Welcome to the UBS virtual event. David Dai, you may begin.
Great, thank you, operator. Hi, everyone. I'm David Dai, one of the biotech analysts here at UBS. Thanks for joining our inaugural virtual oncology day today. We continue our session with Coherus BioSciences. It's our great pleasure to welcome Denny Lanfear, Chief Executive Officer, Theresa Lavallee, Chief Development and Scientific Officer, and Rosh Dias, Chief Medical Officer. Thank you for joining us.
Thanks for having us.
Thank you for having us, David.
Excellent. Team, you know, maybe just start things off. Can you introduce yourself and provide a high-level overview of Coherus, including your pipeline as well as your strategy?
Great. Thank you. David, first of all, let me thank you and UBS for having Coherus BioSciences on today to talk about our company. Coherus BioSciences is a company that is focused on enhancing the lives of cancer patients and delivering a step change in survival. We believe we have the right strategy to drive growth and to accomplish that. Our strategy really is in three distinct pieces that I'll outline for you. The first is the drugs that we have on the market and the drugs that we are bringing to the market. That includes LOQTORZI, our next-generation PD-1 inhibitor, as well as CHS-114, which is our anti-CCR8 antibody T-reg depletor, and casdozokitug, an anti-IL-27 antibody. The second thing to focus on with respect to Coherus BioSciences is the data that we'll be delivering with our development programs that Dr. Lavallee and Dr.
Dias will review for you, coming out around mid-2026. This includes data with CHS-114 in head and neck cancer, a place where we've been quite active, also with CHS-114 in gastric tumors, esophageal, and colorectal, a program that we've recently initiated. We also are very active in liver cancer with casdozokitug, anti-IL-27 antibody, where we've shown some excellent results that Dr. Dias will review for you. Lastly, investors should watch out for deals over the next 6, 12, and 18 months. We have full rights to our product pipeline for both the anti-IL-27 antibody and our anti-CCR8 antibody, and we are seeking ex-US partners to provide for us a validation of the pipeline, but also monetary support for the development programs and cost sharing. We are very active in the U.S. with LOQTORZI in combination with other products. We'll outline that strategy for you in just a moment. Dr.
Lavallee is the architect. Of course, non-PD-1 combinations also. At a 50,000 ft level, I think that Coherus BioSciences has been very strong with its execution across a number of key parts: development, commercial, and with deals. We've established a strong financial track record regarding our sales, our ability to manage our balance sheet, and now our deal revenue. With that, I'm happy to talk a little bit more at a granular level about some of the programs and some of the things that are happening over the next 12 months, which would be interesting for investors.
Got it. Thanks for that overview, Denny. Let's start talking about, you said the lead program, which is LOQTORZI, which is now approved in frontline and second-line nasopharyngeal carcinoma. Maybe you can just level set some of the investors around this PD-1 asset. Can you talk about some differentiation of this asset versus other anti-PD-1 in terms of binding affinity, combinability, et cetera, et cetera?
Yeah, Dr. Lavallee will take that one. Theresa, can you talk a little bit about toripalimab LOQTORZI?
Sure. LOQTORZI is a next-generation PD-1 based on its higher binding affinity. It's more than tenfold higher binding affinity than other marketed PD-1s. Additionally, it has a unique epitope binding the FG loop. Both potency and where it binds can add increased activity. In vitro assays, when we look preclinically, head-to-head with Pembro, we see in a number of assays statistically significantly higher T-cell activation. Clinically, we've seen differentiation in three phase III studies when LOQTORZI is used in combination with chemotherapy. We see activity very similar in PD-L1 high and PD-L1 low. That's very different from the other molecules. In fact, in esophageal squamous cell carcinoma, the other PD-1s, Pembro, Nivo, Tizi, do not have approval in PD-L1 low or zero. In Europe, LOQTORZI was approved based on the Jupiter-6 study, irrespective of PD-L1 status.
We think that really sets our combination strategy up well with our pipeline as well as with others, as you'll go against standard of care with PD-1. Our PD-1 will start at least here, if not here. The combination to get a hazard ratio should increase probability of success.
Got it. That's really helpful. Since it's approved in 2023, we've seen a few quarters of growth. Most recently, in the last quarter, you generated about $10 million in revenue. Can you just help us understand some of the adoption trends you've seen across different segments, including academic settings and also community settings?
Sure. LOQTORZI is the only launch product in the nasopharyngeal space. We have preferred positioning on NCCN guidelines in frontline. We're happy with last quarter's results. We had a very significant increase over the previous quarter. I would point out that the dynamics of the market, though, are that while the academics are early adopters and very cognizant of NCCN, the community setting comprises about 50% of the overall sales. Now, if you're a community oncologist, you see one of these patients maybe once a year, perhaps you see two patients a year. Trying to get mind share is a little challenging with respect to the community oncologist. It's an area where we're sharply focused. However, for guidance, I would say that between now and, say, mid-2028, we expect this market to grow substantially and to reach RP. Overall, the nasopharyngeal market is about a $250 million market.
We expect to land somewhere between $150 million and $200 million peak sales by mid-2028. We expect something along the order of a 10% - 15% growth per quarter, which is a sort of a linear ramp to get us there. We don't expect any strong inflection points along the way, given the dynamics that the patients only show up infrequently, and there's about 2,000 patients in the U.S. As the patients show up, though, I think we're doing an excellent job converting those physicians. We find that they are highly receptive to understanding the compelling data with LOQTORZI.
Understood. What about some of the labor expansion strategies you're planning to do for LOQTORZI over the next few years? How much do you think this is going to add to the top-line revenue?
We are involved in a number of collaborative agreements with others with respect to LOQTORZI. Our stated strategy is that we provide LOQTORZI to others who are moving forward with their clinical trials with innovative moieties. We have partners who are in pivotals. We have partners who are in early phase. We do not do cost sharing on clinical trials. However, when those clinical trials are successful and those partners earn BLA labels for their drug, they will also, at the same time, get a label for LOQTORZI. This is a very low-cost and effective strategy to go forward. I think it's one of the differentiating strategic opportunities that you see with Coherus. We are very much a collaborative, combination-focused company. We believe that is the opportunity, really, to provide the step change in patient survival. With regards to quantitation of that, I think those numbers are all quite large.
There's a number of indications that we are pursuing, for example, with our own products in combination with LOQTORZI, which is the other leg of our combination strategy. Our products, our CHS-114 product, our anti-CCR8 T-reg depletor, as well as casdozokitug, our anti-IL-27, are both being developed in conjunction with LOQTORZI. This underlies really the overarching LOQTORZI strategy. It is differentiated. It is next-gen, but we see it as both a revenue multiplier in combination with these other products and a revenue generator with respect to the NPC market.
Got it. I'd love to hear a little bit more about the combination strategies. We've seen a lot of anti-PD-1 programs combining with ADCs, given that this might give rise to a deeper response or a durable response as well. What are your thoughts around the combinability of LOQTORZI with, let's say, either your own moieties like CHS-114 or other moieties? Is it safe enough to actually be able to combine with other therapies in development?
Dr. Lavallee, do you want to offer a few comments?
Yeah, a really important question. Over a couple dozen studies, the combinability has been published for Tori with chemotherapy, other IO agents, TKIs. We're very excited to see that at the ESMO Presidential Symposium later this month, Tori plus the RC48, the HER2 ADC, partnered with Pfizer and Remegen, will be in that as a world presentation. Phase III data in bladder cancer. We've seen really good combinability as a PD-1 inhibitor would be expected and look forward to continuing to develop that.
Got it. Great. Let's switch gears and turn to the pipeline programs. Let's first talk about the CHS-114, which is a very interesting product, a program, a very interesting mechanism for CCR8, targeting T-regs or CCR8 positive T-regs. Maybe you just give us an understanding of this target. Why is this a compelling target? Talk a little bit more about the mechanism of action for cancer treatment here.
Yeah, so regulatory T cells are the immune suppressive cells. The immune system's about homeostasis. We often see the teeter-totter with, is it activated? Is it off? The regulatory T cells are one of the primary mechanisms to keep balance within the immune system. In fact, they're so important approaches to deplete them in oncology have really been fraught with toxicity, autoimmunity. While it's well understood and well characterized that the presence of regulatory T cells in tumors leads to poor prognosis, resistance broadly to therapies, chemotherapy, radiation, PD-1 inhibitors, they haven't been able to be targeted because of broad depletion. The missing puzzle piece has been a target on the regulatory T cells that would be preferentially expressed in tumors.
That was identified as CCR8 through single-cell sequencing technology, characterizing the regulatory T cells in tumors, finding that CCR8 was highly upregulated and highly prevalent across a broad range of solid tumors. The mechanism of action of CHS-114 is very simple. It's a targeted therapy. It binds and kills. It's an ADCC-enhanced, so a souped-up antibody. When it binds the target, it will kill the cell. It depletes the regulatory T cells, getting rid of that suppressive immune population within the tumor to allow the tumor now to stop evading the immune system.
I would just add to Dr. Lavallee's remarks. We see this as potentially an emerging mega-class of products. It is long sought and a bit of a holy grail in immuno-oncology to be able to turn whole tumors hot and make them subject to the immune system. By impacting this balance that Dr. Lavallee talked about, there is this potential. There is data being generated by a number of teams in various parts on this. The validation of this target is well underway. We feel that strategically, we're very well positioned, as CHS-114 is highly selective. We believe potentially a best-in-class asset in this emerging superclass.
Got it. Maybe you can share some of the clinical data we've seen so far in head and neck cancer, gastric, and esophageal cancers. It helps us understand some of the things we've seen so far.
Sure, Dr. Dias?
Yeah, thanks, David. Given its mechanism of action, I think CHS-114 has potential utility across a multitude of tumor types. In dose escalation, in data that we presented at ASCO 2024, last year, we did show safety with no DLTs all the way up to dose level 7. We showed a pretty good disease control rate in very late-line patients. Specific to head and neck, which is our most advanced tumor type, we presented data at AACR just a few months ago, which showed basically in the combination of LOQTORZI and CHS-114 in seven subjects, out of seven subjects in total, we showed one partial response. The interesting thing about this partial response was it was actually in a very late-line patient, a fourth-line patient who had previously failed a prior PD-1, failed a prior taxane, failed a prior TKI as well. That's very encouraging as we move forward.
Our current study in head and neck is looking at a 40-patient second-line specific combination strategy, looking at two biologically active doses of CHS-114 in combination with LOQTORZI. That is an ongoing study right now. We anticipate results probably around the middle of next year. The other programs you mentioned just very briefly as well, we're also looking at second-line gastric. This is in many ways a somewhat de-risked program because there is proof of concept, proof of principle in terms of the CCR8 class in combination with LOQTORZI specifically. We have an ongoing study in second-line specifically looking at, again, two biologically active doses of CHS-114 in combination with LOQTORZI, also ongoing. We're also looking at esophageal squamous cell carcinoma, both first-line as well as second-line.
This builds upon some of the data that you heard earlier from Theresa in terms of the activity of LOQTORZI irrespective of PD-L1 status specifically, and particularly actually in esophageal squamous cell as well. That's also ongoing. We've also, as Denny mentioned earlier, opened a colorectal study as well, initially starting in fourth line. The intention will be initially to focus on non-liver mets, moving forwards quickly into liver mets, and then also quickly into first-line as well. I think there's potential broad utility across multiple different modalities and tumor types here.
Do you guys have a favorite among the four indications that you're pursuing?
I think we love each of our children the same. I think there's potential across all of them. As we kind of talked about all three, all four of them, there's good rationale for each of those specific tumor types. I think we're certainly excited about all four programs.
I would note, though, that CRC is particularly devastating. First-line CRC is chemotherapy, if you can believe that. As evidenced by the recent JAMA article, this is an indication which is expanding. It's reaching younger and younger patients globally, not just in the U.S. I think, for me, it's the opportunity really to have real significant impact on patients' lives.
Understood, understood. Just looking at the sort of the competitive landscape for CCR8, there's a few competitors, especially from big pharmas. I'm curious, in terms of what do you think are some key differentiations of CHS-114 to be able to differentiate from other assets in development?
Yeah, so CCR8 is a GPCR, which, while it's one of the most successful protein targets for drugs, a third of all approved drugs target GPCRs, there's only a handful of antibodies. That's because the structure of a GPCR makes it notoriously difficult to get a selective antibody. CHS-114 is the only known selective antibody. We screened it against over 5,000 extracellular proteins, so the human proteome, and found the only protein that bound is CCR8. Characterizing some of the competitors, we found off-target binding, things like J-chain, which is highly expressed in the gut. When I see that, I would worry about gut toxicity, which having off-target binding bringing toxicity to your program can really affect the combination strategy, the development, having predictability. The selectivity is a key differentiation. It also has high potency. As I told you, the mechanism is bind and kill.
You'll hear some talking about ligand binding, inhibiting signaling. What I say is dead cells don't signal. Blocking the signaling is, if anything, you could set up competition with the ligand for binding. The last piece is not all of the antibodies are ADCC enhanced. That potency and the killing fraction. Really setting it up, I think, as a pharmacologically well-designed molecule that we've seen clinically, just beautiful T-reg depletion, a great safety profile, and early clinical responses in the tumor types we expect them. Super excited to look for next year's data sets.
Yeah, great. This is really helpful. Let's focus on that top-line data readout in the first half of next year with respect to the 40-patient data in combination with Tori. Maybe just, Dr. Dias, I'm wondering if you can just help us understand some of the data expectations heading to this readout and what are some of the benchmarks we should be watching for for this data readout here.
Yeah, thanks, David. I think as with most things in oncology, and in new oncology specifically, we are looking at the totality of evidence. That is not only one specific measure. It will include safety, overall response rate, duration of response, stable disease, disease control, et cetera. If you look at that, obviously, this is an emerging field with bispecifics, et cetera. In the second-line setting specifically, the current standard of care remains cetuximab. That may not change, given some of the data that's emerging in the first-line setting. The current cetuximab overall response rate is probably in the 13% range, around there, so pretty, very limited. We'd be looking for ORR at least probably 20%. Also, very importantly, as I stated earlier, the other measures also are very important to really kind of round out the totality of evidence.
Got it. That's helpful. OK, great. Let's switch gears. Talk about your second program, casdozokitug, IL-27 antagonist here. You know, quite interesting because it's an autoimmune target. Maybe briefly, you know, also introduce us the mechanism in oncology and what makes it a compelling target in your hands.
You're right. This is a very, very compelling target. The cytokines help balance the immune system. What I really find compelling about casdozokitug because of the IL-27 is the translational biology and how that has read out in the clinic. This is a target that plays a key role in barrier proteins in lung and liver and other, which is exactly where we've seen effect. This is a first-in-class molecule. There's no one else around doing it, and we're very happy to be the pioneers. It was brought forward by Chris Hunter at the University of Pennsylvania. We have a very nice program where we've seen great results in liver cancer, and now we're pursuing lung. Maybe Theresa wants to offer a few insights just with respect to MOA.
Sure. I think the thing that we have to remember with cytokines is context matters. They're immune regulatory, not suppressive or activating. It really depends upon where they are and who's around them. As Denny mentioned, the context that we've seen from the translation, where we've seen in the mouse models, whether it be infectious disease or cancer models, that IL-27 is important in turning off the immune system, the T cells, the NK cells, those killer cells in the lung and the liver. Going into the clinic, it's well understood that antibodies rebalance the immune system in inflammatory diseases. There's a multitude of approved antibodies in the IL-27 family. This is the first demonstration in oncology where we've seen inhibiting a single cytokine leads to immune activation. With that, we saw monotherapy responses in lung cancer.
Then seeing this activity in liver cancer, that translation from mouse to human has a very strong focused program to establish the proof of concept and move forward.
Got it. Yeah, and maybe this helps understand some of the clinical data we've seen so far. I believe you initially saw about five CRs, a 38% OR, and a pretty durable response in combination with atezolizumab and bevacizumab. Maybe just help us understand some of the results here so far. How does that compare to other standards of care in hepatocellular carcinoma?
Yeah, thanks, David. I think the data in first-line HCC, which you've just been referencing, is actually very exciting. We showed data at ASCO GI earlier this year, in January 2024, which showed exactly that data set that you outlined. The triple combination atezolizumab, bevacizumab, and casdozokitug, we did show a 38% overall response rate and a 17% complete response rate. The relevant benchmarks there for the current standard of care atezolizumab and bevacizumab are 30% and 8% respectively. Importantly, that complete response rate was approximately double the current standard of care. That was actually very interesting and exciting. Where have we taken that forwards now? We have an ongoing study right now swapping out the atezolizumab for LOQTORZI. We're looking at the LOQTORZI, bevacizumab, casdozokitug triple combination.
It's a 72-subject study looking at two biologically active doses again of casdozokitug in combination with LOQTORZI and bevacizumab versus LOQTORZI and bevacizumab alone. The aim of this study is, I'd say, probably threefold. Number one, to obviously further characterize efficacy and safety. Number two, to address Project Optimus. Number three, also to define and look at the contribution of components. I think that's the study that's ongoing, and we anticipate releasing some results probably around the middle of next year. One thing I will say, though, is this will be initial results. What we noted with the atezolizumab, bevacizumab, casdozokitug combination is over time that there was a deepening of the responses and an increase in response rate. If we anticipate that to also happen with our triple combination with LOQTORZI, you should anticipate early results followed by further evolving results after that.
Right. Actually, this one thing that you mentioned is the contribution of different components, right? This is a combo therapy. How should we think about the various components that are contributing to the 38% OR and the 17% CR? How confident are you that this is a Casdozokitug-related benefit?
Yeah, in the 30-patient study, the one thing that stands out to me, as Rosh mentioned, is that depth of response, right? A 17% CR rate. I don't think most people appreciate that even PD-1 inhibitors in lung cancer, the CR rate's like 4%. Getting above 10%, I've been in IO since before it was full. Seeing anything above 10% is impressive. It's doubled any phase III study in HCC. That depth of response is distinguishing. The other thing is we've done a lot of characterization from the 30-patient study to look at the biomarker responses and do see association with response and IL-27 inhibition, immune activation. Really looking at that and the levels of IL-27. There is good correlation between the biology and the response.
The current study that Rosh's team is running now with the randomized study with casdozokitug, Tori, bev versus Tori, bev will really address that to set us up for a pivotal study.
Great. We're excellent. Great. I think we're at the top of the hour right now. We can just wrap up here. Thank you so much for taking this time to speak with us. Really appreciate the insight. Looking forward to all these updates next year. It's going to be an exciting time for Coherus.
Thank you, David. Thank you for having Coherus with us today. I would just close by saying that our company is very unique in the space. We have a commercial product. We have best-in-class products. We have first-in-class products. We have a very, very strong team that's executing a cogent strategy. We have a great track record of execution. We look forward to delivering those results for our investors next year.
Great. Thank you so much for joining.
Bye-bye.
Thank you.
Yeah.
Thank you.