BridgeBio Oncology Therapeutics, Inc. (BBOT) September 15, 2026 Conference Transcript

Good afternoon, everyone. I'm Sean Larman, Head of US Mid-Cap Biotech Equity Research here at Morgan Stanley, and welcome to Morgan Stanley Global Health Care Conference. Before we begin, to make you aware of some of the important disclosures, please visit the Morgan Stanley Research Disclosure website at www.morganstanley.com forward slash research disclosures, and if you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have the pleasure of hosting Bridge Bio Oncology Therapeutics with CEO Pedro Beltran, CEO Eden El-Malek, and Ben Yong. So thank you, gentlemen, for your time today.

Thank you.

Maybe just to begin with some broad macro questions before we delve into the specifics of Bridge So, you know, so thinking about the rise in China-led innovation, so really hot topic in biotech, does it change your competitive positioning or how you think about R&D and your BD playbook?

Yeah, thank you, Sean, for the warm welcome. And, yeah, I mean, great question. I mean, obviously, we're super excited about what's going on in China. I think it opens, you know, great opportunities for companies like us that are innovating. I think the way I would summarize the current environment would be, you know, maybe two buckets, right? So one would be the innovation part of the drug development process, and the other one would be the speed, right? So I think on the speed perspective, economics of speed are changing dramatically, and China is playing a huge role there. And, you know, competing against that, I think it's going to be bad. On the other side, on the innovation mechanistic side of things, you know, I think we're still highly competitive there. And so how does that apply to DDOT? I think it's a key point. If you look at, you know, the China environment, maybe in the last few months, you'll see three T12C off inhibitors that have been approved, right? So I think when a mechanism works and people believe in it, I think China is very good at moving at, you know, super high speed, We need making molecules, you know, and those can come back, and people can take advantage of that proven mechanism. But I think on the innovation side, I think it's a plain field. And if you look at what we have done with 8520 being an off-on inhibitor, right, the ability to target that GTP state that has now been replicated. Our breaker molecule, which is, you know, first-in-class breaker of the pf-kinase-alpha-ras interaction, You know, that also has not been replicated, and so I think, you know, as long as we stay very much focused on the things that we can do new, you know, China will be, and it is very competitive on that, but the innovation part, I think, makes you, you know, be able to compete, while if we just try to compete on speed, trying to do a mechanism that is already validating, I think that's a big advantage that, you know, China is showing today. Sure, thank you.

And maybe still on the macro, are you implementing AI across your business, and can you point to a specific example, perhaps, where it's changed a decision, a cost outcome, or even a POS?

Yeah, so, I mean, we obviously are trying to incorporate AI, and then maybe Dan can follow up here, you know, on a daily basis into our workflow. I'm certainly, you know, surprised, you know, from what I see from my team, how faster we can do things. I think from a research perspective, you know, from my biology background, I would say, you know, maybe three things. The first one, you know, really putting together the co-folding tools, so the ability to reiterate hypotheses on a structural basis, you know, instead of having to make every single compound and test the hypothesis, I think AI, you know, has a huge advantage in trying to test this hypothesis in silico, so we do a lot of that for our early research programs. You know, AI coding, I think it's another place where, you know, a lot of the team are using that to try to put our maybe a smaller data set in the context of a much bigger data set and trying to see where there's synergies, what can we learn from what's in the literature, and also reiterate that process, and that, you know, that affects the time at which, you know, we can build hypotheses and test hypotheses. And then I think one maybe a little fun one is the agentic AI part of debating with AI when you have a hypothesis, and you can do that, you know, in a couple of days, you know, really narrow it down to a much better clinical hypothesis or biology hypothesis. And that, you know, I think there's at least a couple of examples of BVLT where we have narrowed down the trial design or, you know, a very key center hypothesis for one of our assets in a much shorter time that it would have taken to, you know, send a group of people to do this and search the literature and come up with a refined hypothesis. So I don't know if you want to add anything to that either.

Yeah, no, I think the impact here is really on cost reduction and cycle time, and especially if you look at, you know, a big part of the cost we don't talk about in BioNTech. We talk about per-patient cost in clinical trials, but a lot of the fundamentals of the ongoing business, right, everything from accounting to finance, regulatory submissions, all of those pieces, I think you're already seeing a high impact.

Sure, thank you. And last question before I dig into 8520. Which policy variable, maybe you'll say all of these, but which policy variable, FDA, Medicare negotiations, MFM may be not so important for you guys at the moment, but tariffs or global pricing, which of those are the most important to your economics or which are sort of highest on your end?

Yeah, I think for this stage of our company, it's all about the FDA interactions, right, trying to really understand how the FDA is changing, especially in a higher medical need like cancer, you know, what can we do to get our data in front of them sooner, agree on trial design. Ben, I don't know if you want to add anything there.

Not much. I think what we are focusing on in terms of the tumor types and the major tumor types, non-smusle, lung, pancreatic, calorectal. So tumor-type-wise, we don't need to think about, you know, some of the niche of tumor-type to begin with that may have an implication in terms of early approval, especially for small molecules. So right now, I think we're still rather too early, so not much in terms of how we think about the timing and prioritization. Sure.

Thanks, Ben. Maybe to go more specific on BBOT, and let's start with 8520. So, reflecting on the data last week, maybe walk investors through what you reported and what stood out to you.

Yeah, so the key goal, you know, obviously we released data, we can go over that, right? The key strategic prioritization that we communicated is really focusing on how we're going to allocate resources for VVLT, you know, in the coming months, right? So we want to make sure that we're going after indications that are high probability of technical success, have a very clear path to registration that we can communicate, And third one, and maybe most important, that there's a large patient benefit that comes from that. And so what you would see in the 8520 setting, which is, again, our G12C off-on inhibitors, there's a small molecule that can bind directly to G12C when it's bound to GTP, and that brings advantages. What we communicated there is a change from the first line to the second line. We show data in two settings, naive second-line data, 60% plus overall response rate that compares very favorable to the GTOF-C off-inhibitors, and then second-line plus data set showing 75% ORR in the 500 milligram dose and 50% plus ORR across all doses in that GTOF-C experienced patient population. And so what we're seeing is that if you look at what's happening in the first line, there's about five trials of GTOC off-inhibitors being combined with PEMBRO. We think that signals from those trials are very positive with, you know, 80% plus ORR, 30-month PFS. We see that in the next three years as the first line, which will leave, you know, a series of patients that are going to be pre-treated with GTOC inhibitors in the second line. And so any G-toss inhibitor needs to be able to work after a previous G-toss. We're targeting the advantage of doing that with 85-20, and that's where we believe we can differentiate in this patient population is we carry the on-state, so we can work after off, and second, we can combine with PEMBRO without the liver toxicity. So that also transpires in the data with no grade 3 liver toxicity in the naive patient population And single-digit percent in both of those attributes really give 8520, you know, the best chance of working in this upcoming market, where the comparer is going to be docetaxel chemotherapy, you know, with single-digit ORR and, you know, maybe four-month PFS. So we feel pretty excited about that opportunity for that molecule.

Right. So I think my next question was about the reprioritization you announced last week, but I think, Pedro, you just answered the question. So thank you. But how should we think about execution and the path from phase one towards registrational development across three mechanistic leaders?

Yeah, I think so. You know, the strategic update we gave last week was a big part of that initiative. And so I think with the G12C program, very clearly we've updated data. Our guidance on that program is for the next update to be in the middle of 2027. And the imperative here for us is, one, to establish what the duration profile looks like in this refractory population, and also to accrue more patients to confirm the signal. At that point, I think we'll be ready to discuss a potential registrational path. And then on the breaker and the PAN-KRAS inhibitor, so our second two programs, that is one cohesive strategy, right? And so we're enrolling across PDAC and CRC, multiple combination regimens, and so our guidance here is, one, a de-risking event in the fourth quarter of this year, so upcoming in the next few months, monotherapy data on both the pancarous inhibitor, BBO-11818, and our breaker, BBO-10203, and then the, you know, bigger and more fulsome data set, including combinations, coming in the middle of next year. And so that's when sort of we'll update on registrational path and those indications.

Sure, thank you. Sort of on combos, but tolerability and combinability have been the real constraints for the G12C class. And last week, the 8520 update again showed no grade 3 liver enzyme elevations. How do you think about that profile as the data set grows and moves into combination? And what would you want to see to be confident it holds?

Yeah, so, I mean, we're very focused on the PEMBRO combination, I would let Ben add here, but, you know, we believe in non-small cell line cancer, you have to be able to do the PEMBRO combo, right? And we designed this molecule with a hypothesis that if you hit the on state and you're able to capture the covalent mechanism of action, meaning detachment of PD and PK, have very low free drug concentrations. When you combine with PEMBRO, you have a much better chance of not having the hepatotoxicity that often you receive because they have to be present essentially all the time to cover And we believe that our data now is showing that, and that is very key for patients. Ben, I don't know if you want to add anything.

Ben C.: Yeah, again, we're really excited about the COMBO data, not just in terms of the response rate we have observed so far, also the safety. And if you look at the spider plot, including the DAC, where you see some of the early adult patients that have been on treatment for over a year, and if you're artificially drawn line, about six months, the majority of patients still remain on treatment. So that means some of the tosses you see is pretty manageable, and those patients are able to stay on treatment for a long period of time.

Sure, thank you. And beyond the roughly 75% of eligible patients staying on treatment past six months, what are you seeing on duration of response in PFS as the data matures? And how do you think about durability, you know, given now?

Yeah, we haven't shared anything further other than the 75%, which, you know, we think is a good number. We're excited about the monotherapy data. We think it compares very well to what others have shown.

Ucombe Strategy now centers on second-line plus inhibitor experienced patients, where there's no approved targeted therapy. How do you see the registrational path there, and how do you think about the commercial opportunity of G12C off state inhibitors move into first line?

Pedro already alluded, exciting the second generation. If you think about the landscape, what was left on the table for those patients who progress on the first-line treatment. So really, single-agent chemotherapy, that's far from optimal in terms of both efficacy and safety. So the bar is really low. We are talking about single-duty or very short duration treatment. So, you can imagine, for a Phase III study, it's not a large Phase III to demonstrate that it's a priority compared to Stenic.

Moving on to 11818. So, earlier this year, you disclosed the first monotherapy pan-KRAS response in pancreatic cancer patients at 56% tumor reduction. You know, with a monotherapy update doing 4Q, what would you see as a convincing signal across KRAS mutations, and how many patients and tumor types is that update likely to cover?

Yeah, so let me just start by saying, you know, part of VVLT, you know, one of the four pillars is that we believe that KRAS is the driver oncogene, right? So we think the best therapeutic index comes from being able to cover KRAS and have a selectivity against HNN, and that's the design of a pan-KRAS inhibitor, BBO 11A18. And so what we're planning on talking about at the end of the year in Q4 is essentially a monotherapy cohort in pancreatic cancer, second line, Where most of the PAN-RAS specific data from competitors has been released so that we can compare what the level of efficacy is in comparison with those settings. Obviously, the safety profile, we believe, is super important. Our initial release in January showed differentiated skin toxicity, so very low rates of skin toxicity, no stomatitis. So we think that's already very differentiated from a PAN-RAS approach, and, yeah, we hope to give a, you know, homogeneous cohort with a significant number of patients. Thank you, Pedro.

And which opportunities do you see PAN-K-RAS as being potentially most differentiated, and how does it sit alongside, you know, mutation selective agents and PAN-RAS approaches in the field?

Yeah, so we see, you know, we see kind of, you know, the sweet spots, you know, if you're able to really focus on that driver oncogene, you have the ability to get multiple mutant isoforms, but you're not hitting NNH, you know, to complicate your safety profile. And then also very important, we believe, is being able to inhibit wild-type KRAS. So there's ample evidence in the literature that amplified KRAS, so non-mutant but amplified KRAS, can drive to more growth. And so we believe that's a potential response resistance mechanism that a G12D-specific inhibitor cannot address. That will have to bear out in the clinic if it's a head-to-head study or comparison across trials. But we will have to see that. Yeah, but those are the advantages of a pancreas approach, and, yeah, that's what we hope to see in the clinic.

Sure, thank you. Moving on to 10203, can you maybe refresh us, you know, what the mechanism is and what it's hoped to achieve?

Yeah, so if you think about our approach of having on-inhibition, right, on-inhibition means you block effector binding. So if you take that now to BBO10203, the molecule binds to piatricinase alpha, right? Piatricinase alpha is the effector. So by binding directly to piatricinase alpha, you block any RAS from binding to piatricinase alpha and activating the AKT pathway. So we like to summarize the mechanism as a pan-RAS inhibitor, but only for the piatricinase pathway, right? And the biology here is that when you block the MAP kinase pathway, the RAF, MEK, ERC pathway, you get reactivation of the AKT pathway as a salvage survival mechanism. And that reactivation can happen through any RAS. So what we see is that when we put a KRAS inhibitor and we see that reactivation of AKT, if we put 10203 in that experiment, we can block completely any reactivation of AKT, And that results in very, you know, cool synergy, both in vitro and in vivo. And so that's what we're trying to replicate, an experiment where we can block optimally both of these pathways and get

the best efficacy with the best therapeutic index. Sure. And on that one, we've got upcoming monotherapy data in 4Q. Can you tell us what indications you're looking at and what we should be looking for in the data?

Yeah, so the 10-203 monotherapy update that we're expecting in Q4 of this year is really just an update on the escalation data we shared earlier this year ahead of J.P. Morgan Conference in January, and so it's an escalation cohort 150 to 750 milligram QD and just extended, you know, safety signals on that patient population, which, again, was largely third-line-plus colorectal cancer patients.

Sure, thank you. And moving over to the platform, so you've talked about a combo between 11818 and 10203, and I think the plan is to concentrate in both CRC and PDAC. Will that concentration remain, or do you see an opportunity to expand into broader tumor types?

Yeah, I think that's our initial area of focus. You know, we see a potential competitive advantage here on both indications, but, you know, this is not, this is just sort of the first step in combination, and, you know, we'll let the data guide us on future combos.

Sure, and I guess, you know, on the combo, how do you see 203's role, and what does the biology suggest it adds on depth and durability?

Yeah, so, I mean, the way we think about a piatricinase pathway in this setting is when piatricinase is driven by mutant RAS, right? So if you look at the biology and the protein-protein interactions, mutant KRAS loves to activate piatricinase alpha, right? And that's very different than wild-type KRAS or N-RAS or H-RAS. So there's a preference for that mutant allele to bind PF3 kinase alpha and activate that pathway. And the thought there is that if you don't do that, if KRUS is not able to activate a PF3 kinase angle, then the cell actually undergoes cell death. So it's classical oncogene-induced senescence from superactivation of the MAP kinase pathway, no PF3 kinase. The cell can deal with the signaling and dies. And so, you know, that's where we see the breaker activity in KRUS mutant tumors. And that, obviously, you know, is mainly lung, PDAC, and CRC, and that's what we're playing.

Sure. Thank you. And I guess as we look into mid-27, when we might get the combo data, you know, what are the key aspects you'd point to in assessing synergies for this internal combo? Sorry. So if you look into the combo data, which I believe is due mid-27, when you look at the key aspects of the combo, what would you point to in assessing the synergies for

Yeah, so I think we will save data mainly around the combinability of those combinations. You know, there are some challenges in terms of combining with the cictosumab with the pine rust. We haven't seen the data because of potential overlapping toxicity around the skin tox. So based on our current data, I think the very differentiated skin toxicity, we haven't seen much. So hopefully we'll be able to show that differentiated combinability, and hopefully on top of that we'll show some meaningful early efficacy with those combos as well.

I think CRC is one place where we think we can differentiate, right? From the three indications, CRC is the one that has 15-20% pediatric kinase alpha mutations by itself, so we think that highlights the biology of pediatric kinase signaling, And so, you know, obviously that will be a place where it's a much wider space, RAS monotherapy, any type of RAS monotherapy has not really shown yet, you know, what we have seen in lung and PDAC. And so, you know, opening the biology agency would be a great way to achieve that, you know, convincing that we have done something differently.

So we've talked about the programs, but as you progress towards registrational studies, how do you weigh up partnerships versus internal ownership of the programs to fruition?

Yeah, absolutely. I mean, we're very active in our internal discussions on business development opportunities. You know, I think really what we're driving towards here across all three programs is a clearly differentiated data set with a clear path to a registrational opportunity. And so I think once we get there, we'll do some more in-depth assessments on potential business development activities. Okay.

And I guess as you look to later stage studies, do you see that RAS is a rising tide dynamic to how the market values the next credible RAS developer, or does an established leader set a higher bar for your data?

Yeah, I think, you know, I would say this is a super exciting time for people involved in drug development and oncology, right? I personally have been waiting for a long time to say that we are finally hitting that driver gene, right? We are doing it now as a community, and I think oncology has a very clear history of, you know, bettering, right? So you always have that first discovery, that first compound that starts to make a difference in the clinic, but inevitably that's followed up by a best next-in-class inhibitor, better mechanism, combination, and I think we're just beginning to do that. And so, yes, I think next-in-class advanced therapeutic against RAS, we will see better

And on the balance sheet, I think you finished Q2 with three, four, four million. You spoiled a half a billion dollar shelf beginning of September. Can you remind us what the runway covers and which catalyst it takes you through to?

Yeah, so it's all three catalysts that we've outlined. So the monotherapy data coming in Q4 of this year, as well as the data across all three programs in combination mid-next year. and essentially covers full phase one development the way we're seeing it now across all three programs with some comfortable buffer. The actual runway guidance is into 2028.

Right. Thank you. So we've had a good run-through on the programs, a good run-through on the upcoming catalysts, sort of how you're positioning, how you think about combinability, and we've also talked through the balance sheet and the runway. Now, did I miss anything? Is there anything that I should have asked that I didn't, or a message you would like to leave investors with?

No, I don't think you missed anything. I think, you know, we're super excited to be playing in this field. As I said, we believe we bring something novel to the table. We have our pillars of what we believe brass biology is important. We have made therapeutics that address those pillars, And, you know, we're really looking forward to, you know, generating data that is differentiated that will help patients with malignancies driven by mutant K-RES.

Well, wonderful. It might be a nice time to talk about the conversation, but thank you for your time, gentlemen. Appreciate it. Thank you.