She's a sell-sider, II-ranked, and she's going to take us through the Boundless Bio story.
Thank you so much, Reni, and thank you very much for having us. We're really excited to be here, and I could not be more delighted to share our story. Again, I'm the Chief Financial Officer of Boundless Bio. Boundless is the first and only clinical-stage public company establishing a new category in oncology that addresses oncogene-amplified cancers through targeting extrachromosomal DNA, or ecDNA. Let me just make a couple of points to sort of provide the overall investment thesis. Oncogene-amplified cancers represent a significant unmet medical need population, which accounts for 25% of all diagnosed cancers. What's important to understand is that there are no approved drugs in oncogene-amplified cancers, with the exception of HER2 inhibitors. It's a big market, 1.3 million new patients per year in our major markets. To our knowledge, we are the only company really targeting this very large white space opportunity.
ecDNA, or extrachromosomal DNA, are cancer-specific circular pieces of DNA, a root cause of oncogene amplification. By targeting ecDNA, we have the opportunity to create a whole new paradigm in cancer therapeutics that treat oncogene-amplified cancers. Spyglass is our drug discovery platform. We use it to identify ecDNA synthetic lethalities. We have moved rapidly into the clinic. We have two programs now in the clinic, and we hope to have multiple data points and readouts over the next 9-24 months. Our first drug is our oral CHK1 inhibitor in phase I/II. Our second is our oral RNR inhibitor and just started to dose patients. We have a novel kinesin in discovery advancing towards a development candidate. We also have a proprietary diagnostic tool that we call ECHO, which we use to identify ecDNA-positive patients to enable patient selection.
We have an experienced management team with a track record of drug and diagnostic approvals, have been involved in several multibillion-dollar M&A activity. We just completed our $100 million IPO, which is a very exciting milestone for the company, cash runway into the second half of 2026, which funds our clinical programs to preliminary proof of concept. This slide should orient you to the opportunity and where we sit in precision oncology. If you look at the top, the industry has focused basically all of its efforts in altered oncogenes or mutations and fusions. They account for roughly 15% of all cancer patients and have been associated with over 40 FDA drug approvals, $20 billion in annual revenues, and approximately $40 billion in M&A deal activity.
At Boundless, we're focused on the bottom part of the screen, altered or rather amplified oncogenes, which again represents 25% of all diagnosed cancers. So it's actually a much bigger opportunity than mutations and fusions. And of that 25%, over half of those are patients with ecDNA-enabled cancers. Again, no drugs approved in that space, with the exception of HER2. And this is what we're focused on. And we see oncogene-amplified as the next frontier of oncology. This is our pipeline. We have three programs. And those programs are focused on different nodes of ecDNA. So our first is replication stress. We're targeting that through a CHK1 inhibitor. That's in phase I/II. Our second asset is an RNR inhibitor, which is addressing assembly and repair. And our third, which is in discovery, is a novel kinesin addressing segregation. We're super excited about these programs.
Just given the limited amount of time that I have today, I'm going to focus my comments on the first program. But just so you know, we have a detailed corporate deck up on our website with more information should you be interested. So let me first establish the unmet medical need. Cancers with oncogene amplifications are more aggressive. They're more difficult to treat. And patients with amplified cancers have worse prognosis. Oncogene amplification is a type of oncogenic alteration where there are extra copies of an oncogene, such as EGFR, FGFR. And those drive tumor growth or resistance. And you can see the graph in the middle. A patient with amplifications versus mutations or fusions have worse survival. And on the right, you see this is a patient with an FGFR alteration. And FGFR amplification compared to a mutation and fusion shows worse PFS of only two months.
So this is obviously a very big unmet need opportunity that we're focused on. This is a list of targeted therapies that you're all familiar with. These are all great drugs targeting CDK4/6, EGFR, FGFR, MET. They're approved for various mutations and fusions. But none are approved for amplification. And it's not for the lack of trying. These companies have tried to address amplifications by using targeted therapies. But the results have been abysmal and have not led to FDA approval. CDK4/6 has shown response rates of about 2%-3% in amplified patients. EGFR, FGFR have shown response rates in the low double digits, again not sufficient for FDA approval. So clearly, a new approach is needed to address this large population. So let me explain to you ecDNA. And we see ourselves as in the we are the leaders in this new biology of ecDNA.
If you can see there on the left, ecDNA are circular units of DNA which exist outside of the chromosome in cancer cells and are a major driver of tumor growth and resistance. The middle and to the left shows the different features of ecDNA and explains why they do what they do. In the middle, you can see that the circular shape of ecDNA enhances transcriptional activity, leading to high oncogene expression. To the right, you can see that ecDNA lacks centromeres, which leads to a non-Mendelian segregation of cancer cells. Again, that drives tumor growth and resistance. So this sort of explains what this role, this little circle is playing in amplified cancers. Our goal is to address vulnerabilities of ecDNA and drug those targets. ecDNA are detected broadly across different tumor types.
In fact, in 14% of all tumors, you see glioblastomas, sarcomas, esophageal, lung cancer, breast cancer, gastric cancer across the range of different solid tumor types. What's interesting is that ecDNA is not present in normal tissue or blood cancers. And again, 14%. And if you do the math, 14% of just in the U.S. population out of the 1.9 million patients diagnosed with cancer, that's over 200,000 patients. So a very large unmet need opportunity. This is an important slide because it, again, demonstrates why targeted therapies have not worked in amplified cancers, particularly with ecDNA. This is a gastric cancer cell model with an amplified FGFR2 on ecDNA. And if you use an FGFR inhibitor in the middle graph up on top, you can see that cell viability comes down, as you would expect. But at day 40, those cells start to grow back.
On the bottom graph, you can see that FGFR copy number drops over time, but is switched out to EGFR. We have another. I haven't included this in the presentation. But if you treat this cell line first with FGFR, you see FGFR goes down. Then if you treat again with an EGFR inhibitor, the FGFR oncogene switches back. So obviously, this is an approach that has not worked. I would say that the big takeaway from this slide is that amplification on ecDNA allows cancer cells to rapidly switch oncogene dependency under selective pressure. This explains why the targeted therapy approach has not worked. In fact, it's akin to a frustrating game of whack-a-mole, where you hit one oncogene and another oncogene pops back up. Again, that's the traditional approach that hasn't worked. We're doing something different at Boundless.
We think it's a much smarter approach. We are exploiting the underlying vulnerabilities in ecDNA-driven cancers to target drug targets essential for ecDNA functionality in cancer. Essentially, we're unplugging ecDNA machinery, which causes genomic plasticity or this uncontrolled growth of tumor cells. This is a picture of Spyglass. It is our unique platform discovery engine for interrogating ecDNA-driven tumors. We think we have the only tool in town, in fact, that is used to investigate drugs for ecDNA-driven tumors. We're very proud of this. The other point I would make is that all the drugs that we've developed were developed in-house. We don't owe any royalties to anybody. These are our own internally discovered programs. This is another depiction of our pipeline, but looking at it differently. This is a life cycle of ecDNA.
Replication stress, we've developed a CHK1 inhibitor to address replication stress, an RNR inhibitor to address assembly and repair, and a novel kinesin to address segregation. I also mentioned that we have a proprietary diagnostic tool called ECHO. We use that. That is designed to detect ecDNA in patients using routine clinical next-generation sequencing data. Also importantly, we have received non-significant risk determination by the FDA for use in our phase I/II POTENTIATE trial of BBI-355. So let me talk about our key, our first program, again, BBI-355. BBI-355 is a phase I/II clinical trial called POTENTIATE for the treatment of monotherapy and combination in amplified cancers in combination with targeted therapies. BBI-355 is an oral CHK1 inhibitor. We believe it's a best in class. We've shown very compelling single agent and combination activity in preclinical models and have moved rapidly into the clinic.
We are now in part two of our study. This is a cartoon which explains why CHK1. What is the biological rationale behind CHK1. As you can see, ecDNA-positive tumor cells have significantly elevated replication stress. CHK1 is a known master regulator of replication stress and keeps those nasty cells, those tumor cells, alive. By inhibiting CHK1, the idea is to destroy those cancer cells reliant on ecDNA with high levels of replication stress while at the same time sparing healthy cells, which is a concept known as synthetic lethality. What's interesting is that very recently, a peer company of ours, a peer company showed very compelling single agent activity of a CHK1 inhibitor in a selected patient population, which gives us even more confidence in our program because we think we have a best in class asset. Again, why do we think so?
We have, I think, what are considered unique properties. Our CHK1 inhibitor is highly potent. It is highly selective. It is orally available. It has clean CYP inhibition. And here, we show single agent activity across multiple oncogenes, MET, FGFR2, CDK4/6, EGFR, MET. And you see the single agent activity of our CHK1 inhibitor. This is another preclinical slide, but really important because it shows, it demonstrates our drug BBI-355 remarkable synergistic combination activity of cancer indications where single agent targeted activity has not proven effective in the clinic. So you can see here on the left oops, I'm not going to if I can just point the green line. The green line is infigratinib for an FGFR2. And you see that it works initially. But at day 14, the tumor cells start to grow out.
If you combine that with our drug BBI-355, you see longer anti-tumor activity and longer durable responses. On the right, you see that with FGFR, that the oncogene copy numbers grow out. But BBI-355 kills those copy numbers. And this is a concept known as a vice grip concept or enhanced synthetic lethality. Together with BBI-355 and a targeted therapy, we're able to show that oncogene amplified cells are killed. Let's see. Oh, it's all right. It's easier for me just to show the whole schema of our phase I/II POTENTIATE trial. So this is we are now in part 2. We just moved into part 2 of this study. This is designed to show clinical proof of concept in multiple solid tumor settings. Part 2 is we are enrolling patients in module 1, which is EGFR amplifications, and module 2, FGFR amplifications.
We plan to enroll patients in module three later in the year, as CDK4/6 is also an interesting opportunity. But we want to be really comfortable with that combination. And then we'll be moving into part three. We think that this is a really robust and thoughtful clinical trial design as it gives us so much optionality and so many shots on goal. And also, if we show success with these modules, our plan is to add other modules with other oncogenes, such as MDM2 or KRAS. So that's where we are. And that's our first program. We are moving as rapidly as we can to show clinical proof of concept. Our second program is BBI-825. It is an oral RNR inhibitor or a ribonucleotide reductase inhibitor. That is also, we just dosed our first patients.
The clinical trial design for this, which is called STARMAP, is very similar to POTENTIATE with a part one single agent dose expansion, part two combination, part three a much expansive study. But this study is a little different. We are developing this drug for cancer with resistance gene amplifications. And our first modules are combining BBI-825 in combination with adagrasib, KRAS G12C, in patients with metastatic colorectal cancer and a BRAF, encorafenib, for metastatic colorectal cancer. And what we are trying to show is that our combination will both treat and prevent resistance that is driven by amplifications. So just to wrap this up, it's a big opportunity, very large TAM, 1.3 million patients with oncogene amplified cancers in our major markets. Of those, over half are on ecDNA, or 750,000 patients.
Our first opportunity on the left, BBI-355, both as monotherapy and in combination, have potential to treat around 180,000 new patients per year. On the right, BBI-825. Initially, we are targeting 18,000 patients. If that's successful, we could go to a much broader patient population, lung, pancreatic, melanoma, and pan-RAS, pan-RAF, if that is a positive study. And our goal is to fill out that whole pie with what we call ecDTx therapies, ecDNA-directed therapies. And again, just to wrap it up, Boundless Bio is leading a compelling and differentiated approach to address oncogene-amplified cancers, oncogene amplifications, huge unmet medical need, one of cancer's remaining unmet medical needs, ecDNA, a root cause of amplifications. We are the leading ecDNA company. We have multiple clinical stage programs with robust preclinical data. ECHO is our diagnostic tool.
We have IP for our first two programs into the early 2040s, 2041 to 2044. Importantly, we have approximately $200 million of cash, which provides runway into the second half of 2026 through, importantly, our next anticipated milestones, both early preliminary proof of concept for 355 and 825. So with that, Reni, I'm all done. Happy to answer your questions.
That's great. So I don't know if most of you know. But Jami, as I mentioned in the intro, has been on the sell side, top-ranked analyst, could have retired into the sunset as far as I was concerned.
Not true.
But decided to take this job. So I guess maybe I'd love to start off by asking, why did you take the CFO job at Boundless?
Right. Well, thank you for the question. For me, I've worn multiple hats in my career. Most of my career, I wore the hat that you're wearing right now, which was an equity analyst. And that role was phenomenal because I got to see so much in analyzing companies. But to be actually working in a company and to be an operator, I think, is a real privilege because now, instead of being in the audience, I'm actually at the podium, figuratively speaking, and making decisions and helping to drive our mission, which is developing these really unique drugs and to get them into patients. And I don't think there's too much that's a pretty exciting mission. And to be part of that is really exciting. But specifically, why Boundless? Boundless is just such a cool story. The biology is really elegant. It's highly differentiated.
Oncogene amplified cancers are a huge unmet need. We're not really competing. I mean, other companies are trying to address different aspects of it. But nobody is going after that space the way we are. We're also approaching it in a totally novel way of biology. And if we're successful, we will create a whole new vertical in cancer therapeutics. That's really cool to me. There are a lot of exciting companies out there. And everybody has their own unique story. But what I love about ours is that no one else is doing it. And we are leading this new frontier in biology. And if we're successful, we'll make a really big impact on patients' lives. So that's why I chose Boundless. Love the team. Love the scientific founders, strong syndicate of investors, and really excited to be part of it.
We just finished an IPO and working towards fulfilling our mission.
So one of the things you talked a lot about the positives, the headwinds, why you're there. You've talked with investors. What are some of the potential tailwinds or things that you're hearing that you feel need to be kind of overcome?
Yeah. Yeah. No, that's a good question. So what are some of those tailwinds? The biggest question that we get is, show me the data. And I think that for us, you just need to give us time. And we are working towards generating that data. But I do think what's happened in the marketplace is that, number one, the macroeconomic backdrop is not very friendly to smallish, high-risk biotech stories, long-duration stories. So the macro backdrop is not ideal. But I can't control that. Number two, the investment community has differentiated between companies with proof of concept in hand, bird in the hand, and those without. We are kind of in between. We're in the clinic. And we are racing towards having that clinical proof of concept. But that's what investors want to see.
The third point I would make is that clearly, there was some pushback initially on our first program. There's still pushback on our CHK1 inhibitor. Why? Because this is a class that has had somewhat of a mixed past. There are no CHK1 inhibitors approved. So yes, we got pushback on our lead program. As I mentioned in my remarks, a peer company, Acrivon, did just recently show very compelling single agent activity with a CHK1/2, slightly different from ours, but primarily similar. It's an injectable. Ours is an oral. But they showed 50% responses in ovarian and endometrial cancer. We are also pursuing that in our monotherapy studies. The point here is that it was in a selected patient population. The CHK1 inhibitors in the past were less selective. They were less potent. They were not in an enriched patient population.
That study gave us a lot of confidence in what we were doing. Those are the headwinds. The tailwinds are investors are just hungry for something new and exciting, cool biology. Most importantly, if we're successful, the opportunity to target a very large TAM or a large market opportunity.
In the last minute we have left, it seems like it's ripe for patient selection and using the diagnostic. But at the same time, depending on the data, there's a chance that you might not need the diagnostics. And so how are you kind of?
Yeah. No, it's a good question and a question that we get often. Hopefully, we won't need the diagnostic tool. But we believe that ecDNA does play such an important role in driving oncogene amplified cancers. So I think going after really understanding the vulnerabilities of ecDNA first and developing drugs that target these nodes of ecDNA gives us the best chance of success in the oncogene amplified market opportunity. But as I showed you with our first trial design, we have a part two. Those patients are patients with oncogene amplified cancers in general. They're not patients who are selected for ecDNA amplifications on ecDNA. They're just the general amplified patient population. Part three, we are using ECHO, our diagnostic tool, to select for ecDNA patients.
If we show responses in part two that are a lot better than responses that we've seen in the literature, which are pretty abysmal, we may not need the diagnostic tool. And we might be able to get a much broader label. But right now, our focus is on ecDNA. All the models out there reflect the opportunity in ecDNA. But there is the opportunity to go broader than that.
Excellent. So our time's up. But I'd like to remind investors that you have two big kind of market inflection points a lot of times in biotech. One is actually proof of concept data. You see a significant increase in market cap. And then, of course, phase III. And so these guys are coming up on that in the second half. And look forward to seeing the data.
Thank you. Thanks for having us.