Montpellier has the oldest active medical school in the world, so a long history of medical and pharmaceutical science. What we do is long-acting injectables, so it is about transforming a drug from pills to a long-acting injection, sub-Q, bioresorbable, which will deliver the drug for a very long time, sometimes one month, like on our lead product. We also have a program with a six-month delivery, so you can imagine the complexity of what we do. We have to control very tightly the release, and then it has to stop at the intended time, and we have to prove to the FDA that, of course, we can do that on any type of patient and controlling the release perfectly.
What you see here is one injection, and this is what will happen under the skin. It is a mix of three things: the API, our own patented polymers, which are diblocks and triblocks of PEG and PLA, very well-known pharmaceutical excipients, and hydrophilic solvent, the MSO. As soon as the formulation hits an aqueous environment, the MSO will escape. Within a second, the polymers will precipitate and capsulate the drug and form the small depot that you see here. This depot will bioresorb and deliver the drug very smoothly. Today, our first product, UZEDY, was approved in April 2023. It is a long-acting injectable of risperidone for schizophrenia and was developed and is being commercialized by our partner, Teva.
We have a second program with Teva based on another schizophrenia drug called olanzapine, which just completed phase three. This program is extremely important, has been raising a lot of interest from the best U.S. analysts and investors as well. It can be considered as a first-in-class multi-billion-dollar product. There was even an article in the Wall Street Journal explaining how this product was reviving Teva. Wave three is the first program we have with AbbVie. We'll come back to that as well. We've signed a major agreement with a $35 million upfront with AbbVie last April.
Wave four will be made out of our R&D pipeline, and hopefully, some of that will be done in collaboration with this new wave of schizophrenia companies that we've seen in the last couple of years: NeuroCrine, Cerevel, Karuna, Intra-Cellular Therapies, CellbiPharma, and others. Wave five, technology extensions, and we'll come back to that as well. Wave one and two should bring us in excess of $100 million revenue in the next three to four years, with a great potential for significant additional revenue thereafter. Our analysts estimate that we could reach $300 million in revenue in 2030, so only five years from now.
UZEDY, again, based on risperidone for schizophrenia, and Richard in a second will tell us why schizophrenia is an area where long-acting injectables are critical. It was launched in mid-2023. 2024 was the first year of first commercial sales, and you can see that it is doing really well with $117 million sales in 2024. This trend should make it a billion-dollar product. This is for schizophrenia only and for U.S. only so far. We are getting mid to high single-digit royalties on this, and we have up to $105 million of commercial milestones available. Teva has been the ideal partner for this, first because they were very good at developing the product with this combination of specialty pharma and generic capabilities.
If you listen to their CEO, Richard Francis, systematically at every earnings call, he will mention both UZEDY and olanzapine LAI as being core of his new pivot to growth strategy. Second, Teva has shown a very strong performance in the space of schizophrenia drugs lately. They have this blockbuster called Austedo, which is now around $1.6 billion in revenue, with a guidance at peak of $2.5 billion. It is the same sales force that is commercializing Austedo, which will commercialize both UZEDY and olanzapine. As we know as well, Teva has the potential to take drugs worldwide as well.
This is a very important slide, maybe the most important slide of this presentation here, explaining the potential of risperidone, UZEDY, and also in a moment, olanzapine. You can see on the left that Johnson & Johnson did a spectacular life cycle management of its oral risperidone, transforming it after patent expiry to a $4.5 billion franchise worldwide of long-acting injectables, $3.5 billion in the United States alone. This is the market that UZEDY is targeting.
Thank you. I'll take the... Is this working? This is not working. Oh, it is. Okay. So thank you. Let me take it from here and talk about what Teva is doing with UZEDY, schizophrenia. To start with, everything we develop at MedinCell is designed to not just formulate because we can, it's to solve a problem. In schizophrenia, the problem is non-adherence. Schizophrenia patients do not take their medicines. In fact, 80% will stop taking their medicines within the first few years. If you don't take your antipsychotics, you tend to relapse. If you relapse, you need hospitalization for several weeks. Even after getting under control, half of those patients will relapse again within the next one to two months.
Here in LAI, it makes a lot of sense and why there has been such an uptake. We know that the antipsychotics are also being used for bipolar disorder. Teva just announced, last summer they announced that they were going to pursue an indication in bipolar disorder with UZEDY. In the last week or two, they announced that, in fact, they had submitted a supplementary NDA for bipolar disorder to the FDA, which was accepted. Again, about a 10-month review time from submission, eight months from file acceptance, to give you an idea of timelines. Bipolar disorder is an approved indication for risperidone, the parent compound, for the oral as well as the every two-week LAI.
Having a monthly and every other monthly formulation for bipolar disorder will be really impactful for patients who right now in bipolar only have Abilify as the only LAI monthly for bipolar. We will see what happens with that one. Trying to move it. There we go. UZEDY, I said what we do at MedinCell is we improve upon formulations, either approved drugs or NCEs. In this case, we were improving the Janssen products predominantly, the products, long-acting injectable, risperidone, paliperidone. UZEDY is subcutaneous, meaning it's a smaller needle, less painful. The Janssen products are intramuscular. For that matter, Abilify or aripiprazole LAI is intramuscular, another advantage for UZEDY in bipolar.
The Teva products require, I'm sorry, the Janssen products require often complex reconstitution. Psychiatrists are not used to doing that. I'm going to stand if you don't mind, are not used to doing that. The MedinCell products, MedinCell Teva, come in prefilled syringes, four doses for a monthly, four doses for an every other monthly, corresponding to the four oral doses of risperidone, two, three, four, and five, making it easy to transition from oral to LAI. Also, because there is an immediate onset of action, you reach therapeutic levels within a day. There is an ease of transitioning from not only orals, but from other LAIs.
The Janssen products do not reach therapeutic levels right away. They require either oral supplementation or titrating injections, so making it easy to transition even from other LAIs. Beyond the formulation, Teva did publish some phase three results, which further differentiated from the Janssen products, particularly improvement in positive and negative symptom scores beyond the first few months. Into the second year, there was still continuing improvement of symptoms, so not just adherence. Then quality of life, very difficult to show benefits in quality of life in CNS, and Teva was able to show that in the second year.
All of this reinforcing the differentiation of UZEDY and explaining why it's doing so well. The other thing I'll quickly mention here is that there have been two recent competitors to both Janssen and to Teva MedinCell. The first one was from Indivior, Perseris, another subcutaneous. However, had limitations on doses it could be used with, lots of injection site reactions, and large needle, even though subcutaneous. Indivior announced last summer that they were withdrawing Perseris from the market, based predominantly on the lack of differentiation not being used, but predominantly U.S. payers announced that they were deprioritizing Perseris in their formularies and elevated UZEDY.
Indivior made the decision to withdraw it. The other one, a product from Rovi. Rovi is a Spanish company, approved intramuscular risperidone in Europe, marketed in Europe, approved in the U.S., but they were unable to find a commercial partner in the U.S., in part because of the success of UZEDY and trying to compete with Janssen. They announced in November that they were withdrawing from the U.S. Again, to the success of UZEDY.
Thank you, Richard. This is the second part of this most important slide of the presentation. I talked a few seconds ago about UZEDY and its potential going after risperidone long-acting injectables. Look at the right side of the slide now. Instead of having a nice multi-billion dollar green box here, Lilly could only do a $40 million franchise with its long-acting injectable of olanzapine. Quite striking because of the risk of PDSS that they encountered during development and the treatments. Next. The financial agreement here is similar to what we have with UZEDY, mid to high single-digit royalties, $105 million of commercial milestones. However, we do have some development milestones left.
Yeah. So again, here the indication of schizophrenia to start with. Olanzapine is not a competitor to risperidone. It's used for more severe patients with schizophrenia, refractory patients, which is up to a third of patients. Olanzapine LAI will not compete. Effectively, because of this post-injection delirium and sedation syndrome we'll talk about, the Lilly product is not being used. Large need for an LAI olanzapine formulation. This PDSS, not very common, less than 0.1% of injections, but severe enough that the FDA put a black box warning on the label, required a REMS program, which psychiatrists are not used to doing.
Most impactful, every patient for every injection must be monitored in the clinic for three hours. Patients are not willing to do that. Psychiatrist offices are not being set up for that. It's just not being used. Hence that $40 million peak sales and dropping. Teva did run a phase three study. Again, the idea here was to limit the risk of PDSS by eliminating the burst. Teva had done a phase one study demonstrating there was no burst, no cases of PDSS. As part of the phase three study, in addition to period one, the eight-week double-blind that you see up there to look for efficacy, Teva also did a 48-week open label safety to capture a minimum number of injections needed to fully explore the risk of PDSS.
That is the value proposition here. They needed that period two, as Christophe mentioned. They reached that study completion end of last year, last patient out in January. They've already announced efficacy results from the eight-week double-blind, showing that each of the three doses of olanzapine, which correlate to the three oral doses of olanzapine, 10, 15, and 20, same as UZEDY story, was statistically significant better than placebo. This is not surprising. Olanzapine is really potent, really strong, but you need this to get the approval. Most, again, beyond the efficacy in the primary endpoint, positive and negative symptoms, they again were able to show statistically significant difference in quality of life measures in schizophrenia.
They showed that in the eight-week double-blind, safety and tolerability were comparable to the oral olanzapine and to the LAI olanzapine. Teva did reach the target, 3,600 injections negotiated with the FDA as a minimum number to explore the risk of PDSS. This bodes well for removing that label restriction on monitoring. Teva will announce the full safety data from the 48-week study Second Quarter of this year, planning on filing NDA later this year, likely sometime late summer, 10-month review time. That brings us to approval sometime first half of 2026. Once it ramps, once it is approved, ramp-up should be much quicker. There really is not much in the way of competition and a huge unmet need. AbbVie.
Thank you, Richard. Wave number three should be this first product we have with AbbVie. We executed an agreement with AbbVie in April this year, 2024. I'm saying this year because our fiscal year is March 31 of every year. This agreement is about developing up to six long-acting injectables. The first one was already underway at MedinCell as a proprietary program. We received $35 million upfront in May. Each program is eligible to $315 million of milestones. Times six, that's $1.9 billion, plus mid to this time low double-digit royalties. Neither the indications or the drugs are disclosed at this time. Wave four of pipeline, Richard.
We talked about UZEDY, olanzapine. I'm going to show you a little bit about our intra-articular celecoxib. We're not limited to subcutaneous. The formulation allows to go into the joint space as well as other places in the body. The advantage in the joint space is that it solidifies right away, just as you saw subcutaneous. That means that what you put in the joint stays in the joint and doesn't go into the systemic circulation where undesirable safety tolerability and where it's really not needed. Beyond that, we have our own internal programs beyond the partner programs. One, Christophe mentioned the six-month contraceptive funded by the Gates Foundation, entering phase one later this year, designed to provide longer-lasting subcutaneous formulation. Existing formulations in contraception that are subcutaneous are two, two and a half months.
Beyond that, women need to use implants, surgical implants, or devices, which is not always desirable. In the developing world, where contraceptives are even more limited in access, provides a longer-lasting contraception there. Hence the Gates Foundation, a malaria program that was funded by UnitAid and Ivermectin, three-month formulation designed to kill mosquitoes. Christophe mentioned the first of six AbbVie programs. In those blue boxes are undisclosed programs, some of which we're working on internally, much like the first AbbVie program was, and some of these others.
Some are NCEs where you need an LAI to enable use, for instance, a twice daily subcutaneous formulation, not really that attractive to take to market. There is an early need for even that NCE to have an LAI. Some others in there are already partnered. This is the celecoxib program. The first phase three study completed last May, looking at post-operative pain and inflammation after knee replacement surgery. The initial results were not positive at the pain endpoint, but were quite significant on inflammatory measures like range of motion at the knee, joint effusion, and walking functional test. It delivered on the safety.
There were no systemic celecoxib AEs, no GI, no cardiac, no renal. Despite missing the primary endpoint in the total population, a pre-specified subpopulation of no prior knee replacement surgery did show significance on pain. With all of that, we are meeting with the FDA this Quarter to discuss next steps. There is a viable regulatory path forward. Depending on FDA feedback, we're looking to move forward with this program beginning later this year. We'll skip through some of the data maybe after. Then additional technology.
Yes, thank you, Richard. Today, what we do well and maybe probably better than anybody else in the world is long-acting injectables of hydrophobic molecules. We have a bit of trouble when it's highly hydrophobic or when it's large hydrophilic molecules, biologics, large peptides, GLP-1s, et cetera. Our original technology is called BEPO, the one that is behind UZEDY and olanzapine LAI. We have an evolution of BEPO called BEPO-STAR, which allows us to expand the capabilities to formulate and also allows us to do even better formulations, better control of the burst, viscosity, and other parameters.
We are currently switching all our formulations to BEPO-STAR. Our R&D priority is to expand to exactly what I was describing, to large hydrophilic molecules. If we are successful, this could expand the potential of the company by five, six times compared to what we can do today. Financials. The company grew profitable as a standalone company with no VCs, no business angels, up to the IPO in 2018, which is remarkable. Then we started to invest to grow our own pipeline, our own capabilities in preclinical, CMC, clinical. Our financials should evolve dramatically in the next couple of years.
Just this year, our fiscal year ending March 31, 2025, should see a revenue increase of about three times compared to the previous fiscal year, with obviously an improvement in EBITDA. Our balance sheet shows about $60 million of debt. $40 million of that is with EIB, the European Investment Bank, but not due until 2027-2028. We are currently negotiating to push it to 2030 to sync it with the milestones of UZEDY and olanzapine LAI. We just did a very successful capital raise two weeks ago now, fresh. We were able to attract tier one U.S. investors. You've got the list here, Adage, Invus, Polar, Wellington Management, BlackRock, Monashi, which hopefully will support us for the future as well. We intend to reach operational profitability in our fiscal year, March 31, 2027. Profitability, a name that we don't hear very often in the biotech world. Midterm, as I said earlier, we think we can get to the $100 million revenue in the next three to four years with EBITDA exceeding 50%. Of course, additional potential from wave one and two at the 2030 horizon and then increasing there.