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

Thank you for standing by, and welcome to the KOL Call to discuss CHS-114 Phase I data. [Operator Instructions] I would now like to hand the call over to Jodi Sievers, Investor Relations. Please go ahead.

Thank you, Latif, and good afternoon, everyone, and welcome to our presentation of the Phase I study results of CHS-114 in CCR8 antibody. The study evaluated CHS-114 as monotherapy and in combination with our next-generation anti-PD-1 toripalimab in patients with advanced solid tumors, including head and neck cancer. Before we get started, I'd like to remind you that today's call includes forward-looking statements regarding Coherus' current expectations about future events. More detail is outlined here on Slide 2. It is my pleasure to introduce our speakers today, starting with Dr. Douglas Adkins. Dr. Adkins is a Professor of Medicine at Washington University School of Medicine, and Director, Section of Head and Neck and Thyroid Medical Oncology Division of Medical Oncology at Washington University School of Medicine. Dr. Adkins is also an investigator on the CHS-114 Phase I study. Joining Dr. Adkins are Theresa LaVallee, Chief Development Officer; and Rosh Dias, Coherus' Chief Medical Officer. Today's discussion will begin with an introduction of CHS-114 and an overview of the preclinical development results by Dr. Theresa LaVallee. Theresa?

Thank you, Jodi, and thank you, everyone, for joining us. As shown on the outline, I will start with the background on the target, the molecule and some of the preclinical work before we dive into the results we presented this morning at the AACR meeting. Next slide, please, and the next slide. So this is an overview of the CHS-114 program, our cytolytic CCR8 targeting antibody. T-regulatory cells is a well-known immunosuppressive cell type and there have been a multitude of approaches attempted to deplete Tregs for cancer immunotherapy that has really lacked the missing total piece, which is a selective target in the tumor for the tumor resident Treg cells. And the overall idea and what we'll show you today from clinical samples is to deplete the Treg cell to allow the tumors to become inflamed and have the CD8 T cells come into the tumor, and turning cold tumors hot and making them immune permissive. Given that this is a targeted therapy, we understand who to treat based on characterization of tumors that have a high density and prevalence of CCR8 positive Tregs, and these include tumor types like head and neck, which will describe our clinical results today as well as tumor types that have been underserved by immunotherapy such as colorectal cancer. Next slide. So overall, as I mentioned, people have tried for decades to target Tregs in oncology, and the problem has been twofold: one, broad depletion of key regulatory cells leads to collateral toxicity, autoimmunity because T regulatory cells are required for homeostasis. Additionally, finding a target that is exclusively expressed on the T regulatory cells and not on normal lymphocytes such as CD4 and CD8 cells has been a challenge. CCR8 seems to have addressed these issues with preferential high expression in tumor-resident Treg cells. And we've shown preclinical data, which I'll briefly walk through today showing that selective depletion, as well as we'll walk through clinical data showing that today. Next slide. The CHS-114 is a highly selective cytolytic antibody targeting CCR8, which is a G-protein coupled receptor. PCCR are notoriously difficult to design antibodies that are selective, given the limited real estate of protein on the outside of the cell. From our characterization shown on the right of our internal stream for lead identification, we found 1 and only 1 antibody that exclusively found human CCR8. When we've characterized competitor antibodies, we've also found that they have cost target finding. So to date, from all the antibodies published, we have the only one that is known to have exclusive binding to human CCR8. Next slide. In preclinical models, this is a B16 mouse tumor model, which is resistant to PD-1. And the idea is that the resistance is being driven by T regulatory cells. So the blue line shows that treatment with an anti-CCR8 antibody deplete the T regulatory cells leading to antitumor activities. But importantly, the red line shows that combining the 2 has enhanced antitumor activity. But images on the right are immunohistochemistry looking at CD8 T cells in the tumor, both PD-1 antibody as well as CCR8 antibody alone treatment, [ least turn ] infiltration of CD8 T cells. But it's really that combination that changes the immune landscape, remodeled the tumor microenvironment to be inflamed with marked infiltration of CD8 T cells. And this image I ask you to remember, so when we show you the clinical data, we can just sketch what we've observed in patient's body. Next slide. So overall, we've characterized a large number of solid tumors for the density of CCR8 positive Treg cells. And you can see on the Y axis for 25 cells per millimeter squared, there's a reasonable density for having a good infiltration of T regulatory cells and there's a large number of solid tumors that have a high prevalence of those T regulatory cells in the tumor. The X axis gives the percent of Tregs in the tumor that are CCR8 positive. And what you'll observe is that the majority of the Treg cells in these tumor types are CCR8 positive, and importantly, head and neck and gastric cancer as well as cervical cancer has the highest level with the majority of the Treg cells expressing CCR8 positive. On the right, we've tried to summarize the field's knowledge to date for our program as well as other programs that disclosed clinical data, and we'll walk you through response data in head and neck cancer patients today in the presentation as well as previously been reported at ASCO last year by a competitor program that they saw activity in gastric cancer when they use their CCR8 antibody in combination with toripalimab. Additionally, there has been 1 PR reported with single-agent CCR8 antibody in gastric cancer. And we've seen long-term stable disease as well as others in colorectal cancer. And another partial response for anti-CCR8 antibody has been reported in non-small cell lung cancer. And we've seen long-term stable disease in an endometrial cancer patients. They're really setting it up now for clinical exploration, particularly in combination with the new modulators like Toripalimab. Next slide. On the poster this morning, we really started by characterizing our 2 pharmacologically active doses. And we had previously presented at ASCO 2024, the dose escalation study, showing good pharmacodynamics as well as safety at doses up to 1,200 milligrams dose level 7. And what we identified was dose level 5 and 6 to be pharmacologically active. This was defined through preclinical experiments. So on the left, we showed taking human PBMCs and treating them with CHS-114 ex vivo that we look for depletion where there's a small number of CCR8 positive Treg cells in the PBMCs. So what you're looking for are for the gray hall to go lower than the control black balls. And you can see that only at 30 and 100 micrograms per ml, do we have statistical significance with the decrease. Furthermore, when we look at the mechanism of action, which is a simple binding kill, so activating and killing from the antibody to [ afucosylated ] antibody through NK cells, ADCC, for myeloid cells, ADCP, we see their EC50 value to be about 30 micrograms per ml. Targeted therapies are known to have a strong IVIVC, In Vitro-to-In Vivo Correlation. So we set our PK trough levels in the clinic to be in the 10 micrograms per ml. Next slide. And here's data from the Phase I dose escalation study saying now that if we take that PK trough level and look for immune activation, in dose levels, the dose level 5 and above that achieved the PK target soon in orange is red. And for blue, dose level 4 and the lower, the heavy lines are the median of all the dose group that dotted line are individual patient data. So we look at interferon gamma as a marker of Th1 immune cell activation as well as activation of CD8 T cells in the periphery with the Ki67 as a marker for proliferation or Granzyme B as a marker for cytolytic activity. And what you can see is only the orange median shows activation that sustained over the dosing interval, from cycle 1, day 1 to cycle 2, day 2, supporting that these 2 dose levels are pharmacologically active. Next slide. Now I'll turn it over to Dr. Dias, our Chief Medical Officer, to introduce the study.

Thank you, Theresa, and good afternoon, and good evening. So what I'll do over the next few slides is to take you through the Phase I clinical development plan. And this slide outlines the overall Phase I design. And as you can see, it's in 3 stages or 3 arms. So Arm 1a is a standard dose escalation in patients with solid tumors and we looked at 20 subjects in up to 7 dose levels. Arm 1b and 2 are dose expansion cohorts in Head and Neck Squamous Cell Carcinoma, the second line and beyond. Arm 1b was monotherapy, 2 doses of CHS-114 in combination with -- or rather in -- with -- Arm 1b was actually CHS-114 monotherapy with 2 paired tumor biopsies, and Arm 2 was combination dose escalation, also in second-line head and neck carcinoma with toripalimab and again, 2 dose levels of CHS-114. The primary endpoint with safety and tolerability and key secondary end points included PK, objective response rate, other additional efficacy markers as well as biomarker endpoints. Next slide. So the Phase I -- the Stage 1a data was presented at ASCO last year. And essentially, we showed monotherapy dose escalation in 20 subjects, and each demonstrated an acceptable safety profile in heavily pretreated patients with advanced solid tumors with no DLTs. In these heavily pretreated patients, we showed a stable disease rate of close to 50%. We showed PK dose proportionality, and we showed depletion of peripheral CCR8 Tregs with which display establishing proof of mechanism, and also we showed proof of specificity in that CHS-114 did not deplete non-CCR8-postive Tregs. And based on this, we expanded 2 specific dose levels of CHS-114. Next slide. So I've already talked about the overall study design. Arm 1a was, as I mentioned, we already presented at ASCO last year. What you'll hear today is the data from Arms 1b and 2, that is the head and neck expansion phases of this study, together with the 2 patients in Arm 1a that had Head and Neck Squamous Cell Carcinoma. What is enrolling now is Arm 3, which is a further expansion in second line head and neck specifically with 2 dose levels of CHS-114 plus toripalimab, 20 patients in each arm up to 40 subjects in total. And again, the primary endpoint is safety and tolerability with the secondary endpoints being PK, ORR, additional efficacy measures as well as biomarkers as well. Next slide. And finally, I'd also like to state that we are expanding into a gastric cancer study as well. And this study is currently open also. We're looking at 40 patients overall, 20 patients in each arm with 2 dose levels of CHS-114 in conjunction with toripalimab and the patient population here is second-line gastric, gastroesophageal junction and esophageal adenocarcinoma. And again, we're looking at safety, tolerability and additional endpoints also. This study is also open and recruiting. And with that, let me hand over to Professor Douglas Adkins to describe today's data in a little bit more detail. Doug?

Thank you, Rosh. I appreciate the opportunity to share with you the results of the data presented by my colleague, [ Frank Gordon ], at the AACR meeting which grew quite a bit of attention. This is a refresher of the study design that Rosh has reviewed. Recall that Arm 1a consists of CHS-114 monotherapy across 7 dose levels. ARM 1b is testing 2 dose levels, DL5 and DL6 CHS-114 monotherapy in the head and neck second-line population. And in Arm 2 is testing the combination of CHS-114 plus toripalimab in the second-line head and neck population, specifically looking at dose optimization with 2 different dose levels, DL5 and DL6. Next slide. So this slide reviews for you the characteristics of the patients and the tumors of patients who participated in this clinical trial and really from a clinician perspective, it reflects what I see clinically and is generally applicable to the population of patients who have recurrent metastatic head and neck cancer. That is patients who are generally in their 60s on average, [ mostly ] males, typically, it's about a 3:1 ratio. And a mixed performance status of 0:1. And as you could see, the median number lines of prior therapy was quite substantial, particularly in the CHS-114 monotherapy cohort. Majority of patients have PD-1-positive disease. Next slide. Upon review of the summary of adverse events, the proportion of patients with adverse events was typical of what you'd expect for people with second-line head and neck cancer. And generally, there was a slightly higher risk of adverse event with the addition of toripalimab plus CHS-114. But the types of adverse events that we saw were things that included anemia and infusion reactions that were mild and manageable with various supportive care measures that did not significantly impact the delivery overall, and there are no treatment-related deaths. Next slide. So on the left-hand panel, it demonstrates the percent change in target lesions from baseline with CHS-114 monotherapy. And you can see that in a persistent population there was disease control and sizable fraction of this data set. On the right-hand panel demonstrates the percent change in target lesions of CHS-114 plus toripalimab, and I note for you that the patient that have partial response, this is only 6 patients and sort of see a decent sustaining partial response and a small cohort like this. It's quite impressive in my experience for a resistant population and expand more on this patient with PR in just a second. On the right side of that second panel, you can see that these responses tend to be relatively durable in this pool of patients. Next slide. So this is a [ service spot ] showing you the durability of responses with CHS-114 monotherapy on the right hand side, CHS-114 plus toripalimab. And you can get a kind of a sense of the combination therapy might offers some additive durability, which I think is important to the discussion. Next slide. I wanted to focus on this patient with a partial response. This is actually a patient of mine treated on this protocol. And this is a gentleman who was 64 years old, nonsmoker who presented to his local oncologist with a right neck mass, back in April 2023. And an examination was found to have a mass in the right base of the tongue, which was the actual origin and the primary tumor site that led to metastases into the right neck mass. The biopsy should confirm this to be a neck cancer squamous cell carcinoma, originating the base of tongue, it was defined to be HPV positive. That was the actual etiology of this cancer, which is an emerging common population in the United States for head and neck cancer. Staging evaluations, multiple lung lesions were noted, which prompted a biopsy of one of those long lesions which confirmed pathologic evidence of metastatic squamous cell carcinoma. This patient's profiling of the tumor showed a PD-1 CPS score, that is relatively low 3% to 5% with a low TMB. Next slide. This is an outline of the sequence of events from the time the patient was diagnosed on the left side in April 2023, until the most recent data seen on the right side. On the left-hand side, you can see this initial diagnosis of HPV-positive oropharyngeal cancer with de novo metastatic disease. The patient was treated by the local medical oncologists using the KEYNOTE-048 trial regimen, which included pembrolizumab plus carboplatin, [ plus 4, 5 year or so ]. And following the initial 2 or 3 cycles, CT scans, unfortunately, surprisingly showed progression of disease. So primary resistance not only chemotherapy but the PD-1-based therapy. Second-line treatment for this patient, which is a little different than usual with a drug called Afatinib, and that was based on some genome sequencing data showing a genomic abnormality EGFR protein. That drug was tried, but failed very quickly within 8 weeks, the response assessment of resistant disease. And then the patient presented for third-line treatment with docetaxel. And after 3 cycles of docetaxel imaging studies that we confirmed the substantial disease progression. But by this point the disease in the right neck was causing significant impingement on the carotid bolt causing chronic sinus syndrome, which causes drop attacks or sinkable events and tremendous pain in the right neck. We confirmed that this was actually squamous cell carcinoma on a repeat biopsies since behavior of this cancer was usually aggressive and resistant. And at that point, I refer the patient back to a short course of radiation therapy to the neck, which did shrink the in-field tumor and did eliminate the drop attack problems from the carotid sinus involvement. Patient returned to me, we restaged the patient after finishing the radiation and the patient's imaging showed that within the radiation field in the neck, there has been a response, but systemically the patient had progressive disease by RECIST criteria. So the patient elected to enroll on the clinical trial with combination CHS-114 plus toripalimab. Next slide. So this is a sequence of images, CAT scan images that demonstrate visually the benefit of this patient experience with combination therapy. On the left-hand side, you can see the pretreatment baseline scan in August of 2024. And what you see the black stone on the right -- on the left-hand side under baselines of black zone on the left, is actually the right lung and the black zone on the right is actually the left lung. So it's actually the patient facing us. And the arrow, the yellow arrow points out these 2 large metastases present that sit on top of the diaphragm. If you look north, very top in the same second of the same lung, you'll see another small module in the very north part of that, the apex of the lung. The patient was then treated with combinations CHS-114 and toripalimab. And on the right, you can see how significant response was not only in the largest lesion above the diaphragm, but also in a smaller one top of the lung. Next slide. This is a separate additional lung lesion in the supradiaphragmatic region in the left lung. And you can see this pretty impressive, in fact, amazing response radiologically with combination CHS-114 plus toripalimab. Next slide. These are additional target lesions per study that demonstrate the sequence of responses. And so these are scans that began on the left baseline. All of one is about 6 weeks after initiating study drugs. All of two is about 4 weeks later, all three was maybe 6 weeks later. And you could see that the response happened early, but it also continued with chemotherapy, we typically get our most evidence of response in the first 2 cycles, and then we don't see any further response. Here, we're seeing not only an earlier response, but a sustained decrease in the target lesions. Next slide. Now in the neck region, the patient has very large neck masses. And on the left-hand panel, you can see the baseline CT scan of the neck. And the arrow is pointing out 2 abnormalities. I want to draw your attention to. Each of these are necrotic lymph nodes. They're involved in malignant cancer. And on the right-hand panel shows you after CHS-114 and toripalimab, you can see an obvious mutual decrease in the size of these neck mass and focus on the arrows where the arrow is pointing that shows the abnormality and these are rounded lymphnodes. On the bottom set in the left-hand panel, you can see 2 abnormalities, the large circle is pointing out a large sound of tumor, which is surrounding the carotid bolt causing this patient [indiscernible] sequential events. And on the left -- on the other side of the patient's neck, the arrow is bringing out a large necrotic neck node involved by cancer. After CHS-114 toripalimab, the right-hand panel shows you the obvious visual decrease in these tumors, which is all clearly with symptomatic improvement in any patients. The important point about this slide is the following: if you look at the KEYNOTE-048 data set, the base patients who really benefited from pembrolizumab as first-line of treatment at distant metastatic disease, those who had recurrent metastatic disease in the neck in the prior radiation field did not benefit. In this case, we have a patient who benefited not only distantly but also been a previously rated deal in the neck. That's very unique in the immunology world for head and neck cancer. Next slide. Theresa?

Thanks, Dr. Adkins. It's really a treat to hear the description from the treating physician. So I'll walk you through the biomarker data, which was a really important aspect. I mean, I walked through the data in blood to show that we had pharmacologically active doses, clearly seeing the response in combination with toripalimab gives us further confidence in our dosing. But using a multiplex assay now for the CHS-114 monotherapy with paired biopsies, we're evaluating CCR8 positivity, FOXP3 as a marker for Treg cells. And then CD8 as the marker for CD8 T cells. DAPI just looks at the overall nuclei for tumor cells and immune cells. So the next slide gives the quantification from the monotherapy paired biopsies. And really, we were thrilled to see this mark decrease in CCR8 positive Treg cells, looking at almost near complete depletion of those cells in the after 2 doses of CHS-114. The graph in the middle kind of gives a percent change. There's been preclinical work that's characterized that there needs to be at least 50% decrease in the Treg cells in the tumor in order to mount an effective antitumor immune response. So we were quite pleased to see between 52% and 97% decrease in the T regulatory cells within the tumors. And then lastly, the graph on the right shows that we have completely remodeled the tumor micro environment to an inflamed tumor. So looking at the ratio of CD8 cells to T cells to the T regulatory cells, you can see that there's a marked increase in what we would call immunologically hot tumors, which we were thrilled to see, because if you remember the mouse data, it really took the combination for CCR8 and PD-1 to see that marked CD8 T cell infiltrate. And these graphs are good for quantification, but I think the next slide, kind of picture tells a thousand words. And so the green on the far left, you can see the top 3 panels are the 4 treatment tumor sample. And then the 3 panels on the right or after the 2 doses of CHS-114. The green showing that the decrease in the CCR8-posiive Treg cells in the tumor after treatment. And then that really lit up tumor with the red in the CD8 T cells, really exceeded our expectations for changing the tumor from cold to hot. And then the image on the far right is the blended image. So next slide. So we're very pleased today to overall show that we have established safety as monotherapy in combination. We've established good pharmacokinetics and PK. So we've shown we hit the target, we tickle the target. And importantly, we have response in the patients that is highly refractory and in the tumor type that we would have predicted should be responsive to CCR8 positive -- CCR8 treatment. So altogether, this really has us excited to continue the dose exploration to address project optimus in combination with toripalimab, and second-line head and neck cancer as well as in gastric cancer. The last slide is overall we think that this is the missing puzzle piece to turning tumors hot and getting rid of the immunosuppressive T regulatory cells, and we look forward to continued development of this program. With that, we'll take questions.

[Operator Instructions] Our first question comes from the line of Michael Nedelcovych of TD Cowen.

The data are very compelling. I'm curious what level of confidence you have and maybe you could point to the data that provide that confidence that the responses you're seeing in the toripalimab combination arm are due primarily to CCR8 targeting as opposed to retreatment with another PD-1 inhibitor and one that potentially could be more potent than its processors.

Well, we do have some data from the checkmate 114 trial for patients who received platinum-resistant recurrent head and neck cancer, and they received Nivolumab monotherapy. And there was a subgroup of those patients who when they came off trial due to progression continued on nivolumab and they monitor whether or not there would be a delayed response with that drug and the risk -- the chance of that response, I believe, if I recall from the data was less than 5%. Obviously, that's not quite exactly answering your question. That's comparing -- that's looking at the same drug as continuation therapy. To my knowledge, I'm not aware of any actual prospective studies switched from 1 PD-L1 inhibitor to another in this setting. I am currently doing a vision initiated trial in which patients have to progress on a PD-1 inhibitor. Every patient on that trial has progressed on pembrolizumab. And we have some patients -- and on the clinical trial they receive a chemotherapy drug plus Nivolumab and some of those patients do not tolerate the chemo drug and receive Nivolumab alone. And I've not seen an added benefit in that sort of setting, which is not exactly to address your question, but it's my own personal experience of moving from 1 PD-1 inhibitor to another. So I don't think I have a good data set to refer you to. But Rosh, do you want to?

No, I think that's absolutely right. We're obviously very encouraged to see this in a patient actually who was fourth line. So I have nothing really to add to that comment.

Our next question comes from the line of Colleen Kusy of Baird.

Congrats on the data presentation. So for us, the biopsy data that you have, I know is for the monotherapy arm. But could you speak to the reduction that you saw in the CCR8 plus the Treg, did those correlate at all to patient outcomes? I know you had some patients that were on treatment longer or any kind of stable disease versus progressive disease? We have a follow-up.

Yes, we didn't see any correlation with the patients who were treated. I mean I think the thing that we were most pleased with the results showing the drug does what it's intended to do and the 2 doses that we had selected based on preclinical data as well as peripheral biomarker data in order to get that market. Now in combination, that overall, for the data that we have reported, there's very limited agent activity. So our development plan is really to do a combination with toripalimab. So seeing a response in the first safety 3 plus 3 design aspect of the study, I think, gets us highly encouraged that we're in the right space. [indiscernible], we'll continue to evaluate that for the 4 patients that are now being evaluated with [ CHS-114 ].

Great. And you spoke to the 50% reduction in Tregs that is typically kind of the threshold that you want to see a benefit. Is that specific for head and neck cancer? And just kind of speak of what that evidence is based on?

Yes. So there's a preclinical publication done by another group that really characterize the activity in mouse model. So it wasn't specific to any disease that was more across the tumor models that they looked at, that they had to achieve 50% depletion to have antitumor activity in a mouse. So we set that as a minimum requirement for us.

Got it. That's helpful. And then for the patients who did achieve a confirmed partial response, will you have tumor biopsy data at some point for that patient?

No. I mean, I guess the good news is when they respond, we don't have to worry.

Sure. And then for the potential combinations you mentioned for -- obviously, toripalimab is ongoing. And then you also mentioned potential combinations with T cell engagers and bispecifics. Can you talk just a little bit more about why those would be interesting combination partners?

Yes. So if you look at the picture of the biopsy, particularly the CD8, I mean, that's the price for me in this study was how high the CD8 infiltrate change and increase. And so a T cell engager, the way that it works, which I know you know, but I'll just walk you through it if that defines the tumor antigen. And then on the other hand, it has the tickle on T cell to activate it to kill the tumor. If there's not a high density of CD8, it's hard to get that, and that's been one of the challenges with solid tumors is getting sufficient drug into the tumor and T cell activation. So by taking away the immune suppressive cells, but also bringing in that large infiltrate of CD8, just from happen chance, just looking at the steric of the T cell engager, it really lends itself. And one of the things that from afucosylated antibodies, particularly for lymphocyte that is a concern for the field broadly is immune-related -- infusion-related reactions or CRS. And we didn't see any of that with CHS-114 in the dose escalation. And so really, the safety profile should lend it to sell to combine with the T cell engagers or bispecifics to really bring in those T cells.

Our next question comes from the line of Brian Cheng of JPMorgan.

Just kind of following up on the last question. Just to confirm, have you looked into the CCR8 or the PD-L1 levels of those who progressed versus the ones who responded? And maybe we'll start there first.

So the patients that responded, we do have the PD-L1 status, which is like a CPS [ of 3 ]. So relatively low, but positive. The TMB low but not immune characteristics and may be consistent with their pembro outcome. But we have an NF1 right now. But obviously, for the next phase study that will be a key outcome and why we're really looking to include tissue to understand that.

Okay. So maybe just on this point, since you haven't done the analysis on dose for progress. So how confident are you that this partial response is not a post positive and whether there is a way to explain the patients who had progressions in your combination cohort?

Well, when my patient came in and had their on-treatment scan, the patient looked at me in the eyes and told me, I think the mass is smaller in my neck. And I said, I think I agree. And the mass was proven, the masses are proven to be smaller on imaging. I was quite astounded frankly, that, that happened. And I brought this to the attention of my colleagues, [indiscernible] that this is a big deal because it's not in my experience as a season investigator to see this occur in an early study of a patient who has resistant disease not only immunotherapy with the targeted therapy and a series of chemotherapies. So for me, it would be hard to come up with a rational explanation why this patient responded independent of the therapy that we administer to the patient. So I think that it's pretty settled in my mind that the treatment did the job. It was temporarily associated. It was sustained over time. And I honestly could not dissect any other alternative explanation.

Our next question comes from the line of Douglas Tsao of H.C. Wainwright.

Congrats on the data. I guess maybe first, as a starting point for Dr. Adkins. So obviously, you had 1 partial responder. I guess, I'm just curious what you think, from your perspective, sort of the potential for this to be used? And obviously, this was a patient with highly refractory disease. Where would you ultimately envision trying to use this product?

Yes. I think that it's important that you understand that second-line plus treatment space for current metastatic head and neck cancer is an unmet need. And -- but what I mean by that is that the patients progress on pembro [ plus or minus ] chemotherapy, there is no real standard of care on a registrational pathway. There's no active standard care that can pull off the shelf. I can administer standard drugs like cisplatin or carboplatin or paclitaxel or 5-FU, but there's no on-label indication in that population. And I can tell you of those standard of care drugs on use, the typical response rates are actually quite low on the order of 10% or less. The actual resistor sponsor are really quite shockingly low. And the duration of responses are very short. So once you fail the pembrolizumab, it's a very dire situation for our patients. So I think that this is a rich market to explore the entire need for patients and from doctors to fill that void and identify an effective therapeutic. Many companies are focused a lot more on the first-line space for various reasons but less so on the second-line space. And the second line recurrent metastatic value deserves similar support and attention for our patients.

Okay. Great. That's helpful. And I guess as a follow-up, just 1 clarification. Theresa, to all the patients that have been in the study, what percent of the proportion that are PD-1 low versus sort of PD-1 high levels?

And I'll have to go back and look at that, Doug. I don't know that right off the top of my head. And I focused on the responding patients, but we will be actively collecting those data.

Okay. Great. And I guess as a follow-up to that. I do you think that, that could have any impact on the results? Or would you think that, that would sort of -- just given Tori's properties to be sort of fairly agnostic to the entire trial?

I think it's a very important aspect with the way the treatment is done in head and neck, and then a question that we will address in further expansion so forth clearly showing activity in CPS less than 1 would be thrilling, and CPS greater than 1 is still a high unmet medical need. And so the question is, are the T regulatory cells, the primary mechanism, the part that gets me excited that it's a possibility that the CPS 0 low could work, is that PD-L1 generally is a marker that there's been an immunologic response. So there's CD8 around their antigen experience, exhausted T cells to reinvigorate. The fact that depleting the Treg was able to really bring CD8s and may open up new opportunities for immune modulation for patients. So we're super excited to look in PD-L1 low to see if we can change that tumor microenvironment to be more responsive.

And Doug, I might just add. So in this study specifically, the vast majority of patients were PD-L1 positive. Again, the responder that we saw had a PD-L1 low status. And I don't know if I can -- if you want to just comment generally in terms of your patient pool or most of your head and neck patients, what level of PD-L1 phase do they have?

A couple of points I would make. And number one, at least in sequential biopsy studies in neck cancer doesn't look like the PD-1 score evolves in a patient over sequential biopsies. So the original biopsy in my patient was a CPS of 3, I think. And the other thing is, I think, even with a CPS-20 or greater, PD-L1 CPS-20 integrator, the response rates seem to be somewhat higher than a CPS of 1 to 19 or 0 for first-line treatment, but the correlation coefficient is really strong. And therefore, it is a difficult -- it's a target, but it's not a highly predictive target. And then the final thing is you have to appreciate that all these patients have progressed on a PD-1 inhibitor already. So they're already showing you that they need something else beyond PD-1 inhibitor to achieve a response. That doesn't mean that they don't need to continue on their PD-1 inhibitor, I think that my mind thinks that they need both drugs to have the optimal benefit. The CHS-114 and toripalimab, to my point.

Thank you. That does conclude the Q&A session and today's conference call. Thank you for participating. You may now disconnect.