Good morning, everyone, and thank you for joining us at the Coherus 2022 Analyst Day event. We are excited to have you here and to be in person. Before we get started, I'll point out that today's presentation includes forward-looking statements regarding Coherus' current expectations about future events. These events include, but are not limited to, statements regarding achieving future cash flows in our portfolio, our long-term growth, our ability to achieve a leading market position in immuno-oncology, revenue growth, profitability, expenses, total addressable market share, and other financial projections, timing or potential for future regulatory filings or approvals for various indications, our ability to launch future products, safety and efficacy of toripalimab and our other product candidates, Coherus' outlook in future years, such as 2026, PD-1 market projections, and Coherus' ability to advance early-stage assets and development.
All of the forward-looking statements we make in the presentation involve substantial risks and uncertainties that are beyond our control and could cause actual results, performance, or achievements to differ from the results, performance, or achievements implied by the forward-looking statements. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are discussed in our press release that we issued earlier today, the slides of our presentation titled Forward-Looking Statements, as well as the documents that we file with the Securities and Exchange Commission, including those in our recently filed annual report on Form 10-K. The forward-looking statements provided in the presentation today are made as of this date, and we undertake no duty to update or revise any forward-looking statements. We have a full agenda today.
We're anticipating as many as four new product launches over the next 15 months, and we're also rapidly advancing our immuno-oncology pipeline. Today, we'll begin with Denny Lanfear to talk about Coherus through 2026. Theresa LaVallee, our Chief Development Officer, will discuss our immuno-oncology strategy and pipeline. Sanjay Khare, our Senior Vice President of Immuno-oncology Research, will discuss our internally sourced immuno-oncology assets. Paul Reider, our Chief Commercial Officer, will then present the planning for our upcoming four product launches that we expect will drive significant long-term revenue growth. Finally, I'll present an overview of our cost structure and the operating leverage inherent in our business model. Then we'll take your questions after Denny wraps things up. Now I'd like to introduce Coherus' CEO, Denny Lanfear.
Thank you, McDavid. Thank you for those forward-looking statements. They were quite comprehensive and complete. The sun will come up tomorrow, and everything else is subject to caveats. Thank you very much. We're really happy to be with you here today. I'm particularly happy to be with you. A lot of you have been with me for many years. Doug Tsao, you know, for example. You know, we started the company back in 2010, and we started this company on the promise of benefit of biosimilars to patients. One thing that is in the DNA of Coherus is benefit to patients. You know, perhaps the decade of 2010 was the decade of biosimilars.
In that context, we're very proud of the accomplishments and the progress that we made, the savings that we delivered to the healthcare system and all. Our mission now, just as it was before, is still for the benefits of patients. What you'll see today is our focus on prolonging survival. Prolonging, you know, survival is a key focus, particularly in immuno-oncology. Now, the biotech business is one of very long time constants. As you can see here, you know, execution is key. The one thing I think that we are focused on absolutely is execution. As I look at this today, this really is very similar to our agenda. You'll first hear from Paul Reider with respect to our execution with the biosimilar portfolio to build cash flows.
We are absolutely focused on YUSIMRY, CIMERLI, the UDENYCA on-body system, and you'll hear a fair amount of detail about that. You'll also hear from Dr. Theresa LaVallee on our toripalimab opportunities, both with and without TIGIT. You'll hear from our research head of immuno-oncology, Dr. Sanjay Khare, about our new innovative products which are coming through. Lastly, you'll hear again from my Chief Financial Officer about how we're going to deliver disproportionate benefit for our shareholders and create synergies. Now, as I was saying, the biotech business is one of long time constants, right? These things take a long time. INDs take a long time, phase IIIs take a long time. It's very important to spread the risk across your portfolio with products in each phase. We take a diversified approach at Coherus.
We, of course, have the toripalimab, a highly differentiated PD-1, which Theresa will talk to you about as a late-stage market-ready asset. We also in mid-stage, going into phase II/III, we have toripalimab in combination with an externally licensed assets such as the TIGIT. Other assets also with respect to our Junshi relationship. Of course, you'll hear from Sanjay in our early stage internal innovation assets. This gives us a full spectrum with our portfolio and our pipeline from preclinical to clinical and late stage. It all starts, of course, with PD-1. As you know, in 2019, we launched UDENYCA, and about four months later, in April that year, we pushed the company to cash flow breakeven. At that time, we began to act very seriously on how to expand the mission of the company beyond biosimilars, particularly in oncology.
Many of you on the calls in those years, in 2020 and 2021, you heard me talk about how we are working on a PD-1 license agreement and so forth. We delivered on that. We delivered for you a PD-1, which we think is fairly well-differentiated and very, very special. In the middle part of this slide, you see some of this. This PD-1 has a very unique binding to PD-1. As Theresa would say to me, you know, epitope really matters. You'll hear more about that today. This PD-1 is distinguishing itself with low PD-L1 data, which you'll hear more about, and we think makes it ideal for combinations. In IO, we think there's a bifurcation of companies, those that have a PD-1 and those that do not. It's essential to have one for one very key reason.
If you go out and you develop a combination therapy with someone's PD-1, at the end of the day, you will need a license to put that on your label to commercially promote, right? You will need to be able to do that. We think this is really essential to have our own. When we looked at these PD-1s, we saw not only one that had excellent safety activity, but one that had a very broad development profile. That's what you see with toripalimab across a number of indications. This is essential because you need to be able to speak to the issue of combination of effect, right, just how much of that happens. Now, with our movement into the innovative space, I would make one key point. Success is built on the failures of the past.
Sanjay will talk to you about how we are looking at the plethora of data that is coming out in a bioinformatic dimension and being able to understand what is going on in the tumor microenvironment, understanding what works and what is not. The key to this is survival curves and taking a genomically driven look at those patients and understanding how that translates to targets. This again is about advancing patient benefit, prolonging survival. As each additional combination therapy is introduced, hopefully it extends the survival of the patients. People get very excited about the immuno-oncology space and the PD-1s, but you have to keep in mind that in some of these cancers, you're talking about patients going from 10.5 months to 12.5 months. These patients are still dying of cancer. There's plenty of room for improvement.
We intend to bring forward three assets, wholly owned, our innovative assets here. Again, Sanjay will speak to you about an ILT4, a CCR8, and a CD73. Of note, we also expect to move into phase IIIs with TIGIT in combination with toripalimab. We expect one additional asset moved into IND per year starting next year. Now, let me turn a moment to the issue of people, which is overlooked a bit, I think, sometimes with companies. Innovation, in my view, does not come from giant buildings and 100 billion-dollar companies. Innovation is spawned in the mind of a brilliant scientist upon inspiration. People do inspiration. People do invention. That's who does these things. This has really been a key focus of the company really from the beginning.
We have made excellent progress building out our scientific brain trust to address immuno-oncology, and you'll talk to many of them here, Dr. LaVallee and Dr. Khare and so on. Our selection of our PD-1 toripalimab was all through our scientific advisory board and our science. It is they that I would thank for their help in picking the right asset. Also our TIGITs and all of our other products are thoroughly vetted through our SAB. People, again, are required for execution. Strategy is well and good, right? As an old mentor of mine once said, you know, "Strategies that are not executable are fantasies," right? That was Kevin Sharer back at Amgen. One of the things that I'm really proud of is the execution of our commercial team.
Guys that have been with me a long time, like Michael Fleming and Michael Chen, who really, you know, both designed our approaches for UDENYCA, really, and really took a deep look at those markets and understood them well. We have continued to build this team out, and they're here for you today. Paul Reider is our Chief Commercial Officer. Paul will be telling you about a number of our products and how we're gonna go forward with each of the biosimilars, as well as toripalimab. There's also a number of other teammates that we have now, which are very tightly focused on successful execution on the commercial dimension. That's what you see here. We expect $1.2 billion in top-line sales in 2026 through the launches that we're putting in place over the next 15 months.
The UDENYCA on-body system, YUSIMRY, our HUMIRA biosimilar, CIMERLI, our Lucentis biosimilar, and of course, toripalimab. I would just add that these are not just pipe dreams and imaginations. You know, our on-body system has shown its worth in clinical trials. We're preparing it. YUSIMRY is approved. CIMERLI, we are very confident it will be approved in August. Toripalimab has shown extraordinarily good data in a number of cancers, including esophageal and NPC, and it has the BLA in front of the FDA. Which all sets us up for 2026, our four-year plan, where we'll have a leading, growing, innovative immuno-oncology company driven off the revenues of commercial products, as I just said. BLAs for toripalimab plus our PD-1 in combinations, two or more assets in clinical stage trials, and a humming engine in R&D, producing a steady stream of products.
You'll hear about all them today, and at the end of the day, I'm confident that you'll walk away confident that Coherus will successfully execute on this mission for you and deliver value to you, our shareholders. With that, I'm going to bring up Dr. Theresa LaVallee, who is directing our development programs. Theresa?
Thank you, Denny, and good morning. It's a pleasure to be here, Theresa LaVallee, Chief Development Officer, and to present to you the opportunity in immuno-oncology as well as our clinical stage IO portfolio. Let's start with the cancer immunity cycle. This shows the mechanistic interplay between the tumor and immune system on how to invoke anti-tumor immune effects. You know, for the 100 years from the Coley through the 1900s, this was really thought about. What's been exciting in the last 10 years is how much we've learned. It's really positioned us to understand that the T-cell, the mighty T-cell, is the core to really invoking anti-tumor immunity.
How that happens, I'm just gonna walk you through it a little bit mechanistically, 'cause I think it will help to see how we're positioning our assets and how we look at them for development. Of course, antigens have to be present and presented. The orange is the T-cell, and the dendritic cell or an antigen-presenting cell, a tumor cell, can present antigens to a T-cell. On the far right, we see that antigen is presented on an MHC to the T-cell receptor, and that triggers signal one. The immune system has a lot of checks and balances. It's not just signal one is sufficient to activate a T-cell, you also need signal two. You can think of this as like multi-factor authentication, right? Signal one, username, password, got it.
You need a push code to get into your account, so you need signal two. The immune system really has these checks and balances so that you can control and not have untoward autoimmunity and those types of things. As we've really learned how this works and how to activate a T-cell, we've seen a number of immunotherapies come forward, including CARs, which takes a genetic approach to add in signal one and signal two in a single construct and have the T-cell attack the tumor. We have bispecific T-cell engagers, where you have a tumor recognition on one end of the bispecific antibody and a CD3 that recognizes the T-cell receptor, so signal one, and looks for signal two within the tumor. Then the checkpoint inhibitors.
They come in, CTLA-4, the first approved, which takes the breaks off signal two. Then I'll talk about a little bit more PD-1 that's really had transformational activity in immuno-oncology because it can affect both signal one and signal two. What does this mean and why is everyone so excited? That's way cool biology, but what does it mean to a patient? The real opportunity is long-term benefit. 1900s, lots of cancer therapies, radiation, chemotherapy, targeted therapy shown in blue. There are definitely survival advantages, but patients with metastatic disease, it's still fatal. Tumors come back. There's not memory from those types of therapies. Resistance to targeted therapy is a real issue. For the immune system, there is long-term memory. As the tumor comes back, it can eliminate the tumor.
It's really this tail of the curve that we all talk about, but this is really remarkable in that there are long-term survivals and cures with immunotherapy, and that's the excitement. Again, building off these Crayola Kaplan-Meier curves from Jim Allison's Nobel lecture, what we really wanna see for the next 10 years, now that we've understood the T-cell, we understand a little bit better how to invoke anti-tumor immunity, how can we get it to not a minority of patients, but a majority of patients? One of the things that's really giving us an advantage is the use of technology. Multiomic, multiparameter biomarker analysis in patients. What I like to say is the human cancer patient is the relevant animal model. Mouse model system's incredibly important, but the immune system's complex.
Profiling of patients and learning about response and non-response is really informing us of who to treat and how to treat. We've learned a lot about the T -cell. It's complicated, and immunologists also really like to have a lot of different cell types and a lot of different markers, so I'm constantly having to study and be like, "What? I didn't know that one." As we think about the T -cell as it differentiates, we've talked about at the beginning with the cancer immunity cycle, how antigen is presented on the left side, so the naive T -cell gets activated. Then there's checkpoints, the PD-1s, the CTLA-4s, the TIGITs that turn it off. There's different stages, though, of exhaustion. You don't just have an exhausted T -cell. There's a lot of states of dysfunction and exhausted.
What we've learned is that at the far right, you have the hyper-exhausted T- cell with all of the exhaustion markers up. Well, this T- cell is completely pooped out, so no matter how much you treat it with checkpoint inhibitors, you can't reinvigorate it. We've learned that the important cell type for PD-1 is the antigen-experienced exhausted or tired, as I'd like to say. The tired T- cell that has stemness. A TCF7 biomarker. What's really interesting is the two checkpoint inhibitors that are expressed here are TIGIT and PD-1. Then we've also learned that there are these exhausted effector T- cells that have other checkpoint inhibitors that can be reinvigorated. Very exciting this month, we saw the approval of the third checkpoint inhibitor target, LAG-3, right? As we've learned more, we're starting to advance.
As we go into the next decade, we also have to be mindful of the interplay between the tumor and the immune system. There are a number of immune suppressive mechanism that the tumor uses to evade the T- cell. While we work to really promote best T -cell fitness, if the T- cell can't get into the tumor, and if it does get into the tumor, if there's a number of suppressive mechanisms like T -regulatory cells, myeloid-derived suppressor cells, cancer-associated fibroblasts, tumor-associated macrophages, those yucky M2 macrophages, they'll really dampen the T -cell response, prevent it from getting in, prevent it from getting activated. I think the next wave of real combination treatments with the PD-1s is attacking the TME to make it more T -cell permissive.
With that opportunity of why we're excited about immuno-oncology, how we're positioning ourselves in immuno-oncology, I'd like to present toripalimab, our PD-1 clinical stage asset that, as Denny mentioned, was in-licensed from Junshi, our partner, who has developed it and has it approved in China and has a multitude of studies. Together with Junshi and their U.S. subsidiary, TopAlliance, we have a - that I'm really hoping plays now.
In recent years, cancer immunotherapy has developed rapidly, especially with PD-1 and PD-L1 inhibitors, which have demonstrated clinical efficacy across multiple tumor types, bringing new hope to cancer patients. Many questions remain about immune checkpoint inhibitors. PD-1, a protein on the surface of T -cells, is a transmembrane immunoreceptor with an ITIM motif and ITSM motif in the intracellular domain. When PD-1 binds to its receptor on the tumor cell, PD-L1, the tyrosine sites in the ITIM and ITSM in the intracellular domain are phosphorylated, and intracellular SHP-2 is recruited to PD-1 and activated. Activated SHP-2 can dephosphorylate and inhibit the downstream PI3K, AKT, and RAS-MAPK pathways in the T -cells, leading to - activity of effector and memory T -cells within the tumor microenvironment. Eventually, the tumor evades the immune system and continues to grow.
Is it possible to prevent immune escape simply by blocking the binding of PD-L1 to PD-1? Scientists found that PD-1 protein, when expressed on the surface of the T- cells, is still able to exhibit a weak inhibitory effect on T -cells, irrespective of binding to its PD-L1 ligand. Thus, the inhibitory effect of PD-1 on T- cells has two pathways. One which is dependent on the binding of PD-1 to its ligand PD-L1, and one which is independent of the ligand. Under the continuous stimulation of tumor antigen on T -cells, the expression of PD-1 protein is gradually upregulated, and the surface expression of PD-1 increases. The inhibitory effect of PD-1, both ligand dependent and ligand independent, gradually accumulates, and the activity of T -cells decreases, eventually leading to T -cell exhaustion.
According to the immune normalization model of Yale University professor Lieping Chen, the human anti-tumor immune response can be thought of in terms of the flow of water from a faucet. The PD-1 pathway turns off the faucet, thus allowing immune escape to occur. Blockage of PD-L1 or PD-1 binding via monoclonal antibodies to PD-L1 or PD-1 only removes the ligand-dependent inhibition, but the ligand-independent inhibition still exists. As T -cells continue to be activated, PD-1 protein expression increases, causing further ligand-independent inhibition, resulting in T -cell exhaustion. Therefore, immune normalization requires not only blocking the binding of PD-L1 to PD-1, but also downregulating the expression of PD-1 protein from the surface of the T -cells. Toripalimab, an anti PD-1 monoclonal antibody, has several unique characteristics. First, the unique binding site of the FG loop can change the monoclonal antibody conformation and enhance affinity.
Second, the PD-1 binding site is large and requires 2,011 square angstrom, resulting in full blockage of the PD-1 protein. Third, half maximal inhibitory concentration is only 0.8 nanomol per liter, which can efficiently bind PD-1. Fourth, KD is only 0.3 nanomol per liter, reducing the on-off rate of the antibody, resulting in a longer-lasting blockade. Additionally, toripalimab has an efficient endocytosis or internalization mechanism, which reduces the expression of PD-1 on the surface of T-cell membranes. Using markers that fluoresce intracellularly, toripalimab was labeled to show the endocytosis process. 30 minutes after administration, a small amount of markers entered the T-cells. After 6 hours, many more markers were detected within the T-cells, indicating the efficient internalization of PD-1 following treatment with toripalimab.
Flow cytometry showed that the expression of PD-1 on the surface of T-cell membrane decreased significantly with the increase of toripalimab concentration or the prolongation of administration time. Toripalimab, a PD-1 inhibitor with unique characteristics, is developing a strong and consistent efficacy and safety profile across multiple tumor types as data readout from pivotal clinical trials, including in melanoma, nasopharyngeal carcinoma, urothelial cancer, esophageal cancer, and lung cancer.
We walk through and reiterate some of the points in the video. As Denny mentioned, I think having worked with Yossi Schlessinger, a structure function person, I really learned that epitope does matter. Thinking about where it binds, it can have different properties, and we know that most relevantly, clinically from HER2. So two antibodies, trastuzumab, pertuzumab, both bind HER2. Trastuzumab has robust single agent activity. Pertuzumab, not so much. So you see the difference of where it binds can have different properties clinically. As described in the video, when we compare toripalimab to pembro and nivo, so the top of this, ribbon diagram structure is the antibody. So the three different antibodies, and at the bottom we have PD-1. And we can see that nivo binds at the N-terminus. This has a conformational change, making the FG loop visible.
Pembro binds at the CD loop, doesn't allow visibility to the FG loop, and toripalimab binds the FG loop with a broad coverage. Additionally, another attribute of antibodies that you really look for in development is potency. You can see here a comparison. Toripalimab is about twenty-fold more potent than the competitors. The video very nicely showed you the internalization properties in these day glow green figures. Anyone who's worked on antibody drug conjugates is used to thinking of antibodies binding, having to be internalized, release the payload. Why would this matter for immuno-oncology? If we think about where our discussion about PD-1 really being a critical node for activating exhaustion in a T-cell, and we're trying to maximize T-cell fitness, getting rid of PD-1 may enable a fitter T-cell.
We know this from the CAR space where they're trying to use CRISPR to knock out PD-1. Again, unique differentiated pharmacological properties of this antibody robustness, but how could this translate to the clinic? What difference does this make to a patient? What you might expect to see is better depth of response, durability of response, or perhaps a new patient population that could be treated with toripalimab. Results that were recently published from the JUPITER-06 study in frontline ESCC with toripalimab in combination with chemotherapy, what we see, as we've seen in all the clinical studies that I've read out to date, robust survival, hazard ratio of 0.61. Noteworthy though, within the JUPITER-06 trial, the activity is independent of PD-L1 status. High or low, you have a hazard ratio of 0.61.
In the KEYNOTE-590 study, if you look within that trial, so not across trial comparison, but really looking at the activity based on patient population of the individual molecules, we see significant activity as would be expected in PD-L1 high, but modest activity in PD-L1 low. We've seen this in other studies in combination with chemotherapy such as our NPC and non-small cell lung cancer study as well. As Junshi presented this wonderful package to Coherus, as we looked through it, what we saw in the early stage clinical studies is that there was robust activity across immunologically responsive tumors. The disease control rate here shows you that we have really nice activity in combination with chemo, 80%+ disease control rate, monotherapy 30%-50%, as would be expected from a PD-1 inhibitor.
Junshi has a large, robust, ongoing phase III pivotal program looking in adjuvant, neoadjuvant, first-line, second-line monotherapy combination approaches across disease types. Our lead indication is NPC, nasopharyngeal carcinoma, a tumor type that is underserved by immunotherapy. These results were presented from the JUPITER-02 study, the phase III study, frontline NPC in combination with chemotherapy at the plenary session of ASCO last year, as well as published in Nature Medicine and featured on the cover. Again, a very nice hazard ratio for PFS of 0.52. Other data continue to read out and be recognized in high-profile scientific venues. In this month in Cancer Cell, the esophageal data was published that I showed you the Kaplan-Meier curves of earlier.
I need to point out one of the things that you could also think about, with the differentiated properties that we presented with a new epitope, higher affinity, internalization, is that we have not observed any new safety signals from toripalimab. It has a safety profile very consistent with a PD-1 inhibitor. Additional studies that have read out are the non-small cell lung cancer study, the CHOICE-01 study, which is a frontline study with toripalimab in combination with chemotherapy. Very similar to the Innovent Lilly study, the ORIENT-11 study that was recently reviewed at ODAC, where the FDA really enlightened us as to their current thinking about single country data. Large indications that are well-served by immunotherapy treatments, there's a multitude of agents approved in multiple lines of non-small cell lung cancer.
Single country data is not observed to warrant regulatory flexibility. In the ODAC and in the op-eds in the New England Journal of Medicine and The Lancet Oncology that were published, it has been repeatedly stated that NPC is a tumor type underserved by immunotherapy. Orphan indication would warrant regulatory flexibility, and we currently have our BLA under review with a target PDUFA date of April 30th. We are working with the FDA and under discussions to figure out how to get inspections in China scheduled, and obviously with pandemic-related travel restrictions, that is a discussion. In addition to noting in tumor types that have or could warrant regulatory flexibility other than NPC, HCC, so liver cancer was highlighted, and Junshi does have a number of studies ongoing there.
We've kind of now defined the bookends, ones that warrant regulatory flexibility, lung cancer, a multitude of agents, big tumor type, no. There's like 900 indications in oncology, so what's in the middle? That's really what we have to figure out and engage in with the FDA and look forward to further guidance from them. Ways that we're approaching this is looking at trials that are ongoing, like our small cell lung cancer study, that really has been underserved by PD-1s, only PD-L1s approved, and the overall survival advantage just two months, 2.7 months. Maybe there's an area to look at if you have meaningful clinical benefit. Then there's ongoing phase III studies in China right now, could we make those multi-regional studies? Those discussions with our partner, Junshi, are ongoing.
Switching to the TIGIT program, also partnered with Junshi, we announced in January that we'd opted in. They have an ongoing phase I study in China. Going back to the biology, just to introduce TIGIT a little further. It's a checkpoint inhibitor, so its ligand is PVR, akin to PD-L1 being the ligand for PD-1. When PVR binds TIGIT, it dampens the T- cell. Okay, now the complicated biology, but this I think really does explain perhaps why PD-1 has been more robust than any of the other checkpoint inhibitors, its role in peripheral tolerance, but also the way that it inhibits signaling. When PD-L1 engages PD-1, it activates a phosphatase SHP-2. The phosphatases take away any activation signal.
What's interesting is when PD-L1 engages PD-1, the SHP-2 turns off signal two, CD28, but it also turns off signal one. Hits both signals, so maybe a more robust node there. Also, in addition to TIGIT and PD-1 having co-expression on that antigen experience exhausted stem-like T -cell, there's crosstalk between the two pathway signaling. PVR binds TIGIT and turns off T-cells. PVR also binds CD226, which is an activating signal. When SHP-2 is activated with PD-L1 binding PD-1, it also turns off CD226. A lot of complex interplay. The bottom line is the two receptors are related from expression and crosstalk and signaling. A biologic rationale for why the combination may have enhanced antitumor activity.
TIGIT is also expressed outside of T-cells on another cytotoxic cell, the NK cell, as well as having immune suppressive properties on myeloid cells like dendritic cells. If you turn off the antigen-presenting cell, so you dampen the APC, you're not gonna get signal one. Then of the T reg, which is a regulatory T-cell that Sanjay will talk to you more about, that can suppress immune response. The anti-TIGIT antibody is called 006, that Junshi is developing. The package that we saw from a preclinical perspective showed potency and binding to TIGIT. On the top left, the red and blue curves are comparing 006 to the benchmark tiragolumab, the Roche Genentech TIGIT molecule. You see equivalent binding potency. The bottom left shows you a cell-based T-cell activation assay, looking at single agent, activation with 006 on its own in green.
Importantly, in combination with toripalimab, targeting PD-1 and TIGIT together in pink, you see enhanced T-cell activation. On the right-hand side of the slide is a preclinical tumor model with a PD-1 TIGIT human knock-in animal. The curves show monotherapy tumor growth inhibition when a mouse is treated with single agent toripalimab or 006. Importantly, when the two are combined, we see dose-dependent improved enhanced antitumor activity, including tumor regression. A strong biologic package to really show this molecule to move into the clinic. Last year, Genentech presented early phase II data from their CITYSCAPE study in non-small cell lung cancer, really showing this combination effect that's been seen in preclinical setting in the clinical setting.
Non-small cell lung cancer treated with atezo, the PD-L1 antibody or tiragolumab atezo, in blue, showing really improved PFS in that. I think, you know, as we all really have been bullish in the IO space about TIGIT, the one disappointment for this study was that it was exclusive to the PD-L1 high. It improves where the PD-1 is already pretty good, but didn't broaden the patient population in non-small cell lung cancer to date. A lot of activity here, and we expect lots of news flow in the TIGIT space over the next year, including transitioning 006 to clinical studies with the active IND in the U.S.
We will rapidly go into dose escalation in combination with toripalimab in the U.S. study with a Coherus-sponsored study, and then expansion phases in the tumor types where Tori's shown activity and has some unique attributes to really benchmark 006 toripalimab data in the field. Working closely with our partner who's continuing development in China to look at multi-regional pivotal studies to advance this quickly. That's the clinical stage portfolio. I think the commercial manufacturing and regulatory expertise of Coherus is well understood from their work with UDENYCA and other biosimilars. What probably isn't appreciated is the strong research capabilities. There's a beautiful facility in Camarillo, California, with antibody expertise, of course, but also immunology and translational bioinformatics capabilities. This really sets up well for new development and early development of an in-house pipeline targeting IO.
This slide shows the IO pipeline. With that, I'll introduce my colleague, Dr. Sanjay Khare, who is SVP of IO. He's a excellent accomplished immunologist and industry veteran. Sanjay.
Well, thank you very much, Theresa. Thank you for listening to the presentation. Next, several minutes, I will be talking about how the research we are doing in immuno-oncology would lead to new combination assets and also help identify patient population that could be treatable with the combinations. Let me tell you a little bit about our approach. What we are trying to do is to learn through bioinformatics data mining effort to understand which patient population is responding and which patient population is not responding. What kind of immune escape mechanism might be triggering in patients where we are not seeing enough efficacy or patients are rebounding. In order to understand that, what we did is took an effort looking at cancer omics data.
These omics data are available from many public sources, TCGA being one of them, but cBioPortal and many other sources. Instead of taking a large approach, we took a deep data dive on these data to understand what science is telling us, and can we identify some potential mechanisms for ultimately potential combinations. Finally, once we identify that will help us in patient selection, trial design, and mechanism of action insights, how these patients can be treated. Going back to 2017 publication from Merck. In this study, investigators showed that the number of patients with high T-cell inflamed gene expression profile are the ones who are responding.
You can see these red squares and also blue triangles. They are stable disease and complete response or partial responses. Many of these patients had pretty good progression free survival. However, there are other patients with a high T-cell inflamed gene expression profile. Those were not responding to anti-PD-1. These are the data comes from nine different tumor types. The overall this has been seen across different types of tumor in two different studies. What this may be suggesting that there are additional immune suppressive mechanisms going on in the tumor microenvironment leading to these patients not responding to anti-PD-1 therapy.
What we did, we used the data from The Cancer Genome Atlas and other additional sources and try to see what kind of mechanisms might be playing a role in these patients not responding to anti-PD-1 therapy. As Theresa pointed out before, many patients could have unfavorable tumor microenvironment because of the presence of regulatory T- cells, myeloid suppressor cells, fibroblasts, and tissue-associated macrophages. We try to focus on these mechanisms while others are still working on immune checkpoint. We already have two checkpoint molecules in our portfolio.
What we are trying to solve is to understand major immunosuppressive mechanism that may address immune escape, and how the combination of drug could potentially lead to turn this unfavorable tumor microenvironment to a favorable tumor microenvironment, thus anti-PD-1 therapies could work much better than what they are doing today. We begin to address this issue by transforming the transcriptomics data into immune cell type. This is not new, but we have been using a different approach, a different algorithm that comprises about 30-45 genes for various immune cell types. We have looked at various tumor types, such as non-small cell lung cancer, small cell lung cancer, and trying to find addressable dominant mechanism of action in those patients.
Finally, find targets based on the biology and develop best-in-class drug candidates. That's what we are doing in our Camarillo labs. How this work is done? We are looking at the databases and also publication. Those are evolving over a period of time as early as 2022. Then we are using number of software and number of other algorithm to convert those transcriptomics data into cell types, immune cell types. Then we are seeing that what kind of immune cell types, particularly suppressive immune cell types, may be interplaying a role. Okay. Let me talk to you about a molecule called ILT4. ILT4 seems to be a key regulator in repolarizing suppressive macrophages turning into inflammatory macrophages.
The reason is it is very important because when ILT4 on macrophages, these are the suppressive macrophages, are binding through HLA-G molecule on tumor cells, these suppressive macrophages turn off immune T- cells. Okay. Now, when you block this interaction, ILT4 to HLA-G, you can turn these immune suppressive macrophages M2 to M1. In addition, what it does that dendritic cells are not able to present antigen to T- cells. Those are called tolerogenic dendritic cells. Presence of the blocking agent would lead to tolerogenic dendritic cells to activated dendritic cells, so you have better antigen presentation in that case. As I said that we have been analyzing these data and from various cancer types, and here is an example in a small cell lung cancer.
What we are trying to do here is to look at signatures relevant to various immune cell types listed here. Here, the lighter the color or towards the red you are seeing is the high signature or high content of that immune cell, and the blue you are seeing is the low content of that immune cell. What you are seeing, the patients called M1 cluster, in the M1 cluster, have a high immune score, and those have hot tumor and probably more responsive to anti-PD-1 therapy or PD-L1 therapies. There's a big cluster of M2 macrophages, about a third of total patients. These patients have fewer immune cells, CD4 and CD8 T- cells here. These patients are not likely to respond to anti-PD-1 therapy unless you change this immunosuppressive pathway.
Here's the prognostic value of what I just said. If patients have high M2 content, they die much faster than patients who have M1 content, and this is without anti-PD-1 therapy. Certainly, we wanted to look at what could be the target of interest in M2 population, and we looked at multiple targets, and we are not the first one. ILT4 jumped, and ILT4 is highly expressed in M2 cells compared to non-M2 cells, non-M2 population. Interestingly, like others have seen, we found that patients with high M1 have higher content of CD4 cells, CD8 cells, CD4 memory resting, and CD4 memory activated cells. Patients with high M2 have very few of those cells.
More recently, number of publications came out demonstrating that when you have more CD4 cells and more CD8 T- cells in the tumor microenvironment, these patients respond better to anti-PD-1 therapy. Once we convert these M2 to M1, the likelihood of those patients will be responding better. Similar to a small cell lung cancer study, we also analyzed the TCGA data for non-small cell lung cancer, and we found a large population, almost a third of the population of all non-small cell lung cancer patients, adenocarcinoma, have high expression of M2. So here, red is high and blue is low. Patients with a high M2 signatures have very few CD4 and CD8 T- cells. About a third of these patients have high M1, and these are the ones who may be better responder for anti-PD-1 therapies.
Certainly, there are chances to make more patients responding to anti-PD-1 therapy when you're converting M2 to M1 by anti-ILT4 therapy. Indeed, this is the publication that just came out a couple of months back in Clinical Cancer Research by Merck. There they have shown that they treated 84 patients, and 34 of those patients received their anti-ILT4 MK-4830 in combination with pembrolizumab. This combination was well-tolerated in patients. 10 out of 34 patients showed objective response in the combination group. In the monotherapy group, only one patient responded. Five of these responders were PD-1 refractory. Okay, pretty good opportunity here. Interestingly, there was durable response seen in over one year in many of these patients.
What we are trying to do is develop ILT4 antibody CHS-1000, and that is going to block ILT4 interaction with HLA-G molecule and making those T- cells more prominent for antitumor immune response. This candidate, we are expecting to file the IND next year. Let us discuss another immunosuppressive cells pretty well known in the literature about regulatory T- cells. Regulatory T- cells are also known to dampen antitumor immune response. There are a number of targets for regulatory T- cells, and many of, and there are some failures, too, for Treg-directed compounds. GITR was one of the molecules present on regulatory T- cells, didn't work out well.
The problem is the Tregs are good to keep the inflammation down, but at the same time, Tregs are not good for antitumor immune response. You want to have a molecule that is overexpressed in the tumor microenvironment, the Treg in the tumor microenvironment. CCR8 is one of the molecule that is highly expressed on Tregs in the tumor microenvironment. What we try to do, looking at the similar type of Treg you have seen before, and again, we are looking at red means high and blue means low. We are looking at the regulatory T- cells right here. Regulatory T- cells are high in about 30% of non-small cell lung cancer patients. We found actually the two clusters for regulatory T- cells.
One is cluster one, the other one is cluster two. The cluster one has regulatory T- cells, and this cluster also has natural killer cells. However, cluster two is low in natural killer cells. When we are developing this antibody that will deplete regulatory T- cells, you need NK cells engagement to kill those regulatory T-cells . Therefore, the patients in the cluster one, high Treg, high NK cells, are more likely to get benefited with anti-CCR8 antibody. Patients with high Treg and low NKs, NK cells have low chance, less chances. This is what bioinformatics data mining is telling us. In a nutshell, when you have patients those have MAC, no MAC or NK cells, basically, even though you have your drug that may be binding to the receptor or regulatory cell, but they cannot be effectively killed.
Because Treg cannot be killed, immune CD8 T- cells cannot work very well to kill the tumor. On the other side, when patients have MACs and NKs, in the presence of anti-CCR8 antibody, they will be able to kill T- regulatory cells, and CD8 cells will be able to kill tumor. We have studied this in multiple tumor types. There are a couple of interesting observation on this slide. Number one, this is limited mechanistic overlap with anti-CCR8 and anti-ILT4 treatment. So that would definitely help a large segment of oncology patients. Here, we are showing data in hepatocellular carcinoma, adenocarcinoma, small cell lung cancer, head and neck, and esophageal.
It seems the large number of patients from 45% ILT4 and CCR8 together, for high Treg and M2 together, all the way up to 65%. Large number of patients are going to be benefited with the portfolio that we are developing. Thank you very much. I will take an opportunity to introduce our Chief Commercial Officer, Mr. Paul Reider.
Good morning. One of the reasons I came to Coherus is the science and the transformation of this company from a pure-play biosimilar company to a future leader in immuno-oncology. The science is very impressive, and I wanna congratulate Theresa and Sanjay for their outstanding work here. They're bringing the products that I get to sell and bring to the marketplace, and that's what I've been doing for the past 30 years. I'm proud to be here working with Denny and my colleagues on this opportunity to bring more medicines to more patients and to improve the lives of these patients. My name is Paul Reider. I'm the Chief Commercial Officer here at Coherus. We are becoming a commercial powerhouse. I'm gonna talk you through that story, but that is a fact.
We are ready to launch four new products over the next 15 months, which is a bit of a daunting task, I must say. It's not often many companies have an opportunity to do this of a size like Coherus. I believe at the end of this presentation and at the end of today, you'll have a high degree of confidence in our team and our ability to execute. To be a commercial powerhouse, you need a number of things. The first thing you need, as Denny mentioned earlier, is a group of powerhouse commercial leaders. Denny mentioned Michael Fleming, our Chief Strategy Officer, who, you know, has been with Denny here at the formation of the company. Reporting to Michael is Abid Rahman. Abid comes to Coherus with decades of oncology marketing experience, Senior Vice President of New Product Planning.
Within the strategy group, Abid and Michael are really focusing on the commercialization strategies for our commercial pipeline of products. Then they get handed over to me and to my team. Joining me today is Steve Svitenko. Steve, if you wanna raise your hand. Hello, Steve. Steve is our senior vice president of market access. I've known Steve as a friend and colleague for a couple decades now. He leads up our payer and PBM teams, our field reimbursement organizations, the patient services hubs and the market access marketing team all rolls up into Steve. Steve's got 20 years of oncology experience, but while he was at AbbVie many years ago, he was on the original HUMIRA launch team.
Some skill sets and experiences that will bode well here for us, as we enter the immunology market with the launch of YUSIMRY. I'll start in the second row to the left. David Sanders heads up our government affairs team. That's a group of four, very skilled, government affairs specialists that really help Coherus advance the policies, the legislation, and the efforts of the biosimilar marketplace. Securing America's Medicines and Supply is a coalition of companies spearheaded by David and by Coherus to ensure that really the biosimilar supply chain, you know, is secured. What we learned through the pandemic is there's great opportunity to do that and to reward American companies who are developing these products here in the United States and manufacturing them here in the United States.
It was also David's efforts that secured our extension of our pass-through status or the enhanced reimbursement for UDENYCA throughout this entire calendar year. John Lane leads up our biosimilar marketing franchise. You know, one thing you learn when you're in the biosimilar business, it's a little bit different than the branded business. It takes skilled commercial leaders that really understand the competitive nature of the biosimilar business, and John's that leader. He built and led Hospira's original biosimilar business unit, and then as through the acquisition by Pfizer of Hospira, took that on and led their very competitive hospital injectable business. John is the perfect commercial leader for our biosimilar business. Reporting into John, he'll be responsible for UDENYCA today and our life cycle of UDENYCA on-body, as well as CIMERLI and the YUSIMRY launches.
We've organized into that franchise. Then Brandon Kotaniemi. We hired Brandon to serve as the Senior Vice President of our immuno-oncology marketing franchise. Brandon will be responsible, and his team, for the launch of toripalimab in the first indication, a nasopharyngeal carcinoma, any follow-on indications or any other of our immuno-oncology products that we'll commercialize in the United States. Brandon's got decades of oncology marketing experience, launching blockbuster innovative brands. This is the team together on the commercial side that will deliver on the full market potential of our products in our pipeline. The other thing you need to be a commercial powerhouse, particularly in oncology, is expertise. In oncology, with majority of the products being administered via injectables or infusions, you need to have a mastery of the complexities of the buy-and-bill ecosystem.
This chart could actually be more complex, and I'm not gonna take you through it. But suffice it to say, to be a commercial powerhouse in oncology, you have to understand this, and we do. We've mastered it, and we understand the interplays between the supply chain channels, the group purchasing organizations, how those support both the hospital and the clinic segments with the patients and the payers all wrapped around it. This is important for UDENYCA. It will be important for toripalimab, and we will bring this expertise into the retina space with the launch of CIMERLI. YUSIMRY, which I'll speak to later, is fulfilled through the pharmacy benefit pathway, so I'll speak to those in my remarks shortly. Another thing you need to be a commercial powerhouse is really a battle-tested, proven, field-facing commercial organization. We built that for the launch of UDENYCA.
We have over 125 field-facing professionals currently operating in the oncology segment today, over 76 from our sales team. We call them oncology account managers. We built in additional capabilities since the launch of the pandemic to focus on specific remote sales team representatives that are highly skilled and trained in working in a virtual environment that will enable us additional share of voice through the pandemic. As oncology accounts have changed their policies and interaction with industry, we'll meet the customer where they are. They wanna meet in person, we'll do it. They wanna meet virtually, we'll do it. We've also increased the size of our key account team. These are the individuals who call on the largest integrated delivery networks, the largest group oncology practices.
They're the quarterbacks, if you will, navigating those large, complex organizations. We've scaled that team up in 2021 in anticipation for the launch of toripalimab this year and our future product launches. We've also added, in addition to our home office marketing organization, this key customer team. This is a decentralized key customer marketing organization that now is dealing at the local level. This is a group of specialized marketers that are working largely right now with the thought leaders, the key opinion leaders in particularly the toripalimab and the head and neck, nasopharyngeal carcinoma space. They'll be the ones post-approval who will be driving the peer-to-peer programs and our speaker programs and developing those toripalimab champions. It's a decentralized marketing organization working hand-in-hand with the home office team.
Want to note here on the far end, shaded, but only shaded to differentiate that that's the medical science liaison team. That's the group of credentialed medical professionals, PharmDs, PhDs, others, who report into my colleague, Rosh Dias, our new Chief Medical Officer. So they follow under the medical organization. I've listed them here because they're field-facing, but they're the ones that are working with the oncologist and the other key opinion leaders through scientific exchange, working on publications, investigator-sponsored trials or any other clinical trials. So that's why they're shaded there. Then finally, this lower group of individuals, we have a dedicated payer team that reports into Steve Svitenko. They call on the national and regional payers, both on the commercial side, Medicare Advantage pieces.
We've got a dedicated team focused on our channel strategy, working directly with the GPOs, and finally, a dedicated field reimbursement support team. You got to have this because when you're launching buy-and-bill products, you know, practices need the billing, coding, reimbursement support. When they have a problem, you know, with a claim, this team is sort of the SWAT team or the SEAL team. They go in, and they help the practice get coverage for the patients. We've got a very dedicated team. I'm gonna show you in a little bit how this is gonna scale with the future product launches. The other thing you need in commercial powerhouse, particularly in oncology and in buy and bill, but for pharmacy as well, is you need to have patient services support and reimbursement support for customers.
Coherus Complete is our patient services and reimbursement hub that supports UDENYCA today. It was built to support UDENYCA by providing insurance verification, benefits investigation, patient financial copay assistance. It was built to scale up. Coherus Complete will continue to be the umbrella-branded patient services hub that will support all of our brands as we bring them to market. UDENYCA today, toripalimab, CIMERLI, and YUSIMRY. It's a scalable service solution. As Denny mentioned, our commitment to patients, I note on the left here just the type of support that we've been able to deliver to cancer patients receiving UDENYCA. We've helped over 11,000 patients get product irrespective of their financial position. If they don't have insurance, we give the drug for free. If they need copay assistance, we help them with that.
Paid out over $10 million over the last three years in financial support, which is a testament to our commitment to making sure every patient gets the product. Again, scalable solution. Finally, what we've done is we've built the playbook to win. This was the UDENYCA commercialization playbook. It's a winning playbook. We're gonna apply the four core elements that you see here on the right to all of our future launches, and I'll draw those parallels for you here shortly. The first element of this winning playbook is customer engagement. We go into every market doing our homework, understanding the issues and the dynamics of the customer, and every customer, because there's usually multiple stakeholders in each one of these that affect product selection and getting drug to patient. We did this for UDENYCA.
It was a reason why we were able to accelerate our launch so rapidly in the marketplace, and we're doing that in every market, and I'll show you that momentarily. Pricing and contracting is also another core capability and part of our winning playbook. We're not gonna be, you know, talking today because for our pipeline assets, we won't disclose what our pricing and contracting will be because those products aren't approved yet. But suffice it to say, we understand those dynamics and how we're going to win in each one of those, not only about how we price the product from a WAC and a list price, but also the contracting that occurs within those various channels and how we can deliver a complete value proposition to our customers. The third point here is one that I, you know, I'm gonna emphasize here throughout the presentation.
You oftentimes don't really think about supply when you're addressing commercial matters. But for Coherus, supply and the ability to deliver abundant supply at the time and throughout the launch of our products has proven to be a competitive advantage. The investments that Coherus made in supply for UDENYCA was the reason why despite being the second pegfilgrastim biosimilar, it rapidly overtook Mylan and Fulphila, who was experiencing supply challenges. Denny and the marketing team and the supply chain team brought to the market hundreds of thousands of units at the time, and it was a core capability. Rich Hameister, who leads up our supply chain and technical operations organization, is here today. He'll be able to answer any questions. But this is going to be vitally important for the launch of YUSIMRY in 2023. We'll speak to that momentarily. Finally, market access.
You can have the best product, you can, you know, deliver the greatest marketing, but if you can't get coverage, if you can't support the patients and your customers to get access to the product, you know, the brand will struggle. Under Steve's leadership, we've been very successful with UDENYCA. We're talking with payers regularly across all of our brands to really understand what it's gonna take to get coverage for our products and get those reimbursed and to continue to deliver through Coherus Complete services and support that patients and customers need. Let me take you through the next few slides. I wanna show you how, you know, that commercial infrastructure, you know, that we built for UDENYCA today, you know, with our one brand will scale over time.
To help you understand that we're not having to rebuild and replicate, you know, commercial teams for each of these products that will be incremental builds. That will really, you know, help to ensure, you know, very efficient commercial resource investment over time. You see here with UDENYCA, you know, our core business, those groups that I noted here. I do wanna note in your packets there was a typo. This on the screen says 76. It's listed in 96. Please make that note in your handouts. But you can see here with the launch of toripalimab being an oncology brand, we have one product. Toripalimab will fall right into our existing oncology commercial team's bag. Our current UDENYCA representatives and account management team and the payer team will also take on toripalimab for the nasopharyngeal indication.
We've had to scale up a bit on our key account team to address the growing nature of the key account organizations, both on the hospital and the clinic side. We had to hire a few marketers, but for the most part, this team will be able to sell toripalimab with very little incremental investment. Very efficient there. I'll show you a little bit of the overlap momentarily. CIMERLI, we'll be able to leverage the payer team, the key account team, and the Coherus Complete team. But because it's retina, we're gonna intend to build a very focused and dedicated and experienced retina sales organization. I'll show you a little bit about the concentration of that market. It's not gonna be in the 60 range.
It can be very focused and dedicated to the retina team, but you gotta have that expertise. We're gonna go out and we're gonna hire it. We'll be able to leverage the vast majority of our market access patient services and key account teams for that. We hired a CIMERLI brand marketer, Nina O'Hara. She's a PharmD with years of experience in the ophthalmology and retina space, and she is leading our launch preparations at this time, which are running right on track. Very, very pleased with our progress there. Then finally, for YUSIMRY, you know, because this is a pharmacy benefit adjudicated product, we'll translate, you know, our expertise that we've gleaned from UDENYCA into the pharmacy side.
Here, this is gonna be, as I'll show you, very much, you know, driven by the payers and the PBMs. You know, Steve's team in getting coverage will be our number one priority in that market, and then we'll build Coherus Complete out. We will also build any appropriate and necessary customer-facing organizations that might be necessary for the launch of YUSIMRY. Typically, the way payers have pharmacy benefit products set up through their utilization management controls and their formularies, they can drive a lot of this through the payers, the PBMs, and the specialty pharmacies. We don't anticipate building hundreds and hundreds of immunology sales force for this particular product. That's not what our intention is. Again, very efficient use of marketing and commercial resource investments.
That's how the cadence is gonna build out and how we'll build the team out. Let me talk a little bit now in transition to each one of the brands in the launches coming up. As we go into these markets, you know, our commercial objective is to capture at peak at least 10% market share. These are large sizable markets, so you could see how those then ladder up to our aspiration of delivering well over $1 billion in top line revenue by 2026. But as you know, as I'll show you with UDENYCA, we did a lot better than that.
That's our minimal commercial objective. Let's start with UDENYCA, and let me take you back a few years ago in 2018 to a product I know very well because I was the launch leader at Amgen for Neulasta. I knew this product, launched it with many of my colleagues 20 years ago. You know, it grew to a $4 billion brand. It was a monopoly for the most part, with nearly 100% market share. Prices were being raised, as you can see, over time, almost 15% between that period of 2016 and 2018. You know, they were gearing up. Looks a lot like the HUMIRA business, actually, doesn't it? It's a bit of a case study.
With the launch of UDENYCA and Coherus, you know, we were able to bring a biosimilar to Neulasta, to pegfilgrastim, and you can see at a greater value. I'll show you our performance here, but this is what we entered into in 2019 when we did the full commercial launch. Saved the healthcare system, we project about $3 billion. It wasn't just the U.S. healthcare system and the patients who benefited from lower out-of-pocket costs, but it was also, you know, a big success for Coherus. This is. If you're gonna bet on our commercial prowess, this is the slide that is our report card, and these are the numbers that we've posted. We entered into that very competitive monopoly market by Amgen and Neulasta.
Over the three years period of time, UDENYCA became the number one prescribed pegfilgrastim prefilled syringe, delivering cumulative $1.2 billion in net sales. It's a blockbuster over the three-year period. At peak, we were over 20%, but we ended Q4 2021 at nearly 18% market share. You talk about supply, again, delivering, you know, 650,000 syringes to patients, and those are patients with cancer, every one of them. We're very proud to be able to deliver every patient every time, and we were recognized by a number of third parties for the successful launch of UDENYCA, cited by many as the most successful launch at the time of any biosimilar. That's our scorecard there. That's why we have great confidence going into our future products.
Now let me talk to you a little bit about how this has unfolded over time. You know, when we talk about the trajectory of UDENYCA and where it's been and where it's going, I wanna focus your attention to the left side of this chart, if you will. This shows the unit share from the third quarter of 2018 to the fourth quarter of 2021. As you can see, UDENYCA was commercially launched. It was approved at the end of 2018, launched in January 2019. You could see how quickly and rapidly UDENYCA was growing share, taking share, despite being the second to market from Mylan and their launch of Fulphila. That share was coming from the innovator, from Neulasta. We were cruising along.
We were taking share by the truckloads, and everything was just going exactly to plan until Q1 2020 and COVID hit. Normally, in other product classes, this may not have been such a sentinel event, but in this particular class it was, because there was only one product with a presentation that was built and designed, you know, to keep patients away from their hospital or the clinic, and that was Neulasta Onpro. Shelter-in-place orders, stay at home, hospitals shutting down, community oncology clinics struggling to manage patient flow because their own staff were getting COVID. This was a challenge, and it created, over the last two years, an entrenchment in customer preference for the on-body device.
As you draw your attention now to what does that mean today and where the market is today, it's really created these two segments of the pegfilgrastim business, the prefilled syringe business, which is listed here, and 48% of the business, nearly half, has been retained in the on-body injector segment of the business. This is despite Neulasta not having Medicare pass-through extension. This is despite Neulasta having the lowest average selling price in the class. It's an entrenchment because of the device. For some of these companies, that could be a real challenge moving forward for their future outlook. But not for us, not for Coherus. The reason why is because in this market, 48% of it valued at $1.8 billion annually. They did $1.5 billion last year, if you look at Amgen's earnings report.
It's not a big problem for us because of this. Because we have our UDENYCA on-body injector. It's real. It's right here. This is actually the device that's being produced by our manufacturing team. This is what these results demonstrated. Last October, we issued the press release, announcing successful pharmacokinetic and pharmacodynamic clinical trial results compared to our pre-filled syringe product with no new safety signals observed. We're not gonna speak to what our competitors have or have not. We just say, "Look, we're putting, you know, the device here publicly, our results publicly, and we're now going to use this as the catalyst for the next wave of growth for UDENYCA, after we file this year and intend for commercial launch in 2023.
Because of this, because of our Embody injector and our position within the pre-filled syringe marketplace, our vision for this brand is to become the market share leader and to overtake Amgen's dominance in this class as the market share leader. In 2022, while we still are competing in the pre-filled syringe market, which is becoming increasingly more competitive, not only because of pressures on pricing by newer biosimilar entrants, but also the anticipation of potential new competitors entering the market. This is gonna be the year where, you know, we're maximizing our near-term revenue, balancing price and share trade-offs because all those pricing decisions you make carry forward. Our strategy is to maximize the long-term revenue potential for this franchise and not just short-term revenue gains by some of the new biosimilar entrants that have come into the marketplace.
You could see that when you look at the second quarter ASP file that was just released publicly. You'll see how ZIEXTENZO, our competitor from Sandoz, has realized those market share gains, you know, when you see their ASP reduced 20%, you know, from last quarter. Those disproportionate price decreases that they brought into the market to grab short-term share are now bearing out in the marketplace. I would expect to see continued erosion of those prices over time. We will be disciplined stewards of ASP. That has been our business model, and we will continue to operate in that capacity. Okay. Now let's turn to toripalimab. You heard about the science of this molecule, which is spectacular. You know, as a marketer, you know, you always love to bring great products that deliver clinical outcomes to patients.
That's what toripalimab is going to do. In nasopharyngeal carcinoma, we'll use the term NPC for short. Nasopharyngeal carcinoma is a rare cancer here in the United States, more prevalent in other parts of the world. We believe in the U.S., somewhere between 0.5 and 2 cases per 100,000 patients are diagnosed a year. What we've learned since coming into this market is because this is a subset of head and neck cancer, that when you're looking into the claims data and talking now with physicians as we have done, we believe that a lot of head and neck cancer patients are coded head and neck, but they're actually NPC patients. I can't tell you know, is the size of the market a third bigger, twice as big?
Not sure yet, 'cause they use often the same chemotherapy. We don't know that. I believe that this market is actually bigger than what the claims data suggests, which is a positive thing. As you see with these patients, they're largely younger patients between 50 and 59, affecting men more often than women, and it's more prevalent in patients of Asian and African descent. The important thing to note here is that this is why the FDA has described this as a tumor type with regulatory flexibility because there's currently no immuno-oncology therapies approved for this indication. Despite the dozens of KEYTRUDA's indications, they don't have it for nasopharyngeal, nor Opdivo. None of them do, nor PD-L1s. If approved, toripalimab would be the first and only PD-1 antibody approved for patients with nasopharyngeal carcinoma.
With chemotherapy, which is currently the standard of care, we can improve that median five-year survival rate of 20%. About 50% of these patients that are diagnosed will have distant metastatic disease at some point in their therapy. There's a long way to go to help these patients, and we intend to do that with toripalimab. I talked about the size of the market. This is the incident population of treated patients with NPC pulling claims data. I think there's a couple thousand of these patients. Many of them get treated with radiation therapy, surgery if they can do it. It's a tough surgery. It's way in the back of the skull, so it's not easy. They'll use radiation, but chemotherapy is the standard of care, typically platinum-based chemotherapy.
In our study, it was combined with gemcitabine-cisplatin. As these patients then get treated with relapsed and metastatic disease, you see here about 1,300 are cycling through a first-line, second-line type of treatment with systemic chemotherapy. Well, toripalimab, the data package with the FDA included the JUPITER-02 study, which was the first-line trial combined with gemcitabine, and the POLARIS-02 trial, which was used in second and later lines of therapy. We would expect our indication would largely be for all lines of therapy. The aspiration for Coherus in this market is to really establish a new standard of care with the combination of toripalimab plus chemotherapy in the front-line setting.
If you look at all of these patients and you just say, okay, if they all got, you know, PD-1s now as part of the new standard of care, and we used KEYTRUDA's WAC price times the average number of cycles that we saw in our trials, you could be looking at well over $100 million category opportunity here. Despite being a rare cancer, you know, we believe has significant commercial upside. Being the only PD-1 antibody, if approved, our aspiration is to have all of it as toripalimab in combination with chemotherapy. Why do we feel so confident in our ability to establish this new standard of care? Well, in oncology, it's all about the science, and that's what we have here. You know, the FDA granted breakthrough therapy designation for this filing.
The data, as Theresa showed you, has been presented at ASCO's plenary session, published on the cover of Nature Medicine. In fact, the NCCN Guidelines Committee for head and neck, and particularly nasopharynx, I have highlighted here in yellow, have already included the JUPITER-02 study as a reference into the guidelines. This normally doesn't happen till well after products are approved. What this means is, you know, we've got the, you know, the validation amongst the top oncology peers in ASCO and in the guidelines committee to pave the way for not only a new standard of care, but for our commercial launch, which is very, very exciting for us. Now I got a couple slides here, again, back to the playbook, customer engagement and strategy and execution. On the left, there are our four strategic imperatives.
I wanna point out something of note because it's also a demonstration of our capabilities here as a company. Denny and the team, you know, achieved this licensing agreement with Junshi and closed not only just what, 14 months ago, January, February. Coherus has really only had this asset for a year. To be where we are today, launch-ready, building out a team with the marketing, the commercial, the medical capabilities, is really extraordinary to be able to do in 12 months. Most, you know, in most cases, you know, companies, you know, you have years to prepare. We've done this in the last 12 months, which is quite extraordinary. Again, another demonstration of our ability to mobilize and prepare for launch. Establishing clinical confidence, I showed you the science.
This is gonna be well established, but we've gotta get out there and tell the Coherus clinical story to physicians and other stakeholders. You could see the work that's already been done with customer engagement and what's planned here, and really understanding the space with the key opinion leaders, multiple advisory boards, engagements, scientific advisory committee. Then what we're planning on with our key customer marketing team to be able to drive the clinical education immediately post-approval to raise awareness and to get patients that are already diagnosed or are pending diagnosis with NPC on toripalimab. This is vitally important. Post-approval, Steve's team will go out and get access and coverage for the product.
Based on our conversations with payers today, because of the unmet nature of this, and we'll be first and only, we would anticipate broad open coverage without any restrictions. Then we'll expand as future indications come into the market. The other way Coherus is demonstrating our transition from being a biosimilar company to now a highly clinical scientific commercial organization, and also to establish our leadership position in immuno-oncology and to be a leader in nasopharyngeal carcinoma, we launched a disease state campaign focused at the oncology community. Check it out. It's npcfacts.com. But because the average medical oncologist doesn't treat a lot of these patients, you know, they don't have the breadth and the depth of understanding about this particular disease.
That's what this campaign is designed to do, and to help them understand the unique nature of NPC versus head, neck, and other cancers. We're getting great uptick on this and that will continue to run throughout the launch period. As we get to launch and commercialization, post-approval, I talked about the synergy of our current team as we launch toripalimab in nasopharyngeal carcinoma. You know, the team's already covering on the vast majority of oncology clinics, hospitals. When we look at the, you know, where NPC patients are treated today, about two-thirds of them are already coming from UDENYCA purchasing accounts. You can see there's high overlap.
You know, really now it's just tweaking the targeting of the current UDENYCA sales force to be able to match it up to the toripalimab target list, but this is all very efficient and could be done at the local level without any challenges. Very efficient launch. The team is trained, and we're ready to go. The PDUFA date is the end of April. Whenever that approval occurs, we will launch.
We've spent the last several months building the team's foundational knowledge in immuno-oncology because you gotta transition now from being a valuable biosimilar selling capability to now having both, and to be able to operate and communicate with oncologists at a deep scientific level, so that we've invested in the training of the team for the last several months, culminated just a few weeks ago with our live national sales meeting, where we dedicated two days to toripalimab training. We had three or four national head and neck KOLs talking about the cancer, and we had a nasopharyngeal cancer patient and his wife join us to talk about their patient journey. We are ready to sell as soon as approval occurs. Selling will also occur through a variety of channels.
You can see on the left, whether it's through live engagements or virtual engagements, we'll meet our customers where they are and using both print and digital. The other capability that we've invested in over the last six months is in our digital marketing capabilities. Brought in a veteran of digital marketing. Hired this person from Bristol Myers that was working on their CAR- T programs, and his job is to elevate Coherus' now digital capabilities for all these upcoming launches. We're expanding that team out. We need to be there, and it was a investment that both Denny and I feel will pay off big for us over time. In conclusion of the toripalimab section, we're very excited, you know, to bring this innovative medicine to patients. It's a high unmet need. Coherus will.
In toripalimab will be the first and only PD-1 antibody approved with chemotherapy here, and we aim to establish a new standard of care for these patients. We're looking forward to launch. Let's turn our attention now to CIMERLI and the ophthalmology retina space. There's a lot of overlap between oncology and retina. You may not think that, but there is, and it largely stems from the fact that this is largely a, you know, clinic-based model. Retina specialists purchase, administer, and bill for the product similar to oncology. The core competency that we have with navigating the buy and bill ecosystem is applied here today. This is a large market. The entire VEGF retinal market is over $7 billion. You can see on the left side of this chart how it's broken down.
EYLEA and Regeneron have the majority of the share with 70% of the dollar share, generating approximately $6 billion annually. Lucentis, which is the reference product to CIMERLI, reported by Genentech in 2021 sales of $1.5 billion in the U.S. Then smattering of the others. You see BEOVU there, which was the Novartis product that was launched and then had safety issues, and subsequently now, Novartis is, you know, essentially gutted their ophthalmology commercial organization. It's still generating, you know, $163 million, but because of the safety concerns, has really been narrowed to a very narrow population. Then you have Avastin. Off-label Avastin used in the retina space.
It's used, you know, in the eye without any indication and without any clinical data to speak of, delivered to retinal specialists by compounding pharmacies. It's very inexpensive, which is why it has such low dollar market share. We believe this market will continue to grow over time because of the establishment of the VEGF class as a known MOA, a known product category, and the fact that the population continues to age and wet macular degeneration and the DME class is really a function of older patients. This is a large and growing market. Why we believe that we'll be able to replicate our success from UDENYCA into the retinal space is part of that customer engagement, first step in our playbook.
You know, understand what the customers and the retinal specialists think, believe, and feel. When we talk to them about, you know, their likelihood to adopt biosimilars, again, they don't have any experience with biosimilars today. When you're asking them these questions, the mindset from which they're coming to is very little knowledge. It's not unexpected that you probably see a third of these doctors saying, "Well, I'm really not sure. I might watch and wait and see what my colleagues do." We were very, very excited to see that over half of them already indicated that they would prescribe biosimilar Lucentis when it's available. You got some right here that say they don't expect using it, and others only if it's mandated by patients.
We're very encouraged by this, and I'll explain how we're gonna help them along here in a moment. We asked them, "Okay, well, if you're gonna adopt these, biosimilar Lucentis agents, on which patient types do you anticipate using it?" We were very excited to learn that biosimilar Lucentis products will come from both newly diagnosed patients and also being switched from other VEGF products. As you can see here, a third of the doctors reported that they would use it for newly diagnosed patients, but 27% say they would switch from other VEGF products, while almost 40% said they would come from Lucentis-branded agents.
This is why we believe here that the entire VEGF market, you know, will be open to penetration, and I'll explain how we're gonna roll that out momentarily. We see our launch into the retina market with CIMERLI. Again, action date by the FDA is August of this year. We see the rollout occurring in three phases. We're in that pre-launch phase right now. Well, what we're doing now is establishing Coherus as a new company into the retina space. Our reputation as an experienced provider of biosimilars in the market is already preceding us, largely because the retinal specialists use group purchasing organizations as part of their supply chain and contracting entities. These are organizations that we work with today through AmerisourceBergen and McKesson and other large groups. They're already hearing about Coherus.
We're also educating the market on biosimilars since it's new for them, similar to what we did with oncology. At the time of launch, our primary effort is gonna be focused on grabbing as much of the branded Lucentis business as we can today. That's the reference point. 40% of doctors said that's largely where their volume is gonna come from, and so we're gonna make that a priority target for us. But because the market is larger and open, in which we establish CIMERLI in the market the positive experience and the value proposition that we're gonna bring, we believe that we'll be able to open up other parts of the anti-VEGF space, either, you know, through Avastin or through EYLEA and growing from both ends. This entire market, we believe, will be in play for us.
We've done a number of customer engagements and continue to meet with retinal specialists through a number of different channels, working with the GPO entities at McKesson and through AmerisourceBergen. There's many large groups of retinal specialists that continue to grow and get larger and larger. What we learned through these engagements are three things. Number one, they need to understand biosimilars because they really don't, similar to what oncologists faced years ago. They're gonna need that in order to reduce any of the hesitancy that they have in adopting biosimilars and CIMERLI at the time of approval and launch. Safety and efficacy, but safety because of the BEOVU experience, is really, really important now. Because of BEOVU, they, you know, and they're injecting in the eye, we have to really spend a lot of time educating on that.
I'll show you the data from our phase III trial that should give them great confidence we'll be able to do that. The practice economics are well. It's a buy and bill model. Because of that, you know, they're managing, you know, not only their cash outflow, but also the reimbursement and cost recovery. This is part of the biosimilar campaign that we're gonna be launching beginning in this quarter. They did a great job. Again, it's came out of our playbook for UDENYCA, but really tailored towards the retinal specialists with these beautiful graphics.
It will really educate retinal specialists, the practice managers, CEOs, allied healthcare providers about the regulatory pathway so they understand the regulatory pathway, why the design of the COLUMBUS-AMD or phase III trial was done the way it was done, and also the broad safety and adoption of biosimilars now that has occurred throughout multiple product categories, including oncology. We're gonna be kicking that off, driving that towards the retinal specialists, and you'll see us at congresses if you're there at any of those retinal meetings. We'll be there. We'll also give them confidence at the time of approval that CIMERLI we'll have a presentation that is similar to Lucentis, which again not only takes the form of an identical amino acid sequence, dosing, and indications that are identical to Lucentis, the same formulation as Lucentis. Also the same storage conditions.
Essentially, what they will have is as close to the reference product with CIMERLI as they'll be able to, which will give them great confidence. Then there's confidence in the clinical data. What you see here on the left is the data from the published phase III study done by Dr. Holz et al, published in Ophthalmology last year. This was comparing CIMERLI, known as FYB201, towards Lucentis. Primary endpoint is shown on the left, which is the change in best corrected visual acuity, BCVA, showing no difference between them, which met the 90% confidence interval. On the right is the adverse event profile, showing no difference in safety. Again, this data set is now being presented and shared at multiple venues throughout the retinal specialist community.
It was presented at AAO, American Academy of Ophthalmology, poster presentations at a number of societies. Dr. Peter Kaiser from the Cleveland Clinic presented at Retina Society last year, and the published manuscript that concluded that FYB201 is biosimilar to reference ranibizumab in clinical efficacy in ocular and systemic safety. Again, we've got the proof source and the science to back this up. Now, the retinal specialist market is smaller than the oncology market. There's about 3,000 retinal specialists practicing in the United States. They're a subset of ophthalmologists, and the concentration of this business is quite unique. When you look at, you know, through looking at claims and demand volume, there are, in this case, about an 80-20 rule, where about 446 accounts that are driving 80% of the anti-VEGF volume. For Lucentis, it's actually more condensed than that.
Which enables us then, as we're designing our field sizing, you know, that we can have a very focused and dedicated team to go after, you know, the largest accounts at the time of launch. Then if we have to build, we can do so later on and build from there. Again, another example of how we'll be very efficient with our resource investments incrementally. To conclude the CIMERLI section, our launch strategy is really gonna focus on four key elements. Granular segmentation, which I just spoke about. Leveraging Coherus' biosimilar expertise and experience, we will be the only company launching into the retina biosimilar space with a proven track record of launching biosimilars in the United States. We'll be the only company to do that. They will see that capability when we bring CIMERLI to market.
We're gonna build on our existing resources and drive the market education, both in biosimilars and the brand pre- and post-launch as appropriate. Again, another new market, large market, very excited to enter. I'm gonna wrap up with some discussion around YUSIMRY, our biosimilar to the reference product, HUMIRA. Let's start left to right on the slide. HUMIRA, as you all know, is a $17 billion brand, number one product in terms of sales in the United States. With the expectation that there are going to be discounts post-approval and post-launch of biosimilars, if you just took a 40% haircut based on discounts, you're still left with a $10 billion market, and our achievement of 10% of that market represents, you know, at least a $1 billion opportunity.
Obviously, we don't know yet where the marketplace is gonna be in terms of discounts, but suffice to say, it would be hundreds and hundreds of millions of opportunity for YUSIMRY and for Coherus. When you look at the indications, we'll expect to gain share across all these indications as our label, since the product's already approved, you can see the prescribing information online around all these. There's a few that we won't have, particularly that are a part of some exclusivity that HUMIRA will have, very small niche indications. This is where the bulk of the business is. As you can see, the payer mix on the right, half of it is covered by commercial insurance. Commercial payers will be very key for early uptake, and that's what Steve and his team's efforts will be focused on.
This is YUSIMRY, approved by the FDA in December of last year. It was a great holiday gift to the company. As you can see, our product presentation is an auto-injector device. I'll speak a little bit more about this device, but it's fantastically done by our brand team. It will be differentiated, look very similar to the reference product, HUMIRA. We're gonna be coming in and launching in the biosimilar market formation period. As you can see on this chart, this is 2023 timeline. Amgen and AMJEVITA will have the first launch in January of next year, and they'll have this period of time in the market before YUSIMRY and a number of other competitive entrants are expected to come in mid-year.
What's key and what we know about biosimilar, the biosimilar market, is you got to be in market formation, and we will be. I'll show you why we believe we'll be set up to win despite these competitors. That's the key point, we're in market formation. Let me speak a little bit. On the left part of this slide represents the various stakeholders that are involved in the decision-making process for HUMIRA and in this class of products in immunology. On the right is the high level map. Let's focus more on the left here momentarily. If you see all the stakeholders, in this particular, because it's adjudicated through the pharmacy benefit pathway and because of the size of this market, payers and PBMs are going to be the most influential decision makers in this class as biosimilar entrants come in.
They will determine the formularies and the products the doctors will be able to have access to write the product, which is why we've earmarked them as being the most influential. Specialty pharmacies dispense these products to patients. They're an important part of this stakeholder chain because they are the organizations that are oftentimes assisting patients with onboarding, collecting the co-pays, shipping the drug to the patients, doing new product education, et cetera, et cetera. Sometimes the insurance company doesn't dictate that the product has to be dispensed by one specialty pharmacy or another. They oftentimes, you know, are in play here, and so very important to that process. Obviously, the doctors are always at the center of this. They're making the diagnosis and working with the patient on the treatment plan.
In pharmacy benefit, unlike buy and bill, where they have the option to oftentimes prescribe and order what they want, here they're gonna be bound by the patient's insurance coverage and the formulary. What they prescribe will often be subject to that. The patients, again, will most likely defer to the doctor and unlikely to significantly influence product selection because of their health plan. As you can see here then on the right, just as we've mastered the navigation of the buy and bill ecosystem, we'll have the same mastery to the pharmacy benefit pathway. Knowing in each step where the leverage points are, where we need to be able to intervene and to be able to influence it. The payers will be at the center of this, and I'll explain more about that right now.
What you see here on the left are the results of the market research and what we gleaned from talking with both payers and PBMs at national and regional levels. What the market revealed is that there are some product attributes that are more important than others, that will drive adoption and selection of which biosimilar in this market. When we went through the exercise and asked them to force rank the level of importance to them in their decision-making, what rose to the top were three. Not surprisingly, price and rebates came out as number one, right? This is the market event that the world is watching in 2023 with HUMIRA and the biosimilar adoption. It is the number one consideration, and I'll speak to this when I talk about this bottom one, interchangeability.
That and dedicated supply were the top two by far. Why is dedicated supply so important? Well, HUMIRA is about 11 million units dispensed annually. That's the unit market size here, 11 million units. When the payers and the PBMs are gonna choose a biosimilar partner to come in, they're gonna expect that partner to be able to deliver a value proposition with price, but to also have the ability to deliver supply. Because what they won't allow to happen is manufacturers that can't deliver that supply, which now then affects their uptake curves and affects all the deals that they have, either with the biosimilar partner in which they've managed or any HUMIRA that is still being rolled through the health plan. Supply is going to be very, very important here. The rest of these things are important formulations.
The citrate-free, sting-free formulation, we'll have that. It's a proprietary formulation. That's important because as they anticipate switching patients from the innovative HUMIRA to the biosimilar, you can't have the stinging agent because then patients will complain, and it will cause disruption in that flow, and they don't want that. Interchangeability. This is what we were told time and time again. We believe Amgen, if you go back and if you listen to their business review, they learn the same thing. Payers have said this is a nice-to-have attribute. It's nice to have. That price will trump interchangeability. Now, why is this so? Well, payers have told us that, two main things. Number one, they've already adopted biosimilars in other therapeutic categories successfully. They know how to move patients, you know, from the reference product to the biosimilar agent.
In the pharmacy benefit, they have the pathways and the tools and the resources. We call them utilization management tools, either through NDC blocks. You just, you know, you put it through, you run the script, you'll get it, or through step therapy or through prior authorizations and differential copays. They know how to manage this. The other important thing is that interchangeability rules vary by state, so it's not nationwide, and they're only applicable to the reference product. Imagine a melting ice cube like HUMIRA is, and as biosimilar uptake is achieved and erodes HUMIRA market share, the applicability of interchangeability becomes less and less important over time because it's only to the reference product, HUMIRA. That short-term advantage, and that's why payers have just said, "We can get this done. We know how to do it.
It's all gonna come down to price." We expect to deliver on those most important attributes with the launch of YUSIMRY. Price and rebates, we've got a lot of room here, from our pricing standpoint. We're gonna come into the market, you know, to be able to get payer coverage and access and on these formularies, and we'll be prepared to offer significant value. We'll also merge that value with supply guarantees. I'll show you in a minute what we've invested in to be able to do that. We're gonna open up specialty pharmacy access. We've got the formulations, but we're not gonna have interchangeability, and we're not gonna invest in those trials because of the reasons I mentioned earlier and what the payers have told us. We're very confident we can succeed without that.
This is the one-two punch, the value and the supply guarantees. This is why investments in manufacturing capacity pay off. We've invested $45 million in manufacturing capacity. Rich will be here to take questions if you have details about this. All I know is that that's steel, and that's beautiful steel, in 5,000 liter tanks that at the time of launch will be able to supply and be prepared to bring to the payers over 1 million units, 10% of the available market size at launch, with scale-up capabilities at the current sites to deliver up to a third of the market potential, which is 3x our market share projection.
We're gonna show up with confidence that we're gonna be able to deliver on these supply guarantees and expect to be a low-cost, high-volume adalimumab manufacturer. To conclude the YUSIMRY section, we are well-positioned to compete successfully when we enter the market in mid-2023. We're gonna be able to compete aggressively on price, abundant supply guarantees, an auto-injector device that has the formulation with the non-sting, citrate-free, with a high-gauge needle that will support patient requirements, and our Coherus Complete support services wrapping around assisting with coverage, copay assistance, et cetera. To conclude, let me end where I started, that we are becoming a commercial powerhouse at Coherus. We've got the expertise and the track record of delivering results and entering highly competitive markets and succeeding.
We've got an infrastructure that's built today for UDENYCA that we can scale smartly for the additional four product launches. These four product launches we project will deliver at least $1.2 billion in top-line revenue by 2026. In every market we enter, our minimal commercial goal will be to achieve at least 10% at peak. This is why we're so confident about our ability to succeed in these markets and why this commercial team is ready to lift off. Thank you very much. Now I'll turn the call back over to McDavid Stilwell, our Chief Financial Officer.
Thank you, Paul. Now I'd like to talk to you about operating leverage inherent in our business model. Earlier this year, we described or projected that our operating expenses for 2022 would be in the range of $415 million-$450 million. What I wanna show you today breaks out the operating expenses by major buckets, by activity, manufacturing and R&D and sales and marketing and commercial, as well as core. You know, in our historical financial statements, the manufacturing expense would be rolled into R&D, but I wanted you to be able to see that activity because it's part of the story. You know, this year, as we've said, we are investing heavily in supply for upcoming new product launches.
You see the manufacturing expense is disproportionately high this year compared to what you'll see in future years. You know, I look at that, and I see that as an expense this year, but it's also an investment that in the relatively near term, I expect will convert back into cash. In 2023, you can see that expense come down. You also see R&D expense decrease slightly. We have ongoing studies for additional presentations of products that we'll be launching near term, and those will wind down in the back half of 2023. You see it begin to tick back up again as we begin to advance some of the earlier stage assets into clinical trials.
You can also see that the commercial spend in 2023 takes on a little bit more of the portion of spend as we launch for the full year CIMERLI and toripalimab, and as the OBI and YUSIMRY come online. In 2024 and beyond, that commercial spend levels out. You can see that R&D spend ticks up some as we begin to advance TIGIT plus toripalimab into phase II studies and as we begin to introduce the earlier stage assets, CHS-1000, CHS-3318, into early-stage clinical development. Remember, one wonderful thing about the deals that we've done, the Junshi deal, by and large limits our R&D, our clinical trial spending, for toripalimab.
That's a very helpful attribute to have such a robust R&D program and to be sharing the cost there. In 2025 and 2026, R&D spend trends higher. We're moving toripalimab plus TIGIT into phase III studies. We are also continuing to advance the CHS-1000, CHS-3318 assets. For the full year 2026, we project operating expenses to increase by only 15%-25% compared to this year. You know, we're doing a lot in the next five years. We're launching four new drugs. We're introducing multiple new programs in the immuno-oncology R&D area. Yet you don't see a massive uptick in our operating expenses. That's because we're already operating at scale. We don't have to bolt on significant new capabilities in order to do all of this.
Turning to revenues that we project in 2026, a few years after the launch of all of these products. You know, today we're introducing a revenue range of $1.2 billion-$2.2 billion. You know, of course, it depends on the four launches that we expect over the next 15 months to succeed. We think that they will. The big swing factor here is just how well do we do in YUSIMRY. We've shown you that we have invested in manufacturing capacity so that we can compete in that market. No matter where price goes, we will be there and able to supply it. We think that we're gonna be very successful here. Another swing factor is how many indications we're able to get approved for toripalimab.
We project that gross margins off of these products will be about 75%, fully burdened, including royalties. We project that we could be profitable in 2024. We think this is a great story. Now I'll turn it back to Denny.
Thank you. Thank you, McDavid. I think as you heard today, and you've seen our company in the past, this company is about execution, okay? There's not too much that we can do about things like COVID, you know, a black swan event that comes through and your competitor has a built-in advantage that's a knife fight in the market and hard for you to do. But even during COVID, we executed exceptionally. We got our PD-1 deal done on great terms. We got YUSIMRY approved. We got our Lucentis biosimilar filed imminently approvable. We got our on-body device tested and ready to go. We went out and we did the job. You're gonna see the same thing across the portfolio as we move toripalimab forward, as we go forward with our new innovative products. Lastly, as we realize the synergies that McDavid just talked about.
This is where we're gonna end up in 2026. Four products on the market selling to $2 billion plus. Embracing the standard of care in lung cancer with toripalimab plus TIGIT, plus other combinations. Plumbing the depths of the cancer immunity cycle, finding opportunities for greater T-cell activation, as you heard from Theresa and from Sanjay. Lastly, leveraging up our R&D organization to be an innovative immuno-oncology company in 2024, built on a solid foundation of execution, sales, positive cash flow. Real products, not dreams. Thank you, guys. We're happy to take questions. You there in ,the front row.
Do you have a, Salim.
Here's a microphone.
There's a microphone for you.
Okay.
Please announce your name. There we go.
Thanks so much. Salim Syed, Mizuho. Thanks so much for the team's color on all this. Super helpful. I guess I had a couple of questions maybe for Paul.
Paul, you mentioned the 27% of retina specialists who are willing to switch patients from other anti-VEGF. I'm just wondering, that 27%, what percentage of the anti-VEGF patients do they cover, given the concentration curves? Were you surveying more of the concentrated or was this kinda spread out? I guess alternatively-
Let's just go one question.
Yeah, it was just kinda related, I guess. Same question said a different way is, what percentage of EYLEA do you think that you'll be able to penetrate with the biosimilar Lucentis product? Thank you.
First of all, it's nice to meet you in person.
Likewise
After only speaking to you over the phone. Thanks for being here. Yeah. When we did the market research, we recruited retinal specialists that treated across the spectrum of VEGF therapies and not really, you know, looking for specialists that had preferences for anyone in particular. What we find in reality is that all of the VEGF products are often used in any typical retinal specialist practice. However, as you see with EYLEA, they tend to have a little bit more of the majority of the share, and that's driven by a couple different factors. Number one is, you know, their preference, you know, for that particular product, either through, you know, dosing or, you know, just their own personal preference that they've slotted in.
What they've told us is, again, because it's not just a function of, you know, patient preference or drug preference, but it's the total value offering of the VEGF product. There's a lot more that goes into that than just the patient type. Do we believe we'll be able to, you know, capture the majority of the EYLEA? I don't think we're going to be that aggressive. However, there are patient types that we've learned that are going to EYLEA now that could be going to CIMERLI. That'll be part of the discussions when we're able to promote CIM. We feel pretty strongly that we'll be able to capture from both sides of it.
Thanks for your question, Salim. Yeah, Chris.
Great. Thanks so much for the time today. I just had a couple TIGIT-related questions. I guess first of all, we're expecting some Roche data in the very near term. How does that impact how you think about investing around the asset? If those data were not successful, would you still move forward here? Maybe conversely, if they were successful, do we think about Coherus following similar indications to what we're seeing for Roche? Is the strategy more about going other places just given the competitive timelines there?
Yeah. Dr. LaVallee, you wanna take that one?
Yes, sure. Thanks for the question, and I agree with Paul, it's so nice to meet people and be in person instead of just on Zoom. It's a great question, and we anxiously await SKYSCRAPER-01 soon, and other readouts later this year. A couple points to think about. Obviously, as the regulatory landscape adapts, would there be opportunities in other places? Lung cancer is a big space, and we've seen that with IO going across the board. We'll actively watch that. The one area that we're keen to further look at in the clinic, obviously, is this opportunity where PD-L1 low activity may be a differentiation. Clearly, if that really bears out in the clinic, it's a fast approach that could have differential activity. I mean, we've had one study readout, so let's wait and see as the class comes.
We'll actively watch that and have our bioinformatics capabilities looking at different indications overall. Since we think it will work generally where PD-1 works, it's a broad opportunity.
Just one follow-up on TIGIT. I don't know if this will be required or not, but in terms of your partner agreement, I know the R&D is capped at some degree from the Coherus standpoint. Is your partner committed to running, I guess, multinational studies here? Or are we thinking just so we don't run into maybe the issues that the PD-1, where the landscape changes. But these studies we're thinking about are gonna be not just China-based studies, I guess, for TIGIT development.
For the folks on the phone, that was a head nod yes. I mean, the wonderful thing with the relationship with Junshi is it's truly collaborative. I mean, we're really partners, and I really have appreciated and enjoyed working with them. Obviously, even in the toripalimab program, we're in conversations about adapting toripalimab to multi-regional studies, and I think working together is in the best interest of the molecule. They have a Chinese study ongoing now. We will do a U.S. study. As we move into a recommended phase II dose and expansion phases, not doing it together might be a disadvantage.
Yeah. I think it's also too important to point out that prior to the license agreement with Coherus, Junshi did not have an ex-China partner to do studies with. They still don't have a European partner, but now they have a very strong U.S. partner with strong U.S. regulatory capabilities. I think this is very positive for the multinational aspect of the studies for them. Yes.
Jason Gerberry, Bank of America. A couple of questions. On the 2026 sales for UDENYCA, thinking about the high and the low end, it looks like on the low end, perhaps you're just playing defense, maybe in terms of that franchise versus the high end, maybe OBI adds more incremental value. Just wondering if you could talk a little bit about the assumptions. When you launch OBI, do you inherit your PFS price point, or could you actually get value for that innovation? My only other question is just there's a lot of chatter, I guess, AbbVie making note that I think this summer we'll learn a lot more about the HUMIRA pricing landscape for both innovator and biosimilars with the negotiations.
Do you expect this to be kinda perpetual continual RFPs, or do you think that the negotiations will kinda stick for a full year, and this will be kind of an annual contract?
Okay. That's three, Jason. I'll let Paul take the first one first with respect to OBI. Paul?
Yeah. Thanks for your question, Jason. So, I think 2022, it's a year of defense, right? It's trying to preserve, you know, the market share that we have without, you know, resorting to the disproportionate discounting that's occurring, you know, with the new biosimilar entrants. This is the year we're gonna be, you know, looking hard at those price share trade-offs because of the future, right? What Amgen has done is they've priced their Onpro and their Neulasta pre-fill ed syringe at the same price, subject to the same ASP. We're looking at all of our options on how we can price to take advantage of the innovation there.
We'll be able to talk to you more about what that pricing strategy is going to be, you know, once we commercialize the product. We see the growth in the franchise in 2023 and beyond, largely coming through from unit and market share volume coming from the originator, and from Onpro.
The other point that I would make with respect to our on-body market penetration is that our announcement of success in the clinic with the device has been met with a fair amount of enthusiasm from the customer base. We have an excellent reputation, of course, with the oncologist. They're very anxious to uptake this product. I think that we'll get very, very strong penetration into the on-body device segment of that market. Now, your last question was with respect to HUMIRA pricing and cycles of pricing with payers. Could you just repeat that one?
Yeah, just curious, like, how the negotiation will go. At the summer, I think AbbVie's indicated, I think that it's gonna be important in terms of setting the contracts for 2023. Do you expect it to be annual, or do you think that this is gonna be aggressive and, like, kind of constant RFPs to try to drive.
Yeah. Could you bring the microphone up? We have Steve Svitenko, who is our Senior VP of Market Access here with us. Steve, you wanna take that one?
Yeah, sure. Appreciate the question. The likelihood because of the competitive intensity when you're talking about eight or nine, that any given contract will go at least a year, but the likelihood that it will go two, I wouldn't think that's gonna be the case. 'Cause it's always in the best interest of a health plan if any one of the competitors comes in and has a better offer, that they would want to listen, right? We're fully considering that in our plans and how to think about it and what we plan to do.
Okay. Great.
Thanks, Jason. Yeah, right. Cowen. Oh, yeah. Sure. Go ahead.
This is Georgi Yordanov from Cowen. I guess just to follow up on biosimilar Lucentis. The retinal space is actually quite unique because we already have a biosimilar-like product with Avastin. Maybe if you can just elaborate a little further, how do you think the pricing there would work out just given that we have that Avastin product on the market and kind of like some of the competitive dynamics? Then just to follow up on that, what are we seeing in terms of other competitor biosimilar Lucentis products coming on the market and the timing of that?
Yeah. The first point I would make is that reformulated Avastin has no label, so it cannot be promoted to the ophthalmologist. Paul, do you wanna take the second half of that question?
Yeah. I mean, it's cheap, right? I mean, it's very inexpensive. So, you know, we hear that a lot, that it's like biosimilar-like. And maybe that's true, but I don't see it like that because it's so inexpensive that, you know, it there are some health plans that require the step-through, right? And physicians, you know, may have to do a trial. But when you go out and you talk to retinal specialists, you know, Avastin is not viewed as efficacious as some of the other branded biosimilar products. And so they will step through that, you know, and move on to other VEGF agents. And you see that happening routinely in practice. So, you know, are we looking to go in at price points that compete with, you know, off-label repackaged Avastin?
No. What we would be looking to do is bring a total value proposition, you know, to the retinal specialist practice, you know, that will differentiate CIMERLI among the others. Then when they're stepping through Avastin and they have to go to the next VEGF brand, that CIMERLI is in that treatment flow, and we'll go there. You know, if they're not encumbered by using Avastin, we're gonna bring a product presentation and value proposition that CIMERLI should be the first choice other VEGF agent for new patients.
The other last point I would make is that we think the VEGF market is very unique. It's of course, as you pointed out, stratified with reformulated Avastin and up through Lucentis, EYLEA, and then the newer, more proprietary products at the top. We think for this point in the market's evolution, Lucentis, a Lucentis biosimilar is very much the ideal entry point where you can expand down, expand up. In a couple of years, when EYLEA becomes available as a biosimilar, that would be of course a great place to go, and that's something that we think about a lot. In the short term here, for the next couple of years, we think a Lucentis biosimilar is the ideal place to wedge into that market and then expand, and that's Paul's plan.
Yeah. Georgi, right? Yeah. We're gonna be coming in in market formation. You mentioned competitive products. There is an approved biosimilar agent that will be expected based on public filings around the same time as we are, mid-year this year. But again, we've seen this story play out before with Coherus. We're coming in at market formation, and we expect you know to be able to compete against any new biosimilar entry.
I think, Sam had a question. Could you say your name, Sam?
I will. Sam Eisenberg.
Thank you.
Exome Asset Management. For maybe some of your scientific colleagues, to what extent do you believe that most practitioners believe that all PD-1s are alike.
Secondly, you've highlighted a differentiation, I guess, between pembrolizumab and toripalimab. Do you believe that was designed purposely? What other aspects of toripalimab are in there that differentiate, either in a small detail or large detail? Can you prove this in the sense of marketing some of these characteristics to professionals?
I think there's three questions there, Sam. Let me try the first part, then I'll hand it over to Dr. LaVallee. Interestingly, during the molecule's genesis and discovery period, the focus was specifically on FG loop epitope binding moieties. They were screened for that. The molecule was actually conceived as a second generation, you know, PD-1 with this intended mechanism of action. When we tested it in our in vitro assays, when we were looking at, for example, 12 PD-1s during our selection process, Sanjay's team saw a very robust in vitro activity, but we really were uncertain why, frankly, at that period of time. To answer your question, yes, it was conceived specifically for this epitope, and its activity.
With respect to your follow-on questions of activity, I'll let Theresa take that one, and then Paul can handle any marketing questions. Go ahead, Theresa.
Thanks, Denny, and thanks for the question. I mean, it's an interesting one, right? To the point, do people think they're different? I've heard both extremes, having been in the IO space since before it was cool in the early 2000s. Like, some people, they're like, "Oh, pembrolizumab's better than nivolumab." The studies I mean, a good PD-1 is a good PD-1, and it's really helping patients, and that's what I can say. You know, I think the data have shown that with the multitude of agents and the studies that have read out with demonstrated improvement in survival across the class. A good PD-1 is a solid PD-1 and an important molecule to have if you're an IO player. Is toripalimab different? I think we're seeing that. We're seeing some differentiation features, and the pharmacology is there, right?
We really need to see it in the clinic, to your point. We have the three studies in combination with chemotherapy, where we've seen activity independent of PD-L1 status. Could that be an advantage for some of our pipeline combinations? Possibly. Other attributes that we're really looking at, 'cause I've mentioned three features clinically that could matter to a patient's depth of response. You know, I think what's underappreciated in the field is if you look in lung cancer, the CR rate, the complete response rate, is less than 6% with PD-1s. That's what you need for cures. Depth of response is really something that would impact the field to get more CR rates. I've had conversations in past lives with the FDA, is that an approvable endpoint? Because that really is linked to survival and cure.
That's something to look at. We're looking through the clinical data to see if that's there or, you know, a big topic in the field is primary resistance and adaptive resistance. Does this internalization feature prevent more adaptive resistance? And those are the types of things we're starting to interrogate both pre-clinically and clinically. Stay tuned.
You know, 2022, I think it's going to be a big year for data readouts, Sam, with toripalimab. In particular, we're watching the small cell study, which should read out sometime mid-year.
Sam, from a marketing standpoint, we're gonna be able to promote, you know, the differentiation in our science, and this will start with nasopharyngeal carcinoma being the first and only PD-1, if approved, you know, for that particular cancer type. There's no bigger clinical differentiation in the marketplace than your label and your data and your placement on guidelines. We'll be able to, you know, expect to have all that. You know, it's a great entry point for LOQTORZI.
I think Doug Tsao has a question. Doug?
Hi, Doug Tsao, H.C. Wainwright. Or Paul, maybe touching on UDENYCA and the launch of the OBI next year, I'm just curious, how important do you think retention of pass-through status, because I think it was extended through 2022? Is there sort of confidence that you'll be able to extend that into 2023 with the launch of the OBI, and do you see that as significant? Another question on the TIGIT. I was just curious on Dr. LaVallee's. Are there any sort of unique characteristics of your TIGIT, similar to what you sort of elucidated with toripalimab? Or is it that you think see the differentiation really in toripalimab and that you just have a really good TIGIT?
Theresa, why don't you take TIGIT first, then Paul, you can backfill with the OBI. Theresa.
We just announced the licensing and finished the period where we can really do data exchange. To date, I will say it's a solid TIGIT. It has all the right pharmacological properties that I would want in an antibody. Differentiation is something we'll continue to explore, but we don't have any data to date to show that it has a unique epitope, but I don't know that, so that's to be explored.
Doug, thanks for your question. On UDENYCA OBI, yeah, you're correct that the pass-through extension is through calendar year 2022. It's unlikely that there'll be, you know, further extension. We're not baking that into our core planning assumptions. You know, Neulasta and Neulasta Onpro has lost pass-through extension, you know, now for years. You know, we expect, you know, to be able to compete irrespective of the pass-through status for that share.
Yeah, why don't you take this question first?
Yes, David Bildner, DB Capital. My question is regarding the biosimilar education in the retinal space for retinal specialists. Is this old jargon or new jargon? Has it been used before in this type of space? And also, do you see some sort of weakness in Lucentis with your entry point after you launch your product that is not available right now to people who follow the space?
Go ahead, Paul.
Thanks for your question, David. You know, the biosimilar education will include a lot of the core components from a messaging standpoint that haven't changed, that are foundational, how the regulatory process was established, why the design of clinical trials are the way they are. That'll be unique to the COLUMBUS-AMD trial because the design and what the FDA required for biosimilars in retina and the design of that trials is different than oncology. There will be some new and customizable messaging from that. But it's really to level set, to build a confidence in biosimilars. What's new over the last two years is the prevalence of new biosimilars adoption and the market share that's occurred in these other therapeutic categories.
Again, demonstration that these products are safe, effective, the uptake across, you know, therapeutic specialty is broad, and that retinal specialists really should expect the same from retinal and ophthalmic biosimilars as in other categories. Regarding weakness, you know, it's an interesting question. I don't know if I'd look at it like that. You know, we look at it in trying to understand why retinal specialists choose the product that they choose and what goes into that. Clinical, you know, safety, as well as, you know, the service components, and then, you know, the practice economics that layer around it because it's a buy and bill. What we're going into with trying to understand where our sweet spot's going to be relative to the entire set and be able to then meet those needs.
Given our track record of, you know, managing ASP and delivering a complete value proposition, we're gonna be very confident and be able to go in and have an attractive offering versus branded Lucentis. I hope that answers your question. I didn't know, maybe you wanted something more provocative. That's how we're looking at it.
We've received a couple other questions regarding the biosimilar and Lucentis program, CIMERLI, online, so I'll ask those. Could you remind us of the economics for CIMERLI? The answer is that we have a partner, Bioeq. We book revenues, and then the deal, we pay royalties, and it's essentially structured as a profit split off of gross margin. Another question comes in that retina specialists make a lot of money prescribing EYLEA, and how can we work with them to make Lucentis into an attractive offering?
Well, first and foremost, Coherus never sells any of our products based on profit margin or spread. That is a compliance line that we never cross. We understand, you know, again, the dynamics of how.
Retinal specialists purchase and bill, and these are factors. You know, there's price and there's contracts and discounts, and those factor into the total value proposition. We have a very good understanding of, you know, the value proposition for EYLEA that's offered to retinal customers. That might be different based on, you know, the customer, their size, their volume, and other things that go into play. You know, we will expect to be able to compete with a similar value proposition that retinal specialists tells us will be, you know, able to drive adoption. Again, you know, I think we're gonna try to, you know, capture early on as much of that branded Lucentis business and then expand from there on both sides.
Okay. We have a question in the front. The gentleman's been very patient. Thank you.
Okay. My name is Brian Bamberger, Private investor. Two questions. The net sales went down from 2020, $475 million to $326 million. I wonder what the cause was. More important, a separate question, considering the planned R&D and manufacturing costs, what can be expected for 2022 and 2023 in terms of net loss or net profit? Of course, what cash do you have? If there's a net loss of significance, what cash do you have to support it?
I'll let McDavid take the second half of that question. I'll handle the first half. We launched the product in January of 2019, and by the end of 2019, our first year, we achieved in excess of 20% market share. We were the highest priced biosimilar on the market in terms of ASP that entire time. By the end of February 2020, we had achieved about 22.5% market share when COVID hit. My personal view is that we were well on our way to about 30% market share at the end of our second year of launch. The reason why we went from the 400s to the 300s with respect to that was COVID.
COVID, as Paul pointed out in his remarks, has been very difficult for us. You know, it's very difficult. You can't get your people in front of the doctors, and you know, there's been a whole host of issues there. With respect to your follow-on question, I'll let our Chief Financial Officer address that.
Sure. We ended the year with $417 million in cash. Shortly after the start of the year, we entered into a credit facility for up to $300 million. We're using that to refinance some existing debt facilities that we have. Then there's also some additional growth capital that is included in that credit facility that's tied to the approvals for toripalimab and for CIMERLI. You know, we haven't provided a net sales estimate for 2022 or 2023. We would expect that we would have net losses this year, and that those net losses would moderate in 2023 as the expenses come down, as I showed you in that chart, but also as the revenues ramp from those four expected upcoming launches.
As we said, we expect that we could become profitable again in 2024. Yeah.
Yeah.
I would only add that we think it's prudent to invest in our business for four launches. We did very well in the UDENYCA business with the launch. We had over 300,000 syringes in the cooler, you know, at launch, which was about 1/4 of the market. Paul talked about this in his remarks. The cornerstone here with the HUMIRA market is also going to be supply. You'll see us investing in manufacturing so we are able to provide supply. We made substantial investments in supply over the past two years, investing about $45 million so we could provide the market with 10% right out of the gate, you know, although we probably won't get to that in the first year, but in up to 30% of that market.
This is all expense and then is reflected you know later and so on. With four launches, we think it's prudent to invest in the business. As McDavid said, you know, we entered into a facility with Pharmakon. It's a team that understands our business very well. We'll make those investments, and we think our investors will be happy with the results.
Thank you. Yes, we have an additional question.
Marc Dlugoff, Atlantic Family Office. A question about Junshi Biosciences. Could you add anything more? I mean, you've given some information, you know, about how good the relationship is. Any more facts you can say about the transparency you have with the company and a little more detail that makes you feel secure with the relationship?
Denny, you mentioned about Junshi has not selected yet an EU partner. Could you be part of that adoption process in Europe?
Thank you. Thank you for the question. Let me first say that we have a very open, transparent and collaborative relationship with Junshi. Dr. LaVallee has a very close relationship with Dr. Patricia Keegan, who is the chief medical officer of Junshi. Shen Yao is the president of TopAlliance, U.S. We speak to him frequently. I have frequent Zooms and telecons with Ning Li, who is the CEO of Junshi. We have very frank and open conversations that are extremely honest and straightforward. We are very impressed with the team at Junshi on a number of fronts. Scientifically, particularly, with respect to toripalimab, and the other assets also that they are bringing forward.
The regulatory strategy that Dr. Keegan and her colleagues have brought forward of pursuing orphan and small indications in the U.S. and then progressively build the label. We think that puts us in a very good position to get an approval in the U.S. Then lastly, with respect to your question about the ex-U.S., ex-China partners, that's. We are of course very, very supportive of our good friends at Junshi, but would not presume to involve ourselves in any discussions unless asked. Yes, Chris Schott, JP Morgan.
Just one quick one. Can you just, I think you mentioned it in the remarks, but just on inspection timelines, the PDUFA, is there any more color you can provide of how difficult or not it's gonna be to get that done before the end of April, given some of the dynamics in China right now?
Yeah. Theresa, do you wanna address that?
Thanks, Denny. Yeah. No, you know, I've always said what makes me really good at regulatory is I worry about everything. A few sleepless nights with pandemic going on. We're working with the FDA to schedule those. They are not scheduled at this time. Clearly with pandemic-related travel restrictions, how do we get around that? That's the dialogue we're having. I mean, given the PDUFA date at the end of April, that is highly unlikely if anyone knows what it takes to do a GMP manufacturing, if it's not scheduled today to get to China quarantine and get the site inspection done. We do have breakthrough therapy designation, and the FDA has reiterated multiple times that this is at the top of the list and a priority for them.
I mean, this is a high unmet medical need with no approved immunotherapies, and we anxiously await a solution.
Yeah, we don't have any further clarity on that, but of course we'll be very forthcoming when we do. You know, unfortunately, this COVID appears to have upticked significantly in Shanghai right about now. As Theresa said, the FDA has indicated to us, it's very, very high priority for them to get this drug approved. Yes, Salim.
Thanks. Salim Syed, Mizuho. Just a quick follow-up to that, Theresa. Have they ruled out virtual inspection then completely or for the-
Yeah, I mean, I think we all wait for April 30 to see what the exact verbiage is, right?
Yeah.
It's a live game, so I would anticipate they need an inspection. This facility has not been inspected.
You know, the FDA has a very difficult job. You know, they actually did another inspection for us with CIMERLI you know, in Europe. They got that done. That's you know right close to the border. You know, I give the FDA really high marks you know for leaning in here and really trying to get these inspections done. I know they come under a lot of pressure, but we are really sympathetic to you know they have a really tough job. We're fully supportive. Yes.
Hi, I'm Myles Lewis, Bishop Capital. To kind of piggyback on the relationship with Junshi, looking at the operating expenses from 2022 to 2026, as far as any license fees or milestone payments, do you see that having any significant impact on the operating expenses during those years?
We paid a $35 million license fee earlier this quarter to complete the licensing of the TIGIT. There's a $25 million milestone payment that would be due on approval of toripalimab. That's actually not included in the operating expenses that are portrayed there. Those fees are not included in the operating expenses that are portrayed there. There's an additional milestone that would be payable based on approval for non-small cell lung cancer. Then there are sales-based milestones in the future.
Thank you for your question. Okay. All right. Well, no further questions, then we thank you all for your attendance at our first annual analyst day. We'll be happy to see you again next year. In the interim, we'll see you at the conferences. Thanks, guys.