Good evening. Welcome to the 43rd Annual JP Morgan Healthcare Conference. My name is Michelle Yap. I'm an associate with the Healthcare Investment Banking team. It is my great pleasure to introduce Coherus BioSciences, who had a tremendous 2024 as they transitioned from a pure-play biosimilar to an immuno-oncology company. With that, please welcome CEO and Chairman Denny.
Thank you. Thank you very much. Thank you very much. I've been happy to be here again, of course, at the conference. I want to thank JP Morgan for the long-time relationship with the bank and for all their assistance and the opportunity to talk to you today. Let me first surprise you, of course, with the forward-looking statements in small print, very accordingly, directing you to the company's SEC filings for further information about the risks surrounding the products, the markets, and so on. And further pointing out that there is a proxy process underway, which will be filed, and you should read all these very, very, very carefully. With that, let me just cover the agenda briefly. So first, we'll talk a little bit about the corporate overview and the strategy.
As Michelle said, we are very happy to be with you here today, having now in the process of completing the company's repositioning to immuno-oncology from biosimilars. I'll spend a little time overviewing that for you, and then I'll talk a little bit about LOQTORZI, our foundational asset that we licensed from our friends at Junshi in 2021 and announced in January that year at this very conference. My good colleague and my Chief Development Officer, Dr. Theresa LaVallee, will then walk you through our pipeline, our innovative pipeline, and the combinations with LOQTORZI. We have some extraordinarily promising assets that we are now developing through phase I and II, which have data readouts over the next 18 months, which will be very, very exciting and, I think, very accretive to shareholder value. Then I'll finish up with two further points.
One, of course, the commercial oncology opportunity, and then lastly, financial results from Q4 and the outlook. So first, with the overview, I am very proud to say Coherus is now a fully integrated commercial stage innovative oncology company. I'll talk in a moment about our need and our belief that you need to have a proprietary PD-1, but we have a very, very strong team, the expertise to develop drugs, the expertise to bring them to the market, a very strong pipeline, and then a track record of very successful marketing in the oncology space in Medicare Part B. So as I said before, we are very proud of our progress in 2024. As you know, we went into the year fairly leveraged.
We had about $480 million in debt, market cap about $150 million, and we are now in the process of concluding or announcing three transactions, one for CIMERLI, one for YUSIMRI, the Humira biosimilar, and lastly, for UDENYCA for some $800 million in non-dilutive capital. This positions us very well for growth in 2025 and beyond to 2030. First of all, with LOQTORZI, which is on the market and growing, has an enviable position in nasopharyngeal cancer, where it is the only approved therapy. A strong pipeline, which Dr. Lavallee will apprise you of. And lastly, a strong balance sheet. We expect to do very well here in Q1. We'll report to you our results here at the end of Q4, but a strong balance sheet, streamlined operations, and I think things moving really very much in the right direction.
LOQTORZI is the building block, and as I said, we brought that into the company in 2021 and LOQTORZI has a very unique epitope, and that really gives it a very unique differentiated position in the PD-1 market and makes it an ideal combination partner for our innovative pipeline. Those pipeline products in combination with LOQTORZI aimed at extending patient survival and this is the mission of my company, is to extend the survival of cancer patients. In doing so, we are addressing a significant market opportunity of some $15 billion, and that is just the trials and the therapeutic focus that we have underway today, which I show you here.
The elegant thing about the way we are proceeding with our pipeline is when you sell a vial of your innovative drug, you also sell a vial of LOQTORZI across all of these indications, by and large developed internally by Coherus, but also developed by our partners, for example, Junshi and Inovio, where we simply supply to our parallel lab at cost, and our partners then do the phase III pivotal clinical trials. Now, let me just talk about LOQTORZI before I turn things over to Theresa very briefly. LOQTORZI, the very interesting thing about it is when it was developed and it was screened, it was screened against the FG loop on PD-1. This is different than other moieties such as Pembro and Nivo, which bind at various places and, of course, have efficacy. But toripalimab have been shown to have disproportionately strong T cell activation.
There's a paper here we can refer you to, and you can take a look. This is a function of two things: A, the binding epitope, but B, the very strong affinity for PD-1, which is 10x that of these other competing molecules. The differentiated benefits are exemplified here, and what you see on the left panel here is PD-L1 high patients, and you can see the efficacy here is the JUPITER-06 study, and below, you see a similar study with Pembro. The difference, though, is in the upper right-hand panel where you see that this efficacy was maintained. The hazard ratio 0.61 was maintained there with these. These are in the low PD-L1 patients, and you look below, Pembro was not. This makes toward toripalimab an ideal combination product.
This difference, this maintenance of efficacy in combination with chemotherapy is demonstrated both in nasopharyngeal cancer, but also in non-small cell lung cancer. We are, of course, very excited about that. A lot of people have asked me, you know, why are you developing another PD-1? You know, what for? There's nine on the market. PD-1s are successful, but there are still significant advances to be made for the benefit of patients. A minority of patients benefit from PD-1s. Further, there is a lack of durability and response. These patients, then at some point, will then progress, and at that point, they progress, they will go on to further and further lines of therapy. Also, there's the issue, of course, is toxicity. We are focused as a company on IO therapies that improve response rates and extend durability. Here's our pipeline. These are all combination assets.
Here's LOQTORZI at the top in first- and second-line nasopharyngeal cancer. It was launched last year. At the end of my talk, I'll tell you a little bit about how that launch is going. We are very pleased with it. It's on the trajectory that we had hoped, and we have a very good line of sight towards the three potential segments where that gets addressed. Theresa will talk to you a little bit about casdozokitug, our IL-27 inhibitor, and CHS-114, our anti-CCR8. The first in liver and lung, and the second in solid tumors in head and neck, and then in gastric. And with that, I'll hand it over to Dr. LaVallee.
Thanks, Denny, so to start, talking about how we're developing toripalimab beyond NPC is with our innovative pipeline, and casdozokitug is an IL-27 antagonist. While it's been validated and appreciated that inhibiting cytokines in inflammatory diseases can rebalance the immune system, casdozokitug is the first antibody to show in an oncology patient that by inhibiting a cytokine, we see immune activation, we have a safety profile that lends itself for combination, and we see monotherapy responses in tumor types that the preclinical models predicted should be sensitive to inhibiting IL-27, giving us a very strong line of sight to proof of concept, so I'll walk you through the data to support these statements, so the mechanism of action for IL-27 is it's secreted from myeloid cells, like tumor-associated macrophages, and it dampens the immune response.
It was first discovered through knockout animals that looking at infectious disease, and what they found was that the animals died, but when they opened them up, that they were devoid of parasites, but they died of immune pathology due to an overactive immune system in liver, lung, and brain. So IL-27 will upregulate checkpoint inhibitors on T cells and dampen cytokine secretion such as interferon gamma and TNF, showing a lack of immune activation, as well as dampening NK cell cytotoxicity. So turning off the two immune cells that are critical for killing the tumor. In preclinical models, looking at anti-tumor activity, we saw some very interesting results, and that we didn't see activity in ectopic, your standard sub-Q mouse tumor model, but we did see activity when the tumor was present in lung or liver.
Again, following the genetic model and really showing there's some specificity to IL-27 in these tissue types. Additionally, looking across solid tumors, we have high expression of IL-27 in lung cancer, and the highest levels of IL-27 transcript are actually found in HCC. So in phase I, we see immune activation in a dose-dependent fashion. So looking on the right-hand side, the heat map, what you'll see is in the dose escalation at three mg per kg casdozokitug, that the red shows that IL-27 signaling is not inhibited, and we do not see immune cell activation. At 10 and 20 mg per kg, we have complete shutdown of the IL-27 signaling and activation of NK cells and T cells, as well as transcription upregulation for interferon gamma.
On the left side, you see the protein showing that important interferon gamma immune cytokine is elevated in cancer patients after dosing with casdozokitug over the course of the dosing cycle. We see monotherapy responses in lung cancer from the phase I dose escalation shown in red bars, and then an expansion phase that evaluated the 10 mg/kg dose as single agent. What was really interesting is that we found two partial responses, particularly in squamous cell carcinoma. Both of these patients were PD-1 experienced and had PD-L1 low or zero tumors. Tumor types that should be not as responsive to PD-1 treatment and seeing that response in two of nine squamous cell carcinoma patients was really exciting.
We currently have a study open where we're looking at second line and greater non-small cell lung cancer in combination with toripalimab, given the nice safety profile that's really lent itself for combination. The other study that we reported on last year at ASCO GI was our first line HCC study. The initial study was done on top of standard of care, atezolizumab and bevacizumab, and what was observed was an improvement in efficacy with an overall response rate of 38% and a median PFS of 8.1 months, which is better than atezo-bev. But importantly, we've also seen a depth of response, and over time, the data has matured to show an improvement in benefit. We licensed this asset from Surface Oncology, and at the time of June of 2023, we announced a 27% ORR compared to the November data cutoff of 38%.
In June of 2023, there were no CRs. In November data cutoff, we have three CRs, and next week at ASCO GI, we'll be presenting the final data set of this study in first line HCC. Importantly, there were no new safety signals on top of atezo-bev, so an important aspect for liver cancer, a disease that has treatments that have a lot of toxicity when you think of sorafenib and other drugs like that that have really burdened these patients. Additionally, activity was observed in viral and non-viral patients and across etiologies. So we're very excited about this, given the strong preclinical data, the high expression of IL-27, and this efficacy observed, so proof of concept here.
And now we have a study open that we plan to have enrollment done this year in a randomized control study looking at casdozokitug plus toripalimab and bevacizumab, building off of the positive phase III study that Junshi Biosciences announced, HepaTorch, where they compared toripalimab plus bevacizumab to sorafenib, showing a positive ORR, PFS, and OS, and that study is currently under review in China for approval. And so the FDA did take a change in stance on single country data in the United States in terms of applying for license, but they have repeatedly said that it counts for contribution of component.
This is really important because toripalimab + bevacizumab has established activity in the disease, and this study with the randomized study to look at toripalimab + bevacizumab versus casdozokitug and toripalimab + bevacizumab will really set up for design of a pivotal study and enable discussions with regulators about the activity. We do have two dose levels of casdozokitug in the study given Project Optimus. While we have beautiful immune activation, all of our activity was seen at 10 mg per kg. We had no safety issues up to 20 mg per kg. The FDA felt that we really needed to show that that dose in more patients didn't add any efficacy. We will look at both doses in this study to then align on a recommended phase III dose for a pivotal study as these results read out. This has orphan drug designation in the United States.
Moving on to another immune suppressive cell that has been well characterized to dampen immunotherapy is the T regulatory cell. CCR8 is an answer to a problem. The first box on the top has a puzzle piece. Targeting T regulatory cells is not a novel concept. It's been tried for decades. The issue with a lot of the expression of targets that have been looked at, like IL-2 receptor, CTLA-4, CCR4, that they're broadly expressed on T regulatory cells, an important cell type for homeostasis. If you really deplete T reg cells in a human, you'll have autoimmune disease. We need that tissue tumor specificity. Through lots of multi-omic studies, it has been found that CCR8 is preferentially upregulated on tumor resident T regulatory cells.
Additionally, the other problem with targeting T regulatory cells is it is a CD4 cell, and many of the targets that I mentioned previously are also expressed on normal lymphocytes. The CD4s and CD8 cells, those are the cells you need to kill the tumor. So you don't want to cause autoimmunity and take out your effector cells, whereas CCR8 really does seem to have that preferential expression. And the idea is by removing the immune suppressive cell, we don't think that's enough to activate anti-tumor immunity, but it really opens up the tumor microenvironment when used particularly in combination with PD1 to turn cold tumors hot by driving CD8s into those tumors and activating the anti-tumor immunity. And for this, you know all the elegant science you can look at, this one's really simple. You bind and kill.
It's a target. It's an afucosylated antibody. Go after tumor types where there's a high density of T reg cells, take them out and turn on that anti-tumor immunity. What I'll show you is in our disease characterization that, of course, hot tumors, warm tumors do have this. Denny mentioned that while PD-1 has revolutionized cancer care, it's still a minority of patients that benefit, including in hot tumors. It's about 30%. Some of those other ones could be because of these immune suppressive cells that would really open up a broader patient population. Equally exciting would be bringing immunotherapy to patients that have been underserved by immunotherapy, such as ovarian cancer, colorectal cancer.
So, CCR8 is one of these proteins that's called a GPCR, a G protein-coupled receptor, goes through the membrane seven times, but there's not a lot of real estate on the outside of the cell to have an antibody. And that's why the majority of drugs against GPCRs are small molecules, because it's notoriously difficult to generate a selective antibody against a GPCR. So, in the initial screen to find 114, getting to lead identification, it was the only antibody that was shown to exclusively bind CCR8. So, mAb2, 3, 4, 5 were other candidates, drug candidates for selection that showed that one of them bound up to 20 different proteins, and this is screening across 5,000 proteins. So, 114 is a really attractive selective potent molecule. There are now 15 CCR8 antibodies in the clinic the last time I counted.
A couple of years ago, we did screen three of those and found all of those antibodies have off-target binding. So when I look at things like J chains, because you say, well, why do you care if it binds something besides CCR8? One, I always worry about PK if you're going to bind something off-target, but also toxicity. So J chain, I would worry a lot about gut tox since it's so important in transit in the gut. So we'll have to watch and see how those data report out. So when we look across tumors, like who to treat with the CCR8 targeted antibody, first at the top left of the slide, what you'll see is when we say, what's the density in the tumor? Where are CCR8- positive Tregs highly abundant? And you can see things like cervical, head and neck, gastric, CRC, esophageal, breast.
There's a lot of different solid tumor types that have an abundance of CCR8 positive T regs. That sets you up for tumor types of interest. The next question is, not every T reg expresses CCR8. What's the prevalence of CCR8 positive T regs in the T reg population? That's the graph at the bottom left, which if you look, gastric, cervical, head and neck cancer have over 80% of the T regs are CCR8 positive. You can really get rid of that immune suppressive cell in those tumor types. Other tumors like lung cancer, ovarian, colorectal have about 50%. We're really trying to interrogate in our clinical studies what's the level of CCR8 positive T regs that really can balance, tip that immune suppression to block PD-1's activity.
We were very pleased at ASCO this year when LaNova Medicines presented data with their CCR8 antibody in combination with toripalimab and showed a 36% response rate in gastric cancer, really giving proof of concept that this high prevalence is driving immunosuppression in that tumor type. And so our phase I that we presented the dose escalation portion of the study at ASCO this past year looked across dose levels. We were excited to see a nice safety profile with no dose limiting toxicities up to 1,200 mg. And then we've now gone on to expand at two pharmacologically active doses to really do dose exploration for a recommended phase II dose in head and neck cancer patients, both as single agent treatment and then rapidly moving into combination with toripalimab because we think that's really where the efficacy is going to be seen.
So also in this phase I study, very important besides the safety aspects of it, we see immediate and sustained depletion of CCR8-positive Treg cells in the periphery at all dose levels tested, showing the potency of this molecule. And when we look on the right-hand side, that does not deplete all Tregs consistent with the safety profile we've seen, really showing that selectivity. And we also have shown that the CD4 and the CD8s are unaffected. There's no change in the circulating levels, really proving the hypothesis that really took this molecule into the clinic. Looking in the phase I dose escalation with a variety of highly refractory solid tumor patients, we did see disease control rate, but as I mentioned, just removing immune suppressive cell, we do not believe we'll have robust single agent activity.
So still see this as an exciting opportunity to go forward. And now we have the head and neck study, and we look in the first half of this year report on data on, I showed you peripheral Treg depletion. We want to look at paired biopsies for intratumoral Treg depletion at the pharmacologically active doses, as well as safety and efficacy as the single agent and combination in head and neck cancer. And we are in the process of opening a gastric cancer study looking at the combination of 114 and toripalimab. So very excited about this program and advancing it with data readouts for early next year.
Thank you, Theresa. Let me now discuss the commercial oncology opportunity both for LOQTORZI, toripalimab, and pipeline. So LOQTORZI is establishing a new standard of care in nasopharyngeal cancer. It is the only FDA-approved treatment for NPC across all lines of therapy. This rare cancer occurs at the back of the nasopharynx. We have category one designation for NCCN, both for the first line and preferred NCCN for second line. We are busy this year with our commercial team establishing ourselves as the standard of care across this indication holistically. LOQTORZI treatment is about 2,000 patients per year, and overall the market opportunity here is about $150 million-$200 million. And I'll address just how quick that ramp will go and how we think we'll hit that in just a moment. We're very pleased that NCCN has revised the guidelines and positioned LOQTORZI at the very top. All other lines of therapy, all other modalities, all other agents are below LOQTORZI.
This is a reflection really of the strength of the data and how well LOQTORZI works in this indication in combination with chemotherapy. The commercial impact for this is significant. First of all, of course, when this occurred last month, and we are busy updating all our promotional materials and our commercial team will be busy educating physicians and payers about this. We intend to leverage these guidelines across to implement these changes, and particularly with respect to the pathways across the institutions. I would point out that this is very unusual for NCCN to make an out-of-cycle change on the guidelines. Instead of waiting, for example, until April, they did this last month. And again, this is a reflection of the strength of the data and the fact that the KOLs have so enthusiastically endorsed this product. There are three segments to the NPC population which we are addressing.
The first is recurrent and locally advanced. This is about a third of the patients in which they should get chemo and then PD-1. The second is the metastatic first line, similarly sized, and third, metastatic second line, but drug treatable. As I indicated, the market's about $150 million-$200 million, and this is the typical treatment paradigm for these patients. Now, with respect to the revenue ramp, which is of interest to us all, of course, the revenue impact for the first two segments is quite high. That is because the patient benefit is also quite high because the patients are on these drugs for a long time. We expect the doctors to keep these patients on therapy as long as they do not progress. The last line of therapy, of course, is a little different.
In the last line, the metastatic second line, these patients are further along, and of course, those patients will get shorter treatment durations. We launched this product in 2024, and we believe that we will ramp this product up, hitting peak sales somewhere around maybe four years out, plus or minus, but these patients will stay on therapy, and of course, they will accumulate and stay on. And we're busy now identifying all these patients as we go forward. Now, let me double-click on this slide. It's a little bit busy, so I'll walk you through it. And this is sort of a reflection of where we are going with the combination pipeline that Dr. Lavallee discussed just a moment. Now, in the upper part of this, you see these blue circles. These are potential CCR8 patients, right?
In the green, you see the potential IL-27 casdozokitug patients. Across the bottom, what you see is the patient population. As you can see with the circles that have a red line around them, these are the subjects of our current investigation: head and neck cancer, gastric, non-small cell, and of course, hepatic HCC. But I would also point out in the lighter circles, what you see like circle 10, which is colorectal cancer or pancreatic cancer, ovarian. These are so-called treatment deserts where there is not an approved PD-1 therapy in which these products can unlock the therapeutic potential of PD-1s by their actions on IL-27 and CCR8s and the T regs and so forth.
These, I think, will give us a lot of ability to pursue these indications, and over the coming years, you'll see us go forward in all of these, in many of them. They stack up like this, and one of the very unique things about our commercialization strategies, I indicated earlier in my talk, is that our ambition is that when you sell a vial of these agents, you also sell a vial of toripalimab. They go hand in hand, and they work synergistically together. What we've done here is break this out for you. You can see how these indications built. This is a $15 billion opportunity, and this is only taking into account the indications that we are pursuing so far. Now, let me just go forward here and talk a little bit about our financial results and the outlook.
We are very pleased with 2024, and we appreciate the patience of our investors as we work through deleveraging our balance sheet and a number of other things. The total year expected revenues are about $255-$260. We're going to do a few things to reconcile here at the end, so we feel this is a tight range for you, which is about $49-$54 for Q4. We're very proud of this. This includes $42 million-$47 million of UDENYCA. As you recall, UDENYCA underwent, very unfortunately, a supply interruption. There were limited days of sales in Q4. However, when we did come back on the market, there was significant enthusiasm for this product. The Coherus UDENYCA on-body device has seen overwhelming demand in the market.
It is viewed as a superior device in a number of ways by the market, and we were partway through adoption in some very large institutions when the supply interruption occurred. I'm pleased to say that those customers waited for us. They appreciated our communication with them, and when we had that product back and available, they are now turning all those sites back on. LOQTORZI is about $7 million-$8 million for Q4, continues to grow. You will see us leveraging the NCCN guidelines through educational materials, getting in the pathways to put LOQTORZI on the ramp as we go forward over the next three, four, five years. In terms of cash, we ended the year with about $125 million in cash, again, very strong position.
As you know, we also announced the transaction to divest ourselves of UDENYCA so we could fully focus on immuno-oncology for $558 million. Over the next two years, you'll see a number of readouts as we advance casdozokitug and our CCR8 agent CHS-114 throughout the clinic. Those are cited here. You see the milestones and the data catalysts. I won't go through this whole slide as Theresa just reviewed it, but just to summarize it for you, through 2025, we will turn over data cards. We have a key meeting, ASCO GI coming up, but first half of 2026, we'll see the advent of some very nice data readouts, both with casdozokitug and CHS-114. My last slide, just to summarize then, we have now assembled a fully integrated commercial stage innovative oncology company. We have completed our movement from biosimilars to innovative oncology.
We're very pleased that we have a PD-1 that has differentiated activity in low PD-L1 states with growing revenue. We intend to combine it with our pipelines you see in the upper right, as Dr. Lavallee reviewed. We have a strong balance sheet addressing our former debt issues very holistically, streamlining our operations. Let me just take a moment to talk about our pipeline in the lower right, which I didn't have a slide on this in the deck. Perhaps it's not so well communicated that we have global rights to our assets, to CHS-114 and to casdozokitug. As we develop data throughout the next 12 and 18 months, our business development team will start to look for partnerships ex-U.S. Those partnerships will do two key things for us.
Of course, they will allow us to monetize rights for those products ex-U.S, which is favorable, but also we have development partners who will share the global strategies and the global costs for our pivotal trials, and we expect to have partners in China and in Europe while we retain rights to the U.S. So thank you very much for that, and we're happy to take any questions that you might have on the company. Thank you, Dr. LaVallee. We'd like to open up the floor for questions. If not, we can proceed to questions that came in online. Okay. After the strategic moves at Coherus last year, how should investors think about the focus for 2025 for the company? What are some of the potential upside drivers that we should keep an eye out for? We think we have a very exciting story now for 2025.
Aside from all the monetary benefits, just focusing on immuno-oncology with such a high potential pipeline, we think, is really going to accrue value. As Theresa talked about, the studies are, I think, coming along very, very nicely. We'll have continued data cards turned over between the last half of this year and the first half of 2026. And on the other hand, we'll also have LOQTORZI on a very nice ramp-up given the NCCN guidelines and some of the traction that we're getting in the NPC market. Thank you. Questions from the audience? Okay. Perhaps one final last question. What do you expect to see in 2025 that will give you some confidence towards the $150 million-$200 million peak sales that you have guided? We believe the $150 million-$200 million guidance is very achievable. It's only a question of how quickly it is achieved, of course.
I think that the most relevant piece of evidence is that the NCCN guidelines were revised out of cycle, and that's really unusual for NCCN. Normally, they would have waited until April. It is a subset, of course, of head and neck, but we had over 100 KOLs who we communicate with, and the enthusiasm that the KOLs had that was driven by the strength of the data, the efficacy and the safety data, which was developed by Junshi, was really, really remarkable, and to have them go ahead and change the guidelines for us to make sure that patients get the right therapy, I think, is really significant, making sure these patients aren't simply on chemotherapy or they're not on another IO agent, another PD1, which either doesn't have data or has negative data.
So I think this is really promising, and this gives us a fair degree of confidence. The second thing that I would say, though, is that our commercial team in oncology is well proven. Our ability really to drive sales in the biosimilar space in buy-and-bill, Medicare Part B, and the medical benefit, I think, was quite renowned, and we're just applying that now in the nasopharyngeal space.
Okay. I think we can wrap up. Thank you so much, Denny.
Thank you. Thank you very much.