Now we will hear from the CEO of Senti Biosciences, Tim Lu. Senti Bio is a clinical stage biotechnology company developing a new generation of cell and gene therapies for patients living with incurable diseases. To achieve this, Senti Bio is leveraging a synthetic biology platform called Gene Circuits to create therapies with enhanced precision and control. Before I pass it off, again, please note that we were not involved in the preparation of any of the presentation materials, and this is not a research recommendation, solicitation, or endorsement of any kind. No investor should rely solely on the information provided in making a decision to invest. Now I'd like to introduce the CEO of Senti Biosciences, Tim Lu. You can share your screen now.
All right. Thank you so much for the opportunity to be here. I'm really excited to tell you about what we're doing here at Senti, really trying to transform the landscape of cancer therapeutics. We're making some forward-looking statements here, so just a brief disclaimer. In terms of an overview of Senti, we are a clinical stage biotech company that's developing something called Logic Gating. As I'll show you, these Logic Gates allow us to target cancers that are previously untargetable by conventional modalities, including T cell engagers, ADCs, CAR T- cells, et cetera. Our lead program, Senti 202, is currently in the clinic. It is designed to attack relapsed/refractory AML and related cancers. We recently reported positive clinical data, both from an efficacy, safety, and durability perspective at the AACR 2025 meeting. We're quite excited to share that with you here today.
Our product enables scalable off-the-shelf manufacturing, which streamlines treatment for patients. The Gene Circuit platform allows us to specifically target cancer cells while sparing healthy cells, a very unique feature that other products are currently unable to achieve. Senti 202 is the company's lead clinical program that we're advancing into and through early stage clinical trials. This technology called Logic Gating does have applications beyond AML, though. We do believe that there's much use of this in areas outside of just the hematological cancers, for example, into solid tumors. We have programs that are actually in active development there as well. Today, I'm going to focus on this Logic Gating Technology. It allows us to essentially separate disease cells from healthy cells and really concentrate therapeutic activity against the disease cells while sparing the healthy cells.
However, I just briefly mentioned Senti does have other sets of technologies that are applicable to the cell and gene therapy space, including arming cells to make them more powerful when they attack cancers, enabling cell and gene therapies to be regulated. You may have seen recently some challenges in the gene therapy space when it comes to potential safety issues. Being able to control what these products are doing in the body is really important. We can do that with our technology platform. We also have the ability to design what we call smart sensors that trigger cell and gene therapies at the right time at the right place. Today, however, I'm going to focus on Logic Gating technology and really tell you why we're developing this key tool.
One of the major challenges in the treatment of cancer is how do you separate cancer cells from healthy cells so that you do not go in and kill the cancer cells, but unfortunately cause a ton of toxicity against the patient. Current Non-Logic Gated approaches, the drugs that are on the market today, including commercially approved CAR T- cells, ADCs, or T cell engagers, generally rely on recognizing a single target. That target has to be found really cleanly on the cancer cells and not on the healthy cells for you to be able to have a therapeutic effect, but that is also safe. If, for example, you are not able to find that single clean target, you are going to have toxicity against both the cancer cells and the healthy cells. That is the case for many, many cancers that are currently not well treated with these technologies.
Our Logic Gate approach fundamentally aims to solve this problem. The way we do that is by recognizing targets on the cancer cells, killing those cancer cells when that happens, but also by recognizing targets on the healthy cells and protecting healthy cells or avoiding killing those healthy cells when that occurs. It is this accelerator and brake that we can build onto a single product that allows us to overcome this fundamental barrier to cancer therapeutics. Our lead indication is focused on treating acute myeloid leukemia. This is a disease that affects 20,000 plus newly diagnosed patients per year. 60% of these patients do relapse or unfortunately progress to death within 12 months. Patients that do relapse have a median survival of about five months. Current standard of care achieves roughly 15% to at most 30-some percent when it comes to complete response rates.
The challenge with AML is that, number one, it's a very heterogeneous disease. To effectively treat it, we need to be able to target the many, many different types of AML cells that are in patients. Number two, though, is that there are no clean targets for AML that are known. In the past, when people have tried to attack AML relying on just a single target, you've at the same time seen very significant toxicities against those patients that have limited the efficacy of those products. Our approach here is to leverage our Logic Gates. The way we build our Logic Gates is through cell engineering. We are using a type of cell called the natural killer cell that we get from healthy adult donors. These natural killer cells can be expanded and genetically modified to express three different proteins.
The first protein is something we call the activating CAR or ACAR. This activating CAR recognizes two different AML targets, CD33 as well as CD123. Both these targets are well validated in the AML space. They're well known to be expressed on cancer cells. The reason why we picked these two is that it allows us to target both AML blasts and AML leukemic stem cells. However, a fundamental challenge with these targets in the past has been that they're also expressed on healthy blood cells. If you don't protect those blood cells from being killed, you have significant toxicity that can happen with these types of therapies. That's what's been seen previously in the clinic. To solve this, we have our Core Technology, which is called a NOT Gate. This is the purple receptor shown here with the inhibitory CAR.
What that does is it recognizes the healthy cell through a target called EMCN. When that happens, it basically provides a do not eat me or do not kill signal to the product. By doing so, we can protect those healthy cells from being killed. Finally, we have something called IL-15 that allows us to boost the overall activity of the cell therapy product. As I mentioned, we recently presented data at AACR, which I'll briefly summarize later on in this presentation. In a nutshell, Senti 202 is very well tolerated, has the potential for outpatient use. This is, I think, a very important part in terms of thinking about the broad commercialization and enabling patient access to this technology.
On the efficacy side, we were very excited to see in our first several patient cohorts that five of the patients we treated achieved an ORR response, and four of them actually achieved a complete response. In addition, we actually looked at something called MRD status in these patients, which is assessing whether there is any minimal residual disease left. All of those patients achieved an MRD negative response. These patients' durability is important here. Actually, our longest-term patient is continuing to be in response. At the time of AACR, that was eight-plus months of durability, which is great for the patient to see. Our ongoing Phase I clinical trial for this product is being performed in adult patients. This is a multi-center, multinational study being conducted both in Australia as well as primarily in the U.S. We have the majority of our sites here in the U.S.
We're assessing two different arms of the protocol. One is at two different dose levels. Dose level one is 1 billion CAR positive NK cells per dose. Dose level two is 1.5 billion CAR NK positive cells per dose. We're also assessing multiple doses in these patients. This is an off-the-shelf allogeneic product, meaning that we can actually repeatedly dose this product into patients and don't have to just give the patients a single shot. We have two different dose schedules, one where we deliver three doses of cells at day 0, 7, and 14. The second schedule is where we do five doses at day 0, 3, 7, 10, and 14. We're able to assess for response at 28 days, and we can give patients multiple cycles of this treatment.
In general, we've seen responses across all of the dose cohorts that we've presented at AACR, both at the dose level one and the dose level two, as well as both schedules. In general, we've decided to select a preliminary RP2D, or that essentially refers to a recommended Phase II dose. That's preliminary. That is potentially the dose we would move forward to into our downstream study. One of the ways in which you assess for activity in AML is by looking at bone marrow blasts. These are AML blasts, for example. In general, our patients at baseline start with a pretty wide range of bone marrow blasts. That is what you expect to see in heterogeneous AML population.
In patients that even started with very, very high bone marrow blast counts, almost all of the patients basically were able to achieve a very significant reduction in the bone marrow blasts to achieve response. One of the ways in which we confirm the mechanism of action of our product is actually by doing something called CyTOF. CyTOF is a method where we can collect the patient bone marrow and do very detailed analysis of all the cells that are actually there. As I mentioned earlier, one of the key cell types that we're trying to attack in AML is something called the LSC or leukemic stem cell. This is a very difficult-to-treat AML population. It's a rare population of AML cells. If you don't kill them, they basically regrow and repopulate the patient's disease.
On the left-hand side here, most of what we found is almost all of these LSCs actually are in the G0 state. What that means is that they're kind of quiescent. They're sort of hiding out and not very active. Because of that, they're very difficult to kill with conventional chemotherapy. That's been well known in the field. On the right-hand side, though, we can see that post-treatment with our product, we see a significant reduction in many of the patients' leukemic stem cell populations. We believe that's correlated with the types of responses that we're seeing in these patients. In patients that achieve our composite CR response, LSCs decrease by over tenfold in these patients, which we're quite excited to see.
In addition to that, as I mentioned, one of the key mechanisms of this product is to enable patients to achieve maintenance of their healthy blood bone marrow. There are two ways of looking at this. One is on peripheral blood counts, for example, looking at patient platelets or neutrophil counts. What you can see from the graph here on the left is when patients initially come onto trial, they oftentimes start with a relatively low or abnormal platelet or neutrophil count. This does get decreased temporarily with the lymphodepletion, which is a brief period of chemical treatment prior to the therapy that all cell therapies essentially go through. That is why you see this low point on the graph on the left here between day 0 and day 14.
For many of our patients, especially those that achieve our complete response rates, we see a significant recovery and actually recovery up to even normal levels of platelets and neutrophils, which is really important for these patients to be able to maintain a healthy functioning bone marrow in the future. On the right-hand side here, using that CyTOF analysis, we continue to also see that if you look at the hematopoietic stem cell population in the bone marrow, that these are actually increased or maintained at a reasonable level in the patients. That is consistent with the protective mechanisms that we have built into this product. As I mentioned earlier, we have seen patient responses across all dose levels with durability up to eight months and ongoing for our patients. We are very excited for these patients to actually be able to achieve these responses. We certainly wish them well.
Our goal is to continue to enroll this clinical trial through the Phase I and to then use that to guide the transition to a potential pivotal study downstream. Now, towards the end here, I just want to briefly mention that our Logic Gate Technology does have broad applicability. As I mentioned earlier, many targets today that are being addressed by ADCs, T cell engagers, or current cell therapies are all essentially crowded around the same indications. That is because only so many clean targets are known. Everyone is essentially attacking the same thing. In contrast, though, there is a huge opportunity outside of those conventional sort of target areas where using our Logic Gate technology, we can go after cancers that basically are more heterogeneous or where you may have to address two or three different targets at the same time.
We're really excited to share this opportunity with the community here. As a company, we really are focused on delivering best-in-class and this first-in-class Logic Gate Technology to patients. We've assembled an awesome team here to execute on this. We're based in South San Francisco. Myself, I was previously at MIT as a professor where this technology originally came from and really been passionate about translating this forward. Dr. Kanya Rajangam is our President, Head of R&D, and Chief Medical Officer, a very deep experience in the cell therapy and oncology development space with multiple approved drugs under her belt. I'll briefly mention here Faraz Siddiqui, who's our SVP of Technical Operations CMC, a lot of experience in cell therapy manufacturing, especially at the commercial scale with his experience previously at Kaikilia. Overall, really excited to continue to advance this program.
In summary, I'll just say that Senti 202 is our lead program. We're continuing to push this program forward. It's our main focus area, at least in the near term. We do anticipate additional clinical data as this phase one enrollment is progressing quite well. We look forward to sharing that with the broader community. We're also very excited about the applicability of gene circuits more broadly into the solid tumor space. We think there's ample opportunity there for us to enhance our pipeline or to partner with other companies to advance those programs forward. With that, I'd like to thank everyone and happy to take any questions.
Great. Thanks, Tim. I think there's a couple of questions in the Q&A. We have a couple of minutes to answer those.
Yeah. We are focused—first question I see here is we do have a focus on synthetic biology and programmable cell therapy. What investor signals matter most now? For us, it's really about now that we've shown human clinical proof of concept with our initial patients, we want to continue to expand and increase patient numbers. That's really our key focus now. As I said, clinicians are very excited about this program and even more excited after the AACR presentation. We've gotten a lot of interest, actually even expanding additional patient cohorts. Our goal right now in terms of this program is clinical execution and continue to showcase what Logic Gates can do for patients. The next critical milestones for us really is more data coming out. Relapsed/refractory AML continues to be a challenging area for patients and for other drug developers.
I think that being said, there are some other companies or other drugs, including the Menin inhibitors, that we can look at to try to understand where the patient efficacy and the bar is and where the FDA is looking at these sort of products. We do believe that Senti 202 has the opportunity to be quite differentiated. Just as a little bit of context, in AML currently, most of the sort of drugs in development now are targeted against genetic mutations. This particular product is agnostic of genetic mutations. It really brings complementary mechanisms to treating this disease. We are really looking to showcase that with our additional clinical data. I think there are some additional questions about other cancers as well as sort of how we compare this to CAR T.
Senti here has always been focused on choosing the right cell type for the right indication. At the heart of it, we are a Logic Gate company, not an NK purist or T cell purist company. For AML, we really believe that NK cells make a lot of sense because these patients do not have a long time to wait. Also, patients with AML oftentimes have dysfunctional T cells. NK can really serve as a safe off-the-shelf product for these sort of patients. For solid tumors, though, there is emerging clinical data continuing to showcase the opportunity and the activity of T cells in those areas. We have done work to showcase that our Logic Gates do work in CAR T. We do think that there are opportunities there to drive solid tumor programs into the clinic.
All right. Thanks, Tim. Appreciate your time. Again, make sure to visit Senti Biosciences Corporate Connect page on the Webull app for updates. That will conclude the Webull Corporate Connect Biotechs webinar. Thank you for everyone's time. Be on the lookout for upcoming Corporate Connect investment webinars highlighting different sectors in the near future. Thanks so much, everyone.