Good morning, everyone. My name is Rok Ben from Morgan Stanley. I have the pleasure of hosting BridgeBio Oncology Therapeutics right here today. Before we get started, Eli, I don't know. You're obviously one of the newest public biotech companies in what's otherwise been a slow year for new issuances. Can you just tell us a little bit about how you and the company got here?
Yeah, thanks, Rok. Yeah, pleasure to be here. Good morning, everyone. I joined BridgeBio initially to run the affiliate that was focused on oncology back at the very end of 2019. As we progressed our programs through research and all our programs are discovered in-house, we became, in parallel, BridgeBio was progressing their programs into phase three and now commercialization, and we were getting ready to enter the clinic. We needed the resources and the focus to drive our programs forward, and BridgeBio really wanted to focus or needed to focus on commercialization of Macaromidas and other things. It just made sense for us to separate into a private company. We did that in May of last year, so May of 2024. We were fortunate to raise $200 million of capital that enabled us to move our programs into the clinic.
After doing that in May, we then dosed our first program in the next month, June, our second in October of 2024, and then our third in March of 2025. Very quickly, after becoming a private company, we had three assets in the clinic. As you mentioned, we just started trading last month on NASDAQ, and that was really the next phase of our evolution as we did a de-SPAC with Helix Acquisition Corp. II. That was a very good deal for us where we announced a PIPE of $260 million plus in February, the very end of February of this year, when we also announced our intent to merge with Helix Acquisition Corp. II. We were able to close that deal in August and had proceeds of about $380 million. Trying to get my make sure my math is right. We had very little redemptions of only 39%.
For us, that was a very important deal because certainly with three assets in clinic and in the oncology space, we need the capital to execute on those programs. As you mentioned, not many new companies are going public this year. From when we announced the deal at the end of February to closing it, there wasn't a single biotech IPO over that span. Definitely the right path for us to get the runway we need to move our programs forward.
Got it. Unique, you're relatively new to bBOT. Can you tell us a little bit around why you joined the team and what got you excited about being part of the BridgeBio Oncology Therapeutics team?
Yeah, sure. Thanks, Rok. I'm Unique Weather, Chief Financial Officer. As Rok mentioned, I joined about six to eight weeks ago. At the outset of it, I've spent quite some time in a lot of cell and gene therapy experiences. Given I wanted to focus really on very innovative small molecule approaches, the challenges with cell and gene and scalability, I wanted to get past that and really join a small molecule oncology company that had multiple different assets. When you look at BridgeBio Oncology Therapeutics and we go through all of our clinical programs, not only those in the clinic, but then those which are in the backup, there is a tremendous opportunity and an unmet need to be able to not only use these assets individually, but more so in combinations.
I think when I look at that, combined with the management team that is currently, of course, with Eli and Pedro, our Chief Scientific Officer, having wealth of experience over decades in this space, a board that is very supportive. When you put together all of these factors, that for me made the decision quite easy.
Thank you. Maybe for all of you, now that you're public and well-funded, what's your vision for the company going forward? Maybe starting with some of the near-term objectives, your long-term vision, and maybe touching a little bit around the market opportunity and the unmet need that you're addressing.
I guess I'll start. The capital that we were able to secure, with the capital that we had from the spin-out, gives us ample runway to test all three of these to proof of concept, which is really important for us and then enables us to make a data-driven decision on the best path forward. The opportunities here are vast. Certainly, our KRAS G12C inhibitor in 15% of non-small cell lung cancer and KRAS addressing G12X tumors, so G12D and B, and for lung, pancreas, and colon cancer. Our second program is a very innovative approach to inhibit PI3Kα signaling in a very novel way, that has very huge opportunities to hopefully change the landscape in how you think about inhibiting that pathway. There are opportunities in breast cancer, both hormone receptor positive as well as HER2 amplified breast cancer, and of course, also in the KRAS main space.
Really large opportunities for us to address many patients with the two most mutated oncogenes in human cancer, RAS and PI3Kα. I don't know if the team wants to add anything.
Yes, I may just build on what Eli said. I mean, we often get this commentary that, hey, the space you're in is extremely crowded, right? I think that's true to a certain extent that G12Cs are seen as the first generation of inhibitors. There's a lot of buzz around pan-KRAS, pan-RAS assets. I think the way we, when you come back to your question about the vision, when you look at PI3Kα breakers that we have, we don't believe, and there's maybe one or two, there are many. Combining that with the KRAS sort of, and you're not attacking both the MAPK pathway as well as the pre-PI3K, which are two of the most mutated, as Eli mentioned. We strongly believe that not only our individual assets are prime time for differentiation, but also combining these assets by themselves.
I think we lay emphasis on the fact that just don't look at BridgeBio Oncology Therapeutics in terms of the individual assets, but also the combinations. That sets the stage for us to really fulfill some of the shortcomings that the current landscape of G12Cs or even current pan-KRAS inhibitors are exhibiting.
I thought the portfolio synergies for the company, I think, are really critical, especially in the KRAS mutant space across lung, colorectal, and pancreatic cancer. Massive opportunity and really something we're excited to be doing.
Got it. Maybe, you know, just had a question around, you know, obviously you're a very grounded chemistry organization. Maybe would love to hear a little bit around how you go about your drug design process, why it's hard to duplicate, and also you maybe using your KRAS on/off as a case study as to how you're able to accomplish targeting both on and the off state.
Yeah, thanks for that question. Yeah, my background is medicinal chemistry. I was recruited by Neil Kumar, the CEO of BridgeBio Pharma, and Professor Frank McCormick, founder of BridgeBio Pharma, to come over from Peloton Therapeutics after we were sold to Merck. At Peloton Therapeutics, we worked on HIF2, which was a well-established target from a biological perspective, but nobody knew how to inhibit it. No one thought you could inhibit a transcription factor. Of course, we proved that was not the case by making L-sudafen lower reg. When we came to, when I say we, I was fortunate enough to bring some of my team with me from Peloton. When we came there and teamed up with Professor McCormick, we took on the breaker challenge, but also we took on on-state of KRAS inhibition.
At the time, this is 2020 now, no one believed you could bind to the SWITCH2 pocket and inhibit the on-state. We took on that challenge. Really, it's in the weeds and in the details of medicinal chemistry and structural biology that enables you to make those molecules, design those inhibitors that enable the inhibition of the on-state. We totally believe that inhibition of the on-state is critical to give patients the best opportunity to benefit from therapy. I think more broadly, when we tackle these programs, and again, it's in a way it's similar throughout my career, you really need to design inhibitors that are going to make a difference, that can drive the high levels of target inhibition in a safe manner. We think we can do that with KRAS G12C inhibitor BBO-8520 by inhibiting the on-state. We think that's critical.
We can go into why we think that is if there's interest. Then pan-KRAS, the same thing. With the breaker program, where you're inhibiting signaling only where it's driven by RAS, that's important because RAS driving PI3Kα is really important in tumor genesis, but not in normal adult physiology. We fully expect that we're going to have no hyperglycemia in patients, even to the point where in our phase one trial, we have no restriction on HbA1c status for patients entering. That's completely different than anyone else in the field. We're trying to do innovative approaches that do require breakthroughs in chemistry in order to do that. I'm glad you asked about chemistry because at times, when you get into the clinic, sometimes we make the joke, people think it's just going down to Rite Aid and getting them off the shelf.
There's a lot involved in designing these inhibitors to make them, you know, hopefully best in class and really to give patients the treatments that we think will really make a difference.
Got it. Maybe switching here a little bit to talk specifically around some of your drug candidates. For starting with your lead candidate, BBO-8520, which targets KRAS G12C, what kind of, what did you see there? How did what you saw compare to your expectations for the drug given? Unique, you mentioned that it's, you know, people say that it's a crowded space. Maybe talk around BBO-8520 in terms of, you know, maybe giving an update on summary of the data, the translatability, et cetera.
Yeah, thanks for that. When we talk about BBO-8520 and the chemistry, as I mentioned, we're a direct binder to the SWITCH2 pocket and we're able to inhibit both beyond and off-state. What that was able to do for us, and let's start with just the pharmacokinetics for a minute, it enables us to get very good efficacy with very low levels of drug. Through the first three cohorts in patients, we have about 1% of the exposure of sodium acid and natric acid. How is that achieved or why is that possible and why is that important? When you are a covalent inhibitor, the advantage is you can act like a hit-and-run mechanism. You can get residence time on the protein of interest, in this case, KRAS G12C, and then you can clear the circulation. If you can do that well, you can get a nice therapeutic index.
If you're an off inhibitor, you cannot do that because you need to be there all the time to wait for cycling. That, as a first principle, can lead to very good efficacy with a differentiated safety profile because you're not going to have large levels of a reactive covalent compound floating around the body. We think that's a very important principle of a non-off inhibitor that I think gets a little overlooked at times. What have we observed? From our data cut in January, we had 10 evaluable patients. We saw a 60% confirmed response rate, even responses at the first dose levels. Those were dose levels of 100, 200, and 300 milligrams qD. Very promising early efficacy there, 60% response rate confirmed. We also, on the safety side, had no grade 3 toxicities and we had no liver toxicities of any grade.
Very different than off inhibitors, which are plagued by grade 3 liver toxicities that get worse when you combine with a checkpoint inhibitor. We really think that positions us well to move into combination with pembrolizumab to go into earlier line settings because we believe we'll be able to combine with very active doses where we can really avoid that troubling liver side effect that the off inhibitors have.
That's fantastic to hear. I think just in terms of thinking about specifically around the white space around the G12C landscape, is your vision that ultimately you will be getting into competing with the established approved agents and competing based on your superior response rate and a better tolerability profile and take the market?
Adan, you want to take this?
Yeah, I think there's been new data that's come out from the off inhibitors in combination with pembrolizumab in first line NSCLC. I think there's certainly an opportunity there, especially when you look at some of the data that's come out with respect to their safety profiles, which again, based on the mechanism Eli described, we should be able to improve on those safety profiles with the on mechanism, as well as the efficacy, especially in TBS < 50%, where pembrolizumab is driving a little bit less of that efficacy in combination.
Got it. Thank you. Perhaps we can switch gears a little bit into your PI3Kα breaker. Can you just, I mean, you touched on this earlier, Eli, but for the benefit of everyone, what is a breaker? How does it differentiate from traditional PI3K targeted assets? Maybe just contextualizing for folks that might be more familiar with the traditional PI3K approaches from a market opportunity perspective.
Yeah. So many people know that the kinase activity of PI3Kα is absolutely required for glucosaminostasis. We took on an approach that should completely avoid that, but it still inhibits signaling in tumors. What BBO-10203 is, this is our RAS-PI3Kα breaker. This is a protein-protein interaction inhibitor that binds specifically and selectively to PI3Kα and what's called the RAS binding domain. That RAS binding domain, you can think of it maybe in the northeast of the protein, and the kinase domain is in the southwest, so it's quite distal from the kinase action. In the presence of our covalent inhibitor, the kinase can still function fine. You can inhibit RAS activation of PI3Kα, which is very important in three tumor settings: HER2 amplified breast cancer, KRAS mutant cancers, and hormone receptor positive PIK3CA mutant breast cancer.
You can inhibit that signaling, but avoid hyperglycemia or the other side effects of kinase activity. In the presence of our compound, the kinase can function fine. If you're an insulin receptor and insulin signaling, that can function fine in the presence of our compound. In tumors, where RAS plays an important role, we inhibit that. Our selectivity comes from the biology, comes from the target. It's not an enzyme or kinase selectivity window, which one can debate whether those are sufficiently large enough to show a difference. In our case, it doesn't matter how much compound you give because it only inhibits the signal where RAS is involved. As I mentioned earlier, that gives a couple of pretty large advantages to this approach. One is patients can be treated with our compound irrespective of their diabetic status, whether they're full diabetics or pre-diabetics.
There's no restriction on HbA1c status for patients to enter our trial. That's one. Two, the addressable patient population is much larger than other approaches that are trying to improve the therapeutic index in the PI3Kα space. For example, if you're a mutant "selective" inhibitor of PI3Kα, you may have an improved therapeutic index over hyperglycemia, although those still have restrictions on HbA1c status. In that case, you cannot address the KRAS mutant population because in 90% of KRAS mutants, PI3Kα is wild type. If you depend on the mutation to get your selectivity, you are not able to address KRAS mutants. Our selectivity, our efficacy is agnostic to the mutational status of either partner. Either RAS can be wild type or mutated, PI3Kα can be wild type or mutated. We inhibit that interaction. That interaction is important in tumors, is not important in normal adult physiology.
Got it. Maybe with your PI3Kα breaker, how does it overall fit with the rest of your portfolio, and how is it synergistic with the other programs?
Yeah. There are three genotypes that we've identified that are sensitive to the breaker program, breaker mechanism: HER2 amplified, positive, PIKC2A mutant, and then the third is the KRAS mutant. This is really where we can take advantage of our portfolio. As I mentioned, others that rely on the mutation status of PI3Kα cannot treat KRAS mutants because PI3Kα is wild type. Here, what we hope to achieve is inhibition of arguably the two most important oncogenic signaling pathways, MAPK and PI3Kα AKT. Inhibiting those two branches of oncogenesis is not a new concept. It's been something that I personally have been involved with for about 25 years. It's just that the tools that we've had up until now did not allow that simultaneous inhibition to be done safely. It wasn't even safe in mice. Certainly, some tried to take it into patients and it was not safe there.
We think the breaker mechanism, which you can think of as a pan-RAS inhibitor of PI3Kα, will give us both the efficacy and the therapeutic index in order for us to achieve full, you know, significant inhibition of both pathways. If we can do that, we think that really could be beneficial to patients with KRAS mutant tumors. It's something we're excited to do both with BBO-8520, our KRAS G12C inhibitor, as well as BBO-11818, our pan-KRAS inhibitor.
Got it. As you're looking to see your initial clinical data in this program, what are you looking to see here in terms of response rate and safety target engagement, but also more importantly, given that you're running it as a monotherapy, it sounds like there's a lot of combination rationale. How should people be thinking about what kind of data or responses you would need to see to be convicted on the overall profile of your drug candidate?
Yeah, our strategy here is to dose through monotherapy as quickly as possible to get into combinations. Historically, inhibitors of PI3Kα axes have not shown tremendously high response rates. It's been more of a survival pathway. We're excited to move the program forward quickly through monotherapy, then open up the combinations. Certainly, people should expect to see achievement of mouse target efficacy models. We have a target engagement assay in TBNCs. You should expect to see high levels of target engagement and differentiated safety. On the efficacy front, we'll see what we see, and then we'll roll into the combinations quickly, which will include three different tumor types: HER2-amplified breast cancer in combination with trastuzumab, KRAS mutant CRC in combination with FOLFOX, and hormone receptor positive PIK3CA mutant breast cancer in combination with fulvestrant.
Given all of the potential ways you could take the breaker, what are the, you know, maybe one or two highest potential opportunities, given the broad combinability profile, just so that folks can try to understand where they should be spending time better understanding the path forward with the breaker?
Yeah, I think it's those three populations, the KRAS mutant in combination, the HER2 amplified, as well as the hormone receptor positive breast cancer. All three of those are sensitive genotypes preclinically, and all three of those we're exploring in the phase one combination arms.
Got it. Now, your pan-KRAS asset, can you tell us a little bit more about that and how it's related to BBO-8520 and what translatability there might be from your initial clinical data there?
Yeah, so our pan-KRAS inhibitor, BBO-11818, really grew out of our G12C program. We took really the structural biology and medicinal chemistry that enabled us to inhibit the on-state of G12C and applied that to a pan-KRAS. It's a G12X inhibitor of KRAS. Importantly, it's selective over H and N, so we spare H and N, and we think that will be important to drive the high levels of inhibition of KRAS. We think that, from preclinical data, H and NRAS will rescue the pathway and compensate in normal cells and allow us to drive the high levels of inhibition. We're excited to test that program in patients with KRAS G12D and V tumors particularly.
Okay. In terms of your development plan, talking a little bit around the ongoing trial and the targeted readout timing?
Yeah, we're projecting data on pan-KRAS in the second half of next year, 2026. Initially, we're focusing on KRAS G12X tumors, and of course, that includes lung, colon, and pancreas cancer. We'll see how the data evolves. As I mentioned earlier, we certainly had the capital to test it out after we observed some data to pick the best path forward there.
Two more questions. One, given you're a rigorous chemistry organization with a lot of DNA in terms of developing your own drugs, any other targets that you're thinking about, just even broadly? I know that you work very hard to get these three molecules into the clinic, but can you talk a little bit around what's to come with your long-term vision?
Yeah, we continue to do active research. As you mentioned, that's in my DNA. We're not disclosing new targets that we're working on, but we are doing that. You know, we also work on, continue to be, I believe, the leader in the breaker field. I think we've just scratched the surface there. We continue to work hard on that area. The research team, which is very productive and very focused, continues to churn out very exciting programs that I think we'll see in the future.
Maybe you can, as you think about the opportunities ahead for the company, what are some of the key upcoming catalysts that you expect that investors should be focusing on? How do you see them de-risking the overall value proposition for BridgeBio Oncology Therapeutics going forward?
Yeah, thanks, Rok. I mean, I think that's a very pertinent question. Given that we have three clinical trials reading out in the course of 2026, and they're all sequential. Q1, as a reminder, Q1 2026, we have data coming out on our BBO-8520 KRAS G12C inhibitor, followed with the breaker data in the first half of 2026. As Eli mentioned, the pan-KRAS second half of 2026. During the course of all of these quarters in 2026, all the data comes out. That allows us actually to make all the database decisions because we can actually then progress with other combinations because you'll have the POC coming out for each of the assets. Now, three clinical programs, people may wonder, as you know, what is your then capital allocation? We've always maintained that once the data comes out, we can then decide where to take forward.
Fortunately, now with the de-SPAC transaction, we have about $418 million in the bank as of Q2 2025. That's enough for us to take all of these programs preregistrationally, as well as extend our cash runway into 2028. You can't say much about that for many companies nowadays, given the volatile environment, but we feel very fortunate to have the capital to have three assets in the clinic and to be able to prosecute all of those.
Great. Anything else that you want folks to know about bBOT that we haven't touched on yet?
I just want to, you know, we've covered a lot of ground here. I just want to reiterate that we believe we have three innovative programs progressing actively in patients, all designed both from a mechanism and from the actual molecules themselves to provide patients, we hope, the best benefit by driving to high levels of target inhibition. We're very excited, as the team mentioned, to do combinations internally, which uniquely positions us to do that. There's not another company that I can think of that has KRAS inhibitors and a breaker. Next year is a big year for us. With the runway that we have, we're in an enviable position to drive all these programs forward and really make a data-driven decision on what the best path forward is. It's going to be exciting 2026 for us.
We really look forward to building a great company and looking forward to those data readouts.
Great. Congratulations on all your recent and past progress, and thank you very much for your time this morning.
Thank you so much for having us here.