Hello and welcome to the Orexo Q4 Interim Report. Throughout the call, all participants will be in listening only mode, and afterwards there will be a question and answer session. Today, I am pleased to present CEO Nikolaj Sørensen, CFO Joseph DeFeo, and Robert Rönn, Head of R&D. Please go ahead.
Thank you very much, and welcome to this fourth quarter interim report presentation. It's clearly been an eventful day on the stock exchange, and I can understand there is some anxiety around Orexo. Having listened to some investors and analysts, I understand some of the concern is around the profitability and our digital therapies. I would put a little extra emphasis on these two areas and hopefully create some calm about the situation for the company. Today, I'm moving to page number two. We will go through some highlights for the quarter. I will talk about some of the business updates in U.S. Pharma, a little on pipeline, but I'm joined by Robert Rönn, who will talk a little about our new technology platform, AmorphOX, and our new project, OX640.
I will talk to digital therapies before Joe DeFeo will go through the financial numbers for the quarter. Finally, I would take a little discussion on the outlook and our future value drivers. Moving to page number five, some of the key achievements for the quarter. We have seen that our U.S. Pharma revenues declined very slightly compared to the third quarter and declined somewhat more compared to the fourth quarter of 2020. This decline that we see year-over-year is to the majority explained by the decline we have seen since early 2019 in UnitedHealth Group and Humana. When we looked at our opioid business, that has been very, very stable. That means that where we have been reimbursed, we have seen a stable development.
We have worked intensely to keep up a very strong profit contribution from our pharma business in the U.S. One of the things that we have seen the last one and a half year during the COVID situation is a difficulty to reach out to the physicians and visit the physicians' offices, which is very important for Orexo because we're the only daily treatment where we have an active promotion to the physicians. With that difficulty, we have also taken the decision to cost contain on the U.S. Pharma side, which is leading to a very strong profitability number of 54% in the fourth quarter.
Our biggest highlights during the quarter is back to some of Orexo's core business, and that's around our pipeline and work on new pharmaceutical products, where we have developed a new platform, AmorphOX. We have launched a new product, OX640, and we have positive data from the pivotal trial of OX124. All of this is something that is a really strong foundation for us to move forward.
On our digital therapies, we have made a change in strategy, a quite severe change, which I think has gone a little unnoticed, even though we have talked about it, is we have moved away from direct-to-consumer promotion, which has been the focus since the summer of 2021 on MODIA and now in 2021 also on deprexis, and moved over to a more B2B marketing model where we are focusing much more on partnership models for distribution of the products. One of the big accomplishment that we worked a lot on during the fourth quarter is that we have been added on, or at least an agreement with Walgreens to be added on to their online platform called Walgreens Find Care.
Now people in Sweden will probably say, "So what is this?" Walgreens Find Care is one, if not the largest care platform in the U.S. when you're searching for healthcare professionals to help you with any condition. You go in and you can basically use that to get quality reviewed and approved products from Walgreens. They're very selective in which services that they put onto the platform and they only have a few options within each category. Walgreens Find Care platform had 135 million visitors in their third quarter, their third financial quarter last year. If we look at 2022, this, I would say from where we are right now, is going to be probably the last of a couple of very heavy investment years.
In 2022, we're reaching one of the most expensive phases in the development of a new pharmaceutical product, and that is just before you're filing because you need to get every data point ready for the FDA's review. We need to get the manufacturing process, we need to quality control the manufacturing process, we need to file it and pay for the filing fee with the FDA. All of this is in every pharmaceutical product. This last phase is quite expensive, and we do expect to see an increased investment in R&D during the year.
However, we also see that our new model for digital therapies, where we're going through partnerships, is going to lower the direct expenses for digital therapies, and the expenses we will have in digital therapy will be more, associated to MODIA and the launch of MODIA, where we have much more synergistic cost base with Zubsolv than what we had when we were direct to consumer promotion. There's a shift in the cost base, but I will also emphasize that a lot of the investments we have right now are non-recurring and are associated with specific events leading into OX124 being filed. It is the MODIA trial, and then we also have some legal expenses to our patent litigation process. That needs to be taken into account.
Should I take all of these expenses away, Orexo would actually be a profitable company. In that way, we have a strong control of our financial situation. Moving to page number seven, which is the Zubsolv market. It's not been that eventful a quarter. We do have the situation where our field force has some hurdles to get to the same productivity as we had before COVID. It's very regional. Some regions have restrictions, others have no restrictions. Some clinics are closing for external visitors, moving to telemedicine, and others have a business more or less like usual.
If we look at the quarter, we have seen a slight decline in the open segment, but really some of the decline that we have on a volume base is driven by UnitedHealth Group and Humana. What we have seen is that the second half, if we take both Q3 and Q4, in terms of sales for Zubsolv has gone up compared to the first quarter, which I think is good. We also see that some of the new market access deals we had, for example, Kentucky Medicaid, where we added in July, so early Q3. When we look at Q4 over Q3, we had a 45% growth in Kentucky. We see the same in several other Medicaid plans that we have good growth, even in Q4.
On an overall picture, this is not enough to compensate for the UnitedHealth Group and Humana and some of the non-reimbursed, reimbursed plans. Looking at the overall market, the market growth has slowed down. We were used to see, or for a couple of years, we saw a double-digit growth. Then we saw a dip here in the first half of 2021, which is still on a year-over-year basis, have a negative impact and some flattening of the curve. In the fourth quarter, we reached a 5% growth of the market compared to last year. This year has started a little stronger, so hopefully we'll see some better growth numbers for this year. There is a lot of logic why this market should grow.
We've seen the COVID-19 effect on physicians and access to physicians have been quite severe. A lot of physicians have closed down or restricted intake of new patients, which made it more difficult to find care. We are seeing that the number of patients people misusing opioids have gone up throughout the COVID crisis, exemplified with the number of overdoses have gone through the roof. We know that there are multiple initiatives on both federal and state level to increase resources, increase access to treatment for opioid use disorder. What we do here is similar issue that we have with Zubsolv to reach customers on the same for digital therapies is that the focus right now for a lot of the bigger healthcare providers is on COVID.
That means that the ability to start a big effort in opioid use disorder as long as we have high numbers of COVID infected is limited. When COVID hopefully soon is gone, I expect this market will see some very good growth numbers. For Zubsolv, the market access has always been very important, and I'm very happy to see that we actually start 2022 stronger than where we started 2021. That happened with the Kentucky Medicaid, where we were added to the formulary. We've seen a very small decrease in the commercial access, where two smaller plans have decided to put us on the non-preferred list, where we before were the preferred list.
We still have some optimism that we can improve the access in the Medicaid segment, and that could be a very important trigger for Zubsolv moving forward. Then the big focus right now on, apart from selling Zubsolv is that we are starting this soft launch, you can say, of MODIA, where we started in Q4 with some awareness campaign. Now we're moving into more of a trial phase before we start a more commercial launch of MODIA soon. We know that every time we present MODIA, the length of the discussions with the healthcare providers is much longer than when we talk about Zubsolv. In that way, it improves the dialogue with the healthcare providers, and it becomes more comprehensive, you can say, when we include MODIA in the discussions.
Moving to our headquarters and pipeline, and I'm moving to page 10. OX124. Really one of the highlights of the quarter was, of course, that we had positive outcome of our pivotal trial for OX124. We saw that we are meeting the requirements for FDA of having a product that is at least as good as the existing products in the market. The focus from now on is that we need to ensure that the commercial manufacturing process and the product is delivering on the quality requirements from the FDA. We need to show stability, which means that we need to show for FDA that we can have a shelf life that is meeting their requirements. And we need to file, of course, the new drug applications, and that's scheduled now in the second half of this year.
If everything goes as planned, we will then have a product that is ready to be launched in the second half of 2023. Right now we are on good track to meet this timeline. Now, also during the quarter, we started to talk about our AmorphOX drug delivery platform. For you to give a little more context about the importance of this platform, I've invited Robert Rönn to join this call. Robert, please take us through the AmorphOX product.
Thank you very much, Nikolaj. We can start at page 12. Very briefly, AmorphOX is an amorphous powder that is rapidly dissolving, it's stable, and it works with a different type of active ingredient. Next slide, please. The AmorphOX platform has been validated in several different human clinical studies that we, Orexo, has performed. This is also the backbone technology that we use in both our naloxone and also our nalmefene products. Obviously, these are products that are developed for the treatment of opioid overdoses, provides patients with a needle-free easy nasal administration. Looking at certain properties and, for example, our OX124 product, one of the properties is that AmorphOX dissolves nearly instantly, even in very small amounts of liquid.
It is remarkably stable, both from a chemical and physical perspective. Obviously, these properties makes the AmorphOX technology an ideal platform for the development of emergency medications. Page 14, please. When we have compared AmorphOX in human studies, comparing it to more traditional liquid-based nasal sprays, AmorphOX has shown superior pharmacokinetic properties. It has shown a more rapid onset, higher peak and overall exposure, as well as lower variability. All these properties are important, especially for rescue-type products. Next slide, please. Another very important property of AmorphOX is that it is very stable, even under accelerated conditions. It works for a broad scope of different active ingredients, and we can see that even very unstable active ingredients can be formulated to provide for storage stable products, which could be of great benefit. Next slide, please.
We also see that AmorphOX has a wide applicability, and especially we see significant potential even outside of the substance abuse field with AmorphOX. Also, we see that AmorphOX has the potential to be used by different dosage forms, can be used for different administration routes, and we also have the possibility to tailor the properties of a certain product to meet certain product needs. Next page, 17. AmorphOX is a patent-protected platform technology, both by ways of already granted U.S. patents covering both OX124 and OX125 until 2039. During last quarter, we also filed several new patent applications that are directed towards different aspects of the platform. Once granted, these patents will provide protection for a few more years, so extending all the way into 2042. Next slide, please. Page 18.
Now I would like to spend a few minutes talking about our latest addition to our pharma pipeline, our OX640 product, which is a nasal adrenaline rescue medication. Going to page 19. Adrenaline is used today for the treatment, or I should say the emergency treatment of allergic reactions and also anaphylaxis. Today, the first line treatment are different kinds of injectable adrenaline solutions. Most particularly or most used are the intramuscular auto-injectors, and the most well-known brand name is called EpiPen. These currently commercialized products, they have significant drawbacks, I would say, and these drawbacks are addressed with our OX640 product.
To start with, we aim to develop a product that is less bulky than the current auto-injectors, and this is a significant problem because today's auto-injectors are relatively bulky and sometimes difficult to carry with you, and this is obviously critical for these patients that they always carry this drug product. Also, OX640 will obviously be a needle-free product, which again, many patients and also caregivers they have a fear of using needles. We aim to develop a product that has a better and more flexible handling and storage. Today's auto-injectors are very restricted in terms of how you can store them. For example, you cannot expose them to hot conditions, for example, and you cannot expose them to cold conditions, and this is something that we are addressing with OX640.
Despite the fact that the auto-injectors require strict handling, they still have a very short shelf life, and this is one of the major advantages that we see with OX640, that our product will have a significantly longer shelf life. Next slide, please. Looking into adrenaline and its stability and why the current products have very short shelf lives. Adrenaline and the currently marketed auto-injectors, they are very sensitive to both heat and light. They also contain antioxidants. These are chemicals that are in there to prevent chemical degradation, and they are also pH adjusted once again to increase the stability. Regardless of all these measures, they still have a short shelf life. What we see with OX640 is that our formulation is very stable to both heat and light.
We do not use any antioxidants or any other preservatives, and we don't need to make any kind of pH adjustments or formulations. Looking at the graph to the right of this slide 20, it shows the comparative stability study that we have performed between one of our OX640 formulations that we can see in blue, in comparison to a commercial auto-injector, which we see in red. Looking at the six-month time point, after six months storage under these conditions, nearly 26% of the adrenaline has disappeared from the commercial auto-injector product. In comparison, if we look at the stable in blue, OX640, at the same time point, six months, only 0.7% of adrenaline has been degraded from OX640.
Obviously, this is one of the key differentiating properties we see for OX640. Thank you, and I hand over to Nikolaj.
Thank you, Robert. I just comment as a non-chemist here. What's the importance of antioxidants and preservatives? It's actually these products can also cause allergic reactions. While you're treating your allergic reaction by adding antioxidants and preservatives, you actually can cause a second allergic reaction for people. If you are a person who is forced to carry one of these epinephrine products, then you are like a lot of people are multi allergic, so you're allergic to a lot of different products. That's important.
I would challenge every one of you if either you are carrying an EpiPen or similar today, or your kids are doing that, and consider whether you would be more comfortable with having a small nasal spray, which you know would work, even if the nasal spray has been placed in a backpack in the sun on the beach or been in a backpack when you are out doing cross-country skiing in the cold. I would for sure use a product that I know works under these temperature variations, and where you do not need to be cautious about storing it in a certain way, not least to talk about the convenience of using a nasal spray compared to an auto-injector. We are very optimistic about the opportunities for OX640.
The next major milestone will be the first clinical exploratory study, which we're performing during the second half of this year. With positive results from that, we would be able to guide more about the development plans. I also see this as an excellent opportunity for Orexo to work with other companies to take a part of the development as we wouldn't. This is a truly global product, where in particular, these properties can be important for countries where you have more severe temperature variations than what we have in Europe. Moving to page number 22, the digital therapies. I get a lot of questions. Are you happy with the development of digital therapies and the sales of digital therapies? Of course I'm not.
There's no doubt about that our expectations when we launched Vorvida during the summer of 2020, and later deprexis direct to consumers would be met by a higher demand, and also that we would see more agility and flexibility for insurance companies and large caregivers to find ways to help us reaching patients who, during COVID-19, had issues getting to their physicians. That has not happened. The direct to consumers, which have always been a secondary objective for us. We saw now when people couldn't find access to therapists, which we have seen a lot of headlines about how difficult it is to find a psychotherapist when you have depression, that we saw that deprexis could be a good alternative.
I would say that had we seen the consumer market as the main market, then the price point we have is way too high because we have put the price into a value that we have created by doing a lot of the clinical research that GAIA have been doing on Vorvida and deprexis and also what we're doing on MODIA. We see this as a tool for healthcare, which should be reimbursed by insurance companies. That process is something we knew from the beginning. We have no infrastructure in place, but we have been overly optimistic about how fast it would take to get all of this stuff in place. Therefore, I would also say it's quite unfair to judge the DTX sales right now and say, "Okay, this is.
There's no demand for these products, clearly, because there's no sales development between the quarters." That's not really true because it's a little like we have a train, but there are no train tracks. Can you adjust the train's ability to come in time when there are no train tracks to drive on? This is where we are with our digital therapies. We have decided to move away from the direct-to-consumer promotion, which was the focus for about a year. Relatively costly because you're addressing a big market in the U.S.. The direct expenses that we have for, in particular, Vorvida and deprexis, have been for this direct-to-consumer advertisement. A lot of those expenses are something that we can reuse as we progress.
We have a lot of commentaries from influencers and others, and we have a lot of media also that have been written about the product, but it has not really generated the demand that we would expect. We do know that the price is a concern for many consumers. What are we doing right now? We mentioned that in the third quarter call that we're moving away from direct to consumer. I mean that there's a shift in the cost base. We're moving away from these direct expenses where there was some cost left in Q4 of earlier committed expenses in the direct consumer cost. Now when that is over, we see that our cost base for DTx has moved more into synergistic cost with Zubsolv.
That means that there would be a field force that will take a cost on DTx, but it will also be cost that is shared with our Zubsolv field force. Our direct expenses to consumer marketing will go down. That means also when we look at the overall cost base for 2022, that we expect our overall selling expenses will go down. That is primarily driven by less direct expenses to DTx, which are not synergistic with Zubsolv. What are we doing now? We continue to focus a lot on partnerships.
What we also decided is to work much more focused with fewer committed partners to ensure that we get a pull-through, that we solve some of the issues that we have seen during the year when we have been in contact with quite a few partners, and we have signed up different clinics and hospitals. If their commitment has not been there to solve some of the reimbursement hurdles that have come up, it has been difficult to really get traction all the way to the end patients. Fortunately, we have a couple of partners who have really been willing to work with us, Trinity Health in North Dakota being the front runner.
We have worked intensively with everyone in their leadership team to solve the solution, how can they work directly out to their network of clinics in North Dakota to integrate our products into their treatment programs and get it reimbursed through the existing treatment programs that exist for people with alcohol issues or with depression. I have been also hoping that one to move faster than what it has done, but I also realize that the devil is in the details. We have a situation where if everyone reads about North Dakota and the impact of COVID-19, you would understand that they have been under severe pressure from Trinity Health on a different issue.
Last week, we had a big meeting in Trinity Health with a full team from Orexo, their full leadership team, 40 clinicians at Trinity Health, where basically both have educational processes. We were sitting down, having workshops for how we're going to implement this. That gave me some optimism that we will, in the near term, see Trinity Health come with some new patients. We have the situation with MODIA. Here to set expectations right, we also had some experience with Boveda Inc that we tried to promote to some of our customers that the reimbursement process was difficult. Here you need to understand that there's no way that a physician in the U.S. is going to buy services that they are not sure that they can get financed through the insurance companies or sell directly to the patients.
Of course, selling direct to the patients, the price again become a topic. This is really about getting insurance companies to cover this. We know that for MODIA, we can get coverage under existing treatment programs, but we need to be sure that we can answer all of the questions we get from physicians. Therefore, we're moving in a process where we have during the late autumn, we have done what we call an awareness campaign, where we have informed physicians about this. We have identified those who are most interested, and we will now move into a trial phase where they can try it on a certain number of patients. We will work with them to test the reimbursement process.
When we're starting a broader commercial rollout during the summer, we will know that we have viable reimbursement pathways and that we will not have issues the doctors experience when they're trying to put patients on these products that would stop them to test it once more. I'm very optimistic about how MODIA has been very well received in the awareness campaign, and I think it's a fantastic fit with Zubsolv , so we feel comfortable about this. the deprexis and Vorvida, it's really about getting this Trinity Health model up and running, and we can then copy-paste it into other large healthcare providers in the U.S., where we fortunately already have agreement with a couple of more healthcare providers who are ready to take on these products. Moving to page 23. where are we with our different channels?
We're working really with three different channels. We're calling consumers, healthcare providers, and employers. On the consumer side, as I said, we have stopped our direct promotion to consumers and are now relying on other partners. We have Sober Grid, the world's largest online community for people with addiction problem, who have been a partner. They have started to roll out deprexis and Vorvida through their peer coaches and are now moving into a phase where they were promoted to the full community. Together with Sober Grid, we have approached several different customers in the U.S., both employers, but also we have approached Walgreens and their Find Care model.
As I said before, Walgreens Find Care is probably the largest, and if not the largest, it's definitely one of the largest online platforms for people who are looking to find care from quality stamped providers that have been assessed by the clinical team at Walgreens Find Care. They had in Q3 2020, according to the earnings call, 135 million visitors. Of course, some of that is driven by COVID. People are seeking help on COVID to seek help to get tests, to get vaccines.
It is an amazing increase as they in 2020 had SEK 30 million on the full year basis. Walgreens is actually a fantastic step forward for our direct-to-consumer promotion and will be a significant quality stamp in any other discussion as this is known to be someone who have high requirements on the providers they include into their network. We're then working with healthcare providers, and here, as I said, Trinity Health is really where we have a lot of focus right now because we want to make this a success, so we know when we're approaching other healthcare providers that we have a model that works. Then we have employers.
We did start with our own direct to employers efforts, which also took some investments during the first half of last year, but have realized that our offer is too narrow for the employers to take. We have signed up with a company called EHBS, who are basically focusing in employer benefits, so healthcare benefits for employers. They have added our products to their services. Also justmiine, who is both a healthcare provider, but they are also focusing on selling healthcare services to employers in the Michigan area. Finally, we have something about moving to page 24. Market access and reimbursement, they are the tracks that we need to have in place to get this one flying. It's not only Orexo, it's the entire digital therapy and digital health space.
We know that there are no established reimbursement programs, but during the fourth quarter, there was a CPT code approved by the American Medical Association, and CPT code is what is used by the insurance companies in the U.S. to manage reimbursement. That was approved during Q4 and is ready for implementation on January 1st, 2023. We also know that CMS, which is the next step after CPT code, you go to CMS, which is Centers for Medicare & Medicaid Services. It's a government agency, and they will then decide on reimbursement for Medicaid and Medicare. They have decided a first reimbursement range for these services, which will also be implemented in January 2023. Then when it comes to our...
This will be an opportunity to get reimbursement on our products on a standalone basis when these CPT codes are ready. What we're working on right now is integrating our codes into medical benefits pathways, and that's where Trinity Health is coming in. How we can set up a treatment program that get approval from the insurance companies, and we can then get the treatment provider will get paid for the entire treatment program, but that would be enough also to cover the cost of MODIA and deprexis. This is exactly what we're doing with Trinity Health, is developing that treatment program, get it anchored with the insurance companies and set up the administrative processes to manage this. That would be an important next step.
For MODIA, we actually know that we already have a bundle, and we have confirmed that that can be included in this bundle of services which is covered for opioid use disorder. When we get it up and running, we're quite certain that that is a program where we can get reimbursed for MODIA through this medical benefit route. With that, I will move into the financial section and allow Joe DeFeo to take us through the financial sections, and I'm now on page 25. Joe, please.
Hi. Good afternoon. If you go to page 26, a picture of our revenue position. Our revenue for Zubsolv did decline year-over-year 6.7% primarily due to the United and Humana programs that were previously exclusive. However, when you look in the middle of the first box, you can see that our second half sales beat our first half sales. We've had higher sales in the second half of the year. When you look at the bottom slide, you could see that our decline in Q4 was only 2%, 2.1% below Q3. We're definitely seeing if you look on the demand side, which are the first three boxes on that waterfall, that the demand declines have dropped off significantly. It's much flatter volume of sales.
It's a negative in Q3 and also versus last year. The wholesaler stocking was less, but this is actually a positive for the company because in Q1 there's less inventory sitting out at the wholesalers than previous years and we did take a price increase on January first of 3%, so that'll be more of the sales in Q1 will be at the higher price. The other positive that's actually going on right now as we get close to closing the month of January is that the U.S. dollar is up about 5% from where it was in Q4. With our revenue being in U.S. dollars, this is gonna be a beneficial outcome in Q1 for Zubsolv sales having a positive dollar where it is as of now.
Next slide, 27 is our P&L. You could see from P&L perspective that we're definitely investing in our future growth drivers. Yes, we do have a negative EBIT versus last year, but this is due to investing in our future growth drivers. Our gross profit is a bit negative. This is mostly due to exchange rates, but also some variances. That fluctuates a lot with when we produce product. We don't always produce at consistent levels every quarter. With the Q4 that also affected our COGS, and should be beneficial now with us sitting with a better inventory position going into Q1. From an operating cost standpoint, yes, we do have higher legal costs due to the subpoena in the U.S. and also the patent challenge in for Zubsolv.
The other parts are our OX124 development expenses, which affects R&D. Also, our MODIA trial is another item in our R&D expenses and our DTx associated expenses in both selling expenses and obviously the MODIA I just mentioned into R&D. As we look at and go into 2022, yes we are guiding to similar operating costs. However, as Nikolaj mentioned, a lot of those are one-time costs. The expensive trials at the end of the cycle for filing OX124 and also the MODIA trial which we started in Q4 and will happen through at least the first half of 2022.
The good news when you look at those two items, OX124 and MODIA, as we're getting ready to file and we're finishing studies, as we go into the future years, these are two products that are heavily synergistic with our U.S. infrastructure. When you look at products, normal products which take a couple of years to get to profitability, we anticipate OX124 and MODIA as they go into launch mode, that will be quicker to profitability because we have a very strong infrastructure in the U.S. That'll be a very positive sign as we launch those products. Nikolaj also mentioned that our cost for Vorvida and deprexis are coming down because we're more into a partnership mode and less into the expensive consumer promotion.
You could see, as I mentioned at the bottom of the right, our EBIT in the U.S. is still a very strong 53%, and we anticipate that to continue this year. As I mentioned a little earlier, with the U.S. dollar about 5% stronger, as much as that continues, that'll make our U.S. business even more profitable and drive that profitability for positive results in 2022. Next slide, 28, is our cash position. You could see that we did have a negative SEK 80 million cash flow from operating activities. However, part of this, over half of this, has to do with some accounts receivable, which one of our major partners or wholesalers in the U.S., we did a negotiation with them.
Instead of having a higher increased cost for that wholesaler, we decided to go with giving them extended terms. It's more of a timing issue. You could see SEK 43 million , roughly around $4 million, is really delayed collections. When you look at that would normally have meant about over SEK 40 million of higher cash position. Our liquid funds are still in a good position over SEK 500 million. Our net cash position is positive. As I mentioned, there's a timing on the accounts receivable that will basically come in a month later than normal. When you look into 2022, we're very conscious of our cash position and our cash flow.
We mentioned a couple of things, myself and Nikolaj, about how we're looking at our expenses, and we will continue to do that and make sure we keep the company in a good position to be able to take advantage of launching our exciting new opportunities as they materialize. With that, I'll turn it back to Nikolaj for legal updates.
Thank you, Joe. Legal update can be done very short. There's actually no update since the last quarter. I will say the patent dispute we have with Sun Pharmaceutical or Sun Therapeutics is ongoing, and if it's following the normal timelines, we would be up for trial during the first half of next year. With the subpoena, nothing has really happened during the last several months. Our financial outlook, we have been a little cautious of what we're saying here. There's a lot of uncertainty around COVID-19, both for Zubsolv sales, but also our digital therapies is something we have seen. Every time we can meet in person, it's much more productive than when we have virtual meetings.
When we look at the key market development, we do expect that the market for buprenorphine naloxone products is a little better than in Q4, so we say 5%-8% growth during 2022. Zubsolv, we are expecting the normal seasonality we have is slightly lower sales in the beginning of the year, partly due to the reimbursement structure in the U.S., than the second half. We're expecting a slight decline on Zubsolv here in the start of the year, and then to have an improvement in the second half of this year. Overall, the development really depends on how COVID-19 will evolve during the year. Is it like my home country, Denmark, where they just removed all restrictions?
I think there's a good opportunity for the market to show good growth numbers and that also impacts Zubsolv. Do we see a continued roller coasting of restrictions and others, then it can have a negative impact. On the OpEx side, as Joe said, we do see a shift now into the OX124 and MODIA trial, and we are reducing expenses for DTx. The fortunate part of that is that for the OpEx side, we see an opportunity. This is non-recurring expenses. When we come into 2023, it's really a question for us, where do we want to place the money in our development pipeline and also in the U.S.? You could say right now, our U.S. Pharma and DTx, so full U.S. operations, they are profitable.
What we are investing in is right now quite heavily into our development pipeline. Into 2023, I think we have a new decision for where should we prioritize, what is the timing of the project. Of course, for our digital therapies, there is a need for them to start to show traction. Otherwise, we will, of course, either shut down or severely restrict the expenses. We won't increase our investments in digital therapies before we see that we do get traction, that we do solve some of the reimbursement issues. If we get all of that solved and we get a good response, we should of course invest into the market to grow the business.
If we don't solve this and we don't get movement in Trinity Health and Walgreens and others, we will of course reduce the spend on digital therapies quite significantly. On an overall basis, we have a very good control of our financial situation, even though that we have invested a lot of money the last two years and will invest some monies this year. When we come to 2023, we are in a situation where we by simple priorities of not starting anything new and expensive, then we could keep a quite strong financial situation in 2023. When we come to OX640, then we have an expensive project right now. In 2023, we're likely to work much more internally on the development, so that we'll have a different cost profile in that year.
Moving to page 32, and I'm soon finished. What is to be expected? I think OX124 is a very exciting market opportunity. The market right now has seen entrance of two generic alternatives, just as I expected. The price point of these generics is more or less in line with the branded product. Of course, Narcan, which is the brand leader, is not an expensive product. To produce this product is very expensive because of the quality requirements from FDA and cannot be done in a normal generic model of using existing supply chains. You simply have to build up a dedicated supply chain to be able to meet the requirements of these products. We have seen the two generics. One came in at a 5% discount and the other one at a 6% discount.
We've seen that the market opportunities when some of the legislative discussions that are in the U.S. right now is to make a mandatory co-prescription of overdose rescue medications together with opioids. If that is implemented, we think this market could be beyond $1 billion market. If that happens, and we take about 10% of that would be a very significant opportunity for us. The adrenaline auto-injector market is a $2 billion market. It's a global market today. It's of course, something that is needed everywhere. There's a very strong increase we see. For some reasons we see more and more people having severe allergies. We think coming in with a nasal spray is something that will definitely add a lot of convenience.
I would also say certainty to people that the product works when it needs to work. Moving to page 34. What are we to expect for the next year here? First half of 2022, we will have Zubsolv launch in Europe. Our partner in Europe is expecting to launch it here in the first half. We will have some first revenues coming in here in the first quarter, not of significance, but it will be revenues coming in to our Orexo. We have our digital therapies partnering progression. Seeing that we can solve the reimbursement issues with Trinity Health will be extremely important for this business venture in the future. We of course expect to see some sales projection progression in DTx.
My expectations to Q1 is not that high, but I do believe that in Q2, we should start to see something on our digital therapies. In the second half of the year, we'll have OX124 filed. We'll have OX640 human trial. We will have MODIA commercial launch, DTx partnering again, Zubsolv market access development. I think both getting certainty about the situation for 2023, but also see if there are new opportunities to grow market access for Zubsolv. We will have Zubsolv launch in Europe, which is 29 countries that our partner is sitting with. We expect to see that being step-wise rolled out as they see opportunities in different markets. The year after, we will have our MODIA trial results. We're expecting them to come in the first half.
We have the patent litigation, which has not been scheduled, but would in normal circumstances happen in the first half. Approval of OX124, and as Joe said, that one is very, very synergistic with both MODIA and Zubsolv in the market. Of course, we expect to see some new product ideas coming out of the AmorphOX platform, either directly with Orexo or in collaboration with other pharma companies. With that, I will leave it open for questions. Thank you for your attention.
Thank you. If you do wish to ask a question, please press zero one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero two to cancel. There will be a brief pause while questions are being registered. Our first question comes from Samir Devani with Rx Securities. Please go ahead.
Hi, everyone. Thanks for taking my questions. I've got just a couple, I guess. Just on the MODIA trial that's ongoing, can you confirm whether you've recruited any patients into that study yet? And if so, how many? I guess that's the first question. Also, Nikolaj, you talked about the reimbursement code, and I was somewhat confused as to whether that code was approved or was being created, because I think you talked about being approved in the statement. Maybe you can just clarify that for me. Thanks very much.
On the first one, MODIA trial, that one is ongoing. We have, at least one and a half week ago, we had 125, I believe. Like everything else, the recruitment is impacted by COVID-19, and we do have several of the centers who temporarily have been forced to shut down because to take in new patients because of the situation with COVID-19. It's a little slower than we expected, but not a lot. We are aiming at 400 patients, but the recruitment has really picked up here after the Christmas period. More than 125 a few weeks back. The reimbursement code is approved by American Medical Association, so that one is confirmed.
CMS has confirmed a reimbursement range for this, for that code. That is ready, but it would be implemented first 2023.
Can you maybe just clarify what if it's been approved, what has to happen before it gets implemented? Why does it take a year for implementation?
It's that of course the question I also had when I saw the notice about the decision. Fortunately, it's not only us. It's every code that were decided on in that time was implemented first in 2023. I simply think it's because these codes needs to be implemented into the insurance company systems, and that takes time because you need to update all the IT systems with all the insurance companies in the U.S., and that's simply the implementation time of these codes. Because it's not uniquely for this one, it's something that was for all the decisions that were taken at the same meeting. I think that is the reason. All insurance companies need to have time to implement and also decide on reimbursement levels.
CMS, they decide on a range that is a guidance for Medicaid and Medicare, which of course normally is below the range that is used in private health insurance companies. I think that is the reason. We know from pharmaceuticals, for example, that the decision by insurance companies are often taken on a half yearly. They say they have either annual or every half year. They make decision on reimbursement of new products. I also think that could be one of the reasons that it simply takes time.
Okay, that's great. Thanks very much.
Thank you, Samir.
Our next question comes from Magnus Bernet with Direkt. Please go ahead.
Yes, hello. I was wondering about the digital therapies. I guess no one expected very much for sales numbers this quarter. I guess many people have higher thoughts about this area as you have. For 2022, what are your ambitions within this field?
Magnus, we have not communicated any numbers for 2022. That's of course been a debate internally what guidance we should come out with. One of the things we would like to get some comfort on is the reimbursement routes and pathways that we have found that they actually work, and we want to see that the patients coming through. Because it's relatively binary. If they don't work, it would be difficult to get out in larger scale. If they do work, we have seen with other therapies who've been integrated into treatment programs of similar nature that the pickup is growing quite rapidly.
To take one example, if Trinity Health actually put this in frontline of people who come in and seek help for depression, that everyone should get deprexis, that even in North Dakota means quite a lot of patients would come in and use deprexis. We are this crossroad which make it binary in terms of volume. What I can say is that our expectations is, of course, to see some good development in particular, it's starting in Q2 and into the second half, but we have not communicated any number.
Very good. Fair enough. Let's see what you can deliver later on.
Thank you.
Our next question comes from Gergana Almquist with Redeye. Please go ahead.
Thank you. I have a question about the AmorphOX platform. You write that it will be the backbone for future project development. Could you elaborate more on the versatility of these platforms? What kind of diseases, what, how big markets are we talking about? Because it's a very big statement to make. It will be the backbone of our future. What applications do you see apart from the adrenaline and.
Thank you for the question. This is Robert Rönn. I mean, we don't see any particular limitation when it comes to certain indications. Obviously, an amorphous powder with these kind of properties.
You can see a lot of different use, not only for nasal emergency products that we are working with. You could also consider using it, as I mentioned, also for different other administration routes, and other dosage forms. I don't see any particular limitation on the type of indication. Obviously, the platform has properties that makes it very good for emergency type of product that requires a rapid onset, for example. That's one particular aspect. The other one is obviously the stability advantages that we see. For example, working with a very sensitive, active ingredient like epinephrine. There are obviously other unstable active ingredients that could benefit from this technology.
I think, Gergana, if we go back to 1999, that was when Orexo had our sublingual technology platform, which since then has led to the development of both Abstral, Edluar, and also Zubsolv. Each of them with their own merits, with some unique properties which have generated new patents for, in particular, Zubsolv. That 1999 invention was also the backbone for these three products in as diverse areas as treatment for opioid use disorder to a sleeping disorder in Edluar. That's a little what we see right now. I think. Just take some dialogues we've had the last few weeks.
We have had a few companies that we haven't been in touch with on other routes and where they stand here, and some of them are very early stage NCE-like products who needs to find a delivery method that works and have thought about doing an injection products. Suddenly we maybe have a solution for them which could make this either as a nasal spray or a sublingual tablet or similar. We have products that we know are used across the world in very sensitive areas at high humidity, large temperature variations, and we've shown that we can make it stable. Right now it's I think we are in a very fortunate situation from Orexo is that we have a lot of ideas.
The big challenge for us is, of course, looking at our financial situation, and also people situation that we need to prioritize which idea to progress with first. We will communicate the projects as we progress. Right now, the big focus is on OX124 to get that finalized. That's our priority number one. OX640, we want to show that it works. We think that has such broad application that we have decided to put it ahead of OX125. Because if we can show that that works, we think that's an opportunity for us to be more creative in our business development discussions with other partners, for example. That's where we are right now. If we should have endless amount of resources, I think we would have another couple of projects that we would start right now.
We need to prioritize.
Understood. Should I see it as a back to the roots kind of story for Orexo, that you are returning to the Pharma R&D and kind of run this in parallel, Digital and Pharma? Or what are your priorities for the future?
I do think that it's in one way, it's back to the roots. Of course, we have been doing Pharma development for all the time. For a period of time, it was very focused around Zubsolv. But now, since the last three or four years, we've been focusing on developing new products. The back to the root is that we develop a product designed for a specific need, and that is OX124 for fentanyl synthetic overdose. In that process, we also develop a new technology that we see have much broader applications, and that is back to where Orexo has been before.
There's no doubt that we are a commercial company and the number one thing for us is right now to get over this investment period and then turn this company profitable again. We're using a lucky situation compared to many other Swedish pharma companies that we had a lot of money that we could spend. We have a continuous cash flow coming from Zubsolv that we can invest. But we of course don't have an endless amount of resources. Now we do a lot of investment, have done that the last two years. We'll do that in 2022. Then we're in a new situation, and I think the profitability is going to become a much bigger focus of the company, and also in the decision to start new projects.
Thank you.
As a reminder, if you do wish to ask a question, please press zero one on your telephone keypad. We have no further questions, so I hand back over to our speakers.
Okay. Thank you. We received two questions on our investor relations mailbox, and one was around the guidance about profitability for 2022 and if possible, coming years. We talked about that. I think we do see 2022 as an investment year, but we are seeing that we're moving into more some final R&D investments on OX124, whereas a lot of the expenses the past year has been on DTx, and we see DTx is going to see reduced spend in the year. The spend that we do have, which to a much higher degree be synergistic with Zubsolv. Then we have another question. As DTx sales reached SEK 2.3 million, are you satisfied with that level, and how do you think the revenues will proceed?
Of course, I'm not satisfied with DTx in 2021. There's no doubt about that. We have invested a lot of money in what we thought could be an opportunity due to COVID-19 and that has not materialized. We have learned a lot. We have produced a lot of material that we can leverage in the future. There's no doubt that when we entered 2021, that is not what we expected when we started the year. When we're looking ahead, I do think we have taken a step back. We have a more partner-focused strategy. We made a big breakthrough with Walgreens, and I think we are now really getting ready with Trinity Health.
With these two, I think we have a good foundation for expanding the partnership model into new companies. We do have several others who are waiting. Again, Trinity Health is going to be the model for other big healthcare providers in the U.S. That was the last comment, and I would thank all of you for taking an hour out of your busy schedule and wish you a great day. Goodbye.