INTERIM TAGMOKITUG CLINICAL DATA – WEBCAST - COHERUS ONCOLOGY INC

Good day and thank you for standing by. Welcome to the interim Tagmo Kika clinical data webcast. At this time all participants are in a listen only mode. After the speaker's presentation there will be a question and answer session. To ask a question during the session you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1, 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Kerry Graham. Please go ahead. Thank you, Heidi. Good afternoon and welcome to GoHarris Oncology's Cagnal-Ketog Interim Clinical Data Disclosure Conference Call. Joining me today to discuss our results are Denny Lancer, Chief Executive Officer of Coheres, Dr. Rosh Dias, Chief Medical Officer, and Dr. Teresa Lavallee, Chief Scientific and Development Officer. Before we get started, I would like to remind you that today's call includes forward-looking statements regarding Coheras' current expectations about future events. Actual results may vary significantly, and we undertake no duty to update or revise any forward-thinking statements. Please see the press release that we issued today for more information on risks and uncertainties. And now I'd like to turn the call over to Danny Lancer. Thank you, Carrie. Today I'll be speaking to you about a few things. We'll first talk about the Tegel and Ketog opportunity in esophageal cancer, and then we will give you a data update on some additional indications. This will be followed by a KOL discussion and then some closing remarks and the Q&A. Joining me today is Dr. Raj Dias, the company's chief medical officer, as well as Dr. Teresa LaValley, the company's Chief Scientific and Development Officer. Later on, we'll be joined by Dr. Doug Atkins from WashU, our Head and Neck Specialist, and Dr. Dan Fang from the School of Medicine at Mount Sinai, who will comment on the GI data. Let me talk a little bit about the pipeline and just make one brief statement. I direct you to the bottom of this slide where we talk about our CasDozo-Ketog program, which we shall not discuss today. I will, however, indicate to you that CasDoZo-KETOG is showing clear dose-dependent activity, both with respect to response and duration. We expect to have a data disclosure for CasDoSo-KetoG in January of 2027. Now, our fight against cancer focuses on overcoming immune resistance because it is there that the battle for extending patient survival is fought, and either won or lost. Appropriately, patient survival has been a key factor in the fight against COVID-19. Patient survival is generally the approval endpoint for regulators. So while our therapeutic focus includes the shorter-term reduction in tumor size, or ORR, as it is important, we pursue clinical benefit, duration of response, and stable disease, where we seek to provide patients more life. This is our commitment to cancer patients to extend their lives. And you can see this clearly here. Lactors are nearly doubling the six-year survival of nasopharyngeal cancer patients on a background in chemotherapy versus chemotherapy alone. This is a textbook example of extending survival by addressing immune resistance, in this case, with checkpoint therapy. So today, we report on our efforts to overcome a core part of cancer immune resistance, and how the immune response mediation activity of Treg cells in the mucosal system, extending top to bottom from head and neck through the GI tract, is hijacked by cancer. We have investigated several cancers along various lines of therapy, including first-line esophageal, second-line Esophagell, second line gastric and GI, second-line head and neck, and fourth-line plus colorectal, which are common at a particularly challenging setting. Dagmokita has demonstrated clinical activity across all of these, and as you will see today, these molecule-solid tumor types with over 120 patients treated. I summarize our findings to date here for you, and, as well as our projected development direction in first-line and second-line esophageal cancer. First, across these studies, we saw a durable response and disease stabilization in pretreated IO-resistant populations, thereby demonstrating the ability to reverse immune exhaustion and rescue T-cells. With these studies we saw broad pan-tumor activity of Tegmo ketone, including in head and neck cancer, with enrichment for HPV-positive disease, and in GI cancers, demonstrating clear dose-related activity. Very importantly, we saw no new safety signals beyond what is seen with PD-1 inhibitors and very manageable safety profile. Now, the esophageal studies have shown particular promise, with the confirmed overall response rate of 75% in all comers, that is inclusive of PD-L1 high and low, and 100% in PD-1 positive patients with an individual of eight evaluable patients in first-line esophageal. Dr. Dias will address this momentarily. The clinical benefit in first line and second line esophagal patients with PD-O negative tumors was also of note. And as I indicated, we now will proceed with an integrated development plan forward in both first and second line, which Dr. Lavalle will further talk about. We plan to expand cohorts to add more patients and add more longer follow-up and this year leverage FDA designations as we've discussed with them, the path forward and these additional cohorts and patients. that, I'll hand the call over to Dr. Dias to discuss the specific results in first-line esophageal for you. Raj? Thank you, Denny, and good afternoon, everyone. So today, I will present data from our TregCheck program. As a reminder, this is an ongoing program with continuing data entry, and so what I will be presenting will be the interim data from the program. We will present from our GI program in four tumor settings, starting with esophageal squamous cell carcinoma in both first line with chemotherapy and in second line. And our esophgeal squamous cell cohorts will be the main focus in our development presentation due to the strong activity we're seeing. I'll also cover upper GI adenocarcinomas and colorectal carcinomas, as well as data in the PD-1 refractory head and neck squamous cells carcinomic cohort. As I go through the various cohorts, I'll cover key efficacy metrics and safety data. For efficacy, as you heard from Denny, the important metrics focus will not only be objective response rate, as well as clinical benefit rate as well, a metric that includes CR plus PR plus stable disease greater than six months. CBR is an important measure of durability in early stage trials, which is particularly important as the benefit of IO has been in extending the tail of the curve and improving survival, which of course is the approvable endpoint. Let me now start first with first-line esophageal squamous cell carcinoma. This was designed as a single-arm safety cohort with 12 treatment-naive patients with advanced metastatic disease, including patients that included both PD-L1 positive and negative tumors. Enrollment is ongoing, and at the data cutoff date, 10 patients have been dosed and 8 patients are evaluable. We investigated our planned go-forward dose of 700 milligrams of tagmaketug in combination with toripalamab and with the U.S. standard of care chemotherapy, that is 5-FU and cisplatin, with safety as a primary endpoint and additional efficacy secondary endpoint. In terms of regional accrual, this was a multi-regional cohort with 20% of patients from the U-S. with 80% from the Asia-Pacific region. This slide outlines the interim clinical activity from the evaluable population in a waterfall plot. Whilst the data set needs expanding, as you can see, tumor shrinkage was observed in 100% of evaluable patients. And as you see from the legend below the waterfall plot showing PD-L1 status, the tumor shrink is importantly was observed irrespective of PD-1 status. So not only for PD-L1 positive patients, but also in patients who are PD-O1 negative, which, as you know, is not within the current approval in the U.S. label for PD1s. In terms of best overall response, of the eight evaluable patients, one patient had a confirmed complete response, and additionally, five patients had a confirmed partial response, of whom two patients continue on treatment, as marked by the vertical arrows, overall representing a 75% confirmed overall response rate. For the two remaining evaluable patient from the far left of the waterfall, one had an unconfirmed PR, so meaning at the time of data cutoff, they had just received a single scan and are waiting for the next scan to see this confirmed, and the other patient had tumor shrinkage, not quite meeting the criteria for a confirmed PR, but showing durability beyond six months and continues on treatment. These two patients were PD-L1 negative, and again, they do not qualify at the moment for IO treatment in the U.S. For the PD-1 positive patients, all responded with either a confirmed PR or CR representing a 100% ORR in this population. Since our data cutoff date of October the 14th, there has been some further improvement in activity with no attrition. We've since verified two additional participant scans that reflect the following. Firstly, the second from left patient with a PD-L1 negative unconfirmed PR has been confirmed. And secondly, a new evaluable patient who is not therefore currently represented on this waterfall has confirmed a PR. If we were to include these additional scans since the October 14th date, the ORR in the evaluable population would go from 75% to 89%, and an ORR in PD-L1 positive patients would be maintained at 100%. For context, and bearing in mind that cross-trial comparisons do have limitations. The current standard of care of a PD-1 with chemo in the first-line setting have shown between a 44% and 59% ORR in PD-L1-positive patients, and so we do remain very encouraged by the interim activity demonstrated here. But as we stress, durability and long-term stable disease is very important, and we look forward to these data continuing to mature. And while these compelling data need to mature for durability, This does warrant cohort expansion to a larger data set, up to 30 or 40 patients. This slide shows a representative CT scan from this cohort, and this is from the patient who had the complete response. Let me first orient you. This is an axial CT scan looking at a cross-section of the upper esophagus, showing an esophageal mass on the top panel and a supraclavicular node on the bottom, with baseline scan on the left and a follow-up scan on the right after almost eight months. The participant had a PD-L1 positive MSS tumor. Looking from baseline on the Left to follow up five on the right what you can see is complete disappearance of the target lesion in the esophagus. This is marked by the white arrow at the center of the left scan which is no longer visible on the follow-ups scan on right. There's also very clear diminution in size of the supraclavicular lymph node that you can see on the scan below. Overall, there was an 88% reduction in target lesions at the time of the reported complete response, and the response had also extended beyond target lesion. All non-target lesions had disappeared after eight cycles, and no new lesions had appeared, representing a very deep response in this patient. The spider plot here represents the eight evaluable patients, and this reflects the speed and the durability of the response. Again, all participants demonstrated tumor shrinkage. We were all seeing this at the first scan, so this represented a very rapid onset of response. In terms of durability, PFS is not as yet mature, but I can highlight a couple of relevant points. Firstly, 50% of patients, so four patients, still remain on therapy, as noted by the red arrow on the end of the relevant patient line. Secondly, two patients have demonstrated activity for close to eight months, with the patient that is in stable disease still continuing on treatment. And note again that this is the patient who is PD-L1 negative, again reflecting activity irrespective of PD-R1 status. So we do anticipate the potential for continued evolution of durability as the median PFS continues to mature. Let me now move on into the second line, esophageal setting. So this, as you know, is a tumor setting where there is a huge unmet medical need, where the current standard of care remains chemotherapy for PD-1 experienced patients or a PD-2 inhibitor for PD1 naive patients. This cohort is an advanced or metastatic esophagal squamous cell population with patients who have experienced progression after treatment with chemotherapy with or without a prior PD-L1. We have a target enrollment of 20 total patients with 300 or 700 milligrams of TAGMO in combination with Tauri and with 10 patients in each dose level. Again, safety is the primary endpoint with efficacy as secondary endpoint and 17 of 20 patients have been dosed thus far. This is also a multi-regional cohort and around 30% of patients were from the US, and this was a population that included PD-L1 refractory as well as PD-O1 naive patients. Let me orient you first to the waterfall plot that you see here. The green represents the 300 milligram dose of TAGMO with 700 milligrams in blue, of course, both in combination with toripalamab. On the legend below, you see best overall response, prior PD-R1 status, and time since last PD-1. And as you can see, of the eight evaluable patients, all but two had a best overall response of either stable disease or partial response, with one patient having a confirmed partial response equating to a confirmed ORR of 16.7% in the 700 milligram dose, and an additional patient having an unconfirmed PR with treatment still ongoing. The confirmed PR was in a patient whose tumor was PD-L1 positive, whereas the unconfirmed PR was in a patient with PD-O1 negative tumor, again, representing activity irrespective of PD-R1 status. The CBR, and that is, as a reminder, CR plus PR plus stable disease greater than six months, was 33.3% in the 700 milligram target dose, representing the potential for this doublet as a chemo-free regimen in this tumor setting. The swimmer's plot for second-line esophageal squamous cell, this showed all dosed patients, and this really does outline the activity we believe to be compelling in this cohort, and that is the clear TAGMO dose response. As you can see, there is a very clear dose response in this randomized cohort. The 700 milligrams TAGMA with taurine blue shows benefit, whereas the 300 milligram dose in green is not sufficient. At the 700 milligram TAGMO dose, we saw both the confirmed and the unconfirmed PR, and also what's pretty striking is the long-term stable disease, showing durability of activity in this dose level. Of note, two patients are still continuing treatment close to eight months, including one patient with a PD-L1 negative tumor. Whilst the data set is small and still maturing, the current median PFS of 5.5 months is encouraging, and with six patients in this cohort still continuing on treatment, several of whom are either in stable disease or unconfirmed PR and awaiting further scans. We do look forward to this data continuing to mature further, too. As a relative comparison, again, with the usual caveats of cross-drawer comparisons, the current standard of care provides a median PFS of between two and four months and overall survival of less than a year. The safety profile for both first line in combination with chemo, and second line as the TAGMA-TORI doublet is very consistent with the overall integrated safety that I'll outline later. In the first line setting, the discontinuation rate is around 40%, but of course this is in combination with chemotherapy and is also very similar to the overall discontinuation rates reported, for example, in Checkmate 648 in the same setting. Across both lines of therapy, there were no Grade 5 TAGPA-related events. most common aids related to any study drug as shown, and the safety profile for both esophageal squamous cell cohorts support continued development. Let me now hand over to Teresa to talk about the integrated plan moving forward for ESDC. Thanks, Josh. We recognize we need more mature follow-ups and clearly more patients, but the signal to date is compelling. And while we see activity across tumor types, which Ross will show you in a couple of minutes. The early interim data here are exceeding benchmarks. The coherence objective for additional tumor types for toropalimab approval beyond MPC has always been through improving standard of care with PD-1 beyond where it is today and bringing immunotherapy to patients who are ineligible. So, we see that that objective is possible in these data sets. So, let's move on to the benchmarks. So shown on the left in gray in the first line setting, you see the three approved PD-1 inhibitors plus chemotherapy in the United States, showing an overall response rate about 50% to 60%. While toropalimab through the Jupiter-6 study is approved in China and Europe, it is not recognized by the U.S. FDA because it uses a different chemotherapy that's not used in U.N. medical practice. It did not include U.K. patients. The TRED-CHECK program incorporates U.S. standard of care and U.F. patients, and we see an overall response rate in the PD-L1 positive patients of 100%. Importantly, patients with PD-1 negative tumors, the FDA removed the label from PD-I. So the only standard of care therapy is chemotherapy. It was the lack of benefit that made them revise the labels. Here we're seeing activity. So 75%, 100% are big numbers. What always you would expect with more follow-up is attrition. We were pleased to see at the first look where we have another partial responder confirmed and a new evaluable patient as a partial response. We maintained 100% and improved the 75% to 89%. So in the second line setting, Rush showed you that swimmer's plot. When those patients are so sick, they can't swallow, they're malnutritioned, they've gone through first-line chemo. When they fail, they fail fast. In the underdose Tegmo-Ketog dose with Torapalimab, we see only one patient made it past six weeks on study treatment. In the 700-milligram dose, we see a number of patients on past 33 weeks. Eight months is the chemotherapy median overall survival endpoint. So that's why we focus on the clinical benefit rate, because this long-term stable disease is meaningful. So, what we show you here is that adding TAGMO T-TUG to toropalimab has improved on PD-1 treatment, has in PD-9 naive patients, and in less inflamed tumors, such as PD-L1 negative. And in the second line setting, we've shown activity in PD1 resistance. So TAGMO's T-TUG can add to PD-L1 in all settings. Next slide. Shown here on the right-hand side of the slide is the data that we've talked about for Jupiter-6 with toropalimab in chemotherapy from the China study, where we see activity irrespective of PD-l1 status, as shown by the hazard ratio being the same. So why do we think this is true? We see this due to potency. Torapalimab has a higher biting affinity and a unique epitope. So when used in combination with chemotherapy, the less inflamed tumor can have activation of the anti-tumor immunity due to this potency, that is not true in the absence of chemotherapy. So, in the second line setting, where IO alone is showing activity in PD-L1 negative patients, that can be attributed to Tragmokita, bringing in that remodeling of the tumor microenvironment and overcoming a less inflamed tumor. So, exactly the objectives of what we wanted with depleting Tregs from the tumor and remodeling the tumor microenvironment. Next slide. So how do we take this forward? We said expand the patient data set to 30 to 40 patients, get more mature follow-up, and engage with FDA about favorable regulatory strategies. So with this compelling activity, what we see is two drugs, two approvals, or two drugs two indications that can really change the treatment landscape in ESCC for a best in disease opportunity. So bringing in the opportunity to take two studies with randomized controlled trials and looking at accelerated approval endpoints with surrogates of ORR and DOR early on, and in the same study, using it to convert using the overall survival endpoint. endpoint. This has been done in the first-line setting by an initiative from FDA called Project Frontrunner, where they're encouraging development in earlier lines of therapy, and this was successfully implemented by Pfizer with the Breakwater study, where they achieved accelerated approval at the end of 2024 on the ORR-DOR endpoint, And about a year and a half later, got full approval based on the OS data. So, next slide, please. So, immediate next steps are meet with FDA and align on the go-forward dose. We've shown you the 700 milligram data. here, you'll see in the next set of studies that the GI tumors do show nice dose response. We see in head and neck cohort that both dose levels are active. We think this is consistent with the biology of that viral-driven tumor and it being highly Treg sensitive. So the lower dose is able to overcome in a highly inflamed tumor to bring anti-tumor immunity and see activity. When we look at the tumor biopsy data in the head and neck cohort, we do see higher immune activation with the 700 milligram dose level, consistently giving us confidence in the 700 milligram dose as the go-forward dose. So, I also want to call your attention to the far right portion of this slide, where we talk about the full BLA package, in that 50% of the spend, 50%of the risk is also on the CMC components. Given the biosimilar heritage of Coheris, we feel confident we can put together a robust and quality CMC package for a BLA submission. And importantly, we've moved all manufacturing for our investigational agents to the U.S., really enabling ease of inspection for the FDA. We will look at all expedited programs and all ability to move these programs forward, the last being Project Orbis, because in mentioning two drug approvals, which adds complexity. In Europe, toropalimab is approved in first-line esophageal squamous cell carcinoma. Project Orbis is an initiative by FDA that allows for concurrent submission and review of BLAs to multiple health authorities, including Europe, Japan, Singapore, Canada, U.S., working collaboratively together. So having toropalimab approved in this indication could be leveraged to decrease the complexity in getting both drugs approved in the U.S. Thank you, Teresa. As you can see, we have launched a very well-considered clinical program with five different indications or lines of therapy. and we have now elucidated a particular indication, esophageal cancer, where we believe we have a very synergistic and executable approach for first and second line. First of all, it leverages the differentiated activity and high unmet need in both settings. We believe there is a highly efficient development path, and as Teresa outlined, one with the potential for accelerated approval, leveraging various FDA indications. There are multiple paths to market, and there is a broad patient population given the ability to address both PD-L1 positive and PD-1 negative with no selection. It's also potentially a global program. As Teresa indicated, Torpalimab is approved in Europe for esophageal irrespective of PD-O1 status, which creates the opportunity for, we believe, ready partnerships. There is also a high disease burden ex-U.S., particularly in Asia, in China, and in Japan and other places, which opens the global development and partnering opportunities, given this very promising data. Here in the U.S. there's approximately 5,000 to 7,000 patients to be addressed across these lines of therapy. As we will be using two novel agents for coherence, this translates to an economic opportunity of about $1.5 billion and a rare indication which is very suitable for our commercialization efforts. With that now, I'll turn the call back over to Dr. Dyes, who will talk to you a little bit about some of the other indications that we evaluated. Thank you, Denny. So let me move on now, first of all, to our head and neck squamous cell cohort. As a reminder, this builds upon the data that we presented last year in 2025 at AACR from earlier stages of this trial, where with tagma monotherapy, we showed clear tumor remodeling to a more cytotoxic state with depletion of the intratumoral CCR8 positive Tregs and an influx of CD8. as you can see in the immunofluorescent slide on the top left panel, and clear antitumor activity with the addition of tori on the bottom left panel with a PR in a fourth-line patient whose tumor was refractory to a prior PD-1, a taxane, and a TKI. The current cohort I'll report on is interim data from the second-line specific population. So this is a relapsed metastatic second-line head and neck population, who must have received a prior PD-L1. We enrolled 43 patients, all in the U.S., 25 in the HPV population, offering 23 were evaluable with 300 or 700 milligrams of TAGMO in combination with TORI, with a roughly equal split between the two doses. Again, safety was the primary endpoint, with additional efficacy measures as secondary endpoints. We communicated at our last earnings call that we have seen activity both in terms of response as well as duration with enrichment of activity in HPV-positive patients, and you can see this in the waterfall plot here. The waterfall shows HPV positive, evaluable patients with both doses, 300 milligrams in green and 700 milligrams in blue, in combination with toripalamab. The majority of the patients with HPV-positive disease, as shown here, did have activity reaching criteria for either a partial response or stable disease at active doses, suggesting that TAGMO is able to rescue PD-L1 resistance at both of these levels. In this HPV positive population, there were three confirmed PRs and one additional unconfirmed PR with activity in both PD-O1-posive and PD- O1-low patients, resulting in an ORR of percent and a CBR of 26 percent the durability in particular was encouraging with several patients in the second line HPV positive population out past six months of treatment we also saw a patient continuing treatment for past one year and this patient still remains on treatment this is encouraging for a couple of reasons firstly as we've mentioned durability is a very important measure of activity because this of course is the best correlate to survival and survival is the approvable endpoint secondly the enrichment of activity in the HPV positive population represents a key area of unmet medical need as many of the emerging therapeutics are either focused in on the HPB negative space or have activity that may be driven by HPV negative populations this suggests the potential for further study in this HPV-positive population importantly with this as a chemo-free regimen, which represents a relative white space in terms of key development opportunity for patient benefit. The other area for potential enrichment that we've seen is with the baseline immune context. The Tumor Immune Regulatory Index, or TIRI, is a tumor-derived CCR8 containing biomarker scores which defines the baselineimmune context. We know that HPV-positive tumors exhibit greater immune sensitivity and Treg-driven immune suppression. What our correlative work shows is that TRE further enriches for both ORR as well as CBR in this HPV-positive population. On the left, we have the HPV negative patients, on the right, HPV positive. I'll make a couple of observations. Firstly, both ORRR and CBR overall are higher in the HPV population over the HPB negative population. Secondly, TIRI does enrich for activity in the HPV negative population, however, in HPV positive patients not only was the ORR and CBR higher than in those that were HPV-negative, but the enrichment by TIRI takes the ORRR from 13% to 18%, and more importantly, the CBR from 26% to 45%. Again, Again this is an improvement in durability and in particular it's encouraging as this represents a potential enrichment factor as we seek to move through the development pathway. In terms of the safety in the second line head and neck squamous cell cohort, this again was consistent with the safety profile seen across cohorts with the most common AEs related to any treatment being fatigue, infusion related reactions and diarrhea. The safety was overall acceptable and manageable, which in this context of emerging clinical trials is, of course, a very important point. I'll now move on to our upper GI adenocarcinoma cohort. This was a relapsed metastatic population, including gastric cancer, gastroesophageal junction, and esophageol adenocarcinoma, which, of course, is all the same adenocalcinoma histology. Patients were HER2 negative with tumors with a lower mutational burden, and all must have received prior chemo with a platinum and 5-FU with or without a prior PD-1. We enrolled 40 patients across the two active doses of 307 or 700 milligrams of TAGMO in combination with TORI, again roughly evenly balanced between the two doses, and again with safety as primary and additional efficacy measures at secondary endpoint. This was a multi-regional cohort with 60% of patients from the U.S. And the predominant anatomical site was gastric, representing around 60% of the population, followed by GEJ and then esophageal adenocarcinoma. And about a third of the patients were PD-1 naive. The waterfall plot here shows the overall activity in the response evaluable population, with the 700 milligram dose in blue and 800 milligrams in green. In our target go-forward dose of 700 mg, we saw four confirmed PRs, resulting in an overall response rate of 23.5%, three of whom were refractory to a prior PD-1, and a CBR rate of just under 30%, both suggesting that TAGMA with Tauri can rescue PD-2 resistance in this population. As you can see in the legend below the waterfall plot, tumor shrinkage was observed in both PD-L1 high and low tumors, and was observed across all three anatomical subtypes, including two PRs in patients with EAC. So again, the latter represents activity in esophageal carcinomas. Six patients from the response-evaluable population still continue on treatment, suggesting that there may be continued potential to improve on this interim data. The tumor plot again shows very clear dose response in the upper GI adenal cohort as well, with 300 milligrams on top in green and 700 milligrams bottom in blue. All responders have thus far been at the 700 milligram target dose, and as you can see, the durability is also more marked in the high dose, with several patients continuing past six months of treatment. This again speaks to the potential for durable benefit in this upper GI adeno cohort. As a reminder, the current standard of care for second-line upper GI addenos remains ramiserumab and paclitaxel, And so a chemo-free doublet would be a very valuable option for patients in this setting. In terms of the safety profile, again, the profile here was consistent with the safety across all cohorts, with the most common AEs that are related being confusion-related reactions, pyrexia, and lymphopenia. There were no grade 5 tagma-related events at either dose. And overall, the safety, again. was acceptable and manageable. And let me end now with our colorectal cancer cohort. Here we look to the very late-line relapsed metastatic population who had exhausted all approved prior standard therapies, including, for example, opseliplatin, irinotecan-based chemo, afluoroperimidine, or others. So this is essentially a fourth line and beyond population with a focus on patients without liver med. The main goal of this cohort was to determine whether we could see activity in this late line setting that may then allow us to move into earlier lines of therapy in colorectal carcinoma. We enrolled 20 patients as a single arm cohort with 700 milligrams of TAGMO in combination with TORI, and again, the primary endpoint was safety with additional efficacy measures as secondary endpoints. This is also a multi-regional cohort with approximately 60% of the enrollment coming from the US. What you see here are the waterfall and spider plots for the response-evaluable population. First, on the waterfall plot on the left, we did see tumor shrinkage in this very late-line population with just over half of the response evaluable population showing some degree of tumor shrink age with one patient achieving a confirmed PR representing a confirmed ORR of 6% and a CBR of 12%. and in addition, we did have several patients with tumor shrinkage approaching but not quite reaching the criteria for a partial response. Additionally, we saw molecular response with ctDNA decline and CEA decreases, as you can see in the legend below the Ward 4 plot, broadly but not universally correlating with tumor shrinking. The spider plot on the right shows the durability in this very late-line population with three patients being treated past 24 weeks, two of whom are still continuing on treatment, which again is not trivial in this very late line population. Activity in this population supports moving to earlier lines, which was our original intent in exploring the fourth line plus setting. And finally, in terms of safety for this CRC cohort, again, this was consistent with the safety profile across cohorts with the most common related AEs being fatigue, rash, and anemia. Overall, again safety was acceptable and manageable with TAGMA-related grade 3 plus events seen in 10% of patients with no grade 4 or 5 TAGMO-related events. So before we move on to our panel discussion, let me just summarize a couple of points. So we're pretty encouraged overall, as you've heard, by the data that we've outlined over the past few minutes, which has shown clinical activity across the cohort and, importantly, an expected and manageable safety profile in combination with TORI and also in combination with chemotherapy. The ability to combine with chemo gives us the ability to move into earlier lines of therapy where it's well known that immunotherapy is more active. Whilst this is interim data, the ESCC data offers a clear potential for continued development in a tumor type that is hugely underserved with a clear unmet medical need. In first line, with strong activity, tumor shrinkage irrespective of PD-L1 status and initial durability. This offers a development opportunity in combination with chemo. In the second-line setting in esophageal squamous cells, activity and clear dose response has been demonstrated, which allows development then as a chemo-free option. Additionally, in the GI cohort, the activity is observed in the 700 milligram dose with the 300 milligram dose showing limited benefit, and that gives us confidence in the data being TAGMA-driven and also in the dose. And the enrichment of activity in HPV-positive head and neck offers a clear path to continued development in an area of relative white space. Overall, we're also encouraged by the safety profile across the program. Earlier in programs through TAGMO monotherapy dose escalation, we showed no DLTs up to 1,200 and low-grade immune-related AEs, showing targeting the CCR8-positive Tregs is relatively sparing of peripheral tolerance. In combination with TORI across over 120 patients, we've also seen no new safety signals over what is known for PD-1 inhibitors. As expected, we did see an increase in immune-related AEs. But importantly, this has been manageable and compares favorably to IO-IO combinations, such as ipinevo, for example, as you can see on the right panel. We've seen comparable safety across both the 300 and 700 milligram doses with similar immune-related AEs. Most of the AEs with TAGMA and TORI were grade 2 or less and resolved with no grade 5 treatment-related AEs, and in our first-line esophageal squamous cell cohort with TAGBA and TORi in combination with chemo, again, we demonstrated a manageable safety profile, no new safety signals, and the majority of AEs were attributed chemo. The safety profile is very similar to other phase three studies with PD-1 inhibitors and chemotherapy that led to their U.S. approval. Overall, the most common treatment-related AEs with the tagmatory doublet have been infusion-related reactions, fatigue, and rash. So let's move on to a brief panel discussion. I'm delighted to be joined by Dr. Doug Adkins, a head and neck oncologist from Wash U School of Medicine, and Dr. Dan Feng, a GI oncologist from the Icahn School of medicine at Mount Sinai. Drs. Adkins and Feng, thank you very much for joining us today to share your perspective. As mentioned, activity across GI cohorts with a particularly strong signal in ESCC that warrants further development is pretty exciting for us, and also with activity in head and neck squamous cell with enrichment in HPV positive patients. I'd be particularly interested in your thoughts initially as clinicians treating these very hard-to-treat cancers about your impressions on the early data across cohorts and how this could fit in with clinical practice. So perhaps we can just start with esophageal squamous cell, particularly in the first-line setting, and really just discuss your initial reactions to the first line data. And I'll just remind you, as you know, we saw an overall response rate of 75 percent in the evaluable population, which then goes up to 89% if we include additional scans since the October 14th cut. So maybe I can open it up to Dr. Feng. Dr. Feng, maybe some initial reactions to the esophageal data, starting with first line. Yeah, thank you. So I am a GI medical oncologist. I treat these diseases and I'm involved in a lot of the early phase drug development in this space. So from more my perspective, I think I want to just highlight a few things so that what my thoughts when I hear and see these data is one, I mean, we know that esophageal claim is actually a very bad disease, very poor prognosis. Most of our patients from the time they got diagnosed with advanced diseases, they have a median survival about 15 to 17 months. This is also a disease that we don't have effective options past the past the first slide. So for me, looking at the frontline data you have with Tori plus Tecmo plus chemo, I was very impressed with the high response rate because you would show the data that close to 90% for all-comer and 100% for the PD-L1 positive patients. I think that it's worth noting that also that the benefits are also seen in the patient with PD-O1 CPF less than one, know we call them PD-L1-negative patients. This is way better than what's been reported in the clinical trial and what we've seen in our everyday clinical practice. In the second line setting, the combo without chemotherapies also has shown really impressive activities because this is a space that we really rely on single-agent chemotherapists and what patients who were previous treated with PD-L1 or PD-1 antibodies, there's really no great option from these for chemo. And a lot of the patients are heavily pretreated when they get to this point. So I think it's worth noting that the combo actually have two responses. I know one is unconfirmed among all the six patients, and including patients who have PD-O1 negative status. So I was encouraged by the data in the front line and the second line setting in the esophageal of squamous cell carcinoma. Thanks, Dr. Feng. You know, you alluded to the fact that we saw activity irrespective of PD-L1 status in the first line setting in particular. What are your thoughts on how this could fit in with the treatment paradigm? Because as we've said previously, PD-1s are not approved in the PD-O1 negative space. Yeah, so I think that this combination definitely have activities that in the PD-L1 negative patient population. So I think if we're going to look into further clinical studies, we should definitely include those patients, and this provides a great option for those patients. Thank you for your perspective. The other point that we were discussing was second-line esophageal, where, as you quite Like you said, these patients are very, very advanced and typically have a very poor performance status. What are your thoughts on the potential for a chemo-free option in this setting in particular? Well, so a lot of times in this patient population, we were using single-agent chemotherapies, right? So I think the chemo free option is quite attractive for the patient in this population. and also especially for the patient who is PD-L1 negative. Yeah, absolutely. Dr. Adkins, did you have any comments on the esophageal data that you saw today? Yes, I agree with Danny. Dan, I think the data showing activity in PD-1-0 patients is particularly interesting and applicable to patient care for which we don't have a good immunotherapy approach. And what were your initial reactions to the overall response rate that you saw in terms of tumor shrinkage across all of the patients? It does seem to be more favorable than comparators in the literature. Thank you, Dr. Atkins. Maybe we can move on briefly to head and neck. You know, you saw the data there with activity overall, but more enriched in the HPV-positive patients. I'd be very interested in your thoughts, Dr. Adkins, on, you know, what is the competitive environment or what isthe unmet need, really, in theHPV- positive space, and, of course, any reactions that you had to the data that you've seen in the head and neck space. There are two striking findings that I observed in review of this data with TAGMO and toripalamab. Number one was the interesting observation of the apparent sensitivity of HPV-positive disease to this combination. And number two was the durability of CBR. The current data in my review of the context of literature shows that for patients with HPV-positive PDA1-refractory, platinum-refractory disease, current drugs result in at best a 10% progression-free survival at four months. When I reviewed the data for TACMO and toripalamab, it looks like that number is close to 40% which is very striking. So although the response rates are relatively low, the durability of clinical benefit rate is striking. And the fact that it's demonstrated in HPV-positive disease is a very unique data set. Generally, most of the registracial pathway drugs that are being pursued in recurrent metastatic head and neck cancer are focused on HPV-negative disease. The number of EGFR by functionals are, for the most part, targeting HPV negative disease. There's very little going on in drug development for the HPV positive population, and that represents about 30% of patients with recurrent meta-static disease. So there's a clear unmet need for looking at strategies to target HPV-positive disease. It looks like Tacotamab, Tacmo, and toripalamab might be that combination worthy of pursuing. Thank you, Dr. Atkins. You know, one of the other things that we think about with HPV positive patients, of course, these patients tend to have, you know, more, a better performance state as often. They tend to be working as well. So I think that may also be a potential opportunity for these patients. What are your thoughts on the safety profile, again, in the context of the emerging therapeutics? I do think it's, in my experience, the combination has been quite tolerable. Many patients have had limited side effects, and the side effects that I have observed that you've shown in your slides, infusion reactions or diarrhea or transaminitis, have been mild and manageable with appropriate therapy. In terms of impact on quality of life, I found it, compared to chemotherapy, far better quality of life on this combination. So I do think there's good rationale for a favorable adverse event profile. Thank you, Dr. Atkins. Very helpful to get your perspective on that. Maybe we can get some initial thoughts, Dr. Feng, from you on the upper GI adeno cohorts and the colorectal as well. As a reminder, I think, you know, a couple of the things that I said was that we saw very clear dose differentiation in terms of activity with the upperGI adeno cohort. also remember that we had those two additional patients with EAC within that cohort, also perhaps forming a little bit of a package here, really, in terms of being able to plant a flag in a real area of unmet medical need in esophageal. What are your initial reactions to the upper GI adeno data that you've seen before we move on to colorectal? Yeah, so we, in this space as one, And I think the few things that I really noticed from the data are, one, as you pointed out, it's the 700 milligrams that really make a big difference. And that's the two effective doses per patient in this population. Two is that I think that in the second-line setting, while we did not really see, I mean, the response rate is somewhat comparable, is not superior to the current standard care chemo chemo plus the ramacizumab option, I think that I definitely would appreciate the toxicity profile, at least I've seen in my own experiences and also from your own data, for these patient population, because this is also a population, a lot of them also, again, very heavily pretreated, because we now use FLOT in the locally event settings. So two is I think that we just unfortunately haven't had the mature PFS data yet, but I'm hoping, based on the trend we've seen right now, I look forward to see the PFS datas because I think in your experiences and also in your preliminary data, this suggests that DO-IO not only is an attractive option for a patient who is heavily pretreated with chemo, but also can potentially have a much more durable response. And the last thing that I do want to note is that I think the responses in PD-L1 pre-treated patient. The vast majority of your patients are in your cohorts or treated with PD-O1 or PD-1 before. And actually, I think the first three out of the four patient responders were actually treated before. So I think that the signal, the efficacy we've seen in patients who were previously treated with PDO1, that's also, I don't think for me, that For me, that's actually really worth noticing. That's exciting. That's awesome. Thank you for, again, your commentary there. Colorectal, as I said in our comments, the whole intention here was to start in the late-line setting, see if we can see activity in a very hard-to-treat population, and then maybe think about progressing early in the treatment paradigm. What do you think of the data in terms of support of that strategy for colorectals? Well, so we've seen the single, we've seen the combination activities, even though it's very limited signals in the event settings. Personally, I think that in the a lot of the colorectal, in my experience, a lot of the corectal patients have gone through two, three years of more therapy until they get on the clinical trial. And the efficacy of IO in that patient population was really was really poor. So I think that with the preliminary, with the limited clinical activities even in the advanced setting doesn't mean that this, I actually personally think that there is potential more activities in the earlier line setting before the patient has gone through years of chemotherapies. And I think colorectal is a space that there's a lot of changes over time, And I do think that an earlier line potentially can have more, we can see more IO activities and that your safety profile actually in the esophageal cancers, as well as your own safety data on the dual and the TACMO plus the TORI, I think that supports us to move into the earlier line to combine with chemotherapies. Very helpful. I know we've taken up quite a little bit of your time. You know, as a company, we're very proud of being able to explore therapeutics in areas of real unmet medical need. So perhaps I could just end with by asking your final comments, particularly on the esophageal space, where we do believe there's low competitive density in terms of the developmental environment married together with a real unnet medical need, So perhaps I can just ask for some final comments, both in the first line setting in terms of development in combination with chemotherapy for this doublet, and also in second line as a chemo-free option as the doublet itself. And Pat, Doug, we can start with you, and then some final thoughts after that from Dr. Feng. Russ, this is for Sabhajil, you said. Yes. Yeah, first line as well as second line. in terms of the unmet medical need, perhaps the lack of the competitive options within this space and the potential for the four-drug combination, so Tagmatori in combination with chemo in the first line and as a chemo-free option in the second line for Tagmatory? Well, combining Tagmo Tori with chemo is a tolerable regimen, and it's important that adding drugs to the chemo as a tolerble combination, and I think that those two agents are clearly tolerable and safe to combine with chemotherapy. The initial activity, particularly in PD-1 and 0 disease, is very promising, and also in patients who have PD-1 refractory disease is very promising. So in both the first line and the second line plus settings, the rationale looks very favorable to proceed forward with those combinations. Thank you, Dr. Atkins. Dr. Feng, any final thoughts on esophageal squamous cell and the data that you've seen? I think the ESCCs really represent a field that has a lot of man needs. I mean, as I pointed out earlier, I think the overall prognosis is still very poor with these diseases. We lost the majority of the patients within the first year and a half. So, and then this is, so for me, a disease is at the, and a lot of times that the esophageal cancer, when recurrent locally, can cause a lot difficult trouble eating and rapid decline in the patient's nutritional status and functional status. So I think there's a huge need to improve the response rate in the front-line setting and also in the second-line settings because we really don't have very good options in there. This is a landscape that's also changing, too. There are other drugs that are currently in development, but I think a pure IO combination provides an attractive option for these heavily pretreated patients as well as for patients who really need doable disease control. Wonderful. Dr. Adkins, Dr. Feng, thank you so much for your perspective. It's been invaluable. Really do appreciate it. I'm going to hand over to Denny again just to close, and then we'll open it up for a Q&A. Thank you, Raj. Let me just briefly summarize where we land on this. Once again, we think that the first and second line offer a very unique, highly integrated, synergistic development opportunity. opportunity. And as you just heard from our KOLs, a significant opportunity. These patients are just tragically underserved. We have differentiated activity. We're building on the existing track record of toropalimab in esophageal irrespective of PD-L1 status. And we have approval in Europe already where it's doing very well commercially. And, we're able to avail ourselves to a number of FDA designations to facilitate a very efficient rapid development plan, such as, you know, orphan, breakthrough status, fast track, and so on. We like the size of the U.S. opportunity. We think it fits very well with our commercial footprint so far and the rare diseases that we have gone after. We believe also that there's a very strong opportunity for ex-U.S.-partnering, given the data we've shown, the dose responses that we've seen, and TAGMO-T could have a clear impact on survivability and durability. I would just say that there's also the opportunity now for us to go forward with some additional combinations. As you know, we do have a study starting with J&J and metastatic prostrate. We're going to get that going here just shortly and be able to tell you about that sometime, I think, in the first quarter, early second quarter. But I think that this data really opens up a lot of opportunities for TACMO, QTUG, and so on. And so with that, we will close. We will thank you for listening in on today and look forward to seeing you at the meeting. Very good. Thank you, Heidi. Why don't we go ahead and join or start the Q&A? Thank you. We will now begin the question and answer session. As a reminder, if you wish to ask a question, you will need to press star 1, 1 on your telephone and wait for your name to be announced. Please limit yourself to one question and one follow-up question. To withdraw your question, please press star 11 again. We will take our first question and the question comes from the line of Paul Cheng from Guggenheim. Please go ahead, your line is open. Hey, thanks for taking the question and for providing this very comprehensive update today. So my first question, can you just comment on any early TFS trends you're seeing in frontline esophageal? Obviously, the durability of response and how that translates to survival will be pretty critical from a regulatory perspective, so just curious on anything you're saying that gives you confidence even at this early stage, and then I have a follow-up. Thank you, Paul, for the question. So, you know, we talked a little bit about the need for this data to mature. It actually is too early, way too early in terms of the esophageal first line specifically to really talk about medium PFS. We will be obviously following. We'll give you updates as they arise. What I can say is that for the evaluable data set, the CBR, which perhaps is at this stage in the absence of a median PFS, perhaps the most informative, we're seeing about an 87% or thereabouts CBR rate. So I think that bodes pretty positively right now. But again, we have to see median PFF ritual and the patient stay on therapy for a little bit longer. Great. So then my second question is on the regulatory path in esophageal. It was great to see the plan for an interim ORR analysis that's sort of contemplated in the phase three. You know, I think otherwise these studies could tend to take three plus years to read out to OS. My question is, what do you view as the bar for response rate to get an accelerated approval in the frontline setting? And then likewise, how confident are you that a positive response rate interim is also possible in second line based on what you've seen? Yeah, great question Paul. And I think at this time what we would need to do is really meet with the regulators. Clearly, if there was an attrition in the signal we're seeing, that would be definitive. So as we get more mature follow-up and more patient data set, we can answer that sufficiently. But there's two aspects. we've shown improvement in response, but also opened up a patient population that is underserved by immunotherapy. So a key point with regulators is with chemotherapy having a 30% response rate and PD-L1 negative, you know, what is required to really show significant improvement um so we'll evolve those numbers in the second line setting i do think the duration of benefit cbr rate would be a discussion we'd have and you've seen that we started to include ctdna and those analysis are ongoing for the esophageal cohort and we talk with the sda about complementing the data sets with molecular response as well Okay, thank you very much. We will take our next question. Your next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open. Oh, hey, everybody, congrats on all the impressive progress, and thank you so much for providing this informative update. Can you talk about the timeline to enroll additional first-line and second-line ESCC patients to enable a regulatory discussion for next steps, and if you expect to provide updates on durability for these reported patients sometime, maybe next year? And then I had a follow-up, if I could, please. Yes, thank you, Jay, for the question. So I'll answer the first part of that, and maybe Teresa can chime in a little bit on timing of any FDA discussions that we can have. So importantly, you know, I think there are a couple of important metrics, right? So we've talked about overall response rate as well as CBR and durability. Remember, the esophageal cohorts have not as yet completed accrual. They're closed, but they haven't as yet competed accruals. So step one, we'll be waiting for the remaining few patients to enroll and dose and then see what the durability is then. So I think that's the most important point. The point about when we can expand, I think this data does support expansion into an additional population to around 30 to 40 subjects or patients. So I Think that's The next immediate step. So I think the question will be, how long, how much durability do we wait for before we start the expansion? I think sometime around the second or third quarter of next year, we could move into an expansion pending further FDA discussions. But I'll let Teresa comment on a little bit more on timing of FDA discussions Yeah, so immediate next steps are to align on the dose, the meeting package is being finalized now so we plan that for the first quarter of next year. You always have your development plan in there in a discussion with FDA. To have a robust discussion with them, we would need a minimum of 30 patients to talk about other favorable regulatory strategies and how to design the magnitude of the benefit, but clearly saying Torapalimab already has orphan drug designation in the U.S. for esophageal cancer, so engaging FDA even through programs like that for Tegmo, KeyTeg is our strategy. Talk often, talk frequently, and really partner with them on our development strategy. Great. Thank you. I appreciate the strategy there. And if I could ask a follow-up, given that toripalamab is approved in first-line ESCC in Europe, and now you have clear efficacy signals for TAGMO plus tori in ESCC, would you consider taking another look at filing tori in ESCC with the FDA? Yeah, I would love that. I don't think 10 patients is going to be enough. I mean, the issue with the data from Jupiter-6 is so that the chemotherapy comparator in that study comes out at above 50%. So the applicability to U.S. medical practice, they have a pretty strong argument. But we will continue in discussions with the European group on their experiences and leverage everything we can to have those conversations as early as possible. Okay, great. And maybe if I could ask one more question. In second line, ESCC, how are you thinking about the patient population for your registrational study? Any differences on PD-L1 status or prior ICI exposure? Would all patients need prior ICA exposure? Yeah, I think that's the beauty of this, right, that we would take all comers. So PD-1 refractory, clearly an unmet medical need. In fact, if you read the FDA comments on the most recent approval in the second-line setting to Zolizumab, they actually comment that they don't even think it's going to be used much because most patients will have PD-L1 in the frontline setting. But having that option to treat all comers, PD-1 refractory, PD1 naive, and irrespective of PD-O1. The other thing to remember is Keynote 181, the PEMBRO approval in the second-line setting, only got approved in PD-L1 high, CPS greater than 10. So I think this really opens up an IO treatment for these patients that they aren't eligible for today. So it's super exciting. Thank you for your questions, Jane. Thank you. Operator, ready for the next question? Of course, we will take our next question, and the question comes from Mike Nedeljkovic from TD Cohen. Please go ahead. Your line is open. Hi. Thank you for the questions. I have two. My first relates to your potential commercial strategy. How does your thinking about potential commercialization in UX versus XUS and partnering strategies play into your thinking about the development path for TagMilk? That's my first question. And then my second question relates to the competitive landscape. I know data are sparse, so comparing your data set to others is very difficult at this point. But are there any data sets you could point to that would help us understand how TACMO would these new data fit into the competitive landscapes? I think gastric cancer may offer the best opportunity there. Thank you. Yeah, thanks for that, Mike. I'll take the first part about partnering a commercial. No, Dr. LaValley, take the second part. Obviously, there's an advantage of having a TORPALM approved in Europe for esophageal, irrespective of PD-L1 status. And so I think then that there's a reasonable opportunity of partnering with someone in Europe and the read-through to the clinical development and so forth. Similarly, in Asia, there's a very high incidence, of course, of soft-gel, well, gastric cancer in Asia. And so, one of the things that we'll do is take this data and begin talking to some parties there. With respect to the development plan, I think, ultimately, I, I could reasonably expect to see, perhaps, 50 or 60 percent of the patients in Asia 30-ish, maybe 40-ish percent of patients in the U.S. and maybe 10 to 20-ish percent of the patients in Europe. So, you know, we've had a longstanding strategy of globalization of these products because we do have global rights, both to Tegmo, Keetuk, and Casdozo. So I think that addresses that very well. Secondarily, I think they were getting some very good experience in these more rare cancers. Nasal pharyngeal cancer has about 2,000 patients in the US incidents per year. This is about 6,000, so it's about three times as large. But I think a lot of the approaches, the infrastructures, and so on, and ways of addressing the market should be very, very similar. I wouldn't contemplate that we have to expand our footprint in order to do so. So I think it would fit in quite well, particularly since you're also promoting Toro Palma at the same time, right? so you have NPC plus esophageal. I think that makes a lot of sense. Overall, I think it's a pretty good fit. Teresa, do you want to talk about that? Yeah, hopefully I understand your question, Mike, so I'm going to answer it, and if you need a follow-up, let me know. So from a competitive landscape, first in esophagal, like all tumor sites today, ADCs are showing some activity. The data in the frontline study that Rush shared with you showing that we can combine and enhance activity with chemotherapy really lends itself to think about combinations there. So continue to add novel combinations and ADCs is a combination that I think makes a lot of sense for TAGMO-CTUG. Additionally, in gastric cancer, I think that's what you asked specifically about, in the second-line setting, these data are still maturing. So the current data sets do not exceed the standard of care benchmark. If it improves, we'll have a different conversation, but it clearly shows activity in the disease. And here again, ADCs are an important regimen, as well as VEGF, another well-known mechanism to combine with Treg depletion. So looking at novel combination strategies now that we've shown a baseline for activity. And thirdly, the analysis for the CCR8 TRE scores across the various tumor types is still ongoing. So if we have any enrichment strategy to move forward with, we would explore that. Thank you very much. Thank you. We're ready for the next question, operator. We will take your next question. And the question comes from Brian Chang from J.P. Morgan. Please go ahead. Your line is open. Hey, guys. Thanks for the questions. Maybe just first, when we look at toys plus chemo performance back in the Jupiter-06 study, I believe in the supplemental, the investigator-assessed response rate was about 72 percent. And here, I think you are reporting 75 percent from men of age at the time of the cutoff. How confident are you that, you know, the contribution of Tecmo here is indeed clinically meaningful and will you be able to need to as you run a later stage studies and have a follow-up? Thank you. Well, thanks for your question, Brian. Dr. LaValle, you want to address that? Yeah, Brian, thanks, and as always, very detailed, so we appreciate that. So, at this stage, like I said, for the Jupiter-6, you're right, it's 72.4% for TORI plus chemo in the Jupiter 6 study. The chemo is 58%, so exceeding the benchmarks. And that's why we said the relevant U.S. benchmarks for comparison here, we believe, is the studies, the three approved U.F. studies in the U.N. The data that we have to give us confidence that TAGMO-KTUG is bringing some of the activity is seeing the activity in the second line setting. So, TORI does not have differential activity in absence of something to stimulate the immune system like chemotherapy. So, TAGMo-KTIG has potentiated PD-1 in a less inflamed tumor. So we'll need to build out the data set in the PD-L1 low. Clearly, we need more patients, more follow-up. We have two patients in thePD-L2 low, so happy to see that depth of response and that durability of response, and we'll continue to build that data set out. Thank you, Brian. I'll just add, Brian, let me just add one more thing. You know, you talked about Jupiter 6. So one thing I'll – I know you know this, but I'll remind you, of course, Jupiter-6 is a China-only study, whereas our study is multi-regional, and I think that's also an important point. The second point to your comment about the addition of TAGMO is I think it's important to look at that question with the totality of the cohort. So, we're seeing not only in second-line esophageal, where there's two arms, we also see in second line upper GI adenos that very clear dose differentiation in terms of the addition of TAGMO2 to TORI at the higher dose as well. Great. Thanks, Dr. Cutler. And maybe just a quick one, just looking at the spider plot that you presented during your webinar here. It seems that a lot of the patients have dropped off before you reach 20 weeks of treatment, even though that they have shown really nice partial responses at the week 12 endpoint. What are the reasons for them dropping off treatment? Which tumor type are you talking about? Are you talking second-line esophageal, or maybe Yeah, frontline, yeah, frontline ESCC. And I mean, second line ESCC, you also had one patient that already dropped off out of the two responders, right? Got it. So let me just summarize some of the safety data there in terms of the drop-off. So we have had four out of 10 discontinuing treatment due to a treatment emergent AE. Now, remember, in the first line setting, is a four-drug combination in combination with cisplatin as well as 5-FU. Cisplatin is well known to have toxicity, in particular, renal toxicity. So a couple of those patients, two of the four, dropped off due to either an elevated creatinine or some form of renal tox. The other couple dropped off because of a rash. So those are the reasons. One thing that we, and so obviously a probable immune related, the rash is probably immune related. So I think that was the split in terms of the actual drop-offs. Patients do still continue treatment in terms of we have some patients who are still on study treatment, as I mentioned. And then also we have a couple more additional patients to add to this specific set. But in terms of your question on drop-off coupled due to chemotherapy-related toxin deposition in particular, which can be litigated. And in a future study, we can, of course, swap out to CARBO, which does not have as much renal tox as an example. Thanks for the comment. Thank you. Thank you, Brian. Thank you We will take our next question. And the question comes from from HC Wainwright. Please go ahead. Your line is open. Thank you. This is from HC. I appreciate me having an opportunity to ask you questions. Most of them have been answered. I have just a couple of them. So, Raj, just to understand how you are framing clinically meaningful benefit as you're targeting in each of these settings, both first line and second line, beyond just the response rate. So for example, in the first line, what duration of response PFS and improvement in especially in swallowing or nutritional status would actually justify having TAGMA added to the PD-1 plus chemo, especially when you account for some of the toxicities and treatment discontinuations that you just talked about. And in the second line, specifically among patients that progress beyond PD-2, you know, what response durability and CFS would make, you know make this chemo free therapy clinically valuable? Yeah, so let me answer both of those questions, and thank you for the question. So your first question was on quality of life, essentially, and how this could affect quality of life. So we did not measure quality of live measures specifically in this initial study. Obviously, it will be a future additional measure that will incorporate into later stage designs. I think it's pretty intuitive that typically when you see a response, their quality of life will improve. So while I can't answer your question about specific metrics for level of improvement in quality of lives measures, that's something we will be looking at in future studies. Also, I'll draw your attention to the CT scans that I showed earlier, which really shows that disappearance of that esophageal mass. And you can imagine, right, how that diminution in size or complete disappearance of an esophagus may help in terms of swallowing or in terms of nutrition status, et cetera. So that's your first question. I think your second question was in terms of what kind of metrics are we looking at in terms of durability for the second line setting. Was that your question? Yes, yes. Okay. So the current standard of care is pretty dire in terms of the median PFS. And, again, while it's not yet mature, what we showed in the second-line setting was a median PFC of around 5.5 months. The standard of care gives you somewhere between two and four, depending on what treatment regime you're talking about. So that's, again, we need to replicate this with a larger patient number and more duration. Again, I'll remind you, we haven't completed accrual as yet, 17 of 20 patients are currently in that second line cohort. So right now, based on a small data set, admittedly with pretty wide confidence intervals, given given the small patient number is pretty encouraging given the rough benchmarks of the current standard of care of two to four months. Thank you. One quick follow-up. Are you prospectively going to define your go and no-go thresholds for these expanded cohorts that you're planning? And would you make that public after your discussion with the FDA? Dr. LaValley, would you like to take that question? Yeah, I don't think that we would make that public. I think it's the totality of the data, as we've always said. I mean, the thing that is compelling in the second-line setting is it is a randomized study, essentially. I mean it's nice to have that dose response, so you can have confidence in the Tegmo-Ketog effect. The other thing that's challenging in the second line setting to your earlier questions is the PD-1 approvals in the first line settings are relatively recent. So data sets in the PD1 refractory patients are nascent. So really setting that up. So it would be a randomized study with looking at comparison to chemotherapy and seeing duration landmark effects that are exceeding expectations. Thank you. Thanks for taking my question. Thank you, these questions are okay. Thank you This concludes today's question and answer session. I will now hand back for closing remarks. Thank you Heidi. And thank you all for joining us today on our TAG Loan Key Tool Data Reveal. I particularly want to thank our two advisors, our KOL clinicians, Dr. Atkins, from WashU, our head and neck specialist, and Dr. Dan Fang from Mount Sinai to give the clinical perspective. And secondarily, I would just urge all of you to reach out to the company if you have any further questions about the data or our plans going forward. We'd be happy to chat, and we'll see you. Bye-bye. This concludes today's conference call. Thank you for participating. You may now disconnect.