Thank you for standing by, and welcome to the KOL Call to discuss CHS-114 phase I data. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. To remove yourself from the queue, you may press star one one again. I would now like to hand the call over to Jodi Sievers, Investor Relations. Please go ahead. Thank you, Latif, and good afternoon, everyone. Welcome to our presentation of the phase I study results of CHS-114 as a 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. Next slide. 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 two. 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. Next slide. 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 T regs for cancer immunotherapy that have really lacked the missing puzzle piece, which is a selective target in the tumor for the tumor resident Treg cells. The overall idea, and what we will show you today from clinical samples, is to deplete the Treg cells to allow the tumors to become inflamed and have the CD8 T cells come into the tumor, 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 + Tregs. These include tumor types like head and neck, which we will describe our clinical results today, as well as tumor types that have been underserved by immunotherapy, such as colorectal cancer. Next slide. Overall, as I mentioned, people have tried for decades to target Tregs in oncology, and the problem has been twofold. One, broad depletion of T 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. GPCRs 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 screen for lead identification, we found one and only one antibody that exclusively found human CCR8. When we've characterized competitor antibodies, we've also found that they have off-target binding. 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. The idea is that the resistance is being driven by T regulatory cells. The blue line shows that treatment with an anti-CCR8 antibody depletes the T regulatory cells, leading to anti-tumor activity. Importantly, the red line shows that combining the two has enhanced anti-tumor activity. The 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 leads to an infiltration of CD8 T cells, but it's really the combination that changes the immune landscape, remodels the tumor microenvironment to be inflamed with a marked infiltration of CD8 T cells. This image I ask you to remember, so when we show you the clinical data, we can discuss what we've observed in patient samples. Next slide. Overall, we've characterized a large number of solid tumors for the density of CCR8 + Treg cells. You can see along the Y- axis, for 25 cells /mm² is a reasonable density for having a good infiltration of T regulatory cells. 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 +. What you'll observe is that the majority of the Treg cells in these tumor types are CCR8+. Importantly, head and neck and gastric cancer, as well as cervical cancer, have the highest level, with the majority of the Treg cells expressing CCR8 +. On the right, we've tried to summarize the field's knowledge to date for our program, as well as other programs that have disclosed clinical data. 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 used their CCR8 antibody in combination with toripalimab. Additionally, there has been one PR reported with single-agent CCR8 antibody in gastric cancer. We have seen long-term stable disease, as well as others in colorectal cancer. Another partial response for anti-CCR8 antibody has been reported in non-small cell lung cancer. We have seen long-term stable disease in an endometrial cancer patient. This is really setting it up now for clinical exploration, particularly in combination with immune modulators like toripalimab. Next slide. On the poster this morning, we really started by characterizing our two pharmacologically active doses. We had previously presented at ASCO 2024 the dose escalation study showing good pharmacodynamics, as well as safety at doses up to 1,200 mg, dose level 7. What we identified was dose level 5 and 6 to be pharmacologically active. This was defined through preclinical experiments. 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 + Treg cells in the PBMC. What you're looking for are for the gray balls to go lower than the control black balls. You can see that only at 30 µg/mL and 100 µg/ mL do we have statistical significance with the decrease. Furthermore, when we look at the mechanism of action, which is a simple bind- and- kill, so activating killing from the antibody to afucosylated antibody through NK cells, ADCC, or myeloid cells, ADCP, we see the EC50 values to be about 30 µg/mL. Targeted therapies are known to have a strong IVIVC, in vitro- in vivo correlation. We set our PK cross levels in the clinic to be in the tens of µg/mL. Next slide. Here's data from the phase I dose escalation study saying now that if we take that PK drop level and look for immune activation in dose levels, dose level 5 and above that achieves the PK target shown in orange-ish red or blue, dose level 4 and belower, the heavy lines are the median of all the dose groups. The dotted lines are individual patient data. We looked at interferon gamma as a marker of TH1 immune cell activation, as well as activation of CD8 T cells in the periphery with the Ki-67 as a marker for proliferation or granzyme B as a marker for cytolytic activity. What you can see is only the orange median shows activation that's sustained over the dosing interval from cycle 1, day 1, to cycle 2, day 2, supporting that these two 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. What I'll do over the next few slides is to take you through the phase I clinical development plan. This slide outlines the overall phase I design. As you can see, it's in three stages or three arms. Arm 1A is a standard dose escalation in patients with advanced solid tumors. We looked at 20 subjects in up to seven dose levels. Arm 1B and 2 are dose expansion cohorts in head and neck squamous cell carcinoma second- line and beyond. Arm 1B was monotherapy, two doses of CHS-114 in combination with, or rather in with, excuse me. Arm 1B was actually CHS-114 monotherapy with paired tumor biopsies. Arm 2 was combination dose escalation, also in second- line head and neck carcinoma with toripalimab and again, two dose levels of CHS-114. The primary endpoint was safety and tolerability. Key secondary endpoints included PK, objective response rate, other additional efficacy markers, as well as biomarker endpoints. Next slide. The phase IA data was presented at ASCO last year. Essentially, we showed monotherapy dose escalation in 20 subjects. We 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. We showed depletion of peripheral CCR8 Tregs, which displayed establishing proof of mechanism. We also showed proof of specificity in that CHS-114 did not deplete non-CCR8 + Tregs. Based on this, we expanded to two specific dose levels of CHS-114. Next slide. I have already talked about the overall study design. Arm 1A was, as I mentioned, 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 two 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 two dose levels of CHS-114 plus toripalimab, 20 patients in each arm, up to 40 subjects in total. 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. Finally, I'd also like to state that we are expanding into a gastric cancer study as well. This study is currently open also. We're looking at 40 patients overall, 20 patients in each arm with two dose levels of CHS-114 in conjunction with toripalimab. The patient population here is second- line gastroesophageal junction and esophageal adenocarcinoma. Again, we're looking at safety, tolerability, and additional endpoints also. This study is also open and recruiting. 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 Worden at the AACR meeting, which drew 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 seven dose levels. Arm 1B is testing two dose levels, DL5, DL6 of CHS-114 monotherapy in the head and neck second- line population. 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 two different dose levels, DL5 and DL6. Next slide. This slide reviews for you the characteristics of the patients and the tumors of patients who participate on this clinical trial. Really, from a clinician perspective, it reflects what I see clinically as generally applicable to the population of patients who have pre-metastatic head and neck cancer. That is, patients who are generally in their 60s, on average, predominantly males. Typically, it's about a 3:1 ratio and a mixed performance status of 0:1. As you can see, the median numbers aligned to prior therapy was quite substantial, particularly in the CHS-114 monotherapy cohort. The 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 would expect for people with second- line head and neck cancer. Generally, there was a slightly higher risk of adverse events with the addition of toripalimab plus CHS-114. 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. There were no treatment-related deaths. Next slide. The left-hand panel demonstrates the percent change in target lesions from baseline with CHS-114 monotherapy. You can see that in a persistent population, there was disease control in a sizable fraction of this data set. The right-hand panel demonstrates the percent change in target lesions with CHS-114 plus toripalimab. I note for you the patient of partial response, this is only six patients. To see a decent sustained partial response in a small cohort like this is quite impressive in my experience for a resistant population. I'll expand more on this patient throughout the 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. This is a swimmers plot showing you the durability of responses with CHS-114 monotherapy. On the right-hand side, CHS-114 toripalimab, you can kind of sense that the combination therapy might offer some additive durability, which I think is important discussion. Next slide. I wanted to focus on this patient of a partial response. This is actually a patient of mine I treated on this protocol. This is a gentleman who was 64 years old, non-smoker, who presented to his local oncologist with a right neck mass back in April 2023. On examination, he was found to have a mass in the right base of the tongue, which was the actual origin of primary tumor site that led to metastases into the right neck mass. The biopsy should have confirmed this to be a mucosal squamous cell carcinoma originating in the base of the tongue. It was defined to be HPV +. That was the actual etiology of this cancer, which is an emerging common population in the United States for head and neck cancer. On staging evaluations, multiple lung lesions were noted, which prompted a biopsy of one of those lung lesions, which confirmed pathologic evidence of metastatic squamous cell carcinoma. This patient's profiling of the tumor showed a PD-L1 CPS score that is relatively low, 3%-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+ or GERD cancer with de novo metastatic disease. The patient was treated by the local medical oncologist using the KEYNOTE- 048 trial regimen, which included pembrolizumab plus carboplatin plus 5-fluorouracil. Following the initial two or three cycles, a CT scan unfortunately and surprisingly showed progression of disease. Primary resistance to not only chemotherapy but the PD-1 base therapy was observed. Second- line treatment for this patient, which is a little different than usual, was a drug called afatinib. That was based on some genome sequencing data showing a genomic abnormality in the EGFR protein. That drug was tried but failed very quickly. Within eight weeks, the response assessment was resistant disease. The patient presented for third line treatment with dose of Taxol. After three cycles of dose of Taxol, imaging studies not only confirmed substantial disease progression, but by this point, the disease in the right neck was causing significant impingement on the carotid bulb, causing carotid sinus syndrome, which causes drop attacks or syncopal events and tremendous pain in the right neck. We confirmed that this was actually squamous cell carcinoma. I want to repeat biopsies since the behavior of this cancer was unusually aggressive and resistant. At that point, I referred the patient back for a short course of palliation therapy to the neck, which did shrink the infield tumor and did eliminate the drop attack problems from the carotid sinus involvement. The patient returned to me. We restaged the patient after finishing the radiation. The patient's imaging showed that within the radiation field in the neck, there had been a response, yet systemically the patient had progressive disease by RECIST criteria. The patient elected to enroll on the clinical trial with combination CHS-114 plus toripalimab. Next slide. This is a sequence of images, CAT scan images that demonstrate visually the benefit that this patient experienced with combination therapy. On the left-hand side, you can see the pretreatment baseline scan in August of 2024. What you see, the black zone on the right, on the left-hand side under baseline, the black zone on the left is actually the right lung. The black zone on the right is actually the left lung. It is actually the patient facing us. The arrow, the yellow arrow, points out these two large metastases present that sit on top of the diaphragm. If you look north, very top in the same segment of the same lung, you'll see another small nodule in the very north part of that, the apex of the lung. The patient was then treated with combination CHS-114 and toripalimab. On the right, you can see how significant the response was, not only in the largest lesion above the diaphragm, but also in the smaller one at the top of the lung. Next slide. This is a separate additional lung lesion in the supradiaphragmatic region in the left lung. You can see this pretty impressive, in fact, amazing response radiologically with combination CHS-114 and toripalimab. Next slide. These are additional target lesions per study that demonstrate the sequence of responses. These are scans that began on the left baseline. Follow-up one is about six weeks after initiating study drugs. Follow-up two is about four weeks later. Follow-up three was maybe six weeks later. You can see that the response happened early, but it also continued. With chemotherapy, we typically get our most evidence of response in the first two cycles, and then we do not see any further response. Here we are seeing not only an early response, but sustained decrease in the target lesions. Next slide. In the neck region, the patient had very large neck masses. On the left-hand panel, you can see the baseline CT scan of the neck. The arrow is pointing out two abnormalities I want to draw your attention to. Each of these are necrotic lymph nodes. They involve malignant cancer. The right-hand panel shows you after CHS-114 and toripalimab, you can see an obvious visual decrease in the size of these neck masses. Focus on the arrows where the arrows point. That shows you the abnormality. These are rounded lymph nodes. On the bottom set, on the left-hand panel, you can see two abnormalities. The large circle is pointing out a large zone of tumor which is surrounding the carotid bulb, causing this patient's syncopal events, or, well, syncopal events. On the left, on the other side of the patient's neck, the arrow is pointing out a large necrotic neck node involved by cancer. After CHS-114 and toripalimab, the right-hand panel shows you the obvious visual decrease in these tumors, which is all correlated with symptomatic improvement in the patient. The important point about this slide is the following. If you look at the KEYNOTE-048 data set, the patients who really benefited from pembrolizumab as first-line treatment had 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 in the previously radiated field in the neck. That's very unique in the immunology world for head and neck cancer. Next slide. Thanks, Dr. Adkins. It's really a treat to hear the description from the treating physician. I mean, I'll walk you through the biomarker data, which was a really important aspect. I mean, I had walked you through 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. Using a multiplex assay now for the CHS-114 monotherapy with paired biopsies, we're evaluating CCR8 positivity, FOXP3 as a marker for Tregs, and then CD8 as the marker for CD8 T cells. GAPA just looks at the overall nuclei for tumor cells and immune cells. The next slide gives the quantification from the monotherapy- paired biopsies. We were thrilled to see this marked decrease in CCR8 + Treg cells, looking at almost near complete depletion of those cells after two doses of CHS-114. The graph in the middle kind of gives a percent change. There has been preclinical work that has characterized that there needs to be at least a 50% decrease in the Treg cells in the tumor in order to mount an effective anti-tumor immune response. We were quite pleased to see between 52% and 97% decrease in the T regulatory cells within the tumors. Lastly, the graph on the right shows that we have completely remodeled the tumor microenvironment to an inflamed tumor. Looking at the ratio of CD8 cells, the 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. These graphs are good for quantification, but I think the next slide, and that picture tells a thousand words. The green on the far left, you can see the top three panels are the before treatment tumor sample. The three panels on the right are after the two doses of CHS-114. The green showing that the decrease in the CCR8 + Treg cells in the tumor after treatment. 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. The image on the far right is just the blended image. Next slide. We are very pleased today to overall show that we have established safety as monotherapy in combination. We have established good pharmacokinetics in PK. We have shown we hit the target, we tickle the target. Importantly, we have response in a patient that is highly refractory in any tumor type that we would have predicted should be responsive to CCR8 treatment. Altogether, this really has us excited to continue the dose exploration to address Project Optimus in combination with toripalimab in 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 immune- suppressive T regulatory cells. We look forward to continued development of this program. With that, we'll take questions. As a reminder to ask the question, you will need to press star one one on your telephone. To remove yourself from the queue, you may press star one one again. Please stand by while we compile the Q&A roster. Again, to queue for a question, please press star one one at this time. Our first question comes from the line of Michael Nedelcovych of TD Cowen. Please go ahead, Michael. Thank you for the question and thanks for the presentation. 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 predecessors. Thanks for the question. We do have some data from the CHS- 114 trial for patients who received platinum-resistant recurrent metastatic head and neck cancer, and they received nivolumab monotherapy. There was a subgroup of those patients who, when they "came off trial due to progression," continued on nivolumab, and they monitored whether or not there would be a delayed response with that drug. The chance of that response, I believe Fred would call from the data, was less than 5%. Obviously, that's not quite exactly answering your question. That's looking at the same drug as continuation therapy. To my knowledge, I'm not aware of any actual prospective studies that have switched from one PD-1 inhibitor to another in this setting. I am currently doing an initiative trial in which patients have to progress on a PD-1 inhibitor. Every patient on that trial has progressed on pembrolizumab. We have some patients, and on the clinical trial, they receive a chemotherapy drug plus nivolumab. Some of those patients do not tolerate the chemo drug and receive nivolumab alone. 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 one PD-1 inhibitor to another. I don't think I have a good data set to refer you to, but Rosh, when it comes to. No, I think that's absolutely right. We're obviously very encouraged to see this in a patient actually who was fourth-line. I have nothing really to add to that comment. Thank you. Our next question comes from the line of Colleen Kusy of Baird. Please go ahead, Colleen. Great. Thanks. Good afternoon. Thanks for taking our questions and congrats on the data presentation. For us, the biopsy data that you have, I know is for the monotherapy arm. Could you speak to the reductions that you saw in the CCR8 + Tregs? 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. Yeah. No, we didn't see any correlation with the patients who were treated. I mean, I think the thing that we were most pleased with was really showing the drug does what it's intended to do in the two doses that we had selected based on preclinical data as well as peripheral biomarker data to give that marked response now in combination. Overall, for the data that we have reported, there's very limited coagulation activity. Our development plan is really to do a combination with toripalimab. Seeing a response in the first safety three-plus-three design aspect of the study, I think gets us highly encouraged that we're in the right space. Got it. Okay. That's helpful. We'll continue to evaluate that for the four patients that are now being evaluated with tori plus 114. Okay. Great. 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? Just kind of speak to what that evidence is based on. Yeah. There is a preclinical publication done by another group that really characterized the activity in mouse models. It was not specific to any disease. It was more across the tumor models that they looked at that they had to achieve 50% depletion to have anti-tumor activity in a mouse. We set that as a minimum requirement for us. Got it. That is helpful. Thank you. For the patient 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, you do not have tumors. Sure. 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? Yeah. If you look at the picture of the biopsy, particularly the CD8, I mean, the surprise for me in this study was how high the CD8 infiltrate changed and increased. A T cell engager, the way that it works, which I know you know, but I'll just walk you through it, is that it finds the tumor antigen, and then on the other end, it has to tickle a T cell to activate it to kill the tumor. If there's not a high density of CD8s, it's hard to get that. That's been one of the challenges with solid tumors, getting sufficient drug into the tumor and T cell activation. By taking away the immune- suppressive cells, but also bringing in that large infiltrate of CD8s just from a happen chance, just looking at the steric of the T cell engager, it really lends itself. One of the things that from afucosylated antibodies, particularly for lymphocytes, that is a concern for the field broadly is immune-related, confusion-related reactions or CRS. We did not see any of that with CHS-114 in the dose escalation. The safety profile should lend itself to combine with the T cell engagers or bispecifics to really bring in those T cells. Great. Thanks for taking our questions. Congrats on the progress. Thank you. Our next question comes from the line of Brian Chang of JPMorgan. Please go ahead, Brian. Hey guys. Thanks for picking our question this afternoon. 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? Maybe we'll start there first. The patients that responded, we do have the PD-L1 status, which is like a CPS of three, so relatively low but positive. TMB low, so not immune characteristics and maybe consistent with their pembro outcome. We have an N- of- 1 right now. Obviously, for the next phase of the study, that will be a key outcome and why we're really looking to include tissue to understand that. Okay. Maybe just on this point, since you haven't done the analysis on those who progressed, how confident are you that this partial response is not a false positive and whether there is a way to explain to patients who had progressions in your combination cohort? Thank you. 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 at my neck." I said, "I think I agree." The mass was proven, the masses were proven to be smaller on imaging. I was quite astounded, frankly, that that happened. I brought this to the attention of my colleagues. This is a big deal because it's not in my experience as a seasoned investigator to see this occur in an early study of a patient who has resistant disease to not only immunotherapy but to targeted therapy and a series of chemotherapies. For me, it would be hard to come up with a rational explanation why this patient responded independent of the therapy that we administered to the patient. 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. I honestly could not dissect any other alternative explanation. Thank you. Thank you. Our next question comes from the line of Douglas Tsao of HC Wainwright. Please go ahead, Douglas. Hi. Good afternoon. Congrats on the data. I guess maybe first as a starting point for Dr. Adkins, you had one partial responder. I guess I'm just curious what you think from your perspective, sort of the potential for this to be used. Obviously, this was a patient with highly refractory disease. Where would you ultimately envision trying to use this product? Yeah. I think that it's important that you understand that the second-line plus treatment space for recurrent metastatic head and neck cancer is an unmet need. By what I mean by that is that when patients progress on pembro plus or minus chemotherapy, there is no real standard of care on a registrational pathway. There's no active standard of care that I can pull off the shelf. I can administer standard drugs like cisplatin or carboplatin or paclitaxel or cetuximab or 5-FU, but there's no on-label indication in that population. I can tell you of those standard of care drugs I use, the typical response rates are actually quite low, on the order of 10% or less. The actual resistance response rates are really quite shockingly low. The duration of responses are very short. Once you fail the pembrolizumab, it's a very dire situation for our patients. I think that this is a rich market to explore in dire need of 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. The second-line recurrent metastatic setting deserves similar support and attention for our patients. Okay. Great. That's helpful. I guess as a follow-up, just one clarification. Theresa, for the patients in the study, what percent or the proportion that are PD-1 low versus sort of PD-1 high levels? I'll have to go back and look at that. Doug, I don't know that right off the top of my head. Obviously, we're focused on the responding patient, but we will be actively collecting those data. Okay. Great. I guess as a follow-up to that, I mean, do you think that that could have any impact on the results, or would you think that that would sort of, just given Tory's properties, be sort of fairly agnostic to the entire trial? Oh, I think it's a very important aspect with the way that treatment is done in head and neck. A question that we will address in the further expansion cohort, clearly showing activity in CPS less than one would be thrilling. CPS greater than one is still a high unmet medical need. 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 zero low could work is that PD-L1 generally is a marker that there's been an immunologic response. There are CD8s around. There's antigen experience, exhausted T cells to reinvigorate. The fact that depleting the Tregs was able to really bring CD8s in may open up new opportunities for immune modulation for patients. We are super excited to look in PD-L1 low to see if we can change that tumor microenvironment to be more responsive. Doug, I might just add, 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. I don't know if, Doug Adkins, if you want to just comment generally in terms of your patient pool, are most of your head and neck patients, what level of PD-L1 status do they have? A couple of points I would make. Number one, at least in sequential biopsy studies in head and neck cancer, it doesn't look like the PD-1 score evolves in a patient over sequential biopsy. The original biopsy in my patient was a CPS of three, I think. The other thing is, I think even with a CPS 20 or greater, PD-L1 CPS 20 or greater, the response rates tend to be somewhat higher than a CPS of one to 19 or zero for first-line treatment. The correlation coefficient is not real strong. Therefore, it's a target, but it's not a highly predictive target. The final thing is you have to appreciate that all these patients have progressed on a PD-1 inhibitor already. They are already showing you that they need something else beyond a PD-1 inhibitor to achieve a response. That does not mean that they do not need to continue on their PD-1 inhibitor. I think that my mind thinks that they need both drugs to have the optimal benefit. This is CHS-114 and tori is my point. Okay. Great. That is very helpful. Thank you. Thank you. That does conclude the Q&A session and today's conference call. Thank you for participating. You may now disconnect.