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Operator
Good day and thank you for standing by. Welcome to the OPTINO's fourth quarter 2022 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Jonathan Neely, Vice President of Investor Relations. Please go ahead.
Jonathan Neely
Good morning, and thank you for joining us today as we review OptiNose's fourth quarter 2022 performance and our plans for the remainder of the year. I'm joined today by our chairman, Joe Scudari, our CEO, Dr. Rami Mahmoud, and our Chief Commercial Officer, Paul Spence. Joe is contributing to the prepared remarks portion of today's call. Rami, Paul, and I will host the question and answer session. The slides that will be presented on this call can be viewed on our website, optinose.com, in the investor section. Before we start, I would like to remind you that our discussions during this conference call will include forward-looking statements. All statements that are not historical facts are hereby identified as forward-looking statements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated by such statements. Additional information regarding these factors and forward-looking statements is discussed under the Cautionary Note on Forward-Looking Statements section of the earnings release that we issued today, as well as under the Risk Factors section and elsewhere in Opti-Nose's most recent Form 10-K and 10-Qs that are filed with the SEC and available on the website SEC.gov and on our website at Opti-Nose.com. Your caution not to place undue reliance on forward-looking statements The forward-looking statements during this conference call speak only as of the original date of this call or any earlier date indicated in such statement, and we undertake no obligation to update or revise any of these statements. We will now make prepared remarks, and then we will move to the question and answer session. With that, I will now turn the call over to Joe Scudari. Joe?
Joe Scudari
Thanks, Jonathan, and good morning, everyone. You've all had the opportunity to interact with Rami over the years in his prior position as President and Chief Operating Officer of the company. But given the recent decision to name him CEO, I'm taking this opportunity to introduce him and to share some perspectives about him on behalf of the board of directors. As you know, Peter recently made the decision to step down as CEO. In that context, the board confronted the question of CEO succession. Obviously, a very important decision for any company, private or public. As the board discussed this decision, we recognized that we were in this somewhat unique position for a company of our size to have a ready now candidate to promote into the position. As you know, Rami has been a part of building OptiNose from its very beginning and has been a very close working partner with Peter. The fact that he can step into the CEO position given that history is an incredible benefit to the company, its shareholders, the management team, all of our people, and the customers and patients we serve. I've known Rami for more than 20 years, dating from the time that we overlapped while we were both employed by Johnson & Johnson. In this case, while Rami served as a member of the management team at Janssen Pharmaceutica, and I served as company group chairman and later worldwide chairman of the pharmaceutical sector. During that period, in the very robust succession planning processes within J&J, Rami was consistently viewed as a rising star with significant upward potential for senior leadership roles, both within and beyond medical affairs and R&D. Over the past five years as chairman of the board for OptiNose, I've had the chance to work more closely with him and further recognize his leadership skills. We all recognize Rami's role in highlighting the development of a chance for chronic rhinosinusitis, but he brings much more to the senior leadership roles he has occupied and the board is confident he will do so as the company's CEO. It's rare to see a senior executive in our industry that is trained as an MD, served in the military, and combines a history of highly productive drug development with exceptional executive and leadership skills. Ramy's been an integral part of building OptiNose into what it is today. And notwithstanding the challenges the industry and the company has faced in the last few years, Ramy is ready now to lead the company into its next chapter of growth. With the filing of the supplemental NDA for the chronic rhinosinusitis indication now behind us, Rami will lead the effort to ensure the company is ready to launch its hands for this very important application. As you know, there is currently no FDA-approved therapy for this disease, and a high level of patient satisfaction with the therapeutic options currently available. The planning is already underway to get the company into the position to successfully launch X-Hands into a marketplace with significant unmet medical need in the not too distant future. I can speak on behalf of the entire board of directors when I say that we are thrilled that this executive transition has already occurred from the prior to the new CEO. We anticipate we will not miss a beat and that Rami will lead this team to the next level of success while maintaining the culture and values that have contributed to the company winning awards for being a great place to work. Thank you all for listening, and now I'll turn it over to Rami. Rami?
Jonathan
Thank you very much, Joe, for your kind remarks, and thank you to everyone listening for joining us this morning. We appreciate you joining us for our fourth quarter update. Before we get started with our business update, I would like to introduce our new Chief Commercial Officer, Paul Spence. Paul was recently, most recently, the Senior Vice President of the US Pharmaceutical Commercial Organization at AMU Therapeutics, a division of Nestle Health Sciences, and has nearly 30 years of experience in the life science and pharmaceuticals industry as a commercial leader, including responsibility for marketing, sales, market access, and commercial operations. His history of relentless focus on commercial execution and lengthy experience building successful commercial organizations and brands out of products with profiles similar to Exhance is a big part of why we believe he will be successful in his role as the new leader of our commercial team. So starting on slide three, we'll go into more detail in a moment, but I'd like to highlight three key takeaways from today's presentation. First, we remain enthusiastic about the potential addition of an indication to treat patients who have chronic sinusitis. Claims data suggest that CS is currently being diagnosed by healthcare providers approximately 10 times more frequently than nasal polyps. And in the current healthcare environment, where off-label use is increasingly constrained by payers, we believe the new indication could enable us to access a multifold larger patient audience and therefore drive significant growth. Second, we announced the submission of our supplemental new drug application in February for Exhance as a treatment for patients with chronic sinusitis. This was consistent with our previous guidance and is an important milestone on the road to a potential approval of the new indication in December 2023. Third, we have refocused our strategy to prioritize the potential launch of Xhance as the first-ever FDA-approved drug treatment for CS. Because of important differences in patient prevalence, frequency of diagnosis, and payer dynamics, we believe the potential for return on investment that can be produced by promoting Xhance following the potential label expansion for CS is significantly greater than the return available from promotion of exams as a treatment for nasal polyps. Because of this, we have, as we enter 2023, structured our business to reduce the use of cash during 2023 and to increase our focus on profitability while preserving the infrastructure and capabilities that will be important to a rapid and successful launch in CS following the potential approval. These principles have shaped our expectations for 2023, and we will discuss those expectations later in the presentation. Turning to slide four, we believe the future approval of Exhance as the first and only FDA-approved treatment for CS has potential to increase the number of patients for whom the product can be promoted by tenfold because claims data suggests that an order of magnitude more patients are currently diagnosed and treated for chronic sinusitis than are diagnosed and treated for nasal polyps. We expect the greatly expanded universe of potential patients to include those that are currently cared for by physicians in our existing commercial footprint, which would significantly grow our potential within the scope of our current activities. We also expect the expanded universe of patients to include patients who are cared for by physicians outside of our current commercial reach. And we are already exploring a number of ways that future outreach to those physicians and patients is possible, including through commercial partnerships, alternative selling models, modest future expansion of our direct selling efforts or by other means. The fact that claims data show a very large number of patients are being diagnosed with CS today, up to 10 million office visits per year are coded for chronic sinusitis-related diagnoses, gives us optimism that it will not be necessary to engage in educational efforts around the prevalence or recognition of chronic sinusitis. The diagnosis is already being made and documented frequently, much more frequently than nasal polyps, in the course of ordinary clinical practice. In addition, you are aware that we believe payer friction is one of the chief hindrances to product uptake, and the fact that a diagnosis of chronic sinusitis is commonly documented in routine practice may help address one of the most important challenges to uptake created by payers today. Specifically, one of the challenges payers create for physicians prescribing Exhance today is particularly allergists or primary care providers who do not routinely perform nasal endoscopy, is asking for attestation to an on-label diagnosis, which today, of course, is a diagnosis of nasal polyps. The new CF indication may be better aligned with current physician practice behaviors and with payer requirements in addition to addressing a larger patient population. As a reminder, today approximately 80% of commercial lives are in a plan that covers ex-hance, And of those, approximately half are in a plan that requires a primary, I'm sorry, excuse me, are in a plan that requires a prior authorization that includes physician attestation to an on-label diagnosis. While we believe more patients could be diagnosed with nasal polyps than are currently being diagnosed, and that some physicians could independently choose to write exams more broadly for patients with insurance plans that don't require attestation to a nasal polyp diagnosis, having a meaningful number of patients in plans that require attestation we believe is deterring many physicians from writing exams broadly or at all. And of course, our promotional efforts today are constrained to nasal polyps. With a CS indication, we believe there's significant potential for more physicians to be willing to write for a broader group of their patients because it will be comparatively much more straightforward to attest to a diagnosis that they are routinely documenting today. Turning to slide six. On February 16th, we submitted our supplemental new drug application in pursuit of the additional EXANT indication for treatment of patients with chronic rhinosinusitis. This is a novel indication for which no drug has ever been approved by FDA. Accordingly, the specific language of this potential future indication is a bit uncertain and may be chronic sinusitis, chronic rhinosinusitis, chronic rhinosinusitis without nasal polyps, or other similar language. From a promotional perspective, we view these terms as interchangeable. Focusing on what's next, we are now in a 74-day window during which FDA will decide whether to accept the SNDA submission for filing. Based on the submission date, we expect that to occur by the start of May. If accepted, the standard FDA review period for this type of application is 10 months, 10 months from the submission date. which would result in an expected FDA action date in mid-December 2023. I will not review data from the ReOPEN program in detail during prepared remarks. However, we have included summaries of the co-primary endpoints in an appendix to today's presentation. ReOPEN was a landmark program and a major accomplishment for our organization and for the field. If there are any questions, we'll be happy to address those during the Q&A session. Turning to slide eight, While our fourth quarter and full year 2022 results were aligned with the expectations that were set in our last call, we are not satisfied with these results. Accordingly, we've made significant changes to our organization as well as to how we plan to operate moving forward. Our initial changes, already implemented, will focus on reducing total expenses while concentrating our commercial investments for growth on our most productive territories and programs. In addition, Our new Chief Commercial Officer, Paul Spence, and his team are evaluating and acting on a number of key factors that we believe underlie the revenue trends observed in the second half of 2022. He's taken on this challenge energetically and with an eye on both improving the tactical quality of our commercial execution and on a variety of potential strategic changes during the coming months. Specific examples of areas receiving attention include improving the efficiency with which active physician interest in prescribing exams is converted to fill the prescriptions that drive net revenue, the rate at which prior authorization paperwork is submitted, the structure and implementation of our copay program, and the size and management of our pharmacy distribution network and our payer strategy. Our commercial team is aware that these and other areas where we are evaluating and considering action this year have potential ramifications not only for our promotional efforts in nasal polyps in 2023, but also for how we are setting the organization up for a successful launch of the much larger new CS indication. I'd like to note that we'll be looking for evidence of performance improvement before we allow our commercial changes to influence our outlook for the full year 2023. As for results, in fourth quarter 2022, there were approximately 27,700 new prescriptions for exams, a decrease of 7% compared to fourth quarter 2021, while a market defined by INS prescriptions written by any physician for any condition, a large component of which are prescriptions for allergic rhinitis, increased by 5% over the same period. For the full year 2022, there were approximately 113,100 new prescriptions for Ex-Hance, a slight increase compared to full year 2021, while the INS market I just described increased by 7% over the same period. Turning to slide 9, in fourth quarter 2022, there were approximately 86,200 total prescriptions for Ex-Hance, a decrease of 8% compared to fourth quarter 2021, while the market, which includes INS prescriptions written by any physician for any condition, a large component of which are prescriptions for allergic rhinitis, increased by 3% over the same period. For the full year 2022, there were approximately 341,000 total prescriptions for ex-ants, a 2% increase compared to full year 2021, while the INS market previously described increased by 4% over the same period. Turning to slide 10. Exhance market share of 5.7% in fourth quarter of 2022 decreased when compared to the 5.9% share in fourth quarter 2021. In the future, we may eliminate or replace this measure because the denominator we use to calculate this fraction has limitations. As a reminder, the denominator for this share includes all intranasal steroid prescriptions written by an audience of approximately 21,000 physicians, which includes a substantial number of prescriptions for indications such as allergic rhinitis, and which does not include prescriptions for the several biologics that are indicated to treat nasal polyps. Breadth and depth of physician prescribing, as measured by the total number of physicians who have patients filling ex-hance prescriptions, had mixed results from fourth quarter 21 to fourth quarter 22. Regarding breadth, in fourth quarter of 22, there were 8,104 physicians who had a patient fill at least one prescription for ex-hance, an increase of 8% compared to fourth quarter of 2021. Regarding depth, the number of physicians who had more than 15 enhanced prescriptions filled by their patients in a quarter decreased by 8% from fourth quarter 21 to fourth quarter 22 with approximately 1,450 physicians in this segment. I will now turn the call over to Jonathan to discuss fourth quarter and full year financial performance and guidance.
Jonathan Neely
Thank you, Rami. Turning to slide 12. As we reported, OP&NOS recognized $20.9 million of Exams Net Revenue in the fourth quarter of 2022, a decrease of 7% compared to fourth quarter 2021 net revenues of $22.5 million. The primary driver of the year-over-year decrease in fourth quarter is the prescription demand that Rami just discussed. Full year 2022 Exams Net Revenue was $76.3 million, an increase of 4% compared to the prior year. Turning to slide 13. Based on available prescription data purchased from third parties and on data we received directly from a preferred pharmacy network, the average net revenue per prescription for the fourth quarter of 2022 was $242, an increase of 1% compared to $240 of revenue per prescription in fourth quarter of 2021. Full year 2022, average net revenue per prescription was $224 and reflects an increase of approximately 2% compared to $219 for the full year of 2021. As we discussed on prior calls, we made a change to our copay assistance program at the start of 2022 that was intended to increase average net revenue per prescription by reducing the number and proportion of prescription fills by commercially insured patients and plans that have a high deductible. We believe this change had the intended effect, reduced our copay assistance expense and increased average net revenue per prescription in the early part of the year. We believe the increase in average net revenue per prescription due to the change in copay assistance helped offset effects of an increasing proportion of our prescription volumes through government plans and increases to contracted rebates and commercial plans, both of which have the effect of decreasing average net revenue per prescription. Turning to slide 15, today we announced our initial financial guidance for 2023. Our guidance reflects our commitment to refocus our strategy to prioritize the potential launch of Exhance as the first ever FDA-approved drug treatment for chronic rhinosinusitis. And I hope the message our investors take home today is that we are focused as a company on preserving cash that we believe will generate a higher return if used to support a CS launch, while maintaining the infrastructure necessary to rapidly and successfully launch the new indication upon approval. First, for the full year of 2023, we expect total operating expenses to be in the range from $90 to $95 million, of which approximately $8 million is stock-based compensation. This is a reduction of approximately $30 million, or 25%, compared to the $123 million reported for the full year of 2022. It reflects actions taken to reduce both employee-related and third-party expenses. Approximately half of the $30 million reduction is attributable to sales and marketing, and the remainder is available to general administrative expenses and reduced research and development that follows from the conclusion of the re-open program. As part of actions intended to reduce total operating expenses for full year 2023, the company reduced its number of territory managers by approximately 15% at the end of 2022. Second, bearing in mind the level of sales and marketing expense reductions and our second half 2022 prescription trends, Our expectation for ExanceNet revenue for the full year of 2023 is between $62 million to $68 million. It is important to note that we are not assuming revenues from a CS launch in our full year 2023 guidance. Third, as part of our expectation for full year 2023, we expect first quarter 2023 ExanceNet revenue to be approximately $10 million. The year-over-year decrease to enhance net revenue for the first quarter of 2023 is a consequence of an expected increase in gross net deductions and an expected decrease in unit ship. The expected increase in gross net deductions in the first quarter of 2023 includes increased rebates and changes in business mix that also influence our full year 2023 net revenue expectations and average net revenue per prescription. We expect average net revenue per prescription to be approximately $200 for the full year of 2023. Finally, as we noted in our earnings press release this morning, all of our financial obligations under the amended and restated Pharmacon no purchase agreement have been classified as current liability under GAAP. Each quarter, we perform forward-looking analyses to evaluate the alignment of the projected performance of our current business, our current liquidity, and the terms of our debt agreement. Under GAAP, the projections we are permitted to use in the analyses are generally based only on the business that we have today, that is, Exhance approved as a treatment for chronic rhinosinusitis with nasal polyps. On that accounting basis, we believe it is probable that we will not be able to maintain compliance with certain financial and liquidity covenants in the agreement. It is important to note that this assessment does not account for revenues from a CSO approval, the potential to add a partner for primary care, and other events that could lead to us achieving compliance in the future. I will now turn the call back over to Rami for closing remarks. Rami?
Jonathan
Thank you, Jonathan. Before moving to Q&A, and as we turn our attention fully forward to 2023, I'd like to take a moment to reiterate our strategic focus this year. First, we believe achieving the first ever chronic sinusitis indication will be a crucial driver of future value for patients and for our company. It's therefore our top priority. Second, we are dissatisfied with our commercial results in 2022. Mindful of the importance of the cash we have today and of the potentially greater value of commercial investment following the future potential CS indication, we have taken and will continue to take action to efficiently generate ex-hance revenue with the current indication. Third, we must prepare our organization to seize the potential opportunity created by a new chronic sinusitis indication by planning for a successful launch aimed at rapidly making the product available to millions of patients in need. This will require a range of efforts during 2023 to position ourselves for an inflection in 2024. With that, I'd like to thank you for your attention this morning and open the call for Q&A.
Operator
As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from Brandon Foulkes with Cantor. Your line is now open.
Brandon Foulkes
Hi, thanks for taking my questions and congratulations, Rami, on the appointment. Maybe just from me, how quickly can you ramp the CS label uptake, just given sort of we go back to the revenue covenants in the first quarter of 2024? And then similarly, can you just elaborate a bit more on the first sort of headwinds you're seeing in 2023 and why could those different 2024 with the CS indication in the label? Thank you.
Jonathan
Hey, Brandon, and thank you. So obviously we're not sharing a CS forecast for 2024 at this time, but I'll just share a couple of general thoughts about the nature of the launch for CS. The first thing I'll say is that this is the launch of a new indication, not a de novo launch of a new product into the market. So we have the advantage of physicians who are already in established relationships with our commercial organization. We have the advantage of the distribution channels that are already in place. We have the advantage of many of the prescribers that we'll be talking to already having a general familiarity with the product, all of which may not be the same if we were launching a product de novo into the marketplace. So those things, I think, will facilitate the adoption of the product more rapidly than it might be if we were launching new. On the other hand, it's never a good idea to underestimate the potential impact of payer barriers. We are aware of that and we'll be working to address that. And as I noted earlier, there's a variety of reasons to think that the CS indication actually will be much easier to prescribe than the nasal polyp indication, you know, for the reasons I discussed earlier. So those are just some general thoughts that I think could suggest, you know, the rapid and successful launch of CS in 2024. I don't know, Paul or Jonathan, if you wish to add anything.
Jonathan Neely
No, I think that's good. Yeah, I think, you know, in terms of, you know, typical first quarter cadence, you know, for 2024. I think, you know, each year we talk a little bit about, you know, the start of year, you know, resets on out-of-pocket expenses for patients. You know, I think, you know, typically that results in a lower, you know, revenue per, you know, prescription in first quarter as patients, you know, meet that out-of-pocket minimum and, you know, there's kind of greater reliance on our copay assistance program during that period. I think our expectations at the beginning of next year would be similar to what they are each year in terms of that dynamic.
spk17
Great. Thank you very much.
Operator
Please stand by for our next question. Our next question comes from Gary Natchman with BMO Capital Markets. Your line is now open.
Gary Natchman
Hi, guys. Good morning. So, you know, with a lot of the evaluation of the commercial components and strategies that you highlighted that you're doing this year, it sounds like you're taking a close look at everything. So, you know, what are the areas where you think you need to have the greatest change and how long it'll take to affect those changes? And then with the reduction in territory managers by 15%, where does that put the size of the sales force currently?
Jonathan
So, Gary, I'll start, and then I'll ask Paul if he has any additional comments to add. And thank you, Gary, for your question. The first thing I'll address is the last question. The current number of territories that we have deployed is 77, and we think that allows us to cover the sort of most potential, the physicians with the greatest potential from our current universe, not understanding, of course, the product's been on the market for several years, and we have a better sense of physicians who are prescribing today than we had when we initially launched. So with regard to the areas of action, you observed that it sounded to you, I think, like we were acting in every area of commercial, and I'm kind of glad that you reached that conclusion because we've sort of opened the full book to reevaluate all aspects of our commercialization So nothing is off the table for consideration. Having said that, the areas that I specifically mentioned as examples are areas where we think a greater focus or attention is likely to produce the greatest potential for a change, the greatest difference during 2023. The timeline for the expectation for change varies depending on which of those areas we're talking about. So some of those things, Paul and his team have already acted to look for changes. Some of those things have been subjected to fairly intensive analysis, and we expect action to be following here later during March or during the spring. And the timeframe for seeing the difference in the market, again, varies by which of those tactics we're talking about. Paul, would you like to add anything?
Gary
Yeah, Gary, thank you for the question. So to start the year, there's actually several areas that are receiving particular attention, as Rami had mentioned. A particular note, we just came from our national sales meeting where we were focused on several things. One most importantly was improving the efficiency with which active written enhanced prescriptions are converted to filled dispensed prescriptions that ultimately are going to drive greater revenue. In particular around that, stronger patient positioning and improving the quality and speed of PA submission was a lot of our tension last week as we were together. In addition, the structure and implementation of our co-pay program, the size and management of our pharmacy distribution network, and our payer access strategy are all receiving particular attention as well. Okay, that's helpful.
Gary Natchman
Yeah, yeah, no, it did. I mean, it sounds like things are going to be evolving over the course of the year, and I'm sure we'll get updates on all these different areas. But, you know, when it comes to thinking about the CF launch, you know, do you have any sense of how much of an effort you're going to need behind that at this point? And, you know, just, Rami, talk about some of the discussions you might be having with potential co-promote partners and what some other sales alternatives might be. You mentioned that in the prepared remarks.
Jonathan
Um, yeah, sure. Gary. And thanks for that, for that question. Um, so we are doing a lot during 2023 to prepare, um, to be able to have a rapid and successful launch, uh, as we, as we head into, into next year with the new indication, should we receive that in December? And some of those things require this kind of lead time. So Paul alluded to, um, uh, payer access, you know, payer access as ramifications, not just now. obviously, as ramifications for 2024. And many of the negotiations happening now are specific to contracts, which will come into force at the beginning of 2024. So there's a lot of things we have to do now to be ready for next year. The overall commercial investment, the size and distribution sort of footprint of our direct selling structure and sort of some other major selling efforts I don't expect that to change substantially in size. It's not so much about having to ramp up the size of it going into 24. It's more about changing the content and the strategy and the manner of execution in order to shift the focus to this newer, more commonly diagnosed, you know, easier to see sort of widespread uptake indication. So it's not an issue so much of size as of style or quality of the work that we'll be doing, if that's sort of what you were getting at with regard to the plans for our commercial infrastructure. Is that getting at the issue you're asking about, Gary?
Gary Natchman
Yeah. No, I mean, that's helpful. But, you know, as far as potential co-promotes and then you said other types of selling alternatives for chronic sinusitis. And if you're not going to change the size of the footprint, then there's other ways that you'd be able to tap into that larger market, I presume.
Jonathan
Right. Well, so, Gary, the way we're thinking about this is that there's a substantially increased potential within our current specialty audience. And that's what I was talking about before. But as you said, there's a lot of potential outside of our current specialty audience also. And we have to think creatively about the ways in which our company can realize the benefits of getting the product in the hands of patients who need it in that much larger audience. The most obvious way, and one we would like to see if possible, of course, is if we're able to engage in some kind of commercial partnership with an organization that has an existing infrastructure that allows promotion into that primary care audience. And we are planning to continue to actively pursue conversations with organizations that have the necessary infrastructure and an interest in a product that creates leverage with that infrastructure. So that would be one way of our organization seeing potential benefit from that. I also alluded to the possibility that there are other ways we might see those benefits, ways that might not involve having to share value in the same ways as we might have to in a primary care partnership. And those ways are a little less certain but worthy of exploration right now during our lead time up to the new indication. For example, there appear to be emerging models in the marketplace for mechanisms of reaching out directly to patients and sort of using nontraditional promotional mechanisms to engage those patients, get them access to providers able to make an appropriate diagnosis, and, if appropriate, prescribe the product for them and to fill that prescription in ways that include our current pharmacy network or potentially other mechanisms for fulfillment that may increase efficiency and outreach for a broader population that's not within our current specialty universe. I don't want to define what that looks like yet because, as I said a minute ago, it's something that we are beginning to actively explore. It looks like there are some potential um mechanisms by which this may be possible um and i want to be clear that we are not um we're not closed-minded we are open-minded to a variety of potential mechanisms for getting the hand the product in the hands of patients who who may need it that are outside of our specialty care outside of our specialty care universe okay great um and that's just last one you know a little bit more on the net revenue per prescription coming down to 200 from 240
Gary Natchman
If you guys are going to be focusing more on profitability this year, is that mostly volume-driven or, you know, there are different programs that you're factoring into that? And could we expect you, if this is just going to be a transition year, with the CS indication to get it back up to the levels we saw last year? Thanks.
Jonathan
Yeah, no, that's a really good question. And it is a significant decrease in our projected average net revenue per prescription. Jonathan, would you like to comment on that?
Jonathan Neely
Yeah, sure. I mean, Gary, thanks for the question. You know, so the guidance that we put out, you know, of approximately $200, you know, for average net revenue per prescription, you know, it incorporates, you know, some changes in business mix, you know, as well as, you know, higher gross net deductions within lines of business. And I believe that, you know, I think in a rising interest rate environment that may lead to customers carrying less inventory at the end of 2023, than they did in 2021 and 2022. I think some of where we ended up, I think, in 2022 was the result, I think, of some benefits that you wouldn't necessarily plan for at the start of a year. As a reminder, last year we started out with guidance for the year of approximately $210 per TRX. And so we ended up the year at approximately $224. So I think in terms of looking at business trends around mix of business, also making some choices to contract a little bit further into certain government lines of business, which is driving mix into those lines of business, which are relatively less profitable but still good lines of business. can have halo effect with physicians who also serve commercial patients. You know, those things are all kind of, you know, in the mix for our initial guidance here for an expectation of $200 per TRX. Okay.
Gary Natchman
But it sounds like this might be more of the new normal. So even with CS, it'll be more in this level, or could it get back up a little bit, even if not for the 224? Yeah, I think...
Jonathan Neely
You know, probably the other thing that I would note is that, you know, at the start of the last two years, you know, we made some changes to our copay assistance program. You know, in 2021, you know, we made a change to the copay assistance program that was focused on, you know, reducing the number proportion of prescriptions that were coming from patients who were in commercial plans that did not cover exams. In 2022, you know, we made a change to the copay assistance program. Again, kind of intended to reduce the number and proportion of prescriptions, but this time from patients who were in commercial plans with a high deductible, which cover expense. Both of those kinds of lines of businesses are relatively less profitable for us, or in certain cases can actually be unprofitable lines of business for us. We haven't made a similar kind of profitability optimizing change to copay assistance at the start of 2023, but that doesn't mean that we can't look at things like that as we move forward. Okay, that's helpful. Thank you.
Operator
Please stand by for our next question. Our next question comes from Glenn Santangelo with Jeffries. Your line is now open.
Glenn Santangelo
Oh, yeah. Thanks for taking my question.
Glenn
Now, I just wanted to talk about the balance sheet a little bit. I mean, you know, you're ending the year with $94 million in cash. And, you know, it's sort of based on that new revenue guidance of $68 million, you know, versus the outlook for operating expenses, you know, that you're providing. I mean, you kind of gave us enough of the pieces here, but I just wonder if you could just sort of summarize that. and give us your expected sort of cash burn in 2023?
Jonathan
Hey, Glenn. Thank you for the question. I'll turn that one over to Jonathan also.
Jonathan Neely
Yeah, sure. Thanks, Glenn. Yeah, I think you kind of hit the nail on the head. I think we've given you enough pieces to maybe put the math together yourself or yourselves. But, you know, obviously, you know, we ended the year with $94 million in cash. As you point out, we structured our business to reduce use of cash in 2023, again, while preserving the infrastructure and capabilities important to a rapid and successful launch in CS following potential approval. The midpoint of our revenue and operating expense ranges, they imply approximately a $20 million improvement to operating income relative to full year 2022. And I think, you know, the way we're structured as a business, we expect that similar improvement to the use of cash. And so then, you know, as a note for folks, if you don't have the press release open or the 10K open later on, our use of cash in 2022 was approximately $67 million.
Glenn
Right, right. So I'm correct sort of assuming that burn kind of comes down in the $30 to $40 million range.
Jonathan Neely
Um, yeah, I mean, I think, I think the, you know, the kind of midpoint of the operating expense and, um, revenue view would apply, you know, um, approximately $20 million. If you want to kind of range it out with the high and low ends of those things, it's probably somewhere between 15 and $25 million improvement. I think as an organization, you know, we would, um, yeah, try to try to aim for the higher end of that range, you know, not pair up, um, low case revenues with high case, um, operating expenses. So, yeah, I think we would strive to be approximately 20, but maybe a little bit better than 20 within those ranges.
Glenn
Jonathan, that's fine. Then just sort of as a follow-up, I did want to talk about sort of where that will leave you, right? I mean, I think the company's always been pretty much leaning towards the opportunity to enter into some type of commercial partnership, right, in anticipation of the CF indication. Any thoughts with respect to timing around that? I mean, you're sort of laying out, you know, a timeframe for hopefully a PDUFA in mid-December. I mean, you know, have those conversations started? Do you think we could expect to see something in the second half of the year? Or do you think that's kind of more, you know, would come in 2024 post-approval?
Jonathan
So, Glenn, I'll comment on that. So, it's very difficult in advance of reaching an agreement to say exactly when an agreement might be reached. I can say that we have in the past, and I certainly intend right now during 2023 to engage in a variety of conversations with organizations that may have interest in promoting the product into the large audience that we're not reaching with our own commercial footprint. Whether those organizations will prove to be interested in closing an arrangement prior to the PDUFA date, whether they may be interested in seeing the PDUFA approval before closing an arrangement, and what exactly the terms of such an arrangement might be. Those are uncertain. I don't know the answer to those questions yet. But with regard to whether we'll be engaged in active conversations during the course of this year, the answer is definitely yes.
Glenn Santangelo
OK, thanks.
Operator
Please stand by for our next question. Our next question comes from David Anselm with Piper Sandler. Your line is now open.
David Anselm
Thanks. So I guess I'll just sort of, you know, sort of cut to maybe an obvious question, but I think an important one. You're entertaining a co-promote here. I know that's something you've talked about going back to the IPO, but just given... where things are with the business and given the potential challenges regarding interest in owning a piece of the asset here why don't you just entertain a sale of the company and do you think that that may be the the better alternative here just given all the moving parts how do you think about that
Jonathan
So, David, I'll comment on that, and then Johnson, I'll invite you to comment if you have anything to add. But for all the reasons that you've described, David, and others, we are evaluating a wide range of strategic options, and I think sales of the company is within the range of options that we're considering. It always has been, and it will continue to be. It's certainly not the only option. The only possibility we're considering, as I said earlier, we are actively planning to engage in, you know, conversations about a primary care promotional partnership and, you know, plan to do everything necessary to continue to operate the company independently. But in no way does that preclude possibility of conversations about, you know, M&A type transaction either. So we will continue to entertain all strategic options as we go forward through 2023.
David Anselm
And then as a follow-up, as you look at the launch in CS, you've talked about the potential for greater penetration within your existing prescriber base. So is it fair to say that that's where, at least early on in 2021, the rollout, that's where most of your growth is going to come from. And if that is certainly the case, then what is the urgency to entertain a primary care partnership ahead of approval or around the approval?
Jonathan
So, David, the potential for the product, we think, is very substantial within our current you know, sort of commercially contacted our direct selling audience and indirect selling. Our specialty audience has a lot of new potential with the new indication. And we do intend to go after that assertively with our own infrastructure. But that doesn't mean that there's not a lot of additional potential outside of the audience that we're currently calling on. And we really don't have the resources to to go after that, certainly not with a traditional direct selling model. So it means that if we are able to reach a primary care partnership, you know, starting on day one after the approval, there is potential in a very large audience that we're just not going to be able to efficiently access ourselves. And primary care partnership would give us a vehicle for being able to increase the potential value available to us and increase the number of patients who are able to be treated. So it would be incremental value very much worth having, you know, for a variety of reasons that we'd like to see, but that doesn't mean that we're not going to see substantial incremental value within our current audience. So I'm not sure, though, if I've answered your question, David. Did that address what you asked?
David Anselm
It did. I guess I'm just struggling with, you know, the urgency to, you know, find a primary care partner. I mean, don't you call on a certain basket of high-volume general practitioners already? And if so, how many do you call on?
Jonathan
Yeah, no, David, I think it's appropriate for us to have a sense of urgency around finding a primary care partner. And that's not because there's not a lot of potential in our current audience. There is. But the sooner we can get a primary care partner, the sooner we can access an otherwise untapped large potential audience. And while it's true that we do have a small number of, I'll call it a specialist-like primary care physicians in our call-on universe, it's a very small number in comparison to the number of primary care physicians that one might ideally choose to engage if you had a primary care promotional infrastructure program. What's our current number right now?
Jonathan Neely
Yeah, I mean, David, just for a sense of scale, you know, I think when you think about the number of specialty-like primary care physicians in our current call-on universe, you know, we're talking about a number that's, you know, a few thousand as opposed to, you know, when you look at the broader opportunity in primary care, I think historically, you know, we've looked at, you know, there's potentially an audience of you know, somewhere around 50,000 physicians who are, you know, kind of the higher value prescribers in the chronic sinusitis space. And so, you know, it's just a completely different order of magnitude in terms of the number of physicians that somebody with appropriate infrastructure, you know, that would be leverageable with this opportunity could reach if we were to partner with them.
David
Got it. Thank you.
Operator
I show no further questions at this time. I would now like to turn the conference back to Rami for closing remarks.
Jonathan
I'd like to thank you all very much for joining us this morning for our review of the full year performance in 2022 and our forward look into what we expect may be coming in 2023. And we look forward to talking to you again in a few months with our first quarter results. I hope everyone has a wonderful day.
Operator
This concludes today's conference call. Thank you for participating.
spk01
You may now disconnect.
spk20
The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 11. you Thank you. you
spk00
Thank you. you
Operator
Good day and thank you for standing by. Welcome to the OPTINO's fourth quarter 2022 earnings call. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Jonathan Neely, Vice President of Investor Relations. Please go ahead.
Jonathan Neely
Good morning, and thank you for joining us today as we review Optinosis' fourth quarter 2022 performance and our plans for the remainder of the year. I am joined today by our Chairman, Joe Scudari, our CEO, Dr. Rami Mahmoud, and our Chief Commercial Officer, Paul Spence. Joe is contributing to the prepared remarks portion of today's call. Rami, Paul, and I will host the question and answer session. The slides that will be presented on this call can be viewed on our website, optinose.com, in the investor section. Before we start, I would like to remind you that our discussions during this conference call will include forward-looking statements. All statements that are not historical facts are hereby identified as forward-looking statements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated by such statements. Additional information regarding these factors and forward-looking statements is discussed under the Cautionary Note on Forward-Looking Statements section of the earnings release that we issued today, as well as under the Risk Factors section and elsewhere in Opti-Nose's most recent Form 10-K and 10-Qs that are filed with the SEC and available on the website sec.gov and on our website at optinose.com. Your caution not to place undue reliance on forward-looking statements The forward-looking statements during this conference call speak only as of the original date of this call or any earlier date indicated in such statement, and we undertake no obligation to update or revise any of these statements. We will now make prepared remarks, and then we will move to the question and answer session. With that, I will now turn the call over to Joe Scudari. Joe?
Joe Scudari
Thanks, Jonathan, and good morning, everyone. You've all had the opportunity to interact with Romney over the years in his prior position as President and Chief Operating Officer of the company. But given the recent decision to name him CEO, I'm taking this opportunity to introduce him and to share some perspectives about him on behalf of the board of directors. As you know, Peter recently made the decision to step down as CEO. In that context, the board confronted the question of CEO succession. Obviously, a very important decision for any company, private or public. As the board discussed this decision, we recognized that we were in this somewhat unique position for a company of our size to have a ready now candidate to promote into the position. As you know, Rami has been a part of building OptiNose from its very beginning and has been a very close working partner with Peter. The fact that he can step into the CEO position given that history is an incredible benefit to the company, its shareholders, the management team, all of our people, and the customers and patients we serve. I've known Rami for more than 20 years, dating from the time that we overlapped while we were both employed by Johnson & Johnson. In this case, while Rami served as a member of the management team at Janssen Pharmaceutica, and I served as company group chairman and later worldwide chairman of the pharmaceutical sector. During that period, in the very robust succession planning processes within J&J, Rami was consistently viewed as a rising star with significant upward potential for senior leadership roles, both within and beyond medical affairs and R&D. Over the past five years as chairman of the board for OptiNose, I've had the chance to work more closely with him and further recognize his leadership skills. We all recognize Rami's role in highlighting the development of the chance for chronic rhinosinusitis, but he brings much more to the senior leadership roles he has occupied and the board is confident he will do so as the company's CEO. It's rare to see a senior executive in our industry that is trained as an MD, served in the military, and combines a history of highly productive drug development with exceptional executive and leadership skills. Ramy's been an integral part of building OptiNose into what it is today. And notwithstanding the challenges the industry and the company has faced in the last few years, Ramy is ready now to lead the company into its next chapter of growth. With the filing of the supplemental NDA for the chronic rhinosinusitis indication now behind us, Rami will lead the effort to ensure the company is ready to launch its hands for this very important application. As you know, there is currently no FDA-approved therapy for this disease, and a high level of patient satisfaction with the therapeutic options currently available. The planning is already underway to get the company into the position to successfully launch X-Hands into a marketplace with significant unmet medical need in the not too distant future. I can speak on behalf of the entire board of directors when I say that we are thrilled that this executive transition has already occurred from the prior to the new CEO. We anticipate we will not miss a beat and that Rami will lead this team to the next level of success while maintaining the culture and values that have contributed to the company winning awards for being a great place to work. Thank you all for listening, and now I'll turn it over to Rami. Rami?
Jonathan
Thank you very much, Joe, for your kind remarks, and thank you to everyone listening for joining us this morning. We appreciate you joining us for our fourth quarter update. Before we get started with our business update, I would like to introduce our new Chief Commercial Officer, Paul Spence. Paul was most recently the Senior Vice President of the U.S. Pharmaceutical Commercial Organization at AMU Therapeutics, a division of Nestle Health Sciences, and has nearly 30 years of experience in the life science and pharmaceuticals industry as a commercial leader, including responsibility for marketing, sales, market access, and commercial operations. His history of relentless focus on commercial execution and lengthy experience building successful commercial organizations and brands out of products with profiles similar to Ex-Hance is a big part of why we believe he will be successful in his role as the new leader of our commercial team. So starting on slide three, we'll go into more detail in a moment, but I'd like to highlight three key takeaways from today's presentation. First, we remain enthusiastic about the potential addition of an indication to treat patients who have chronic sinusitis. Claims data suggest that CS is currently being diagnosed by healthcare providers approximately 10 times more frequently than nasal polyps, and in the current healthcare environment where off-label use is increasingly constrained by payers, we believe the new indication could enable us to access a multifold larger patient audience and therefore drive significant growth. Second, we announced the submission of our supplemental new drug application in February for X-HANDS as a treatment for patients with chronic sinusitis. This was consistent with our previous guidance and is an important milestone on the road to a potential approval of the new indication in December 2023. Third, we have refocused our strategy to prioritize the potential launch of Xhance as the first-ever FDA-approved drug treatment for CS. Because of important differences in patient prevalence, frequency of diagnosis, and payer dynamics, we believe the potential for return on investment that can be produced by promoting Xhance following the potential label expansion for CS is significantly greater than the return available from promotion of exams as a treatment for nasal polyps. Because of this, we have, as we enter 2023, structured our business to reduce the use of cash during 2023 and to increase our focus on profitability while preserving the infrastructure and capabilities that will be important to a rapid and successful launch in CS following the potential approvals. These principles have shaped our expectations for 2023, and we will discuss those expectations later in the presentation. Turning to slide four, we believe the future approval of Xhance as the first and only FDA-approved treatment for CS has potential to increase the number of patients for whom the product can be promoted by tenfold because claims data suggests that an order of magnitude more patients are currently diagnosed and treated for chronic sinusitis than are diagnosed and treated for nasal polyps. We expect the greatly expanded universe of potential patients to include those that are currently cared for by physicians in our existing commercial footprint, which would significantly grow our potential within the scope of our current activities. We also expect the expanded universe of patients to include patients who are cared for by physicians outside of our current commercial reach and we are already exploring a number of ways that future outreach to those physicians and patients is possible, including through commercial partnerships, alternative selling models, modest future expansion of our direct selling efforts, or by other means. The fact that claims data show a very large number of patients are being diagnosed with CS today, up to 10 million office visits per year are coded for chronic sinusitis-related diagnoses, gives us optimism that it will not be necessary to engage in educational efforts around the prevalence or recognition of chronic sinusitis. The diagnosis is already being made and documented frequently, much more frequently than nasal polyps, in the course of ordinary clinical practice. In addition, you are aware that we believe payer friction is one of the chief hindrances to product uptake, and the fact that a diagnosis of chronic sinusitis is commonly documented in routine practice may help address one of the most important challenges to uptake created by payers today. Specifically, one of the challenges payers create for physicians prescribing Exhance today is particularly allergists or primary care providers who do not routinely perform nasal endoscopy, is asking for attestation to an on-label diagnosis, which today, of course, is a diagnosis of nasal polyps. The new CF indication may be better aligned with current physician practice behaviors and with payer requirements in addition to addressing a larger patient population. As a reminder, today approximately 80% of commercial lives are in a plan that covers ex-hance and of those, approximately half are in a plan that requires a primary, I'm sorry, excuse me, are in a plan that requires a prior authorization that includes physician attestation to an on-label diagnosis. While we believe more patients could be diagnosed with nasal polyps than are currently being diagnosed, and that some physicians could independently choose to write exams more broadly for patients with insurance plans that don't require attestation to a nasal polyp diagnosis, having a meaningful number of patients in plans that require attestation we believe is deterring many physicians from writing exams broadly or at all. And of course, our promotional efforts today are constrained to nasal polyps. With a CS indication, we believe there's significant potential for more physicians to be willing to write for a broader group of their patients because it will be comparatively much more straightforward to attest to a diagnosis that they are routinely documenting today. Turning to slide six. On February 16th, we submitted our supplemental new drug application in pursuit of the additional expense indication for treatment of patients with chronic rhinosinusitis. This is a novel indication for which no drug has ever been approved by FDA. Accordingly, the specific language of this potential future indication is a bit uncertain and may be chronic sinusitis, chronic rhinosinusitis, chronic rhinosinusitis without nasal polyps, or other similar language. From a promotional perspective, we view these terms as interchangeable. Focusing on what's next, we are now in a 74-day window during which FDA will decide whether to accept the SNDA submission for filing. Based on the submission date, we expect that to occur by the start of May. If accepted, the standard FDA review period for this type of application is 10 months, 10 months from the submission date. which would result in an expected FDA action date in mid-December 2023. I will not review data from the ReOPEN program in detail during prepared remarks. However, we have included summaries of the co-primary endpoints in an appendix to today's presentation. ReOPEN was a landmark program and a major accomplishment for our organization and for the field. If there are any questions, we'll be happy to address those during the Q&A session. Turning to slide eight, While our fourth quarter and full year 2022 results were aligned with the expectations that were set in our last call, we are not satisfied with these results. Accordingly, we've made significant changes to our organization, as well as to how we plan to operate moving forward. Our initial changes, already implemented, will focus on reducing total expenses while concentrating our commercial investments for growth on our most productive territories and programs. In addition, Our new chief commercial officer, Paul Spence, and his team are evaluating and acting on a number of key factors that we believe underlie the revenue trends observed in the second half of 2022. He's taken on this challenge energetically and with an eye on both improving the tactical quality of our commercial execution and on a variety of potential strategic changes during the coming months. Specific examples of areas receiving attention include improving the efficiency with which active physician interest in prescribing exams is converted to fill the prescriptions that drive net revenue, the rate at which prior authorization paperwork is submitted, the structure and implementation of our copay program, and the size and management of our pharmacy distribution network and our payer strategy. Our commercial team is aware that these and other areas where we are evaluating and considering action this year have potential ramifications, not only for our promotional efforts in nasal polyps in 2023, but also for how we are setting the organization up for a successful launch of the much larger new CS indication. I'd like to note that we'll be looking for evidence of performance improvement before we allow our commercial changes to influence our outlook for the full year 2023. As for results, in fourth quarter 2022, there were approximately 27,700 new prescriptions for exams, a decrease of 7% compared to fourth quarter 2021, while a market defined by INS prescriptions written by any physician for any condition, a large component of which are prescriptions for allergic rhinitis, increased by 5% over the same period. For the full year 2022, there were approximately 113,100 new prescriptions for Ex-Hance, a slight increase compared to full year 2021, while the INS market I just described increased by 7% over the same period. Turning to slide 9, in fourth quarter 2022, there were approximately 86,200 total prescriptions for Ex-Hance, a decrease of 8% compared to fourth quarter 2021, while the market, which includes INS prescriptions written by any physician for any condition, a large component of which are prescriptions for allergic rhinitis, increased by 3% over the same period. For the full year 2022, there were approximately 341,000 total prescriptions for ex-ants, a 2% increase compared to full year 2021, while the INS market previously described increased by 4% over the same period. Turning to slide 10. Exhance market share of 5.7% in fourth quarter of 2022 decreased when compared to the 5.9% share in fourth quarter 2021. In the future, we may eliminate or replace this measure because the denominator we use to calculate this fraction has limitations. As a reminder, the denominator for this share includes all intranasal steroid prescriptions written by an audience of approximately 21,000 physicians, which includes a substantial number of prescriptions for indications such as allergic rhinitis, and which does not include prescriptions for the several biologics that are indicated to treat nasal polyps. Breadth and depth of physician prescribing, as measured by the total number of physicians who have patients filling ex-hands prescriptions, had mixed results from fourth quarter 21 to fourth quarter 22. Regarding breadth, in fourth quarter of 22, there were 8,104 physicians who had a patient fill at least one prescription for ex-hands, an increase of 8% compared to fourth quarter of 2021. Regarding depth, the number of physicians who had more than 15 ex-hands prescriptions filled by their patients in a quarter decreased by 8% from fourth quarter 21 to fourth quarter 22 with approximately 1,450 physicians in this segment. I will now turn the call over to Jonathan to discuss fourth quarter and full year financial performance and guidance.
Jonathan Neely
Thank you, Rami. Turning to slide 12. As we reported, OP&NOS recognized $20.9 million of Exams Net Revenue in the fourth quarter of 2022, a decrease of 7% compared to fourth quarter 2021 net revenues of $22.5 million. The primary driver of the year over year decrease in fourth quarter is the prescription demand that Rami just discussed. Full year 2022 Exams Net Revenue was $76.3 million, an increase of 4% compared to the prior year. Turning to slide 13. Based on available prescription data purchased from third parties and on data we received directly from a preferred pharmacy network, SAM's average net revenue per prescription for the fourth quarter of 2022 was $242, an increase of 1% compared to $240 of revenue per prescription in fourth quarter of 2021. Full year 2022, average net revenue per prescription was $224 and reflects an increase of approximately 2% compared to $219 for the full year of 2021. As we discussed on prior calls, we made a change to our copay assistance program at the start of 2022 that was intended to increase average net revenue per prescription by reducing the number and proportion of prescription fills by commercially insured patients and plans that have a high deductible. We believe this change had the intended effect, reduced our copay assistance expense and increased average net revenue per prescription in the early part of the year. We believe the increase in average net revenue per prescription due to the change in copay assistance helped offset effects of an increasing proportion of our prescription volumes through government plans and increases to contracted rebates and commercial plans, both of which have the effect of decreasing average net revenue per prescription. Turning to slide 15, today we announced our initial financial guidance for 2023. Our guidance reflects our commitment to refocus our strategy to prioritize the potential launch of Exhance as the first ever FDA-approved drug treatment for chronic rhinosinusitis. And I hope the message our investors take home today is that we are focused as a company on preserving cash that we believe will generate a higher return if used to support a CS launch while maintaining the infrastructure necessary to rapidly and successfully launch the new indication upon approval. First, for the full year of 2023, we expect total operating expenses to be in the range from $90 to $95 million, of which approximately $8 million is stock-based compensation. This is a reduction of approximately $30 million, or 25%, compared to the $123 million reported for the full year of 2022. It reflects actions taken to reduce both employee-related and third-party expenses. Approximately half of the $30 million reduction is attributable to sales and marketing, and the remainder is available to general administrative expenses and reduced research and development that follows from the conclusion of the re-open program. As part of actions intended to reduce total operating expenses for full year 2023, the company reduced its number of territory managers by approximately 15% at the end of 2022. Second, bearing in mind the level of sales and marketing expense reductions and our second half 2022 prescription trends, Our expectation for ExamsNet revenue for the full year of 2023 is between $62 million to $68 million. It is important to note that we are not assuming revenues from a CS launch in our full year 2023 guidance. Third, as part of our expectation for full year 2023, we expect first quarter 2023 ExamsNet revenue to be approximately $10 million. The year-over-year decrease to enhance net revenue for the first quarter of 2023 is a consequence of an expected increase in gross net deductions and an expected decrease in unit ship. The expected increase in gross net deductions in the first quarter of 2023 includes increased rebates and changes in business mix that also influence our full year 2023 net revenue expectations and average net revenue per prescription. We expect average net revenue per prescription to be approximately $200 for the full year of 2023. Finally, as we noted in our earnings press release this morning, all of our financial obligations under the amended and restated Pharmacon no purchase agreement have been classified as current liability under GAAP. Each quarter, we perform forward-looking analyses to evaluate the alignment of the projected performance of our current business, our current liquidity, and the terms of our debt agreement. Under GAAP, the projections we are permitted to use in the analyses are generally based only on the business that we have today, that is, Exhance approved as a treatment for chronic rhinosinusitis with nasal polyps. On that accounting basis, we believe it is probable that we will not be able to maintain compliance with certain financial and liquidity covenants in the agreement. It is important to note that this assessment does not account for revenues from a CSO approval, the potential to add a partner for primary care, and other events that could lead to us achieving compliance in the future. I will now turn the call back over to Rami for closing remarks. Rami?
Jonathan
Thank you, Jonathan. Before moving to Q&A, and as we turn our attention fully forward to 2023, I'd like to take a moment to reiterate our strategic focus this year. First, we believe achieving the first ever chronic sinusitis indication will be a crucial driver of future value for patients and for our company. It's therefore our top priority. Second, we are dissatisfied with our commercial results in 2022. Mindful of the importance of the cash we have today and of the potentially greater value of commercial investment following the future potential CS indication, we have taken, and will continue to take, action to efficiently generate ex-hance revenue with the current indication. Third, we must prepare our organization to seize the potential opportunity created by a new chronic sinusitis indication by planning for a successful launch aimed at rapidly making the product available to millions of patients in need. This will require a range of efforts during 2023 to position ourselves for an inflection in 2024. With that, I'd like to thank you for your attention this morning and open the call for Q&A.
Operator
As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from Brandon Foulkes with Cantor. Your line is now open.
Brandon Foulkes
Hi, thanks for taking my questions, and congratulations, Rami, on the appointment. Maybe just from me, how quickly can you ramp the CS label uptake, just given sort of we go back to the revenue covenants in the first quarter of 2024? And then similarly, can you just elaborate a bit more on the first sort of headwinds you're seeing in 2023, and why could those differ in 2024 with the CS indication in the label? Thank you.
Jonathan
Hey, Brandon, and thank you. So obviously we're not sharing a CS forecast for 2024 at this time, but I'll just share a couple of general thoughts about the nature of the launch for CS. The first thing I'll say is that this is the launch of a new indication, not a de novo launch of a new product into the market. So we have the advantage of physicians who are already in established relationships with our commercial organization. We have the advantage of the distribution channels that are already in place. We have the advantage of many of the prescribers that we'll be talking to already having a general familiarity with the product, all of which may not be the same if we were launching a product de novo into the marketplace. So those things, I think, will facilitate the adoption of the product more rapidly than it might be if we were launching new. On the other hand, it's never a good idea to underestimate the potential impact of payer barriers. We are aware of that and we'll be working to address that. And as I noted earlier, there's a variety of reasons to think that the CS indication actually will be much easier to prescribe than the nasal polyp indication, you know, for the reasons I discussed earlier. So those are just some general thoughts that I think could suggest, you know, the rapid and successful launch of CS in 2024. I don't know, Paul or Jonathan, if you wish to add anything.
Jonathan Neely
No, I think that's good. Yeah, I think, you know, in terms of, you know, typical first quarter cadence for 2024. I think each year we talk a little bit about the start of year resets on out-of-pocket expenses for patients. I think typically that results in a lower revenue per prescription in first quarter as patients meet that out-of-pocket minimum. And there's kind of greater reliance on our copay assistance program during that period. I think our expectations at the beginning of next year would be similar to what they are each year in terms of that dynamic.
spk17
Great. Thank you very much.
Operator
Please stand by for our next question. Our next question comes from Gary Natchman with BMO Capital Markets. Your line is now open.
Gary Natchman
Hi, guys. Good morning. So, you know, with a lot of the evaluation of the commercial components and strategies that you highlighted that you're doing this year, it sounds like you're taking a close look at everything. So, you know, what are the areas where you think you need to have the greatest change and how long it'll take to affect those changes? And then with the reduction in territory managers by 15%, where does that put the size of the sales force currently?
Jonathan
So, Gary, I'll start and then I'll ask Paul if he has any additional comments to add. And thank you, Gary, for your question. The first thing I'll address is the last question. The current number of territories that we have deployed is 77. And we think that allows us to cover the sort of most potential, the physicians with the greatest potential. from our current universe and understanding, of course, the product's been on the market for several years and we have a better sense of physicians who are prescribing today than we had when we initially launched. So with regard to the areas of action, you observed that it sounded to you, I think, like we were acting in every area of commercial. And I'm kind of glad that you reached that conclusion because we've sort of opened the full book to reevaluate all aspects of our commercialization So nothing is off the table for consideration. Having said that, the areas that I specifically mentioned as examples are areas where we think a greater focus or attention is likely to produce the greatest potential for a change, the greatest difference during 2023. The timeline for the expectation for change varies depending on which of those areas we're talking about. So some of those things, Paul and his team have already acted to look for changes. Some of those things have been subjected to fairly intensive analysis, and we expect action to be following here later during March or during the spring. And the timeframe for seeing the difference in the market, again, varies by which of those tactics we're talking about. Paul, would you like to add anything?
Gary
Yeah, Gary, thank you for the question. So to start the year, there's actually several areas that are receiving particular attention, as Rami had mentioned. A particular note, we just came from our national sales meeting where we were focused on several things. One most importantly was improving the efficiency with which active written enhanced prescriptions are converted to filled dispensed prescriptions that ultimately are going to drive greater revenue. In particular around that, stronger patient positioning and improving the quality and speed of PA submission was a lot of our tension last week as we were together. In addition, the structure and implementation of our co-pay program, the size and management of our pharmacy distribution network, and our payer access strategy are all receiving particular attention as well.
Gary
Okay, that's helpful.
Gary Natchman
Yeah, yeah, no, it did. I mean, it sounds like things are going to be evolving over the course of the year, and I'm sure we'll get updates on all these different areas. But, you know, when it comes to thinking about the CF launch, you know, do you have any sense of how much of an effort you're going to need behind that at this point? And, you know, just, Rami, talk about some of the discussions you might be having with potential co-promote partners and what some other sales alternatives might be. You mentioned that in the prepared remarks.
Jonathan
Um, yeah, sure. Gary. And thanks for that, for that question. Um, so we are doing a lot during 2023 to prepare, um, to be able to have a rapid and successful launch, uh, as we, as we head into, into next year with the new indication, should we receive that in December? And some of those things require this kind of lead time. So Paul alluded to, um, uh, payer access, you know, payer access as ramifications, not just now. obviously, as ramifications for 2024. And many of the negotiations happening now are specific to contracts, which will come into force at the beginning of 2024. So there's a lot of things we have to do now to be ready for next year. The overall commercial investment, the size and distribution sort of footprint of our direct selling structure and sort of some other major selling efforts I don't expect that to change substantially in size. It's not so much about having to ramp up the size of it going into 24. It's more about changing the content and the strategy and the manner of execution in order to shift the focus to this newer, more commonly diagnosed, easier to see sort of widespread uptake indication. So it's not an issue so much of size as of style or quality of the work that we'll be doing, if that's sort of what you were getting at with regard to the plans for our commercial infrastructure. Is that getting at the issue you're asking about, Gary?
Gary Natchman
Yeah. No, I mean, that's helpful. But, you know, as far as potential co-promotes and then you said other types of selling alternatives for chronic sinusitis. And if you're not going to change the size of the footprint, then there's other ways that you'd be able to tap into that larger market, I presume.
Jonathan
Right. Well, so, Gary, the way we're thinking about this is that there's a substantially increased potential within our current specialty audience. And that's what I was talking about before. But as you said, there's a lot of potential outside of our current specialty audience also. And we have to think creatively about the ways in which our company can realize the benefits of getting the product in the hands of patients who need it in that much larger audience. The most obvious way, and one we would like to see if possible, of course, is if we're able to engage in some kind of commercial partnership with an organization that has an existing infrastructure that allows promotion into that primary care audience. And we are planning to continue to actively pursue conversations with organizations that have the necessary infrastructure and an interest in a product that creates leverage with that infrastructure. So that would be one way of our organization seeing potential benefit from that. I also alluded to the possibility that there are other ways we might see those benefits, ways that might not involve having to share value in the same ways as we might have to in a primary care partnership. And those ways are a little less certain but worthy of exploration right now during our lead time up to the new indication. For example, there appear to be emerging models in the marketplace for mechanisms of reaching out directly to patients and sort of using nontraditional promotional mechanisms to engage those patients, get them access to providers able to make an appropriate diagnosis, and, if appropriate, prescribe the product for them and to fill that prescription in ways that include our current pharmacy network or potentially other mechanisms for fulfillment that may increase efficiency and outreach for a broader population that's not within our current specialty universe. I don't want to define what that looks like yet because, as I said a minute ago, it's something that we are beginning to actively explore. It looks like there are some potential um mechanisms by which this may be possible um and i want to be clear that we are not um we're not closed-minded we are open-minded to a variety of potential mechanisms for getting the hand the product in the hands of patients who who may need it that are outside of our specialty care outside of our specialty care universe okay great um and that's just last one you know a little bit more on the net revenue per prescription coming down to 200 from 240
Gary Natchman
If you guys are going to be focusing more on profitability this year, is that mostly volume-driven or, you know, there are different programs that you're factoring into that? And could we expect you, if this is just going to be a transition year, with the CS indication to get it back up to the levels we saw last year? Thanks.
Jonathan
Yeah, no, that's a really good question. And it is a significant decrease in our projected average net revenue per prescription. Jonathan, would you like to comment on that?
Jonathan Neely
Yeah, sure. I mean, Gary, thanks for the question. You know, so the guidance that we put out, you know, of approximately $200, you know, for average net revenue per prescription, you know, it incorporates, you know, some changes in business mix, you know, as well as, you know, higher gross net deductions within lines of business. And I believe that, you know, I think in a rising interest rate environment that may lead to customers carrying less inventory at the end of 2023, than they did in 2021 and 2022. Yeah, I think some of where we ended up, I think, in 2022 was the result, I think, of some benefits that you wouldn't necessarily plan for at the start of a year. As a reminder, last year we started out with guidance for the year of approximately $210 per TRX. And so we ended up the year at approximately $224. So I think in terms of looking at business trends around mix of business, also making some choices to contract a little bit further into certain government lines of business, which is driving mix into those lines of business, which are relatively less profitable but still good lines of business. can have halo effect with physicians who also serve commercial patients. You know, those things are all kind of, you know, in the mix for our initial guidance here for an expectation of $200 per TRX. Okay.
Gary Natchman
But it sounds like this might be more of the new normal. So even with CF, it'll be more in this level, or could it get back up a little bit, even if not to the 224? Yeah, I think...
Jonathan Neely
You know, probably the other thing that I would note is that, you know, at the start of the last two years, you know, we made some changes to our copay assistance program. You know, in 2021, you know, we made a change to the copay assistance program that was focused on, you know, reducing the number proportion of prescriptions that were coming from patients who were in commercial plans that did not cover exams. In 2022, you know, we made a change to the copay assistance program. Again, kind of intended to reduce the number and proportion of prescriptions, but this time from patients who were in commercial plans with a high deductible, which cover expense. Both of those kinds of lines of businesses are relatively less profitable for us, or in certain cases can actually be unprofitable lines of business for us. We haven't made a similar kind of profitability optimizing change to copay assistance at the start of 2023, but that doesn't mean that we can't look at things like that as we move forward. Okay, that's helpful. Thank you.
spk01
Please stand by for our next question.
Operator
Our next question comes from Glenn Santangelo with Jeffries. Your line is now open.
Glenn Santangelo
Oh, yeah. Thanks for taking my question.
Glenn
Now, I just wanted to talk about the balance sheet a little bit. I mean, you know, you're ending the year with $94 million in cash, and, you know, sort of based on that new revenue guidance of $68 million, you know, versus the outlook for operating expenses, you know, that you're providing. I mean, you kind of gave us enough of the pieces here, but I just wonder if you could just sort of summarize that and give us your expected sort of cash burn in 2023?
Jonathan
Hey, Glenn. Thank you for the question. I'll turn that one over to Jonathan also.
Jonathan Neely
Yeah, sure. Thanks, Glenn. Yeah, I think you kind of hit the nail on the head. I think we've given you enough pieces to maybe put the math together yourself or yourselves. But, you know, obviously, you know, we ended the year with $94 million in cash. As you point out, we structured our business to reduce use of cash in 2023, again, while preserving the infrastructure and capabilities important to a rapid and successful launch in CS following potential approval. The midpoint of our revenue and operating expense ranges, they imply approximately a $20 million improvement to operating income relative to full year 2022. And I think, you know, the way we're structured as a business, we expect that similar improvement to the use of cash. And so then, you know, as a note for folks, if you don't have the press release open or the 10K open later on, our use of cash in 2022 was approximately $67 million.
Glenn
Right, right. So I'm correct sort of assuming that burn kind of comes down in the $30 to $40 million range.
Jonathan Neely
Um, yeah, I mean, I think, I think the, you know, the kind of midpoint of the operating expense and, um, revenue view would apply, you know, um, approximately $20 million. If you want to kind of range it out with the high and low ends of those things, it's probably somewhere between 15 and $25 million improvement. I think as an organization, you know, we would, um, yeah, try to try to aim for the higher end of that range, you know, not pair up, um, low case revenues with high case, um, operating expenses. So, yeah, I think we would strive to be approximately 20, but maybe a little bit better than 20 within those ranges.
Glenn
Jonathan, that's fine. Then just sort of as a follow-up, I did want to talk about sort of where that will leave you, right? I mean, I think the company's always been pretty much leaning towards the opportunity to enter into some type of commercial partnership, right, in anticipation of the CF indication. Any thoughts with respect to timing around that? I mean, you're sort of laying out, you know, a timeframe for hopefully a PDUFA in mid-December. I mean, you know, have those conversations started? Do you think we could expect to see something in the second half of the year? Or do you think that's kind of more, you know, we'd come in 2024 post-approval?
Jonathan
So, Glenn, I'll comment on that. So, it's very difficult in advance of reaching an agreement to say exactly when an agreement might be reached. I can say that we have in the past, and I certainly intend right now during 2023 to engage in a variety of conversations with organizations that may have interest in promoting the product into the large audience that we're not reaching with our own commercial footprint. Whether those organizations will prove to be interested in closing an arrangement prior to the PDUFA date, whether they may be interested in seeing the PDUFA approval before closing an arrangement, and what exactly the terms of such an arrangement might be, those are uncertain. I don't know the answer to those questions yet. But with regard to whether we'll be engaged in active conversations during the course of this year, the answer is definitely yes.
Glenn Santangelo
Okay, thanks.
Operator
Please stand by for our next question. Our next question comes from David Anselm with Piper Sandler. Your line is now open.
David Anselm
Thanks. So I guess I'll just sort of, you know, sort of cut to maybe an obvious question, but I think an important one. You're entertaining a co-promote here. I know that's something you've talked about going back to the IPO, but just given the where things are with the business and given the potential challenges regarding interest in owning a piece of the asset here why don't you just entertain a sale of the company and do you think that that may be the the better alternative here just given all the moving parts how do you think about that
Jonathan
So, David, I'll comment on that, and then Johnson, I'll invite you to comment if you have anything to add. But for all the reasons that you've described, David, and others, you know, we are evaluating a wide range of strategic options, and I think sales of the company is within the range of options that we're considering. It always, you know, it always has been and it will continue to be. It's certainly not the only possibility we're considering. As I said earlier, we are actively planning to engage in conversations about a primary care promotional partnership and plan to do everything necessary to continue to operate the company independently. But in no way does that preclude possibility of conversations about M&A type transaction either. So we will continue to entertain all strategic options as we go forward through 2023.
David Anselm
And then as a follow-up, as you look at the launch in CS, you've talked about the potential for greater penetration within your existing prescriber base. So is it fair to say that that's where, at least early on in That's where most of your growth is going to come from. And if that is certainly the case, then what is the urgency to entertain a primary care partnership ahead of approval or around the approval?
Jonathan
So, David, the potential for the product, we think, is very substantial within our current sort of commercially contacted our direct selling audience and indirect selling. Our specialty audience has a lot of new potential with the new indication. And we do intend to go after that assertively with our own infrastructure. But that doesn't mean that there's not a lot of additional potential outside of the audience that we're currently calling on. And we really don't have the resources to to go after that, certainly not with a traditional direct selling model. So it means that if we are able to reach a primary care partnership, you know, starting on day one after the approval, there is potential in a very large audience that we're just not going to be able to efficiently access ourselves. And primary care partnership would give us a vehicle for being able to increase the potential value available to us and increase the number of patients who are able to be treated. So it would be incremental value very much worth having, you know, for a variety of reasons that we'd like to see, but that doesn't mean that we're not going to see substantial incremental value within our current audience. So I'm not sure, though, if I've answered your question, David. Did that address what you asked?
David Anselm
It did. I guess I'm just struggling with, you know, the urgency to, you know, find a primary care partner. I mean, don't you call on a certain basket of high-volume general practitioners already? And if so, how many do you call on?
Jonathan
Yeah, no, David, I think it's appropriate for us to have a sense of urgency around finding a primary care partner. And that's not because there's not a lot of potential in our current audience. There is. But the sooner we can get a primary care partner, the sooner we can access an otherwise untapped large potential audience. And while it's true that we do have a small number of, I'll call it a specialist-like primary care physician in our call-on universe, it's a very small number in comparison to the number of primary care physicians that one might ideally choose to engage if you had a primary care promotional infrastructure. What's our current number right now?
Jonathan Neely
Yeah, I mean, David, just for a sense of scale, you know, I think when you think about the number of specialty-like primary care physicians in our current call-on universe, you know, we're talking about a number that's, you know, a few thousand as opposed to, you know, when you look at the broader opportunity in primary care, I think historically, you know, we've looked at, you know, there's potentially an audience of you know, somewhere around 50,000 physicians who are, you know, kind of the higher value prescribers in the chronic sinusitis space. And so, you know, it's just a completely different order of magnitude in terms of the number of physicians that somebody with appropriate infrastructure, you know, that would be leverageable with this opportunity could reach if we were to partner with them.
David
Okay. Got it. Thank you.
Operator
I show no further questions at this time. I would now like to turn the conference back to Rami for closing remarks.
Jonathan
I'd like to thank you all very much for joining us this morning for our review of the full year performance in 2022 and our forward look into what we expect may be coming in 2023. And we look forward to talking to you again in a few months with our first quarter results. I hope everyone has a wonderful day.
Operator
This concludes today's conference call. Thank you for participating. You may now disconnect.
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