Hi, everyone, and thank you for joining the H.C. Wainwright 26th Annual Global Investment Conference. My name's Arabella, and I'm an analyst on the corporate access team at H.C. Wainwright. H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 senior analysts and over 636 companies covered across all sectors. Please visit hcwco.com for more information. At our global investment conference, we have over 6,600 companies presenting in multiple sector tracks, including life sciences, cryptocurrency, blockchain and fintech, technology, media and telecommunication, clean tech, metals and mining, and growth. Please join us for one-on-one meetings, corporate presentations, and panels that will be available live and streaming September 9th-11th 2024. With that being said, have a productive and enjoyable day, and I'd like to introduce John Celebi, the President and CEO of Sensei Biotherapeutics. Thanks, Arabella. Thank you to you for the introduction, and thank you to H.C. Wainwright for the opportunity to present to you all today. I'm gonna be talking to you today about Sensei, the opportunity ahead with some of our near-term milestones, our platform, which is focused on conditionally active antibodies, and most importantly, our lead program, which is SNS-101, targeting the immune checkpoint VISTA. Just a reminder that we are a publicly traded corporation, and there may be forward-looking statements in the presentation here today. Let me start off by giving you a bird's-eye view of Sensei Bio. First of all, we have a proprietary approach that we use to harness what we call conditionally active antibodies. In a very high-level sense, these are antibodies that only bind their targets or become activated under certain conditions, and we'll talk about exactly what we do with SNS-101 to enable the druggability of VISTA. Now, right now, that antibody, SNS-101, is in a phase I-B study, what we call a dose-expansion study, again, targeting VISTA, and we'll talk about VISTA as an immune checkpoint and its breadth and potential in multiple indications in just a minute. But so far, what we've been able to achieve clinically is an ability to overcome some of the prior challenges with VISTA, and specifically, those include poor PK as a result of what we call TMDD, target-mediated drug disposition, as well as safety issues, most specifically cytokine release syndrome, which seems to be a class effect of VISTA. Now, I mentioned we're in a dose expansion portion of our study now. That data is expected by year-end, and we do expect that to be an important and big milestone for Sensei. We also have three other early-stage drug candidates, which we're still working on preclinically, and hope to file an IND in the next several quarters or years. And we have a good cash position. We have a cash runway into the fourth quarter of 2025, which should fund our operations and our clinical study into phase II for SNS-101. Let me start with a little bit of background on VISTA. What is VISTA? It's a B7 family member. That's the same family of proteins that is PD-1. It's a known immunosuppressor, and we believe, as others believe, that it's mediated through its interaction with PSGL-1, which is a T cell receptor. We know that it is upregulated on myeloid cells that some people call myeloid-derived suppressor cells. And it also has increased expression on tissue-infiltrating immune cells, specifically when other immune checkpoints, like PD-1, drugs fail. Perhaps the most important point I'll make on this slide is that VISTA itself is activated in a pH-sensitive manner, and I bring that up because that is exactly the mechanism through which we achieve conditional activation. So, VISTA is present, as you see in the cartoon on the lower left here, on myeloid lineage cells. Under low pH conditions, it engages with PSGL-1, and T cells are suppressed. However, upon interaction with our antibody, a blocking antibody, VISTA can no longer engage PSGL-1, and T cell proliferation and activation are engaged. We engage with VISTA through a very specific antibody that targets histidines on the surface of VISTA, and these histidines are responsible also for the binding of VISTA to PSGL-1, and that is how SNS-101 disrupts the interaction with PSGL-1. Through this, pH-sensitive binding, we've been able to overcome the hurdles that I mentioned earlier. Most specifically, here's an example from Johnson & Johnson. They were the first company in the clinic with a VISTA antibody called, we call five-eight-eight, for short. They had to halt the study after treating only twelve patients due to pretty severe cytokine release syndrome at a very low dose. Now, CRS is a class effect of VISTA antibodies. The only other company that has disclosed clinical data for their VISTA antibodies is Pierre Fabre, excuse me, one of two others, and they also disclose CRS. So this does appear to be a class effect. And the other feature of J&J that was challenging is the PK profile, and as you can see from the chart on the right, after about 26 hours, their antibody was undetectable. That is due to the TMDD associated with the massive expression of VISTA on myeloid cells. So these are two challenges we had in mind very early on that we wanted to target clinically, and the data we announced at ASCO, which I'll get to in a moment, shows that we've been able to overcome both of those challenges. But first, a little bit more background on SNS-101. As you can see here, it is a very specific low pH binder. On the left, you can see that it binds VISTA at pH 6 quite potently in the picomolar range, and at pH 7.4, there's essentially no binding. It does not bind at physiological pH, and that's how we're able to avoid what we believe is the target-mediated drug disposition as well as cytokine release syndrome. We're able to disrupt VISTA's interaction with PSGL-1 quite potently, as you can see here at a potency of about seven nanomolar, and we've also done co-crystallography to show exactly where we bind on the surface of VISTA. Now, SNS-101 is sort of a case study for our platform, and as you can see here, if the antibody's in circulation in neutral pH, the SNS-101 does not engage its target, whereas at acidic pH, it engages very strongly. You can see some of the data here on the right. The first set data set is flow, and you can see, compared to our competitor antibodies, Pierre Fabre and J&J, those antibodies clearly engage in monocytes and neutrophils, both subsets where VISTA expression is strong, whereas SNS-101, the curve does not shift to the right, indicating no binding. However, in the tumor, which is typically a more acidic pH, you can see rapid accumulation of SNS-101 after only six hours, and it persists. So data not shown here, we also know that SNS-101 is present at 24 hours. So this antibody behaves exactly as we designed it, and that's how we've been able to achieve the clinical results we have to date. Now, this is not a niche opportunity. VISTA is well known to play a role in multiple cancer types, and we're only listing some of them here. Collectively, between the four tumor types that we're expanding into now, non-small cell lung cancer, melanoma, head and neck cancer, colorectal cancer, this accounts for 2.6 million new patients per year. That's incidence across the U.S. and the EU7. This is a large market. It is growing very rapidly, and there is an unmet need, because only 20% of patients experience an objective response to current checkpoint inhibitors. Let's talk about our clinical study. We recently announced the completion, sorry, the dose escalation results for our phase I dose escalation in monotherapy and in combination with PD-1. And as you can see here, we were able to dose up to 15 milligrams per kilogram in both mono and combo. That's a dose about 50-fold higher than where J&J had to halt their study, again, demonstrating the safety potential of this program. We're now into the phase I dose expansion, and here the patient population is a little bit different. It's in four specific patient populations that I just mentioned on the prior slide, and as you can see here. We also have been in the process now of refining and optimizing our phase II design, as you can see here on the right. That'll be either with or without cemiplimab, which is our PD-1 inhibitor of choice. So before we go into the data for our phase I dose escalation study, let's talk about the patient disposition. We enrolled about 34 patients in total, 16 in the monotherapy, 18 in combination. Of those, we have treatment ongoing for two each in the monotherapy and combination therapy, so those patients have been on for some time. 14 patients in the monotherapy are discontinued, and 16 in the combination, and as you can see the breakdown here below. Not too much to comment on here in terms of the patient demographics. Pretty typical for an early phase I study on the left. On the right of this slide, I would simply point out that, you know, also not unlike a phase I study, we typically got cold tumors on this study. Cold tumors are typically those that do not respond to checkpoint therapy, and here, I'm defining a cold tumor as one in which they typically don't respond to PD-1 monotherapy. And so you can see here, head and neck cancer and kidney cancer were the two types that we did enroll a few patients in, but all the rest you see here, MSS colon, endometrial, esophageal, et cetera, those are indications that typically patients are unresponsive to PD-1. So again, not unusual, but I think what is unusual is that the number was so high. Perhaps 85% was a little bit higher than we expected going into the study. That is what it is. Again, the main goal of our study was first and foremost to show that the drug was safe, that we could get to a good pharmacologically meaningful dose level, and also show that we had good PK. Here's a summary of our adverse events, and as you can see here, there were no dose-limiting toxicities observed. Pretty typical overall adverse events. Most were grade one or grade two. We did see a little bit of CRS, grade one CRS, which suggests that CRS, we're on target here, so it's we never want safety issues, but we were a little bit relieved that we did see some CRS in these patients, and that it was transient, and easily overcome. This is a little bit of a zoom in on the CRS. So you can see we've included here not only the two grade one CRS's that I just mentioned, but also two grade two infusion-related reactions, which often have symptoms similar to CRS, but occur either during infusion or just afterwards. Whereas CRS can typically occur several hours later, and you can see that here. But again, overall, mild, SNS-101 has only been associated with mild CRS-like events, and I think we've been able to show here that we've been able to overcome probably the key hurdle that has prevented further development of VISTA antibodies to date. The other goal I mentioned was showing that we had good PK, and as you can see here, both monotherapy and in combination, SNS-101 has a linear. Has shown a lack of target-mediated drug disposition. This PK profile supports once every three-week dosing. That's important. That's the same dosing schedule as most PD-1s, and there's no change on PK with the combination, so we're very excited about that. No changes in key inflammatory cytokines. This is totally consistent with our preclinical data. This is also consistent with the clinical observations I pointed out earlier with CRS. So now let's turn to efficacy. These are the results that we announced in April, as of April 30th 2024, at ASCO. On the top, you'll see the monotherapy, and on the bottom is the combination. Again, seven patients here in the monotherapy achieved stable disease as their best overall response, and there were some very interesting patients monotherapy-wise. One in particular, pembrolizumab-resistant, HPV-positive head and neck patient, had a tumor regression of about 17% at our highest dose. So that's very interesting to us. We also had a patient with a maxillary sinus tumor that continues on treatment for 42+ weeks at a lower dose, and one patient with leiomyosarcoma that has been on study for quite some time as well. So those are interesting observations to us. In the combo, and we'll zoom in a little bit on these patients on the next slide as well, we had a couple of patients that were very interesting to us because they're very difficult to treat with PD-1. In particular, MSS endometrial and MSS colon cancers have been shown to be resistant to PD-1, and here you can see, one patient with a partial response, as of April thirtieth, had a 59% decrease, and then the MSS colon, which had a 27% tumor shrinkage. Also very interesting, one RCC patient had a tumor regression of 18%. This was also associated with an immune-mediated toxicity, which was very interesting to us as well. I promised I'd talk a little bit more about the two patients that had the largest tumor regressions. Here on the left, you can see, this was an IO-naive MSS endometrial cancer patient that achieved a partial response at a dose of three milligrams per kilogram of SNS-101, plus PD-1. This patient history here is summarized here. You can see this patient had prior, prior treatment that ended in September of 2023 before coming onto our study earlier this year. This patient experienced a very interesting grade III diabetic ketoacidosis four days after their third cycle of treatment, and this is on label for Libtayo, the PD-1, but it is very rare. So of course, we were very interested in that, and we continue to monitor for ketoacidosis in other patients. But this is considered an immune-related event. And since the patient remained on study, we've continued to track this patient, and again, tumor shrinkage of about 59%. The other patient that we have seen here is of interest, is a MSS colon cancer patient. Again, microsatellite stable colon cancer is typically unresponsive to PD-1. This is a patient that had was fairly unresponsive to prior therapy, seven lines of prior therapies, and came onto the study and experienced a 19% decrease after six weeks and a 27% decrease after 12 weeks. Unfortunately, at week 18, the patient's tumor began to grow again and that patient, I believe, is now off study. But nonetheless, 27% tumor shrinkage in a patient that had fairly. That was also PD-1 negative was something that we took great note of. So just to summarize, our early ASCO 2024 summary, we feel, with SNS-101, we've been able to overcome some of the most important milestones associated with VISTA inhibition, in particular, the CRS hurdle that has plagued so many other prior efforts, the PK issues that have also been a challenge, and we have initial signs of anti-tumor activity, which we hope to expand on at the end of the year, when we announce the initial results from our dose expansion study. So we believe we're well-positioned now to really be the first company with an anti-VISTA antibody to test VISTA at pharmacologically relevant dose levels, and therefore, the whole hypothesis associated with VISTA. What's coming next for this program? Well, we've continued now again into the dose expansion. The dose expansion is very important. It allows us to optimize our phase II study design. Here, we're focusing on patients with hotter tumors. That's really a subset of patients we didn't have a great opportunity to explore during the initial phase of the trial. So we're exploring two different dose levels. We're exploring hot tumors in a more specific patient population here in dose expansion. Most likely, all of these patients will have received and failed a prior PD-1 or PD-L1. We're gonna enroll about 50 to 70 patients, and we're doing all that with keeping our cash runway guidance unchanged, which again, is right now through the fourth into the fourth quarter of 2025. We're looking forward to sharing the initial data from this dose expansion cohort in the fourth quarter of this year. And that's all I have here today. I wanna thank H.C. Wainwright for inviting us to present at their conference, and I look forward to meeting with all of you at the conference itself. John, thank you so much for such an interesting presentation. We really appreciate the time and effort that goes into preparing it, and we're grateful for your flexibility and your presence at our conference this year. So from the whole H.C. Wainwright team, thank you so much. Thank you, Arabella.