Hello everyone, and thank you for joining the H.C. Wainwright 27th Annual Global Investment Conference. My name is Arabella Ng, and I'm an associate on the equity research team at H.C. Wainwright. It's my pleasure to introduce Senti Biosciences. Senti Bio is a clinical-stage company founded to create a new generation of smarter medicines for patients living with incurable diseases through synthetic biology to design and optimize proprietary gene circuits. It's my pleasure from the company to introduce Timothy Lu, the CEO, and Jay Cross, the CFO. Timothy, the floor is yours.
Great. Well, thanks a lot for the opportunity to be here. Happy to tell you about Senti. Short disclosure statement. So here at Senti, we are focused on transforming the treatment of cancers with what we call Logic Gate technology. So what this allows us to do is build therapeutics that can selectively recognize and kill cancer cells while protecting healthy cells from being affected. This technology works for both NK cells and T cells, as well as other cell types. And we've chosen for our lead program to focus on treating a disease called relapse/ refractory AML with our SENTI-202 program. As I'll describe to you in a bit, we use a Logic Gate that allows us to attack CD33, as well as FLT3.
These are two targets that are well known in the AML space, but also to protect healthy cells by recognizing something called Endomucin and sparing those healthy cells from being killed. This program is being advanced in a multinational, multi-center clinical trial where we've demonstrated positive preliminary efficacy data with significant CR rate and durability presented at AACR earlier in April. We also received orphan drug designation for this program earlier this summer, and we will have additional Phase I data to present before the end of this year. Beyond AML, we have the ability to take this technology into other related indications, including MDS, as well as into solid tumors, where we think this challenge of targeting cancer while sparing healthy cells is really important.
So here at Senti, we've focused on designing something we call gene circuits inside of living cells using what we call Logic Gate technology, where we can actually engineer multiple receptors into cells to recognize cancer cells while sparing healthy cells. I'll go into a little bit more detail in a little bit how this works. We also have the ability to outfit our cell and gene therapies with additional technologies, including arming them with one or more payloads to enhance their efficacy, something called the Regulator Dial that allows us to use small molecules to control their activity, to control for safety or to boost efficacy, and something called Smart Sensors that allows us to program when and where our cell and gene therapies are active. Next slide, please.
So here at Senti, what we have focused on is to use this technology to solve one of the central problems in oncology today. So in cancer, if you think about all of the existing T cell engager programs, ADCs, even conventional CAR T cell therapies, they're all faced with one central problem, which is identifying a clean target that's only found on the cancer cell and not found on the healthy cells, because how these programs work is they're basically directly cytotoxic against any cells expressing that target. If you can't find such a clean target, those diseases are not well treated with these current modalities. And as a result, you see a ton of crowding between CD19, BCMA, even HER2, and some of these other targets, because those are the targets that are clean enough for some of these existing modalities to play.
Here at Senti, we're focused on areas that don't have a clean single target, where there's not a lot of competition going on, where we can deploy our Logic Gate technology to solve this problem by recognizing multiple targets. Some of them on the cancer cells we can kill, and some of them on the healthy cells we can protect, and that allows us to get much better killing and discrimination between healthy and cancer. Next slide, please. It wasn't working earlier, but it works now, so we have built a best-in-class Logic Gated pipeline. We have our SENTI-202 program that I mentioned. We've presented positive data at AACR, and we will have data later at the end of this year, sort of further bolstering this data set, and we do have additional programs in the solid tumor space that we will be announcing later this year as well.
Next slide, please. All right, so AML is a tremendously difficult disease to treat. It affects about 20,000 patients in the U.S. per year. A large majority of these patients, unfortunately, experience relapse or death, oftentimes within 12 months. If you are in the relapse/refractory AML category, your median survival is about five months or so. And even the most recently approved drugs, including the menin inhibitors that received FDA breakthrough status, are seeing CR rates only in the 20%-30% range, with durabilities anywhere from four and a half months to six months or so. AML is a particularly difficult disease to treat because it's very heterogeneous. There's no single target that marks an AML blast or an AML leukemic stem cell, which you need to be able to kill to achieve deep responses.
Any of those targets that people have identified are expressed on the AML cells, but also on healthy hematopoietic stem cells or other healthy cells in the body. As a result, there's been a challenge to find a good therapeutic window in the past. Oftentimes with these drugs, you're killing the healthy cells while you're killing the cancer cells, and it's really difficult to achieve the efficacy that you want. We've designed SENTI-202 to overcome these problems. SENTI-202 is an off-the-shelf allogeneic NK cell product that's derived from healthy adult donors. This cell is engineered with three specific genes. The first gene is what we call an activating CAR, which kills AML blast and leukemic stem cells based on recognizing two different targets, either CD33 or FLT3.
Both these targets are well known in the space, have been clinically validated in the past, and by going after both the targets, we can increase the overall killing activity of the product. These targets, however, are also expressed on healthy cells. So in the past, when people have tried to attack targets like CD33 or FLT3 or even some other ones that are well known in the AML space, like CD123, you get some significant toxicities against the bone marrow or the endothelial cells that limits the efficacy of the program. So to solve this issue, we have a second gene that we've engineered into the product called the ICAR or inhibitory CAR. What this does is it recognizes those healthy hematopoietic stem cells and protects them from being killed.
It does this by recognizing a target called Endomucin or EMCN, which is highly expressed on the healthy cells, but minimally expressed on the cancer cells. And this basically provides a protection signal against the killing. Thirdly, we have a gene that expresses a protein called IL-15 that's expressed both on the cell surface, but also secreted, and this helps bolster the overall activity of the product. Next slide, please. So SENTI-202 is an off-the-shelf allogeneic CAR NK product. We basically develop a whole protocol here to isolate healthy NK cells from selected donors. We engineer them with our gene circuit, and then what we can do is expand these cells and cryopreserve them. So anytime a patient comes on our study, we basically can ship out the frozen vials the next day.
At the clinical study on the right-hand side, these cells are basically thawed and then infused. This overcomes many of the traditional logistical challenges, as well as the cost challenges associated with autologous T cell therapy, which requires very patient-specific manufacturing. In addition to that, one of the reasons why we decided to go with NK cells for this particular product is it's quite challenging oftentimes to actually identify and generate high-quality autologous T cells in AML patients. Their immune system oftentimes is not very functional. So we have an ongoing Phase I clinical study in adult patients. We can enroll patients from either relapse/refractory AML or MDS or other related heme disorders. Basically, you have to come on with either CD33 or FLT3 positivity. This trial is being run in a multinational, multi-center clinical trial, and we've been exploring two different parameters in terms of dose escalation.
One is two different dose levels for the cells themselves. So on the left-hand side here, the SENTI-202 dose is either at 1 billion CAR- positive cells per dose or 1.5 billion CAR- positive NK cells per dose, and on the right-hand side, we've been exploring two different dosing schedules. So in both these schedules, there's a lymphodepletion step early on, followed by either three doses of the cells or five doses of the cells. Dose schedule one, you get cells at day zero, seven, and 14, and schedule two, you have it at day zero, three, seven, ten, and 14. We can assess for efficacy at 28 days. And then based on continuing sort of evidence of clinical benefit for the patients, we enable the patients to go through multiple cycles of treatment. Next slide, please. We did present data for this program at AACR 2025.
This data I'm showing you here was as of April in 2025. What we looked at across high-risk relapse/refractory AML population, these patients generally were on the older end, about a year or less from diagnosis. That is actually demonstrating these are fast-progressing patients in many cases. These patients have been through a variety of prior treatments, including fludarabine, Ara-C, venetoclax, or even bone marrow transplants in the past, and many of our patients were actually classified as adverse risk by ELN 2022 or primary refractory in terms of not responding to their primary treatment. Next slide. One of the important things about this product is actually a very well-tolerated program. Unlike some of the autologous CAR T programs, which have a significant CRS rate, ICANS rate, or other neurotoxicity-type syndromes, our product was very well tolerated by patients.
We do have the ability to deliver this drug to patients in an outpatient setting. And some of our schedule one patients, for example, because we're divvying the dose one week apart, that's very conducive to a more outpatient community-type setting, which we're excited about in terms of downstream accessibility for the product. In general, the AEs that we did identify were generally hematologic and related to the lymphodepletion. As you'd expect with lymphodepletion, there's a drop in your hematopoietic and as well as immune system counts. But as I'll show you later, consistent with our mechanism of action, patients that did respond in our trial, we found strong evidence that we were protecting those healthy cells and we had good recovery of the immune cell population.
Based on this data, we did select a preliminary recommended phase II dose using that dose level two, so 1.5 billion CAR- positive NK cells per dose using the dose schedule one, which is the three doses over a two-week time period. Subsequently, we have announced that we've confirmed this as our go-forward RP2D dose, and we are in the process of doing dose expansion right now in the clinical study using this particular dose and schedule. Very excitingly, we saw responses observed across all of the dose cohorts. At the AACR meeting, we reported that five out of seven of the patients overall achieved an ORR level response. That includes CRs as well as MLFS patients. Four out of seven of the patients achieved a CR itself, which was really exciting to see. All of those patients achieved the best response of MRD negativity.
MRD is a way of measuring residual tumor burden using methods such as flow cytometry or next-generation sequencing. It's very sensitive. And the fact that these patients achieve that MRD negative response, I think bodes well for their outcomes. Across all the patients, we saw significant bone marrow blast reduction. We had a wide range of bone marrow blast levels upon enrollment of the study at baseline, even up to 90% or more. And except for perhaps one patient, we saw a significant reduction in blasts across all of the patient population. So there's clear anti-tumor activity across all of the patient population that we looked at, a significant amount of the patient population that we looked at. Next slide, please. In terms of durability, so durability is an important outcome for these patients.
Again, this is as of April, and we're continuing to follow these patients, and we'll have significantly more durability data report later this year. But the patients that did respond, we were very excited to see anywhere from four- to eight-plus months of durability in terms of their responses. And these were all ongoing as of the data cut that we reported at AACR. So this bodes well for those patients that did respond. I think this also compares very favorably to existing drugs that are out there, as I mentioned. Some of the drugs that have been approved already under breakthrough status are roughly in that four- to six-month time period. Next slide, please. All right, so some of the key things we wanted to also confirm is here, beyond just looking at response levels, blast reduction, et cetera, are we actually killing the leukemic stem cells?
Leukemic stem cells in AML constitute this really difficult-to-treat population of cells that can repopulate the entire tumor burden, and if you look on the left-hand side here, we took basically LSCs from bone marrow samples across many of our patients that we looked at, and we looked at, for example, what cell cycle status were they in. The vast majority of these cells were actually in the G0 state, which means that they're essentially quiescent, and that indicates why LSCs are so difficult to treat with conventional drugs like chemotherapy. They just don't respond well to those cases.
On the right-hand side, using a method known as CyTOF, which is a method of basically multi-parametric analysis on cell surface markers, we were able to identify leukemic stem cells in the bone marrow of our patients and saw significant reductions in the LSC counts across many of our patients, especially the ones that achieved CR had over tenfold decrease in the leukemic stem cells. So that was exciting to see and very consistent with our mechanism of action for this particular product. In particular, that FLT3 target is a very good target for these leukemic stem cells. Next slide, please. So one of the things I highlighted earlier is that targets like CD33 and FLT3 are found on healthy hematopoietic stem cells.
As a result, if you just treat with these sort of single-target approaches, you can get very significant bone marrow suppression in these patients, which is not ideal in terms of their outcomes. We looked at two different criteria here in terms of are we able to protect those healthy cells from being killed. On the left-hand side, this is looking at peripheral blood, both looking at platelet count levels as well as neutrophil levels. What we can see is that initially at treatment, there's lymphodepletion, which causes a reduction in platelet and neutrophil counts. Towards the end of the cycle, we see significant improvement of these neutrophil and platelet counts all the way back up to normal for some of our patients.
This is exciting to see for the patients and portends a good outcome in terms of recovery of their healthy bone marrow system. On the right-hand side here, if we look at healthy hematopoietic stem cells in the bone marrow, especially in patients that did respond, in general, we saw a maintenance of appreciable levels of HSCs or even increases in some cases. So this is, again, consistent with the way we designed this product to protect that healthy blood counts from being killed. Next slide, please. Across many of our patients, we looked at the PK profile. As you'd expect, this is an allogeneic cell therapy. The mode of treatment here is really repeat delivery of multiple doses and also the ability to deliver across multiple cycles.
So this is a different method compared to autologous cell therapies where you're trying to deliver a single product upfront and hoping that product lasts forever. Instead, here, this is a much more drug-like approach where we can deliver multiple doses, multiple cycles. And as you expect with allogeneic cell therapies, these cells don't last forever. We do see, in general, consistent with other allogeneic T cell, allogeneic NK cell therapies that have been described in the past, we see generally cells persisting roughly in about a two-week time period, but able to see appreciable levels of the cells with repeat dosing. So next slide. So in summary, what we saw at AACR 2025 was really exciting. We saw significant efficacy and durability data that positions this drug really well to be one of the leaders in relapsed/refractory AML.
We saw PK that was consistent with the design of the product, and looking at the CyTOF analysis of the bone marrow and safety, this is quite consistent with how we designed the product. This is well set up to be really an accessible and safe product for patients that can generate responses. We got a significant amount of clinical interest based on this presentation, and we are exploring now the ability to advance this product into other types of indications, including pediatric AML, newly diagnosed AML, MDS. Those are all possible areas in which we can expand this into. Our focus towards the end of this year is to update this trial with more data on the relapse/refractory AML population.
And that will lay out the course for what we're going to do next in terms of interacting with the FDA and what a downstream pivotal study may look like. In the remaining few minutes, I just want to highlight some of the opportunities to take this technology beyond AML. Logic gating is not just a one-trick pony in hematology space, but there's a lot of indications in the solid tumor arena. Next slide, please, where existing modalities, ADCs, T cells, engagers, et cetera, are again fighting over the same pie because they're relying on the same targets to go after. There's a whole range of solid tumors that are not well addressed by these single-target approaches, and we have developed our logic technology to actually go after some of these programs.
So one of the other things we'll do later this year is highlight some of the additional targets that we can go after using, for example, T cell programs against solid tumors. If you jump forward two slides, please, to slide 22. Next slide, please. We've shown that we can actually apply our logic gates to the solid tumor space. If you just click forward one more slide, thank you. We've shown that actually we can adapt our logic gate technology to go after the solid tumor space. This is a proof of concept experiment that we've described in the past where we can go after a target called CEA, which is prevalent in colorectal cancer.
There have been other phase three studies using this in a biologics format or even a TCE, sorry, a TCR-based T cell format where they've seen significant anti-tumor activity going after CEA, but challenges again with the therapeutic window because CEA is found on healthy cells. So what we've done here is engineer a CAR T product that can target CEA, but also protect healthy cells, including epithelial cells that may express CEA using a target called VSIG2. And these are just some videos we wanted to show you where we're mixing cancer cells in red with healthy cells in green in a mixed cell experiment. So if you click on the first video with no treatment, you can see both the T cells and no T cells present. You can see both the cancer cells and the healthy cells proliferating.
If you click again, you can see that if you go after CEA on its own, both populations of cells are killed. But if we have our special logic gate technology to go after CEA, but not VSIG2, one more click, please, you can see selective killing of the cancer cells in red and sparing of those healthy cells in green. So we're really excited where this is going. So just to summarize, if you click forward, one more slide, please. So in summary, we have developed what we believe is a best-in-class logic gated cell therapy pipeline, initially targeting AML. Our SENTI-202 program, we've completed dose finding, demonstrated our RP2D dose. We will have more data towards the end of this year with our full set of Phase I clinical study program, and then we'll outline essentially what's coming next in terms of the pivotal study.
We've also demonstrated that this program can work to address solid tumors. And so we're really excited for this to really be a really new way of treating cancer in a way where you're not forced to rely on a single target to distinguish between cancer cells and healthy cells, but we have now much better fine-grain discrimination between disease and healthy. So with that, I'd like to thank you for your time and happy to take any follow-up. Appreciate it.