Advancing Chordoma Drug Discovery and Development

Talk about capability exists playing out the aviation level capability and the knowledge generated talk about our key priorities and financial and forward. Um, you know, part of that. Now bringing new therapy is commanded of this growing pipeline of increasingly powerful gas therapy to apply that to comments. And then parallel, we created a new therapy for an hour with Sprite Gas, and that The person that I work in is behind that who is responsible for driving that for bringing new drugs, new or elements by investing in the basic science that is, by engaging companies that have given by seeing a direct CFI, expected officer and the entry. But right now. Uh, we can talk with you about what's happening in the world of discovery and developing everyone. Um, On the capital of the entire resistance, uh, we see the development. So that's what we are beginning to, uh, there are two main acts First hand is usually the foundation we are achieving. The other hand, that's which essentially identifying vulnerabilities for no longer shared on, uh, the drug discovery, uh, is already happening, uh, in other side. And then, uh, we probably heard those experiments So over the past 20 years of the foundation, um, same five years and, uh, specifically purchasing so that the wealthy first that is not factor Drugs that are already produced for other diseases and actually constant. And we should message progress in that area where we talk from design where the, uh, should be charged in drugs now having, uh, three active drugs for that benefit, uh. And about fifteen percent locations for tumors shrink substantially. Okay, that tumor shrinkage, uh, it's growing for over over two years. So that in many ways is tremendous achievement and investment work of the foundation and the research. At the same time, it's obviously not the right tax. That we have to develop, uh, newer better guarantees towards that all issues can experience long term. So this play our strength is, uh, large focus on the research side, where now we are primarily focusing on repurposing experimental focus because our edge next generation guarantees are not And we're focusing on discovering development new drugs as per year. And so this, both of these new packs require us to collaborate a lot more closely than we did before. Um, so it's involved in terms of the needs and economics of the person, uh, so that means for us researchers that have to be a long read, can't be, and have to be opportunistic to make sure the repair gets built that you can get size and investment that other communications are. So the first part of my box is on, uh, discovery and As we think about being advancing opportunistic, uh, on, uh, long term, uh, what that means is really kind of, uh, playing the risk of numbers that we have to us. A lot of times that's that's lowering the risk, that's de-risking, uh, uh, participation, um, just getting all these balls to getting it a shot, and, uh That part of developing these capabilities is establishing the ability to literally screen thousands and thousands of contents for these companies. So we have a lot of effort in the lab into establishing those capabilities. And as you heard a little bit earlier today, also part of that is keeping our ears in the ball content that we are almost aware of advancing. Technology and new modalities that could cause variables. So where's that level? I think over the past ten years, as we see in this chart, there's been a tremendous uptick in the number of break theory chart discoveries over that map, uh, that discovered. The inflection point this curve year, which is 2022, when we finally That is not only allowed for the initiation of a tremendously greater number of regular drug discovery programs. As you can see from the shape of the blue here on this current side, in shape of blue there, uh, not only enabling initiation of new regular drug discovery programs, but we're advancing new structural programs. Second stage stage of thirst stage, of course, resolves nutritional. That's also an important part of the process. Not only are, uh, we smart, um, but companies want to make quick further decisions. They want to go with the impact. And a lot of this is made to get by the capabilities that we've developed in the lab. So because of this over the past couple of years, Breaker has gone being kind of a target that many countries come in touch with now. Foundation in basic science over the past couple years, and also basically the fact that technology have collabored much more attractive authority. And so that's one thing that we're constantly interested in keeping an eye on is how technology and how science are advancing. So we can identify these new approaches that might work really well. One of those approaches, um, that is kind of novel that, um, I'd like to share with you today just as an example, uh, new area on the breaker fragments of the rap buried protein that are sending on the soft surface being abuses. And, uh, we heard earlier this week at a research workshop from several of our grand teams. That if identify fragments of a breakthrough that the immune system essentially recognizes as max cells, much like it will recognize as a pathogen virus. So in a way these breakthrough fragments are analogous to a virus, and they activate immune response or even augment that immune response yes And so it's part of multiple carriage approaches from the potential vaccines that Josh mentioned, uh, to multiple handle body based approaches, multi-caritant approaches as we heard Dr. Schwab earlier today. And as a foundation, what we're actively doing at this very groundwork so we can acquire some new wave of industry investment gracefully, break three fragments of service specifically Okay, so we are setting our work to other products for the next peries understanding rate period products and soil service in those are not extend the trust for larger interest of the markets that extend economics. Allow us to screen And we were very excited to announce just yesterday a research project in partnership with the Mark Foundation for Cancer Research. We go funding a series of grants in 2027 that were intended to specifically build the neighboring framework for this type of therapy approach. Another approach regarding the Is a traditional starting directly design stuff. Many of you have heard of the TBX challenge, which is the price competition launched, uh, a year and a half ago, which was identified campaign. Registration for the TVX challenge just closed on September 1st before we had ex- And all at least 26 participants enrolled in the challenge across four different continents, nine different countries. We estimate that challenge leveraged well over five million dollars in company resources by, um, equivalent success part of that economy. And, uh, this graph shows kind of the progression of the challenge over time. And this is companies on four basis and one percent three several companies have, uh, but, um, that side, um, the, uh, is like that person. We have first developed the compound next minute regular cycle that you can be shifting for the funding program. So this was, uh, huge news, um, in the site and, uh, and importantly, regular Breaker belongs to a set of proteins all in transmission factors. There's about sixteen hundred percent of the human genome. Many of them are implicated in driving various different cancer. Common cancer, rare cancer. Only one percent of these transmission factors have improved in the EPR, 99% Right here, you see that time to understand. So, so those are some of the, uh Very quick, quickly delivered exciting discovery and term maker my office, um, where, um, some of our current priorities are exploring joint competitions. So we're saying taking those reactive joints that we now have to combined other experimental energies to get Uh, personalization, we heard about that today. Uh, Dr. Bottom talked about action might be a lot of identification of my own perspective that this class area comes as well. And then question Uh, as the case for, um, regular drug discovery, um, identifying new technologies that are being developed for other humanities and understanding apply, um, those technological and medical advances to how Josh mentioned, um, et cetera, those types of things, how can we apply those advances permanently for So the very most big level of what drone recursive requires is learning stone requires us to identify that our share and other information. So this is where this cover initiative comes not very And this practice has showed up very well in the last discovery. There's no problem, uh, three main focus areas. We have five, uh, different rates that are focused on the identification of hardware water buildings order on, and associated by one Understand which patients should example is constant on this front collaboration between CFI and other teams identify the potential five marker response PG partners for evaluate this five marker by another area of focus reference So understanding how foractive documents hear about so the expert in this others work this way, uh, the discovery that cords indeed cancer diesel of the streamers keep the cost, so we often get in their early Research has suggested some natural process where we can open up the door and let those deep built inside the tumors that they can destroy. The third area of discovery is not technologies, such as heat surface parents cover, and three large areas let them fire surface parts from solar. That are shared with others which have to us being active. So thus creating a total for us. Crucially, having a lab enables us to validate the reference and processes quickly set up for rest. And last year. Uh, the foundation's for our screening programs over the past ten years and continuous number of current concepts of our screening program. And with the launch of State Labs 2022, uh, we have made, uh, teacher self-based studies that allow us to produce more lendings more than 38 so that we can So for Sri Offship, hypotheses for confidence that requires processing classes. So to snapshot our issue here, we have currently four for the law process from miles. And a number of other third day concepts are starting to progress a lot of the service based on some of the research that's on the lab and all the research. That we think that might be a half trial based on future costs and that third case based. So we hope that, um, some of these people, um, in the near future, and The obvious one of the most exciting things that I've been a part of society process for sixty hours. But it's a further process. Actually, process much clear. But that's where. It targeted the set of machine that's possible for 60%. All this kind of like bomb back to the machine, okay? And so it's not a new idea, it's not our idea. It's actually one of the research that went brewers in Boston. Those researchers found that, uh, that the class of drugs called CK could suppress the Production of Ray and European Brighters didn't want to tell that, um, and then beside that the right are two of these containers for supplying operator production. These first generation containers really not carrying drugs for a period of reasons based on the fact that there are various participation case, which affects the profile So, um, so these controls weren't regular options, but it was this proof of concept. And the hypothesis was that two C cases, CT nine and Casey seven, were main Case responsible regular. In the year that ensued, the source of life second generation is K7 and CT nine, and we're, uh, NAT area of drug development. So we tested the CA selected second generation CP7. We were quite confused because we saw that it did not interfere with the production point period. We also did the CD not in place and found the same result, which it did not at all interfere with production point. So we scratched the head, the factory order, we found, we found the correct factory element. And it turned out it was 512 in person. We had the legacy equal thirteen inputs. On that day, we're the ones that were responsible for interfering with the customer gray. We look at real call in the microscope paint cells green with the gray period inside the cellar. You see one of the 512 percent or 15 grave inside the cell. And we look at cell ice acid. So buyers on these grasses, the liability and the intersects with the trust or increasing justice trust five different cell models that increase the damage. Um, so their liability is, um, uh, increasing as we increase the concentration. There's company in the space based on drive for the C2 character index Uh, we've been in touch with the past couple months, and, um, I think we've, uh, we generate a little bit of issues, um, with that. So they share data, and I think it's not very interesting today, but we'll speak to our team posting deliverance and share our research and, um, on behalf of the People decided to be supported, um, continue to generate interest, um, such that. So, um, I'm gonna wrap up here. I shared three exciting approaches for targeting for you today. There's the direct marketing process and the name by challenge. There is a new service targeting process we're excited about Um, the status of, uh, groundwork, uh, on that point, and then we have this interesting part of hypothesis that are discussion about that could potentially should the data continue to, uh, support, uh, the between trial in the future. Josh has already gone over, uh, our team and now we can head on to the next Um, there's a first patient operator drugs trial, launched in trials of three of those trials, um, active drugs that are lost. Then we want to bring the efficiency to the same labor, uh, so most of all, thank you all for being here.