Hello everyone, and thank you for tuning in to the H.C. Wainwright 27th Annual Global Investment Conference. My name is Mai, and I'm a Research Associate here at H.C. Wainwright. We're excited to introduce you to about 600 companies presenting at our conference this year across our key sectors of life sciences, cryptocurrency and fintech, clean tech, metals and mining, and TMT. Now I'd like to welcome John Celebi, President and CEO of Sensei Biotherapeutics. Sensei Biotherapeutics is a clinical-stage biotech company developing conditionally active antibodies for cancer using the Tumor Microenvironment Activated biologics (TMAb) platform. I yield the floor to John to introduce himself and the company.
Thank you, Mai. Good afternoon, everyone, and thank you for joining us today. 2025 has been a year, a defining year for Sensei Biotherapeutics. This is the year we move from early signs of promise into more mature, commercially relevant efficacy signals, particularly as we prepare to share our phase I to dose expansion results at the upcoming European Society for Medical Oncology, or ESMO, Congress in October. Our lead program, Solnerstotug, is advancing as the first credible VISTA-targeted therapy to fully exploit myeloid biology. With upcoming progression-free survival data by year-end, we believe we're on the verge of delivering a potential breakthrough in one of the largest and most competitive markets in oncology. Some forward-looking statements. What makes Sensei compelling is threefold. First, Solnerstotug is designed to solve the liabilities that derailed earlier VISTA-focused antibodies.
It binds selectively in the acidic tumor microenvironment, sparing healthy tissue and avoiding the toxicity and poor pharmacokinetics that forced others to abandon the field. Second, our phase I/II trial has already shown multiple responses and benefit in patients with PD-L1 resistant tumors. Patients typically have response rates in the single digits when rechallenged with PD-1. Third, the market opportunity is enormous. PD-L1 therapies are a $50 billion market. VISTA is expressed in the majority of solid tumors, and we believe it plays a central role in both primary and acquired resistance. The opportunity here is to open a new checkpoint pathway, and one that could rival the scale and impact of PD-L1 itself. Our platform has broad commercial potential, but our near-term focus is on Solnerstotug. Through a supply agreement with Regeneron, we are evaluating it in combination with their PD-1 inhibitor, Libtayo, across a spectrum of tumors.
This collaboration underscores the innovation of our approach and the growing recognition of VISTA's role in immunotherapy resistance. On this slide, you'll see how Solnerstotug works. VISTA is an immune checkpoint protein broadly expressed in tumors and myeloid lineage cells, where it drives immunosuppression. Importantly, it's implicated not only in innate resistance, but also in acquired resistance to PD-1 therapy. Unlike earlier approaches, Solnerstotug binds selectively in the acidic tumor microenvironment where it matters most, blocking the VISTA-PSGL-1 interaction inside the tumor while sparing healthy tissue. This pH selectivity is what differentiates Solnerstotug. It's a first-of-its-kind approach designed to unlock VISTA biology in a safe, scalable way. Here, we zoom out to the broader commercial context. Nearly all solid tumors express VISTA, creating opportunities across multiple high-value indications.
To put the market in perspective, PD-L1 therapies represent one of the largest drug classes in all of medicine, generating tens of billions in annual sales. VISTA, with its broad and consistent expression, could follow a similar trajectory. PD-L1 inhibitors dominate, yet resistance remains a major issue. This is where Solnerstotug comes in. Our phase I trial began appropriately with a strong focus on safety. Remember that the first generation of VISTA antibody programs were halted due to severe cytokine release syndrome and poor PK. Our philosophy was, let's show as rapidly as possible that we can overcome these liabilities. We did. Solnerstotug has demonstrated a favorable safety profile, no dose-limiting toxicities, linear pharmacokinetics, and only low-grade, manageable cytokine release events. In sharp contrast to earlier VISTA programs that were halted for toxicity. These results gave us confidence to move into dose expansion, where we could begin exploring efficacy.
In the dose expansion phase, we zeroed in primarily on hot tumors, patients who had previously responded to PD-1 but then progressed. In this setting, historical retreatment response rates for PD-1 rechallenge are in the single digits. This trial enrolled about 60 patients across hot tumors, such as lung, melanoma, head and neck, and a cold tumor type, MSS colorectal cancer. We're going to focus on the hot tumor types today since this is the cohort we look to for efficacy. As you can see in the patient demographics, about 90% of hot tumor patients received and progressed on a PD-1 therapy in this cohort. This is a very tough-to-treat group, and historically, responses to PD-1 rechallenge are in the single digits. Against that backdrop, Solnerstotug performed remarkably well and showed favorable activity. On this waterfall plot, each bar represents a patient. You'll notice multiple tumor shrinkage.
Importantly, all PD-1 resistant patients who had shrinkage remain on therapy with the potential for continued benefit. This is precisely the kind of durable activity you want to see with immunotherapy. The inflection point in this plot is midway, meaning about half the patients had tumor shrinkage. The swimmer's plot shows a time element to the data and depicts durability. Several patients remain on treatment for extended periods, some continuing beyond what we would expect. This pattern, long tails of durable benefit, is what defined the success of PD-L1 agents and what we believe can also define Solnerstotug. This is perhaps the most important measure of activity, and one we'll focus on as we prepare for the ESMO Congress in October. Let me highlight a few examples.
This patient was a PD-1 resistant cell carcinoma who achieved a durable complete response and remains on treatment despite progressing on a prior PD-L1 therapy. Another carcinoma patient achieved a partial response despite being on multiple rounds of immunotherapy, including Ipi/Nivo, the most potent immunotherapy combination on the market today. A patient with MSI high colorectal cancer, who had previously progressed on PD-1, achieved a partial response at week 36. These cases overall reflect the broader trend, early signs of durable benefit in patients with acquired resistance, one of the hardest problems in oncology. The theme for 2025 at Sensei is durability. Investors and physicians both know that immunotherapies are measured not just by whether they work, but how long they will work. By year-end, we will present full phase I/II dose expansion data, including six-month PFS.
This is an important commercially relevant benchmark, one that will help define Solnerstotug's profile and shape the design of our phase II program. The venue for this evolution is significant. In October at ESMO, our data will be featured in a mini oral session. That recognition reflects the importance of our work, and we believe it will be an inflection point in how the world views VISTA as a therapeutic target. On this slide, we compare outcomes across published benchmarks in PD-L refractory and second-line patients. You'll see that the bar here is low and that the duration of benefit is poor. Only 10% - 34% of patients that progress on prior PD-L1 therapy make it to the six-month mark. Progression free. Turning to safety in the expansion cohort, most adverse events were grade one or two. Cytokine release was again low grade, manageable.
We did not see the severe toxicities that derailed earlier VISTA programs. Overall, Solnerstotug continues to be well tolerated both as monotherapy and in combination with Libtayo. Now looking ahead, the next major step for Sensei is to initiate phase II studies in 2026. We envision multiple phase II trials aligned with both unmet medical need and commercial potential. We'll be expanding on this plan post ESMO and look forward to providing additional details. To close, let me leave you with a few key points. First, Solnerstotug is the first VISTA-targeted therapy to demonstrate clinical activity with a favorable safety and PK profile. That's meaningful. Our phase I/II data shows multiple responses and durable responses in PD-L1 resistant tumors, a setting where very few options exist. This year, we will deliver a critical milestone, our mini oral presentation at ESMO in October with full dose expansion data.
We're well positioned financially with a cash runway into 2026 to deliver on these critical milestones and prepare for phase II. We believe Sensei offers investors a rare opportunity to be part of the first successful unlocking of VISTA's myeloid biology, a checkpoint pathway with the potential to reshape immuno-oncology. Thank you, and I look forward to the discussions ahead.
All right, thank you, John, for a wonderful presentation and sharing the Sensei Biotherapeutics story with us. We appreciate the time and effort from yourself and your team that went into this presentation, as well as, of course, your presence at our conference this year. We hope to see you again at next year's conference, and thank you all for tuning in.