Rosh Dias
Analyst · Guggenheim
Thank you, Denny. I'm pleased to report that 3 of our studies have completed full enrollment, and I'm able to provide some initial color on emerging data sets. In addition to our [ CADILYZE ] study in first-line HCC already being fully enrolled, our TAGMO cohorts in both head and neck squamous cell and colorectal cancer are also now fully enrolled. However, other cohorts have yet to complete patient accrual. This is important to keep in mind since as we approach initial data readouts for our clinical program, the 2 key determinants of data timing will be the numbers of patients in study and also the numbers of scans that may be required to provide a meaningful indication of activity. In addition to providing information of response, having a sufficient number of scans provides valuable information on durability of activity for both response and stable disease. This is particularly important as much of the benefit with IO has been seen in extending the tail of the curve, i.e., the durability of activity. We have 2 active protocols and one to initiate in the coming few months, and let me take each pipeline program in turn, starting first with the TREGCHECK program for tagmokitug, our highly selective CCR8 cytolytic antibody. Our first protocol is looking at TAGMO in head and neck squamous cell carcinoma. This is a 40-patient study investigating 2 doses of TAGMO in combination with TORI in a second-line head and neck squamous cell population, asking the very specific question of whether we're able to reverse PD-1 resistance in the second-line population. As mentioned, I'm pleased to report that this is now fully enrolled. The study builds upon the prior data we previously communicated at AACR last year, where in earlier stages of this same study, we demonstrated clear tumor remodeling with TAGMO monotherapy and a partial response in a fourth-line patient with HPV-positive head and neck squamous cells out of 7 patients who received a combination of TAGMO and TORI. The ongoing study is yet to have a sufficient number of patients reaching maturity of data that would trigger formal data cleaning, but I can make the following high-level comments based on emerging data from a subset of patients. Firstly, the combination of TAGMO and TORI have thus far shown an acceptable and manageable safety profile. Secondly, we've seen evidence that the addition of TAGMO to TORI for the treatment of PD-1 resistance in the second-line head and neck population has shown activity with respect to response rate and treatment duration. In particular, in our analyses of baseline tumor samples, preliminary data from the early batches of samples indicates there may be an immune context that enriches for patient benefit. Based on the small sample size of the data we have in the subset of patients with matched biomarker data, we're seeing greater activity in patients who are HPV positive, an area where there remains a significant unmet medical need and in patients who have a higher tumor immune regulatory index or TIRI score, a point on which Theresa will elaborate on momentarily. With the important caveat that these initial observations are based on data that is not yet fully mature and importantly, the data that has not yet been formally cleaned and may therefore be subject to change. If these trends persist with further maturation of data, this may support an [indiscernible] strategy in head and neck squamous cell carcinoma. I anticipate further maturation of the data over the coming months, including analysis of the remaining biomarker samples and current projections indicate we're likely to have all patients having had sufficient follow-up and biomarker analyses to enable a formal disclosure in October. Moving on to our second protocol, which investigates TAGMO in a selection of GI cancers. Cohort A is a second-line upper GI adeno population, including gastric adenocarcinoma, esophageal adenocarcinoma and GEJ cancers with 40 patients, again, with 2 doses of TAGMO in combination with TORI. Whilst we are nearing completion of accrual, we have not yet done so, and therefore, it's too early to make any more detailed comments on this cohort. In terms of our projections, we anticipate that the full complement of patients will have had a sufficient number of scans in the coming months, and therefore, we currently anticipate the ability to report data later this year. Cohort B and C are investigating the TAGMO-TORI combination in second-line and first-line esophageal squamous cell carcinoma, respectively. Enrollment continues in both cohorts. The second-line cohort is looking at 20 patients with the doublet combination and the first-line cohort adds in chemo as well to the doublet as a safety cohort of 12 patients. Thus far, we've seen an acceptable and manageable safety profile. Cohort D evaluates TAGMO in combination with TORI in colorectal carcinoma with 20 patients in the fourth-line plus MSS population with initial focus on non-liver mets and with an intention to expand to a potential additional 21 patients and also a liver mets population. I'm very pleased to say that despite being the last cohort to start, we've completed accrual of the initial 20 patients, which really is a clear recognition of the unmet medical need in colorectal carcinoma. Current projections indicate that all 20 patients should have had a sufficient number of scans in the next couple of months, and so we continue to anticipate initial data to be available later this year. Finally, the third protocol, which is designed to accommodate TAGMO combinations with novel agents remains on track to initiate in the fall time frame with its first cohort of TAGMO in combination with Pasritamig, J&J's T-cell engager in metastatic castrate-resistant prostate cancer. Let me end with Casdozo in hepatocellular carcinoma. This is a 72-patient study investigating the Casdozo-TORI-bev combination in the first-line HCC population and is designed to achieve 3 things: data to support both contribution of component and Project Optimus and of course, to further characterize efficacy and safety. As a reminder, this builds upon the encouraging data from the prior study where Casdozo was added to the current standard of care, atezo and bev. Despite completion of accrual in March, currently only around 50% of patients have had 3 scans. Thus, we have not as yet reached a sufficient level of data maturation to trigger a formal analysis. Additionally, the ctDNA and baseline IL-27 level collection and analysis is still ongoing. With this in mind, we anticipate initial data availability in Q4 this year. With that, I'll turn it over to Theresa. Theresa?