Welcome back, everybody, to TD Cowen's Oncology Innovation Summit. You are in the Coherus Oncology session, and we're very pleased to welcome Coherus' top management, Denny Lanfear, CEO, Rosh Dias, Chief Medical Officer, and Theresa LaVallee, Chief Development Officer. Thanks for joining us. So Denny, over to you for some opening remarks, and then we'll launch into some questions around your pipeline and portfolio.
Thank you, Michael, and thank you to TD Cowen for having us today to talk about our company. Coherus is an innovative oncology company. We have an approved PD-1 in the United States, Loqtorzi, which we have launched into nasopharyngeal carcinoma at the beginning of Q1. Happy to provide you an update on how that is going. We also have very active programs in our pipeline on the tumor microenvironment. I'll let Dr. Dias and Dr. LaVallee talk to you a little bit more about that. One key thing we have, I think, is a very creative and innovative development strategy for both Loqtorzi and for the TME-focused pipeline assets that you'll hear a little bit more about today. With that, Michael, I'm happy to take all your questions on any topic comes up and how things are going with Loqtorzi or whatnot.
Great! Well, why don't we start there? How is the NPC launch for Loqtorzi progressing?
Loqtorzi launch is going well. It's very, very consistent with our projections. Of course, this is a rare cancer with a relatively small number of patients, about 2,000 patients per year. We're very pleased how it's going so far. Dr. Dias can talk a little bit about the breadth of the indication and how that allows us to move very broadly into NPC with all lines of therapy. One thing about Loqtorzi, it was very, very effective in this particular indication. All the data is quite impressive, so we're doing, I think, quite well. We're moving forward with that. We feel that the product really is going to get across all lines of therapy, as I indicated.
Great. You recently announced some, interesting partnerships in which Loqtorzi will be used as the backbone for various combinations being tested in different indications. Maybe you could give us a rundown of, some of those announcements and some of those collaborations.
Yeah, I'll let Dr. LaVallee address that for you. Theresa?
Yeah. So as we started off launching Loqtorzi at NPC with the profound overall survival is the start. Really, the way that we see to further develop Loqtorzi is a three-pronged strategy. The first being combination with our internal pipeline to do combinations with Loqtorzi and another agent to further advance survival across larger indications, as well as going into head and neck more broadly. The other thing is through partnerships, so a lot of the big pharma players are deprioritizing their checkpoint inhibitors, and that has been an advantage for us, where we've had several folks call us that had relationships that were in desperate need of a PD-1.
Given the quality of the data on Loqtorzi, showing high potency, as well as some differentiation in the clinic with activity in combination with chemotherapy and PD-L1 high and PD-L1 low, that seeing that potency really has become a PD-1 partner of choice. So we've announced the second prong is pivotal studies, so near-term registration opportunities with partners. Our partner, Junshi Biosciences, is developing toripalimab with their innovative pipeline and have an ongoing phase III in small cell lung cancer with their BTLA antibody. As it registers in the United States as the U.S. development and commercial partner, we would have toripalimab in the U.S. Additionally, Inovio was the partnership we announced, where we would go into combination with their DNA vaccine against HPV in HPV-positive head and neck cancer, and look forward to that pivotal study starting later this year or early next year.
Then the other, the third prong of the strategy is more of a discovery-based, that PD-1 is a foundational treatment for, in oncology, and most people are looking for PD-1 combinations to further extend that. So we just announced the partnership with Cancer Research Institute, really the premier research entity in the immuno-oncology space, again, recognizing Loqtorzi 's potency and differentiation as a next-generation PD-1, to put toripalimab in their ovarian cancer study with partnerships with other companies. So the combination that we're starting off with is with ENB Therapeutics.
It has an endothelin B antagonist and some early clinical data showing some efficacy in ovarian cancer. So CRI will run that study with the two companies in partnership to look at early-stage data, and we have conversations with several partners ongoing, so we hope to announce more later this year about other looks, to be able to do discovery through and look at clinical data to make decisions about co-development and things.
Great! Well, lots to come on that front. You, of course, have your own vibrant internal pipeline. Perhaps the lead candidate is casdozokitug. Hopefully, I pronounced that correctly. So maybe you could give us a quick overview of that molecule and where it stands in development.
Rosh, should it maybe?
Yes, absolutely. Thanks for the question, Michael. So, I'll talk about a couple of our pipeline agents. So starting with IL-27, casdozokitug, this is obviously, as we've communicated previously, a first-in-class agent, also the only clinical stage IL-27 in development. And what we have communicated so far in terms of clinical data is, first of all, clinical data in non-small cell lung cancer. Data presented at ESMO IO in December 2023, so last year, showed that in a patient subset of about 40 subjects, we showed two monotherapy responses. Both of these were in PD-L1 refractory subjects, which obviously is very rare, and very encouraging. And also, both of these subjects were PD-L1 low or negative, and squamous cell carcinoma, where arguably the clinical need is greater.
So we're taking that forward now with an ongoing study looking at the combination of toripalimab with casdozokitug in non-small cell lung cancer, second to fourth line. That's active currently in the U.S., and we will be following that up with a larger phase III, looking against the current standard of care, which is docetaxel. We do anticipate data from our current ongoing combination study in either later this year or very early next. The second program is in hepatocellular carcinoma, and that builds upon the very nice data that was presented at the combination of atezo, bev, and casdozokitug. What we showed there was a 38% overall response rate, which included three complete responses. Again, very encouraging data.
And what we showed also was that the responses and the datasets, compared to about nine months ago, the response rate had increased, and also we had deepening of responses, which is pretty much exactly what you'd like to see. So we're following on that data now with, obviously, a toripalimab combination. We anticipate starting a triple combination, including toripalimab, bev, and casdozokitug in the second half of this year, and we will follow that on then with a wide program looking at phase II and then phase III against the current standard of care, which is casdozokitug .
Maybe for folks that aren't familiar with casdozokitug, IL-27 being the only program in clinical development, really what attracted the target is it's well understood and validated in humans that antibodies against cytokines can rebalance the immune system, mostly in inflammatory diseases. I mean, the IL-27 family has a number of approved agents for inflammatory diseases like IL-23, IL-6, IL-12 is in that family. So, but it really, it has been not seen for oncology to date. So the attraction of the phase I dataset was showing the direct translation from the mouse to the humans, where we saw the lack of IL-27, either through genetic ablation or through pharmacology, using antibodies to block IL-27 in the mouse, that we saw an overstimulation of the immune system when challenged by either infection or cancer in the lung and the liver.
So, that activation of T cells and NK cells, IL-27 will dampen that by turning them off. Removing IL-27 overstimulates the immune system, is what you want in cancer. So, seeing that direct translation into humans, where we see dose-dependent inhibition of IL-27 signaling in human cancer patients, when we have complete inhibition of the IL-27 pathway, we see activation of NK and T cells. Importantly, it's with a very nice safety profile, so it really lends itself for combinations. So, inhibiting IL-27 activates immunity, has a good safety profile, and we've seen monotherapy responses in tumor types that were predicted from the mouse. So, I think really following that biology and further developing the cytokine to show that we can do the same thing in oncology is a really exciting opportunity.
That's great. So, I mean, it sounds like relatively well-validated biology, at least in the preclinical arena. You mentioned that, casdozokitug has the potential to be first in class. Are there any potential clinical competitors on the horizon? And if not, why do you think that might be?
Yeah, I mean, that's always-- So the aspects in oncology is usually it's FOMO, right? So everybody jumps in on a target 'cause the science gets well understood, and everybody goes after it. I think for cytokines, it's really been a challenge. It's complex biology, and this understanding that it's an immune system and that it's not just a genetic alteration or the T cell, it's the whole aspects of it. And IL-27 really has a context-dependent immune suppression. And so what is nice is when you can see translation from preclinical models into the clinic, it really gives you that line of sight. So I think many people have tried cytokines in oncology and haven't seen the efficacy, but I don't know that they've followed the biology, and that's really been the complaint about immuno-oncology, is this carpet bombing approach.
Let's just do a bunch of phase IIs and see what hits. Whereas this, we've really seen that, like I've said, that translation, where in the mouse, we only saw activity in the lung and the liver. And then to see in humans, I mean, if you asked me to predict if inhibiting IL-27 would shrink a tumor in humans, I would have said no. I would have been wrong. So when you see better activity than you anticipated, that's a place to run. So other folks, I think why they haven't picked up on the datasets, we haven't heard of a competitive program, but we'll take that opportunity and continue to pursue it.
There's only one cross-cutter.
Right. Well, I mean, that's, that's exactly where we wanna be. So, we'll look out for those data around the turn of the year. Maybe we can move to, CHS-114, your CCR8 molecule. We're gonna get some early data at ASCO in about, well, less than a week now. Maybe you could give us a similar overview of that molecule, its stage of development, and, perhaps preview the data that, some of which we've already gotten in the abstract.
So I can talk about the clinical data, and maybe, Theresa, you can talk a little bit about the mechanism and the biology. So we have an ongoing program, obviously, with CHS-114, which we're very excited about. There are obviously several others in development as well. We are, we feel we're pretty well competitively positioned. So the data that you'll see at ASCO is based upon the dose escalation part of the program, and you'll see broadly. I won't spoil the full data, but what you'll see is broadly some PK data. You'll see some data on Treg depletion, and then, most importantly, probably for a phase I study, you'll see its safety. So those are the three things to look out for with the ASCO data.
Again, it's data from the dose escalation portion. We'll be moving on from the dose escalation portion, which is now complete, on into expansion into head and neck, where the disease linkage is pretty strong. And we'll start that initially with a monotherapy, biopsy-based approach to be able to look at intratumoral Tregs, and then move on, following that, into the combination with tori pretty quickly. Maybe, Theresa, you can talk a little bit about the specific biology.
Yeah. So I think T regulatory cells obviously help with that homeostasis, right? So when immune system's activated, T regulatory cells turn it down. It's clearly been a target in oncology for a long time, and the challenge has been getting selectivity because if you broadly take out Treg cells, you get a lot of autoimmunity. So that toxicity has limited it as a target. Really, science that has looked at, where can we get more specificity on tumor-resident Tregs? CCR8 was identified as being preferentially and highly expressed in solid tumors. It's a GPCR, so that's one of the seven transmembrane domain proteins that doesn't have a lot of extracellular protein sticking out of the cell.
So GPCRs are challenging for antibody development, and one of the things that really attracted us to the Surface program, whereas we had our own internal program, we're finding it a challenge to get high selectivity to CCR8, that it didn't bind other proteins. And Surface was screened at over 5,000 proteins and found only to bind CCR8. So our molecule, that by binding Surface, we accelerated our discovery program by 2.5 years and saved $15 million to get into phase I with what we would consider a best-in-class molecule. Because looking at three of the other competitors, they all have off-target binding, which could lend to toxicities, could have PK problems, you know, so those are things that I would worry about there. So this is an antibody that binds and kills the unwanted cell and opens up the tumor microenvironment.
Again, just taking out a suppressor cell may not be enough for robust single-agent activity. The one competitor program that has presented data at ESMO IO, the Lanova program, showed a single PR in non-small cell lung cancer. But I think another tumor type that we're particularly excited about for this program that has been underserved by immunotherapy is colorectal cancer has a lot of Tregs in it, and that's been one of the mechanisms that's been hypothesized to dampen why the checkpoint inhibitors haven't worked there. So we're super excited about this program and are aggressively moving it forward.
Very interesting. So the data that are in the ASCO abstract, should we expect some additional data, perhaps, in the presentation? Or do we mostly know what will be presented?
Y eah, it'll cover those three aspects that I talked about. And obviously, we'll go into those in a little bit more detail, but it's essentially PK Treg depletion, which is a proxy, obviously, for proof of mechanism, and then most importantly, again, safety. So those are the big three buckets of what you'll see, and you'll see some additional detail within those three buckets.
Okay, great. And, Theresa, you mentioned colorectal cancer as being a potential tumor type of interest for this mechanism. What are some other indications where you think Tregs might have a prominent role?
Yeah, so the nice part is there's several of them. So gastric cancer, head and neck cancer. Head and neck cancer is one of the highest, and it's also the mechanism of the antibody killing, killing is mediated by NK cells, and head and neck is particularly rich there, and that's why we're doing our expansion phase in head and neck to go very quickly into a tumor type. That makes a lot of sense. But breast cancer also has a high degree of Tregs, bladder cancer. So it's, it's a broad list of lung cancer. The highest are the cervical, gastric, head and neck, but the colorectal lung also has a lot.
Okay.
So it's a broad opportunity, both in combination with PD-1 as well as other mechanisms.
Okay. And were many of these tumor types represented in your initial dose escalation?
It was an all-comer phase I, highly refractory, with multiple lines of therapy prior to it, so we did have a good smattering of tumor types.
Okay. Great. We have a few minutes left. I wanna leave a little bit of time to discuss another of your pipeline agents, CHS- 1000. So maybe you could give us an overview of this, and this is in the IND-enabling stage, I believe, with an IND expected soon. Maybe you could give us an update on the expectations for when that agent might enter the clinic.
Yeah, so again, another highly immunosuppressive cell type is the M2 macrophages. So a little different because macrophages, inflammatory, and M1 macrophages are needed to promote an immune system. We're so focused on the T cell, the T cell, the T cell, but we forget it's an immune system that you need. It needs help. It needs to be in an inflammatory environment to have a productive immune response. So in this case, what we're trying to do is take the immunosuppressive cell and turn it to a pro-inflammatory cell, and ILT4 is a myeloid checkpoint. So by inhibiting ILT4, you trigger the macrophage to be pro-inflammatory. It also promotes dendritic cells, which in order for T cells to be activated, you need the T cell to bind a dendritic cell or an antigen-presenting cell.
So it has two mechanisms that would really promote the T cell, so lending itself to PD-1 combination. And there was a study published in Science Translational Medicine from Johns Hopkins, where they did a meta-analysis from melanoma patients that were treated with checkpoint inhibitors and found that high M2 macrophages and low PD-L1 predicted for lack of response to checkpoint inhibitors. So really taking clinical data, tumor samples, and saying, "If you have high macrophages, will you respond to a PD-1?" And the answer was no. So those data really tell you by looking for those patients and combining with something like toripalimab should promote more patients getting benefit from checkpoint inhibitors. So this is a highly potent molecule that has really strong pharmacology, and we do expect FDA feedback soon within this quarter, and to transition it to the clinic shortly thereafter.
Got it. Okay. And how has this hypothesis fared so far around ILT4? Are there any clinical data where you could get some insight into whether this is a robust mechanism of action with an anti-cancer response, or are we awaiting those data from other molecules?
Yeah, so there's a couple competitor programs, and Merck broadly presented at AACR, a number of programs, where they saw some efficacy in head and neck and gastric cancer. At AACR, they showed those data. It was what they considered a signal that they would not prioritize. I think that they're looking for other things in their pipeline. I see it as that having a hint of efficacy that we can follow up on and doing more patient enrichment to give a stronger signal. Additionally, outside of the antibodies that are in development, looking at ILT4, which we're closely watching, there have been small molecules targeting M2 macrophages.
So there was a molecule called iganalisib that showed the activity in terms of polarizing macrophages and some early signs of activity in triple-negative breast and melanoma cancer, and that correlated with the biopsies where they showed they got inflammatory macrophages. So we'll continue to pursue those clinical signals to enrich for our programs.
Great. Well, we have, we're right at the top of the half hour. Denny, maybe I can turn it to you for any closing remarks, and we'll look forward to your presentation at ASCO.
Well, thank you, Michael, and thank you once again to Cowen for having us today. Just to loop back for a moment with respect to Loqtorzi launch, I should mention that we have some real-world evidence there, that from a large oncology practice network here in the U.S., that we're batting about 70% as far as being selected as a PD-1 or a nasopharyngeal cancer. So we think that's very good. We're monitoring that very closely, but we're very pleased once again with the way the launch is going, and we'll look forward to seeing you at ASCO.
Great. Well, thanks so much for your time, and thanks to everyone on the line.