's an ENT and allergy specialist or a primary care doctor. Next slide, please. We ran two pivotal trials in order to get this indication. Our trials showed that we do deliver. The product delivers exactly what it is doctors are looking for. Two randomized control trials initially released by the peer review journal in January came out in paper form, I think, Sunday or Monday of this week. 120 sites in 13 countries. We demonstrated statistically and clinically significant improvement in the symptoms of chronic sinusitis, in the amount of inflammation inside the sinus cavities, and particularly exciting, we showed a large decrease in the rate of acute disease exacerbations. I'm not aware that that's ever been shown before with any kind of topical treatment in the nasal cavity for this disease. Lastly, I'll mention that we did a pre-planned Type I error-controlled analysis of the patients who entered the trials having already been using a standard delivery nasal spray. So that would be something like Flonase or Nasonex, a standard delivery nasal spray, and who still had persistent symptoms. And what we found is that those patients also had a statistically significant improvement in symptoms. That's important because it's very common for patients to present to a doctor having already used a standard delivery nasal spray. And it's helpful for doctors to know that those patients also have the opportunity to get improved symptoms. Next slide, please. So I'll approach a close here by saying that if you were to, if you were to imagine what you would like to have in the context of a product and a market to help you predict success, to give you the best possible opportunity for success, you would imagine a lot of these characteristics that we have with our situation right now. You would want a differentiated product. You would want a very large market that you were entering into. You would want to have a high degree of unmet need, and you would want that unmet need to already be recognized and not something that has to be engendered by physician education. You would want strong promotional responsiveness, and you would want a limited competitive field. We have those things. Large potential. CS is a $10 billion annual addressable market potential, and that's without activation of currently dissatisfied dropout patients. We have a high degree of unmet need. More than 80% of patients with this disease are frustrated and actively know they have the disease and symptoms and would like to have relief. We have good promotional responsiveness. We've shown that in response to our chronic sinusitis product profile, prescriber intent to use the product goes up more than fourfold. And we have a high degree of differentiation. This is the first and only product indicated for the treatment of chronic sinusitis, regardless of phenotype. Plus, we have this incremental benefit now for the first time ever of reducing exacerbations by up to 60%, 66%. Next slide, please. So I'll close there, Serge, and go back to you and see if there are any questions or any additional discussion that you might like to have. Absolutely. Thank you, Ramy. And just as a reminder, anybody has questions, they can submit them via the portal or email them to me. And I will ask them. I guess for me, first question. So clearly, the label expansion significantly expands the TAM, the market opportunity. With your current sales force, what do you estimate you can capture from that TAM? So as we showed on an earlier slide, we think that about 30% of the total currently diagnosed and treated population presents in the specialty audience. And we can get a large fraction of that specialty audience with our current sales force. Strategically, in 2024, it's not our intent to meaningfully increase our operating expense. We're actually trying to control our operating expense pretty carefully. So we intend to stay with 75 sales territories. We will increase product sampling, peer-to-peer education, CME, those kinds of things to help support the launch. But by and large, we think with 75 territories, we can make tremendous inroads into the specialty space. The 70% of the market in primary care is not something we can access effectively with our current commercial footprint. We don't have any aspirations to build a primary care sales force. We are open to the possibility of primary care partnerships to enable us to go into that space. We also think there are some strategies for entry into that space, the highest potential doctors that may not even require a partner, particularly emerging digital and nonpersonal promotion type approaches. Got it. And I guess as a follow-up, what is the level of awareness for your product at this point? So XHANCE has a pretty high degree of awareness in the specialty audience right now, ENT and allergy, but a comparatively low level of awareness in the primary care audience. Which is consistent with where we've been promoting for the last several years. So that awareness, though, I just want to say one more thing about the awareness. The awareness is related to not just the product itself, but also the indication. So for 5-6 years now, we've been talking about use of the product for the treatment of nasal polyps, which is the on-label indication that we had prior to this approval. So many doctors think of it as a treatment for nasal polyps, a treatment for a disease where there are alternatives. Part of our educational task now is to go out and show this new data and explain why it is different for a disease which is much more commonly diagnosed and for which there are no alternatives. In terms of payer coverage and access, maybe if you can talk about what it was prior to the label expansion and whether you expect any changes going forward now that you've secured that label? That's a great question, Serge. So about 70% of people in the United States are in an insurance plan that covers XHANCE today. And we really don't expect that to change materially. From before the indication to after the indication. So it's not the number of people who are covered that we expect to change. What we expect to change is the difficulty with which utilization management can be appropriately addressed by physicians. So I'll be more specific. When people are subjected to a prior authorization for our product, there are three key criteria most commonly. One, you need to be an adult. We're not indicated for pediatric use. Two, many plans require you to have previously tried and failed on a standard delivery nasal steroid. And number 3, you need to have an on-label indication. Up until about a month ago, that meant you had to have a diagnosis of nasal polyps. As I said earlier, that's only diagnosed 6 or 650,000 times a year. Now we have chronic sinusitis as an on-label indication. We know that it's in patient records currently being diagnosed 10 or 12 million times a year. It'll be far easier to compliantly overcome those prior authorizations that restrict the product to on-label indication. And you mentioned the net price of the product has continued improving. So I assume there's been price increases and/or improvements in gross to nets. Where does it currently stand, I guess, on a gross to net basis? And where could it go, I guess, once you get to steady state? Yeah, so just for clarity, the biggest action that we have taken to try to influence the average net revenue per prescription is modifications in our copay program. What they've done is they've tried to help encourage filling of prescriptions that have the potential to be profitable for us and help to reduce the proportion of our prescriptions that are unprofitable, where we actively lose money on every prescription that's filled. By shifting those proportions, we can increase the average net revenue per prescription. That's what you saw mostly in the Q4 of last year. We believe that will be durable and can continue on through 2024, which is why we issued the guidance we did for an increase in average net revenue per prescription in 2024 relative to 2023. Got it. And then obviously your product has seen some uptake, consistent growth, reaching about $70 million in 2023. So clearly there's a user base of this product. With this new label and better coverage, a lesser prior auth. Do you expect this user base will significantly expand their prescription writing for the product? Yeah, we do, Serge. So even in the specialty space where we are now, we expect more doctors to choose the product because more doctors are actively treating chronic sinusitis. Even the doctors who have currently prescribed the product, often for nasal polyps, we expect to have much more use because now they have more patients for whom the product is indicated and for which there's evidence that the product can really help. So we expect growth in the average number of prescriptions for the doctors who are seeing these kinds of patients. And we expect an increase in the number of physicians who are using the product. Got it. Okay. Maybe just to wrap up. If you can just highlight if you think there's some facets of the Optinose story that remain underappreciated or misunderstood. Well, so that's a tough one, Serge. I think there's a number of things that are kind of underappreciated right now, but I don't think it's very common for there to be a first and only type breakthrough for such a common disease. When you think about first and only breakthrough treatments, you tend to think about uncommon diseases. That's wonderful when that happens. It really is. But it's really uncommon to have such an unbelievably prevalent disease. Many people either have it themselves or know someone, family, friends who have this condition. It'd be unusual not to, actually. It's rare for something like that to have no approved treatments. So I think it's underappreciated how this product is such an important breakthrough as a first and only for such a common condition. Got it. Okay. Well, thank you for your time this afternoon. I think a great overview of Optinose, and we look forward to seeing the expanded launch of XHANCE with its new label. We're all very excited. Thank you for having us. Thank you.