Coherus Oncology, Inc. (CHRS) Earnings Call Transcript & Summary

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, 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 in 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. And 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've 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 4 new product launches over the next 15 months, and we're also rapidly advancing our immuno-oncology pipeline. And so 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 4 planned 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, and then we'll take your questions after Denny wraps things up. But now I'd like to introduce Coherus' CEO, Denny Lanfear.

Thank you, McDavid. And 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 who've been with me for many, many years. Doug is out, for example. 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. And perhaps the decade of 2010 was the decade of biosimilars. And in that context, we're very proud of the accomplishments and the progress that we made, the savings that we delivered to the health care system and all. And our mission now, just as it was before, is still for the benefits of patients. And what you'll see today is our focus on prolonging survival. Prolonging survival is a key focus, particularly in immuno-oncology. Now the biotech business is one of very long time constants. And as you can see here, execution is key. The one thing, I think, that we are focused on absolutely is execution. And 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 of both with and without TIGIT. And you'll hear from our research head of Immuno-oncology, Dr. Sanjay Khare, about our new innovative products, which are coming through. And 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. So it's very important to spread the risk across your portfolio with products in each phase. And we take a triad approach at Coherus. We, of course, have the toripalimab, 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 externally licensed assets such as the TIGIT. Other assets also with respect to our Junshi relationship. And of course, you'll hear from Sanjay, on 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. And it all starts, of course, with PD-1. As you know, in 2019, we launched UDENYCA. And about 4 months later, in April that year, we pushed the company to cash flow breakeven. And at that time, we began to act very seriously on how do we expand the mission of the company beyond biosimilars, particularly in Oncology. And 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. And 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. And as Theresa would say to me, epitope really matters. And 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'll need to be able to do that. So we think this is really essential to have our own. And 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. And 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, and 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. And 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. And this, again, is about advancing patient benefit, prolonging survival. As each additional combination therapy is introduced, hopefully, it extends 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 3 assets, wholly owned. Our innovative assets here, again, Sanjay will speak to you about an ILT4, a CCR8 and CD73. Of note, we also expect to move into Phase IIIs with TIGIT in combination with toripalimab. We expect 1 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 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. And 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. But our selection of our PD-1, toripalimab, was all through our scientific advisory board and our science is they that I would have thanked for their help in picking the right asset, but 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? But as an old mentor of mine once said, strategies that are not executable are fantasies, right? That was Kevin Sharer back at Amgen. One of the things that I'm really, 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 both designed our approaches for UDENYCA and really took a deep, 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 going to go forward. He chose the biosimilars as well as toripalimab. But there's also a number of other teammates that we have now, which are very tightly focused on successful execution on the commercial dimension. And 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. And I would just add that these are not just pipe dreams and imaginations. Our on-body system has shown its worth in clinical trials, and we're preparing it. YUSIMRY is approved. CIMERLI, we are very confident it will be approved in August. And toripalimab has shown extraordinarily good data in a number of cancers, including esophageal and has an NPC as the BLA in front of the FDA. Which all sets us up for 2026, our 4-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; 2 or more assets in clinical stage trials; and humming engine in R&D, producing a steady stream of products. You'll hear about all of 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 our shareholders. And 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. So let's start with the cancer immunity cycle. This shows the mechanistic interplay between the tumor and immune system on how to invoke antitumor immune effects. So for the 100 years, from the -- wholly through the 1900s, this was really thought about. And what's been exciting in the last 10 years is how much we've learned. So it's really positioned us to understand that the T cell, the mighty, mighty T cell is the core to really invoking antitumor immunity. And how that happens, I'm just going to walk you through it a little bit mechanistically because I think it will help to see how we're positioning our assets and how we look at them for development is, of course, antigens have to be present and presented. So 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. And on the far right, we see that antigen is presented on an MHC to the T cell receptor. And that triggers Signal 1. So the immune system has a lot of checks and balances. And so it's not just Signal 1 is sufficient to activate a T cell. You also need Signal 2. So you can think of this as like multifactor authentication, right? So Signal 1, user name, password, got it. But you need a push code to get into your account, so you need Signal 2. And the immune system really has these checks and balances so that you can control and not have untoward autoimmunity and those types of things. And so 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 1 and Signal 2 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 1 end of the bispecific antibody and a CD3 that recognizes the -- oops, the T cell receptor, so Signal 1, and looks for Signal 2 within the tumor. And then the checkpoint inhibitors. So they come in, so CTLA-4, the first approved, which takes the brakes off Signal 2. And 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 1 and Signal 2. So what does this mean? And why is everyone so excited? That's way called biology, but what does it mean to a patient? The real opportunity is long-term benefit. So 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. So as the tumor comes back, it can eliminate the tumor. And so 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. And so again, building off these [ Creole ] Kaplan Meier curves from Jim Allison's Nobel Lecture, what we really want to see for the next 10 years, now that we've understood the T cell, we understand a little bit better how to invoke antitumor immunity. How can we get it to not a minority of patients, but a majority of patients. And so one of the things that's really giving us an advantage is the use of technology, multiomic multiparameter biomarker analysis in patients. What I'd like to say is the human cancer patient is the relevant animal model. So mouse model system is incredibly important, but the immune system is complex. So profiling of patients and learning about response and nonresponse is really informing us of who to treat and how to treat. And we've learned a lot about the T cell. So that -- and 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. But 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. But then there's checkpoints, the PD-1s, the CTLA4s, the TIGITs that turn it off. So there's different stages though of exhaustion. So you don't just have an exhausted T cell, there's a lot of states of dysfunction and exhaustion. So 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 experience exhausted or tired, as I'd like to say, the tired T cell that has stemness. So a TCF7 biomarker. And what's really interesting is the 2 checkpoint inhibitors that are expressed here are TIGIT and PD-1. And then we've also learned that there are these exhausted effector T cells that have other checkpoint inhibitors that can be reinvigorated. And very exciting this month, we saw the approval of the third checkpoint inhibitor target like 3, right? So 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. So there are a number of immune suppressive mechanism that the tumor uses to evade the T cell. So 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, there's [indiscernible] M2 macrophages. They'll really dampen the T cell response, prevent it from getting in, prevent it from getting activated. So I think the next wave of real combination treatments with the PD-1s is attacking the TME to make it more T cell permissive. So 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. And together with Junshi and their U.S. subsidiary, TopAlliance, we have a video that I'm really hoping plays now. [Presentation]

I'll technically walk through and reiterate some of the points in the video, as Denny mentioned, I think having worked with [indiscernible] at structure function, person I really learned that epitope does matter. And thinking about where it binds, it can have different properties. And we know that most relevantly, clinically, from HER2. So 2 antibodies, trastuzumab, pertuzumab, both bind HER2. Trastuzumab has robust single-agent activity. Pertuzamab, not so much. So you can see the difference of where it binds can have different properties clinically. And so 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 3 different antibodies. And at the bottom, we have PD-1. And we can see that nivo binds at the end terminus. This has a confirmation 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. And you can see here a comparison, it's about 24 -- toripalimab is about [ twenty fold ] more potent than the competitors. So the video very nicely showed you the internalization properties in these dayglow green figures. So anyone who's worked on antibody drug conjugates is used to thinking of antibodies binding, having to be internalized, release the payload. So why would this matter for immuno-oncology? So 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. And we know this from the CAR space where they're trying to use CRISPR to knock out PD-1. So 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? And so 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. And so 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 have 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. So high or low, you have a hazard ratio of 0.61. In the KEYNOTE-590 study, if you look within that trial, so not a cross-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. So as Junshi presented this wonderful package to Coherus, as we look through it, what we saw in the early stage clinical studies is that there was robust activity across immunologically responsive tumors. So the disease control rate here shows you that we have really nice activity in combination with chemo, 80-plus percent disease control rate, monotherapy, 30% to 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. And our lead indication is NPC, nasopharyngeal carcinoma, a tumor type that is underserved by immunotherapy. And 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 we've published in Nature Medicine and featured on the cover. And 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. And 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 ORION-11 study that was recently reviewed at ODAC, where the FDA really enlightened us is to their current thinking about single country data. So large indications that are well served by immunotherapy treatments, there are some multitude of agents approved in multiple lines of non-small cell lung cancer, single country data is not observed to warrant regulatory flexibility. But in the ODAC and in the [ OPEDS ], in the New England Journal of Medicine and 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 30. 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. So in addition to noding, in tumor types that have -- could warrant regulatory flexibility other than NPC, HCC, so liver cancer was highlighted. And Junshi does have a number of studies ongoing there. So we've kind of now defined the bookends, ones that warrant regulatory flexibility, lung cancer, a multitude of agents, big tumor type, no. But there's like 900 indications in Oncology. So what's in the middle? And that's really what we have to figure out and engage with the FDA and look forward to further guidance from them. But 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 2 months, 2.7 months. So maybe there is an area to look at if you have meaningful clinical benefit. And then there's ongoing Phase III studies in China right now, could we make those multiregional studies? And those discussions with our partner, Junshi, are ongoing. So switching to the TIGIT program, also partnered with Junshi, we announced in January that we 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 as PVR, akin to PD-L1 being the ligand for PD-1. So 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 many of the checkpoint -- any of the other checkpoint inhibitors, its role in peripheral tolerance but also the way that it inhibits signaling. And so when PD-L1 engages PD-1, it activates a phosphatase, Shp2. So the phosphatases take away any activation signal. So what's interesting is when PD-L1 engages PD-1, the Shp2 turns off Signal 2, CD28. But it also turns off Signal 1. So hits both signals, so maybe a more robust node there. But 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 2 pathway signaling. So PVR binds TIGIT and turns off T cells. PVR also binds CD226, which is an activating signal. When Shp2 is activated with PD-L1 binding PD-1, it also turns off CD226. So a lot of complex interplay. The bottom line is the 2 receptors are related from expression and crosstalk signaling. So a biologic rationale for why the combination may have enhanced antitumor activity. So 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. So if you turn off the antigen presenting cells, so you dampen the APC, you're not going to get Signal 1. And then if the Treg, 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. And the package that we saw from a preclinical perspective showed potency and binding to TIGIT. So 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. And the bottom left shows you a cell-based T cell activation assay looking at single agent activation with 006 on its own in green. And then 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 in a preclinical tumor model with a PD-1 TIGIT human knock-in animal. And the curve shows monotherapy tumor growth inhibition when mouse is treated with single agent toripalimab or 006. And again, importantly, when the 2 are combined, we see dose-dependent improved enhanced antitumor activity, including tumor regression. So a strong biologic package to really show this molecule to move into the clinic. And 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 and the clinical setting. So 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 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. So 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. But 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. So 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 is showing activity and has some unique attributes to really benchmark 006 tori data in the field and working closely with our partner who's continuing development in China to look at multiregional pivotal studies to advance this quickly. So 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. And 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. So this really sets up well for new development and early development of an in-house pipeline targeting IO. And this slide shows the IO pipeline. And with that, I'll introduce my colleague, Dr. Sanjay Khare, who is SVP of IO. He's an excellent accomplished immunologist and industry veteran. So Sanjay?

Well, thank you very much, Theresa. And thank you for listening to the presentation. In the 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. So let me give you -- let me tell you a little bit about our approach. So 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 and what kind of immune escape mechanism might be triggering in patients where we are not seeing efficacy or patients are rebounding. So in order to understand that, what we did is took an effort looking at cancer -omics data. And these -omics data are available from many public sources, TCGA being one of them, but cBioPortal and many other sources. And 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. And finally, that will -- 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. And you can see these red squares and also blue triangles. They are a stable disease and complete response or partial responses. And many of these patients had pretty good progression free survival. However, there are other patients with high T cell inflamed gene expression profile, those were not responding to anti-PD-1. And this is -- these are the data comes from 9 different tumor types. So overall this has been seen across different types of tumor in 2 different studies. What is maybe 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. So what we did, we used the data from The Cancer Genome Atlas and 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. And we try to focus on these mechanisms while others are still working on checkpoint. We already have 2 checkpoint molecules in our portfolio. RECONNECT. So what we are trying to solve is to solve, understand major immune suppressive mechanism that may address immune escape and how the combination of drug could potentially lead -- 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. And how we began to address this issue by transforming the transcriptomics data into immune cell type. And this is not new, but we have been using a different approach, a different algorithm that comprises about 30 to 45 genes for various immune cell types. And we have looked at in 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. And finally, find targets based on the biology and develop best-in-class drug candidates. That's what we are doing in our Camarillo labs. So how this work is done? We are looking at the databases and also publications, those are evolving over a period of time as early as 2022. And then we are using a number of software and a number of other algorithms to convert those transcriptomics data into cell types, immune cell types. And then we are seeing that what kind of immune cell types, particularly suppressive immune cell types may be interplaying the role. Okay. So let me talk to you about a molecule called ILT4. And ILT4 seems to be a key regulator in repolarizing suppressive macrophages turning into inflammatory macrophages. And the reason is it is very important because when ILT4 on macrophages, these are the suppressive macrophages, are binding through a LAG molecule on tumor cells, these suppressive macrophages turn off immune T cells, okay. Now when you block this interaction ILT4 to its LAG, you can turn this immune suppressive macrophages M2 to M1. In addition, what it does that dendritic cells are not able to present antigens to T cells. Those are called tolerogenic dendritic cells. And presence of the blocking agent would lead to tolerogenic dendritic cells to activate the dendritic cells. So you have better antigen presentation in that case. So as I said, that we have been analyzing these data from various cancer types. And here is an example in small cell lung cancer. And what we are trying to do here is to look at signatures relevant to various immune cell types listed here. And 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 cells. So what you are seeing that patients call M1 cluster, in the M1 cluster have high immune score. And those are -- those have hot tumor and probably more responsive to anti-PD-1 therapy or PD-L1 therapies. But there's a big cluster of M2 macrophages, about 1/3 of total patients. And these patients have fewer immune cells, CD4 and CD8 T cells here. And these patients are not likely to respond to anti-PD-1 therapy unless you change this immunosuppressive pathway. And here is 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. So 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 for CD4 cells. CD4 cells, CD8 cells, CD4 memory resting and CD4 memory activated cells. And patients with high M2 have very few of those cells. More recently, a 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. And once we convert these M2 to M1, the likelihood of those patients will be responding better. Similar to small cell lung cancer study, we also analyzed the TCGA data for non-small cell lung cancer. And we found a large population, almost 1/3 of the population of all non-small cell lung cancer patients with adenocarcinoma, have high expression of M2. So here, red is high and blue is low. So patients with a high M2 signatures have very few CD4 and CD8 T cells. And about 1/3 of these patients have high M1 and these are the ones who may be better responder for anti-PD-1 therapies. So 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. And indeed, this is the publication just came out in a couple of months back in clinical cancer research by Merck. And there, they have shown that when they treated 84 patients, and 34 of those patients received their anti-ILT4 MK-4830 in combination with pembrolizumab. And this combination was well tolerated in patients. 10 out of 34 patients showed objective response in the combination group. In the monotherapy group, only 1 patient responded. And 5 of these responders with PD-1 refractory, okay? So a pretty good opportunity here. And interestingly, there was durable response seen in over 1 year in many of these patients. So what we are trying to do is -- and we are developing ILT4 antibody, CHS-1000, and that is going to block ILT4 interaction with HLA molecule and making those T cells more prominent for antitumor immune response. This candidate is -- we are expecting to file the IND next year. Let us discuss another immune suppressive cells pretty well known in the literature about regulatory T cells. And regulatory T cells are also known to dampen antitumor immune response. Immunosuppressive -- so there are a number of targets for regulatory T cells. And many of -- and there are some failures too for Treg-directed compounds. Ketter was one of the molecule present on regulatory T cells, didn't work out well. The problem is that Tregs are good to keep the inflammation down. But at the same time, Tregs are not good for anti-tumor immune response. And you want to have a molecule that is overexpressed in the tumor microenvironment, the Treg in the tumor microenvironment. CCR8 is one of the molecules that is highly expressed on Tregs in the tumor microenvironment. And what we tried to do, looking at the similar type of reg you have seen before, and again, we are looking at red means high and blue means low. And we are looking at the regulatory T cells right here. So regulatory T cells are high in about 30% of non-small cell lung cancer patients. But we found actually 2 clusters for regulatory T cells. One is Cluster 1, other one is Cluster 2. The Cluster 1 has regulatory T cells, and this cluster also has natural killer cells. However, Cluster 2 has -- is low in natural killer cells. So 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 1, high Treg high NK cells, are more likely to get benefited with anti-CCR8 antibody. And patients with high Treg and low NK cells have low -- less chances. So this is what bioinformatic data mining is telling us. 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. And because Treg cannot be killed, immune CD8 T cells cannot work very well to kill the tumor. On the other side, when patients have MAX 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. And we have studied this in multiple tumor types. What we have -- there are a couple of interesting observations on this slide. Number one, this is limited mechanistic overlap with anti-CD CCR8 and anti-ILT4 treatment. So that would definitely help a large segment of oncology patients. And here, we are showing data in hepatocellular carcinoma, adenocarcinoma in small cell lung cancer, head and neck and esophageal. And it seems like there are a large number of patients from 45% ILT4 and CCR8 to -- for high Treg and M2 together, all the way up to like 65%. So a large number of patients are going to be benefited to 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. It's 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. And the science is very impressive, and I want to 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. And 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. And we are becoming a commercial powerhouse. I'm going to talk you through that story, but that is a fact. And we are ready to launch 4 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. But 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. So to be a commercial powerhouse, you need a number of things. But 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 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. So within the strategy group, Abid and Michael 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 want to raise your hand. Hello, Steve. So Steve is our Senior Vice President of Market Access. I've known Steve as a friend and colleague for a couple of 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. So 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 road to the left. David Sanders heads up our vice -- our Government Affairs team. That's a group for very skilled government affairs specialists that really help Coherus advance the policies, the legislation and the efforts of the biosimilar marketplace. Securing America's medical supply chain is a coalition of companies, spearheaded by David and by Coherus to ensure that really the biosimilar supply chain is secured. And what we learned through the pandemic is there's a 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. 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 is that leader. He built and led Hospira's original biosimilar business unit. And then as through the acquisition of Pfizer of Hospira, took that on and led their very competitive hospital injectable business. So John is the perfect commercial leader for our biosimilar business. And reporting into John, he'll be responsible for UDENYCA today in our life cycle of UDENYCA on-body as well as CIMERLI and the CIMERLI launches. So we've organized into that franchise. And then Brandon Kotaniemi. Hired Brandon to serve as the Senior Vice President of our Immuno-oncology Marketing franchise. So Brandon will be responsible and his team for the launch of toripalimab in the first indication in nasopharyngeal carcinoma, any follow-on indications or any other of our immuno-oncology products that will commercialize in the United States. Brandon's got decades of oncology marketing experience launching blockbuster innovative brands. So 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 oncology, is expertise. And 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. And this chart could actually be more complex, and I'm not going to 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. And 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 and working in a virtual environment that will enable us additional share of voice through the pandemic. And as oncology accounts have changed their policies and interaction with the industry, we'll meet the customer where they are. They want to meet in person, we'll do it. They want to 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 are the quarterbacks, if you will, navigating those large complex organizations. So we've scaled that team up in 2021 in anticipation for the launch of toripalimab this year and our future product launches. And 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. And 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. But it's a decentralized marketing organization working hand in hand with the home office team. I want to note here on the far end, shaded not to -- but only shaded to differentiate that that's the medical science liaison team. That's the group of credentialed medical professionals, phar MDs, 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 trial. So that's why they're shaded there. And then finally, this lower group of individuals. We have a dedicated payer team that reports into Steve. They call on the national and regional payers, both on the commercial side, Medicare Advantage pieces. They -- we've got a dedicated team focused on our channel strategy and 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, practices need the billing, coding, reimbursement support. So when they have a problem 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. And so we've got a very dedicated team. I'm going to show you a little bit how this is going to 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 co-pay assistance that it was built to scale up. So 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. So it's a scalable service solution. And 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 co-pay assistance, we help them with that. Paid out over $10 million over the last 3 years in financials, which is a testament to our commitment to making sure every patient gets the product. But again, scalable solution. And then 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 going to apply the 4 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. But 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 going to be 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'm going to 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. And 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. And 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 Hamister, 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. And finally, market access. You can have the best product. You can 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, the brand will struggle. And 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 going to take to get coverage for our products and get those reimbursed and to be -- continue to deliver through Coherus Complete services and support that patients and customers need. So let me take you through the next few slides. I will show you how that commercial infrastructure that we built for UDENYCA today with our one brand will scale over time. And to help you understand that we're not having to rebuild and replicate commercial teams for each of these products that will be incremental built. And so that will really help to ensure a very efficient commercial resource investment over time. So you see here with UDENYCA, our core business, those groups that I noted here, I do want to note in your packets there was a typo. This on the screen says 76. It's listed in 96. So 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. So very efficient there. And I'll show you a little bit of the overlap momentarily. For CIMERLI, we'll be able to leverage the payer team, the key account team and the Coherus Complete team. But because of retina, we're going to 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. So it's not going to be in the 60 range. It can be very focused and dedicated to the retina team, but you got to have that expertise. So we're going to go out and we're going to hire it. But we'll be able to leverage the vast majority of our market access, patient services and key account teams for that. Hired a CIMERLI brand marketer, Nina O'hara. Years of -- she's a phar MD 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. So very pleased with our progress there. And then finally, for YUSIMRY, because this is a pharmacy benefit adjudicated product, we'll translate our expertise that we've gleaned from buy and bill into the pharmacy side. But here, this is going to be, as I'll show you, very much driven by the payers and the PBMs. And so Steve's team in getting coverage will be our #1 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. But 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. So we don't anticipate building hundreds and hundreds of immunology sales force for this particular product. That's not what our intention is. So again, very efficient use of marketing and commercial resource investments. So that's how the cadence is going to build out and how we'll build the team out. Let me talk a little bit now and transition to each one of the brands in the launches coming up. And as we go into these markets, our commercial objective is to capture at peak, at least 10% market share. And 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 I'll show you with UDENYCA, we did a lot better than that. So that's our minimal commercial objective. So let's start with new -- 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. So I knew this product, launched it with many of my colleagues 20 years ago. And it was a $4 billion -- 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. And they were gearing, it looks a lot like the HUMIRA business actually doesn't it? So it's a bit of a case study. But with the launch of UDENYCA and Coherus, we were able to bring a biosimilar to Neulasta to pegfilgrastim. And you can see at a greater value, and 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 health care system. We project about $3 billion. And so it wasn't just a U.S. health care system and the patients who benefited from lower out-of-pocket costs, but it was also a big success for Coherus. And so this is -- if you're going to bet on our commercial prowess, this is the slide that is our report card. And these are the numbers that we've posted. So we entered into that very competitive monopolistic market by Amgen and Neulasta. And over the 3 years period of time, UDENYCA became the #1 prescribed pegfilgrastim prefilled syringe, delivering cumulative $1.2 billion in net sales, a blockbuster over the 3-year period. At peak, we were over 20%, but we ended Q4 2021 at nearly 18% market share. And you talk about supply, again, delivering 650,000 syringes to patients. And those are patients with cancer, every one of them. So 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. And when we talk about the trajectory of UDENYCA and where it's been and where it's going, I want to focus your attention to the left side of this chart, if you will. This shows the unit share from the third quarter 2018 to the fourth quarter of 2021. And as you can see, UDENYCA was commercially launched. It was approved at the end of 2018, launched in January 2019. And 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. And that share was coming from the innovator, from Neulasta. And we were cruising along. We were taking share by the chunks and everything was just going exactly to plan until Q1 2020 and COVID hit. And 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 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 2 years, an entrenchment in customer preference for the on-body device. And so you draw your attention now to what does that mean today and where the market is today? It's really created these 2 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. And 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 prefilled syringe product with no new safety signals observed. So we're not going to speak to what our competitors have or have not. We just say look, we're putting 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 to -- for commercial launch in 2023. So because of this, because of our in-body injector and our position within the prefilled 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 prefilled syringe market, which is becoming case-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 going to be the year where we're maximizing our near-term revenue balancing price and share trade-offs because all those pricing decisions you make carry forward. So we have -- 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 biosimilars entrants that have come in the marketplace. And 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's realized those market share gains when you see their ASP reduced 20% from last quarter. So those disproportionate price decreases that they brought into the market to grab short-term share are now bearing out in the marketplace, and 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. And as a marketer, you always love to bring great products that deliver clinical outcomes to patients. And that's what toripalimab is going to do. In nasopharyngeal carcinoma, we'll use the term NPC for short. The nasopharyngeal carcinoma is a rare cancer here in the United States, more prevalent in other parts of the world. But we believe in the U.S., somewhere between 0.5 and 2 cases per 100,000 patients are diagnosed a year. But what we've learned since coming into this market as 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 or coded head and neck, but they're actually NPC patients. So I can't tell you is the size of the market, 1/3 bigger, twice as big, not sure yet because they use often the same chemotherapy. We don't know that. But I believe that this market is actually bigger than what the claims data suggests, which is a positive thing. But 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. And 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 indication, they don't have it for nasopharyngeal nor OPDIVO, none of them do, nor PD-L1s. So if approved, toripalimab would be the first and only PD-1 antibody approved for patients with nasopharyngeal carcinoma. And with chemotherapy, which is currently the standard of care we can improve that median 5-year survival rate of 20%. About 50% of these patients that are diagnosed will have distant metastatic disease at some point in their therapy. So there's a long way to go to help these patients, and we intend to do that with toripalimab. So 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 of 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. So they'll use radiation. But chemotherapy is the standard of care, typically platinum-based chemotherapy, and our study was combined with gemcitabine cisplatin. But as these patients then get treated with relapsed in metastatic disease, you see here for about 1,300 are cycling through a first-line, second-line type of treatment with systemic chemotherapy. We toripalimab, the data package with the FDA included the JUPITER-02 study, which was the first-line trial, combined with gem-cisplatin and the POLARIS-02 trial, which was used in second and later lines of therapy. So we would expect our indication would largely be for all lines of therapy. But 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 frontline setting. And so if you look at all of these patients and you just say, okay, if they all got PD-1s now as part of the new standard of care and we used KEYTRUDA's WACC price times the average number of cycles that we saw in our trials, you could be looking at well over a $100 million category opportunity here. So despite being a rare cancer, we believe has significant commercial upside. And being the only PD-1 antibody, if approved, our aspiration is to have all of it as toripalimab and combination with chemotherapy. And why do we feel so confident in our ability to establish this new standard of care? Well, oncology, it's all about the science, and that's what we have here. 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. And 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 until well after products are approved. So what this means is we've got 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 talk just -- I've got a couple of slides here again, back to the playbook, customer engagement and strategy and execution. So on the left, there are 4 strategic imperatives. I want to point out something of note because it's also a demonstration of our capabilities here as a company. But Denny and the team achieved this licensing agreement with Junshi and closed not only just, what, 14 months ago, January, February. And so Coherus has really only had this asset for a year. And 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. In most cases, companies 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. But establishing clinical confidence, I showed you the science. This is going to be well established. But we've got to get out there and tell the Coherus clinical story to physicians and other stakeholders. And you could see the work that's already been done with customer engagement and what's planned here, really understanding the space with the key opinion leaders, multiple ad boards, engagements, scientific advisory committee. And 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 pending diagnosed with NPC on toripalimab. So this is vitally important. Post approval, Steve's team will go out and get access and coverage for the product. And based on our conversations with payers today because of the unmet nature of this and will be first only, we would anticipate broad open coverage without any restrictions. And 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 at npcfax.com. But because the average medical oncologist doesn't treat a lot of these patients, they don't have the breadth and the depth of understanding about this particular disease. And so that's what this campaign is designed to do and to help them understand the unique nature of MPC versus head and neck and other cancers. And so 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. The team is already covering on the vast majority of oncology clinics hospitals. And when we look at the -- where NPC patients are treated today, about 2/3 of them are already coming from UDENYCA purchasing accounts. And so you can see there's high overlap. So 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. So very efficient launch. And the team is trained and we're ready to go. The PDUFA date is at 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 got to transition now from being a value largely 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 2 days to toripalimab training. We had 3 or 4 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. And so we are ready, 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 will meet our customers where they are in using both print and digital. The other capability that we've invested in over the last 6 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 an investment that both Denny and I feel will pay off big for us over time. And so in conclusion of the toripalimab section, we're very excited to bring this innovative medicine to patients. It's a high unmet need. Coherus 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. So we're looking forward to launch. Let's turn our attention now to similarly in the ophthalmology retina space. So 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 clinic-based model, retina specialists purchase, administer then bill for the product similar to oncology. And so the core competence 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. And then smattering of the other, you see Beovu there, which was the Novartis product that was launched and then had safety issues and subsequently now, Novartis is essentially gutted their ophthalmology commercial organization and it's still generating $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 in the eye without any indication and without any clinical data to speak of delivered to retinal specialists by compounding pharmacies. But it's very inexpensive, which is why it has such low dollar market share. And we believe this market will continue to grow over time because of the establishment of the VEGF class is 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. So this is a large and growing market. And 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, understand what the customers and the retinal specialists think, believe and feel. And when we talk to them about their likelihood to adopt biosimilars. Again, they don't have any experience with biosimilars today. So when you're asking them these questions, the mindset from which they're coming to is very little knowledge. And so it's not unexpected that you probably see 1/3 of these doctors saying, I'm really not sure. I might watch and wait and see what my colleagues do. But we were very excited to see that over half of them already indicated that they would prescribe biosimilar Lucentis when it's available. You got some here that say they don't expect using it and others only if it's mandated by patients. But we're very encouraged by this, and I'll explain how we're going to help them along here in a moment. But then we asked them, okay, well, if you're going to adopt these biosimilar Lucentis agents, on which patient types do you anticipate using it? And again, 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. And as you can see here, 1/3 of the doctors reported that they would use it for newly diagnosed patients, but 27% say they would switch from other VEGF products well, almost 40% said they would come from Lucentis branded agents. This is why we believe here that the entire VEGF market will be open to penetration, and I'll explain how we're going to roll that out momentarily. So 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 3 phases. We're in that prelaunch phase right now. Well, what we're doing now is establishing Coherus as a new company into the retina space, and 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. And these are organizations that we work with today through AmerisourceBergen and McKesson and other large groups. So 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 going to 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 going to come from, and so we're going to make that a priority target for us. But because of the market is larger and open and once we establish similarly in the market, the positive experience and the value proposition that we're going to bring, we believe we'll be able to open up other parts of the anti-VEGF space, either through Avastin or through Eylea and growing from both ends. So 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 Health and through AmerisourceBergen. There's many large groups of retinal specialists that continue to grow and get larger and larger. But what we learned through these engagements are 3 things: Number one, they need to understand biosimilars because they really don't, similar to what oncologists faced years ago. And they're going to 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're injecting in the eye, we have to really spend a lot of time educating on that. And I'll show you the data from our Phase III trial that should give them great confidence we'll be able to do that. But practice economics as well. It's a buy-and-bill model. So because of that, they're managing not only their cash outflow, but also the reimbursement and cost recovery. So this is part of the biosimilar campaign that we're going to be launching beginning in this quarter. It's -- they did a great job. And again, it came out of our playbook for UDENYCA, but really tailored towards the retinal specialists with these beautiful graphics. But it will really educate retinal specialists, their practice managers, CEOs, allied health care providers about the regulatory pathway, so they understand the regulatory pathway. Why the design of the COLUMBUS-AMD, our 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. And we're going to be kicking that off, driving that towards the retinal specialist and you'll see us at Congress is if you're there at any of those retinal meetings will be there. We'll also give them confidence at the time of approval that similarly will have a presentation that is similar to Lucentis, which again, not only takes the form of an identical amino acid sequence, dosaging and indications that are identical to Lucentis, the same formulation as Lucentis and also the same storage conditions. So essentially, what they will have is as close to the reference product with some early as they'll be able to, which will give them great confidence. And then there's confidence in the clinical data. And what you see here on the left is the data from the published Phase III study done by Dr. [indiscernible] 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 meant the 90% confidence enteral. And on the right is the adverse event profile showing no difference in safety. So 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, clinical efficacy in ocular and systemic safety. So 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. There are a subset of ophthalmologists, and the concentration of this business is quite unique. And when you look at through looking at claims and demand volume, they're in this case, about an 80-20 rule where about 446 accounts that are driving 80% of the anti-VEGF volume. And for Lucentis, it's actually more condensed than that, which enables us then as we're designing our field sizing that we can have a very focused and dedicated team to go after the largest accounts at the time of launch. And then if we have to build, we can do so later on and build from there. But again, another example of how we'll be very efficient with our resource investments incrementally. And so to conclude the CIMERLI section, our launch strategy is really going to focus on 4 key elements: granular segmentation, which I just spoke about. I'm sorry. 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. And they will see that capability when we bring CIMERLI to market. We're going to build on our existing resources and drive the market education, both in biosimilars and the brand pre and post launch as appropriate. So again, no other new market, large market, very excited to enter. I'm going to wrap up with some discussion around YUSIMRY, our biosimilar to the reference product, HUMIRA. So let's start left to right on the slide. HUMIRA, as you all know, is a $17 billion brand, #1 product in terms of sales in the United States. And 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 at least $1 billion opportunity. Obviously, we don't know yet where the marketplace is going to be in terms of discounts. But suffice it 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 is already approved, you can see the prescribing information online around all these. There's a few that we won't have, particularly that are part of some exclusivity that HUMIRA will have very small niche indications. This is where the bulk of the business is. And as you can see, the payer mix on the right, half of it is covered by commercial insurance. And so commercial payers will be very key for early uptake. And that's what Steve and his team's efforts will be focused on. So this is YUSIMRY approved by the FDA in December of last year. It was a great holiday gift to the company. And as you can see, our product presentation of an auto-injector device. I'll speak a little bit more about this device, but it's fantastically done by our brand team. We'll be differentiated, look very similar to the reference product, HUMIRA. And we're going to be coming in and launching in the biosimilar market formation period. As you can see on this chart, this is 2023 timeline. Amgen and AMGEVITA 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 midyear. But what's key and what we know about biosimilar, the biosimilar market, is you got to be in market formation, and we will be. And I'll show you why we believe we'll be set up to win despite these competitors. But 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. So if you see all the stakeholders in this particular because it's adjudicated through the pharmacy benefit pathway. And because of the size of these markets, 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 that 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 on-boarding, collecting the co-pays, shipping the drug to the patients, doing new product education, et cetera, et cetera. And sometimes, the insurance company doesn't dictate that the product has to be dispensed by one specialty pharmacy or another. So they oftentimes 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. But in pharmacy benefit, unlike buying bill, where they have the option to oftentimes prescribe and order what they want, here, they're going to be bound by the patient's insurance coverage in the formulary, and so what they prescribe will often be subject to that. And then the patients, again, will most likely defer to the doctor and unlikely to significantly influence product selection because of their health plan. And so as you can see here then on the right, just as we've mastered the navigation of the buy-and-bill ecosystem will have the same mastery to the pharmacy benefit pathway and knowing in each step where the leverage points are, where we need to be able to intervene and to be able to influence it, but the payers will be at the center of this, and I'll explain more about that right now. So 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. And 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. And when we went through the exercise and asked them to force rank level of importance to them and their decision-making, what rose to the top were 3. Not surprisingly, price and rebates came out as #1, right? This is the market event that the world is watching in 2023 with HUMIRA and the biosimilar adoption, but it is the #1 consideration. And I'll speak to this when I talk about this bottom one, interchangeability. But that dedicated supply were the top 2 by far. And 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. And so when the payers and the PBMs are going to choose a biosimilar partner to come in, they're going to expect that partner to be able to deliver a value proposition with price, but to be -- 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, which they manage, or any HUMIRA that is still being rolled through the health plan. So 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 they anticipate switching patients from the innovative HUMIRA to the biosimilar, you can't have the stinging agent because then patients will complain that it will cause disruption in that flow, and they don't want that. Interchangeability. This is what we were told time and time again. And 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, and that price will trump interchangeability. Now why is this so? Well, payers have told us that 2 main things. Number one, they've already adopted biosimilars and other therapeutic categories successfully. They know how to move patients from the reference product to the biosimilar agent. And 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 put it through, you run the script, you don't get it or through step therapy or through prior authorizations and differential co-pays. So 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. So 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. So that's 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 going to come down to price. And so 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. And we're going to come into the market to be able to get payer coverage and access 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 going to open up specialty pharmacy access. We've got the formulations, but we're not going to have interchangeability, and we're not going to invest in those trials because of the reasons I mentioned earlier and what the payers have told us. So we're very confident we can succeed without that. But this is the 1-2 punch, the value and the supply guarantees. This is why investments in manufacturing capacity pay off. We've invested $45 million manufacturing capacity. Rich will be here to take questions if you have details about this. But all I know is that that's steel, and that's beautiful steel in 5,000 liter tanks that at the time of launch we'll 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 1/3 of the market potential, which is 3x our market share projection. So we're going to show up to be able -- with confidence that we're going to be able to deliver on these supply guarantees and expect to be a low-cost, high-volume adalimumab manufacturer. So to conclude the YUSIMRY section, we are well positioned to compete successfully when we enter the market in mid-2023. We're going to 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, co-pay assistance, et cetera. And so to conclude, let me end where I started. 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 4 product launches. And these 4 product launches we project will deliver at least $1.2 billion in top line revenue by 2026. And 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. And now I'll turn the call back over to McDavid Stilwell, our Chief Financial Officer.

Thank you, Paul. So 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 to $450 million. What I want to 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. 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. So this year, as we've said, we are investing heavily in supply or upcoming new product launches. And so you see the manufacturing expense is disproportionately high this year compared to what you'll see in future years. And 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 we'll 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 tori 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, and so that's a very helpful attribute to have such a robust R&D program and to be sharing the cost there. And then in 2025 and 2026, R&D spend trends higher. We're moving tori 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% to 25% compared to this year. So we're doing a lot in the next 5 years. We're launching 4 new drugs. We're introducing multiple new programs in the immuno-oncology R&D area. And yet, you don't see a massive uptick in our operating expenses. And 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. And then turning to revenues that we project in 2026, a few years after the launch of all of these products. Today, we're introducing a revenue range of $1.2 billion to $2.2 billion. Of course, it depends on the 4 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 going to be very successful here. Another swing factor is how many indications were 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, and now I'll turn it back to Denny.

Thank you, McDavid. So 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, a black swan event that comes through, and your competitor has built an 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 own body device tested and ready to go. We went out and we did the job. You're going to see the same thing across the portfolio as we move toripalimab forward, as we go forward with our new innovative products. And lastly, as we realize the synergies that McDavid just talked about. And this is where we're going to end up in 2026. 4 products on the market selling [ $1.2 ] billion plus. Embracing the standard of care in lung cancer with toripalimab plus TIGIT, plus other combinations. Going -- plumbing the depths of the cancer immunity cycle, finding opportunities for greater T cell activation, as you heard from Theresa and from Sanjay; and 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...

There's a microphone for you. Please announce your name. There we go.

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. So Paul, you mentioned the 27% of retina specialists who are willing to switch patients from other anti-VEGFs. I'm just wondering that 27%, what percentage of the anti-VEGF patients do they cover given the concentration curves? Were these -- were you surveying more of the concentrated? Or was this kind of spread out? And I guess, alternatively... .

Well, let's just go one question. .

Yes, I was just kind of related, I guess, same question said a different way. What percentage of Eylea do you think that you'll be able to penetrate with the biosimilar Lucentis product?

First of all, it's nice to meet you in person after only speaking to you over the phone. Thanks for being here. Yes. So when we did the market research, we recruited retinal specialists that treated across the spectrum of VEGF therapies and not really 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 of different factors. Number one is the their preference for that particular product, either through dosing or just their own personal preference that they've slotted in. But what they've told us is, again, because it's not just a function of 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. So do we believe we'll be able to 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. And so that will be part of the discussions when we're able to promote so. But we feel pretty strongly that we'll be able to capture from both sides of it.

Thanks for your question, Salim. Yes, Chris?

I just had a couple TIGIT-related questions. So 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 assets? So if those data, I guess, we're not successful, would you still move forward here? And maybe conversely, if they were successful, do we think about Coherus following similar indications to what we're seeing for Roche? Or is the strategy more about going other places just given the competitive timelines there?

Yes. Dr. Lavallee, do you want to 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 ] soon and other readouts later this year. So a couple of points to think about. So 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 I-O going across the board. So 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. And 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, but we'll actively watch that and have our bioinformatics capabilities looking at different indications overall. But since we think it will work, generally where PD-1 works, it's a broad opportunity.

And just one follow-up on TIGIT. I don't know if this will be required enough. 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 okay, [indiscernible] just so we do right into maybe the issues that we have the PD-1 with landscape changes? But these studies we're thinking about are going to be not just China-based studies, I guess, for TIGIT development.

So for the folks on the phone, that was a head nod, yes. So 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 tori program, we're in conversations about adapting tori to multiregional 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. But as we move into a recommended Phase II dose and expansion phases, not doing it together might be a disadvantage.

Yes. I think it's also 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. So I think this is very positive for the multinational aspect of the studies for them. Yes.

Jason Gerberry, Bank of America. So a couple of questions on the 2026 sales for the 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 can talk a little bit about the assumptions. And when you launch OBI, do you inherit your PFS price point? Or could you actually get value for that innovation? And then 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. So do you expect this to be kind of perpetual continual RFPs? Or do you think that the negotiations will kind of stick for a full year and this will be kind of an annual contract?

So that's 3, Jason. I'll let Paul take the first one, first, with respect to OBI. Paul?

Yes. Thanks for your question, Jason. Yes. So I think 2022, it's a year of defense, right? It's trying to preserve the market share that we have without resorting to the disproportionate discounting that's occurring with the new biosimilar entrants. And so this is the year we're going to be looking hard at those price share trade-offs because of the future, right? And so what Amgen has done is they priced they're Onpro and their Neulasta prefilled 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. And so we'll be able to talk to you more about what that pricing strategy is going to be once we commercialize the product. But we see the growth in the franchise in 2023 and beyond, largely coming 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 [ Paris ]. Could you just repeat that one?

Yes, just curious to know how the negotiation will go in the summer. I think as these indicated, I think that that's going to be important in terms of setting the contracts for 2023. So do you expect it to be annual? Or do you think that this is going to be aggressive and like kind of...

Could you bring the microphone up? We have Steve Svitenko, who is our Senior VP of Market Access here with us. Steve, do you want to take that one?

Yes, sure. I appreciate the question. The likelihood because of the competitive intensity when you're talking about 8 or 9, that any given contract will go at least a year. But the likelihood that it will go to, I wouldn't think that's going to be the case because it's always in the best interest of a health plan if anyone of the competitor comes in and has a better offer that they would want to listen, right? But we're fully considering that in our plans and how to think about it and what we plan to do.

Thanks, Jason. Yes, right. Cowen? Sure. Go ahead.

This is Georgi Yordanov from Cowen. So I guess just a follow-up on biosimilar Lucentis. The retinal space is actually quite unique because we already have a biosimilar like product with Avastin. So 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? And 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.

Yes. So the first point I would make is that reformulated Avastin has no label. So it cannot be promoted to the ophthalmologist. Paul, do you want to take the second half of that question?

Yes. I mean it's cheap, right? I mean it's very inexpensive. And so 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 there are some health plans that require the step through, right? And physicians may have to do a trial. But when you go out and you talk to retinal specialists, Avastin is not viewed as efficacious as some of the other branded biosimilar products. And so they will step through that and move on to other VEGF agents and you see that happening routinely in practice. So are we looking to go in at price points that compete with off-label, repackaged Avastin, No. But what we would be looking to do is bring a total value proposition to the retinal specialist practice that will differentiate similarly amongst the others. And then when they're stepping through Avastin and they have to go to the next VEGF brand, that similarly is in that treatment flow and we'll go there. But so if they're not encumbered by using Avastin, we're going to make the -- bring a product presentation and value proposition that similarly should be the first choice of the 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 point out, stratified with reformulated Avastin and up through Lucentis, Eylea and then the newer, more proprietary products at the top. So we think for this point in the market's evolution, Lucentis, 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 is a biosimilar, that would be, of course, a great place to go, and that's something that we think about a lot. But in the short term here, for the next couple of years, we think the Lucentis biosimilars, the ideal place to wedge into that market and then expand, and that's Paul's plan.

Georgi, right? Yes. So we're going to be coming in, in market formation. You mentioned competitive products. So there is an approved biosimilar agent that will be expected based on public filings around the same time as we are midyear this year. So -- but again, we've seen the story play out before with Coherus. We're coming in at market formation, and we expect 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 Isaly 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 of I guess between Pembro and tori. And do you believe that was designed in purposely? What other aspects of tori are in there that differentiate either in a small detail or large detail? And can you prove this in the sense of marketing some of these characteristics to professionals?

I think there's 3 questions there, Sam. Let me try the first part, and then I'll hand it over to Dr. Lavallee. Interestingly, the -- during the molecules genesis and discovery period, the focus was specifically on FG loop, epitope binding moieties. There's a screen for that. The molecule was actually conceived as a second-generation PD-1 with this attended mechanism of action. When we tested it in our in vitro assays when we're looking at, for example, a dozen PD-1s during our selection process, Sanjay's team saw a very, very robust in vitro activity, but we really were uncertain why, frankly, at that period of time. So 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? So to the point, do people think they're different. I've heard both extremes having been in the I-O space since before it was cool. In the early 2000s, like some people like, oh, Pembro is better than Nivo. But the study is all -- I mean, a good PD-1 is a good PD-1, and it's really helping patients, and that's what I can say. 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. So a good PD-1 is a solid PD-1 and an important molecule to have if you're an I-O player is tori different. I think we're seeing that. We're seeing some differentiation features, and the pharmacology is there, right? But we really need to see it in the clinic, to your point. And so we have the 3 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. Are there attributes that we're really looking at, as I've mentioned, 3 features clinically that could matter to a patient depth of response. So 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. So that's what you need for cures. So depth of response is really something that would impact the field to get more CR rates and have had conversations in past lives with the FDA, is that an approvable endpoint because that really is linked to survival and cure and that's something to look at. So we're looking through the clinical data to see if that's there or a big topic in the field is primary resistance and adaptive resistance. So does this internalization feature prevent more adaptive resistance. And those are the types of things we're starting to interrogate both preclinically and clinically. So stay tuned.

2022, I think, is 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 going to be able to promote the differentiation in our science, and this will start with nasopharyngeal carcinoma being the first and only PD-1, if approved for that particular cancer type. So 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 expect to have all that. So it's a great entry point for toripalimab.

I think Doug Tsao has a question. Doug?

Doug Tsao, HCW. Can you just, 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 OBI ? And do you see that as significant? And then another question on the TIGIT. I was just curious, Dr. Lavallee, are there any sort of unique characteristics of your TIGIT similar to what you sort of elucidated with tori? Or is it that you see the differentiation really in tori that you just have a really good TIGIT?

Theresa, why don't you take TIGIT first, then Paul, you can backfill with it.

Yes. So we just announced the licensing and finished the period where we can really do data exchange. So to date, I will say it's a solid digit. 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, you're correct, the pass-through extension is through calendar year 2022. So it's unlikely that there'll be further extension. So we're not baking that into our core planning assumptions. But Neulasta and Neulasta Onpro has lost pass-through extension now for years. And so coming into the market, it will be a level playing field. And so we expect to be able to compete irrespective of the pass-through status for those -- for that share.

Yes. David [ Bildner ], DB Capital. My question is regarding biosimilar education in 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, your entry point, after you launch your product that is not available right now to people who follow this space?

Go ahead, Paul.

Thanks for your question, David. So 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 will be unique to the COLUMBUS-AMD trial because the design and what the FDA required for bond similars in retina, and the design of that trial is different than oncology. So there will be some new and customizable messaging from that. But it's really to level set to build a confidence in biosimilars. And what's new over the last 2 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 therapeutic specialty is broad and that retinal specialists really should expect the same from retinal and ophthalmic biosimilars is in other categories. Regarding weakness, no, it's an interesting question. I don't know if I look at it like that. We look at it and trying to understand why retinal specialists choose the product that they choose and what goes into that, clinical safety as well as the service components and then the practice economics that layer around it because it's a buy and bill. So what we're going into with trying to understand where our sweet spot is going to be relative to the entire set and be able to then meet those needs. And given our track record of managing ASP and delivering a complete value proposition. We're going to be very confident to be able to go in and have an attractive offering versus branded Lucentis. So I hope that answers your question. I didn't know, maybe you wanted something more provocative, but that's how we're looking at it.

We've received a couple of other questions regarding the biosimilar Lucentis program similarly online, and 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. And then another question comes in that retina specialists have -- they 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. But we understand, again, the dynamics of how retinal specialists purchase and billing, and these are factors. So there's price and there's contracts and discounts, and those factor into the total value proposition. So we have a very good understanding of the value proposition for Eylea that's offered to retinal customers. That might be different based on the customer, their size, their volume and other things that go into play. And so we will expect to be able to compete with a similar value proposition that retinal specialists tells us we'll be able to drive adoption. So again, we think we're going to try to capture early, early on as much of that branded Lucentis business and then expand from there on both sides.

We have a question in the front. The gentleman has been very patient. Thank you.

My name is Brian Bamberg, I'm a private investor. 2 questions. The net sales went down from 2020, $475 million to $326 million. I wonder what the cost was. And more important, a separate question. Considering the planned R&D and manufacturing costs, what are the deposit -- what can be expected for 2022 and '23 in terms of net loss or net profit? And of course, what cash do you have if there's a net loss of significance, what cash do you have to support?

Yes. 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. So my personal view is that we are well on our way at about 30% market share at the end of our second year of launch. The reason why we went from the $400 million to $300 million with respect to that was COVID. COVID, as Paul pointed out in his remarks, has been very, very difficult for us. it's very difficult. You can't get your people in front of the doctors, and there's been a whole host of issues there. With respect to the -- 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. And then there's also some additional growth capital that is included in that credit facility that's tied to the launches for -- or excuse me, for the approvals for toripalimab and for CIMERLI. 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 4 expected upcoming launches. And as we said, we expect that we could become profitable again in 2024.

I would only add that we think it's prudent to invest in our business for 4 launches. We did very well in the UDENYCA business with the launch. We had over 300,000 syringes in the cooler at launch, which was about 1/4 of the market. Paul talked about this in his remarks, the corner of the realm here with the HUMIRA market is also going to be supply. So you'll see us investing in manufacturing, so we are able to provide supply. We made substantial investments in supply over the past 2 years, investing about $45 million. So we could provide the market with 10% right out of the gate all the way, we won't get to that in the first year. But in up to 30% of that market. So this is all expensed and then is reflected later and so on. But with 4 launches, we think it's prudent to invest in the business. And as McDavid said, we entered into a facility with Pharmakon. It's a team that understands our business very, very well. And we'll make those investments, and we think our investors will be happy with the results. Yes, we have an additional question.

Mark [indiscernible] of Atlantic family office. A question about Junshi Biosciences. Could you add anything more? You've given some information 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? And Denny, you mentioned about Junshi has not selected yet an EU partner. Could you be part of that adapt adoption process in Europe?

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. Sheng Yao is the President of TopAlliance U.S. We speak to him frequently. I have frequent Zooms and telecoms 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 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. And 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, JPMorgan.

Just one quick one. Can you just -- I think you mentioned it in the remarks. But just on inspection timelines, you have the PDUFA. Just any more color you can provide of how difficult or not it's going to get -- is going to be to get that done before the end of April given some of the dynamics in China right now? .

Yes. Theresa, do you want to address that?

Thanks, Denny. Yes. Now I've always said what makes me really good at regulatory is I worry about everything. So a few sleepless nights with pandemic going on. So we're working with the FDA to schedule those. They are not scheduled at this time. And clearly, with pandemic-related travel restrictions, how do we get around that, and 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 inspection done. So 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 immunotherapy and we anxiously await a solution.

We don't have any further clarity on that. But of course, it will be very forthcoming when you do. But unfortunately, COVID appears to have upticked significantly in Shanghai right about now. But as Theresa said, it's -- the FDA has reflected to us. It's a very, very high priority for them to get this drug approved. Yes, Salim?

Yes, Salim Syed from Mizuho. Just a quick follow-up to that, Theresa. They ruled out virtual inspection then completely or for the...

Yes. I mean I think we all wait for April 30 to see what the exact verbiage is, right? So it's a live game. So I don't -- I would anticipate they need an inspection. This facility has not been inspected.

Yes. I would say they have -- they're really trying to -- the FDA is a very difficult job. They actually did another inspection for us with CIMERLI in Europe. They got that done. That's right close to the water. So I give the FDA really high marks 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 -- the really tough job. So we're fully supportive. Yes?

Miles [ Lewis ] [indiscernible] Capital. To kind of piggyback on the relationship with Junshi. Looking at the operating expenses from '22 to '26, as far as any license fees or milestone payments, do you see that having any significant impact on the operating expenses during those years?

So 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 [indiscernible], and that's actually not -- 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, and 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. And I'd be happy to see you again next year in interim. We'll see you at the conferences. Thanks, guys.