Conference Transcript - ONC 2026-06-08

Lin Hai-Zha, Analyst — China Biotech Analyst

All right. Thank you, everyone, for joining this session. My name is Lin Hai-Zha. I'm the China Biotech Analyst. Today, with great privilege, we have the opportunity to host the management from B1 Medicines. On the further right of the stage, we have Aaron Rosenberg, the CFO, and Mark Lanasa, the CMO, joining this file side chat. So welcome. And I think B1 Medicine has shown very exciting data at ASCO this year, and investors have been highly anticipating some exciting news from our solid tumor pipeline. Besides that, we have done extremely well for our hematology pipeline. Burkinza is by far the number one BDK inhibitors globally, and we are continuing to see exciting clinical progress from our BCL-2 inhibitors and the BTK degraders. So I think the first question, I think, would be about our clinical strategy. You've taken a very disciplined, data-driven approach to prioritizing the pipeline with the five highlighted cornerstone programs for solid tumor, as well as a few deprioritized programs that you shared at the quarterly results. What is the go-versus-no-go bar for the clinical data? What is your vision on the solid tumor franchise over the next five years?

Mark Lanasa, Analyst — CMO

Thank you, Lin Hai, and thank you very much for having us present this morning. So, yes, we have brought a lot of molecules into the clinic, and it is our aspiration to bring additional internally discovered as well as some partnered molecules into the clinic. Through this, we have been very disciplined in our early phase approach. We think that this is critically important in allowing us to progress a large portfolio as a mid-sized organization. So put simply, when a molecule is coming to the clinic, the teams are asked what would a differentiated medicine look like for the target patient population in development, and that is something that is expected of the teams at the time of the first in human study, and by understanding what a differentiated medicine would look like, we're able to establish clear go-no-go criteria. If the programs are meeting those criteria, then great. We'll look to expand those programs, and we've highlighted five programs that have met those criteria and are on track to a Phase III study start. We highlighted three of them at their recent ASCO. but we also announced that there were other programs that we have stopped because they weren't meeting those criteria, and these include some programs that we had previously highlighted based upon previously based on very strong preclinical data. So we think that that disciplined approach is really critically important to be able to progress and prioritize a broad pipeline of innovative molecules.

Lin Hai-Zha, Analyst — China Biotech Analyst

Can you be a little bit more particular and preferably with examples? I know that differentiation or differentiated medicine can look very differently, or we have very different requirements when we are talking about different indications or different molecules.

Mark Lanasa, Analyst — CMO

So ultimately it comes down to what is the target population for development. Since we recently disclosed some data, I can make a few examples. So, for example, for CDK4, what we were excited about with that molecule is really strong efficacy data with a response rate of approximately 70% across two different cohorts. We feel that that's clearly differentiated from what the CDK4-6 molecules deliver at a range of, say, 50% to 55% in a frontline patient population. So that hits our GOH criteria in combination with favorable PK and safety and whatnot. And then for GPC3, where our target patient population had a cellular carcinoma, There, the molecule exceeded our GO criteria with a response rate of 30% and a very clean safety profile. So for both of those molecules, we have confidence that they not only deserve to go to phase three, but can eventually be impactful medicines. We'll have a similar conversation about PRNT5 in the second half of the year. And again, we're applying that same lens to all of the molecules that we bring into the Our CAT6AB that we started in last December, you know, again, what does the differentiation molecule will look like in later Lyme breast cancer.

Lin Hai-Zha, Analyst — China Biotech Analyst

Yeah, I think we're all very excited about the oscaridose, but we can definitely discuss deeper about that later. I want to briefly touch about our pipeline or the clinical pipeline targets. We mentioned the target of to deliver 8 to 10 NMEs per year. How do you maintain the speed without sacrificing quality in clinical decision-making, and more particularly with China being increasingly recognized as an innovation source, how would you describe B1's strategy to leverage China innovation, given that we are targeting to deliver this amount of NMEs per year? Would you like to start?

Mark Lanasa, Analyst — CMO

So what's really important to understand is that our internally delivered development work is global by its nature, that we are the leading sponsor of early phase research in Australia or the leading sponsor of early phase research in South Korea. And therefore, we're not only moving quickly, but we're moving quickly globally. And this enables us to generate data that, again, enables us to have those go criteria, but also by having global patient data, we can have confidence that the data does not have significant determinations based upon ethnicity or region and that it will meet the needs of global regulatory agencies. We recognize that there are a lot of exciting molecules that are emerging from China as well as other global regions. Our BD approach is fundamentally global, but when we look at, again, our development model by being global in its nature, we think that that has substantial advantages over other, shall we say, regional models.

Aaron Rosenberg, CFO

Yeah, I think that's really well said, and given our global plan, we're able to identify and seek opportunities for business development in all the geographies in which we operate. We've done excellent investments in business development with innovation that's been sourced from China, or B7H4 is an example of that. We recently announced a very interesting deal in the I.O. space for a tri-specific with a company called HHBio that emanated out of China. But we've done deals globally as well in all the geographies. So ultimately, our clinical development organization is global first, and that puts us in a really strong position relative to competition to really deliver quality with speed to ensure that these innovations get to patients as fast as possible.

Lin Hai-Zha, Analyst — China Biotech Analyst

Yeah, thanks. One quick follow-up on that. I think it's, of course, part of B1's highlight on the clinical execution, And I think in more recent presentations, B1 has been highlighting what they call the global development superhighway, right? How should we understand this competitive edge compared to other global pharmaceutical companies, especially that we're seeing more global MNCs that are getting deals with China biofarmers that include early-stage integrations, which the China biopharma companies could also be very quick in terms of getting the clinical proof of concept data.

Mark Lanasa, Analyst — CMO

Yeah, so I recognize the importance and the intent of the question. Again, what I would highlight really is the global nature of our development organization. So it's important to understand that we have fully internal development capabilities across clinical development and clinical operations, statistics, regulatory, and so on. But we also have in-house manufacturing, and we run our studies globally. So yes, there may be some molecules that are able to generate limited data sets within a specific region, but when those molecules are partnered, there's always a certain amount of work that goes into the transition to the partner. And then often there will have to be a duplication of earlier data sets to ensure the generalizability of those data sets. So any speed that might have been captured through a single-region approach is then lost through the process of reglobalization. For our CDK4 molecule, we went from the global first patient dose to our global first phase 3 patient dose in only 30 months. We believe we're going to replicate that for our B7H4. Our GPC 3 by 401BB will be shorter than that. So we really believe that we're industry-leading in speed, not only from phase one to phase three, but then also from readout to submission and so on.

Lin Hai-Zha, Analyst — China Biotech Analyst

And I want to briefly touch on our most recent earnings performance. I think it's another big, strong quarter, and we also raised our full-year 26 guidance. If we're looking a little bit more in detail, we can see that for the full year of 26 guidance for the EBIT level was upgraded from 750 to 850 for the full year. And if we consider that in one queue the EBIT level was 250, that is more than one-fourth of the full year guidance, how should we understand the numbers here and particularly does the guidance leave room for higher R&D spending for the rest of the three quarters? And how do you balance the spending in both selling R&D while maintaining the continuous operating leverage?

Aaron Rosenberg, CFO

That's great, and thanks for the question. I think we've talked for a long time about our intent to run the business both as a growth organization but also as one that does it so in a sustainable way. And, you know, sustainability is ultimately translating that growth to margin expansion and ultimately, and most importantly, free cash generation. And I think you see those kinetics in action in our Q1 results. We feel very comfortable with the current year that enabled us to raise, as you said, our guidance on revenue by $100 million across the range to $6.3 to $6.5 billion on the top And that translated to a bottom line improvement of $50 million across the range. to $800 to $850 on a GAAP operating income basis. As you said, Q1 was quite strong in terms of its income generation. We did affirm our OPEX guide for the year, and I think that reflects our continued investment in our core capital allocation priorities that's continuing to drive and invest in our commercial businesses that are driving profitable growth, and as well as our clinical opportunities. and you saw the great data at ASCO. I'm sure we'll spend some time talking about that, as Mark alluded to earlier. And obviously, you know, that was investment that we've contemplated in our full-year guide in terms of OPEX, and that's what translates to the guidance that we updated with our Q1 results.

Lin Hai-Zha, Analyst — China Biotech Analyst

And I think if we talk about earnings, one thing that we have to talk about is Burkinza. And especially we're talking about Burkinza is entering, it's already becoming the global number one. It's capturing more than 3% or 5% shares globally. And a natural question is, what is the room for growth further? And specifically, we've seen that for the EU part, it currently accounts for roughly one quarter of U.S. sales. How do you see the potential in the EU market versus the U.S. market?

Aaron Rosenberg, CFO

No, thank you for the question. We're very happy that Brickinza became the number one BTKI that eclipsed that curve toward the second half of 2025 globally. We had done so earlier in the United States. And that's really behind strong performance in all the geographies in which we operate. We've talked historically, you were touching a bit on geographic mix, we've talked historically that our European business, as an example, was a little later in its launch trajectory than the United States, and important rest-of-world markets are even earlier than that in terms of their launch trajectory. And you see that in the results where, you know, the United States grew in the mid-30% range, high 20s on a volume basis. Our European, Perkinza, was more like 60%. There's some FX in there, but still very strong demand-generated growth. And our rest of world markets doubled in Q1. So I think that reflects the launch lifecycle of the brand. So we do see continued opportunity in all of our geographies to continue to drive demand through new patient share. And, of course, the geographies that are a little earlier in their lifecycle have higher growth rates. As we get bigger, obviously growth rates in their percentage terms, those will naturally come down, but we continue to drive new patient starts, driven behind the differentiated clinical data for Burkinza. You know, at ASCO, we shared, you know, another update to our Sequoia data going to 6 1⁄2, that unprecedented PFS at 72% over that time period, And really, that's noncomparable as you look at the other medicines in the class in terms of its absolute PFS over that long of a time period. And ultimately, that's what's translating to utilization in the marketplace. Sure. I do want to have one question specifically for Sironoclax.

Lin Hai-Zha, Analyst — China Biotech Analyst

Because we are seeing recently the good news from this drug. approved in China followed by the approved in the U.S. We have seen very strong conviction on this drug in terms of both better colorability and extremely encouraging high and durable and deep responses. How do you see the early product launch, especially how do we expect to get this drug in terms of the near-term launch? And based on the China performances or the China observations, what has been the early physician feedback on this drug? Maybe I'll start.

Mark Lanasa, Analyst — CMO

So my understanding from MIT, our CMO for hematology, is that the prescriber feedback in China has been very positive, both in terms of efficacy as measured by MRD rates as well as the safety profile and the tolerability by patients compared to what prescribers have experienced with other molecules in the class. That said, I would say that this is similar to the feedback we've received on the development side, the Celestial 301 study or fixed duration therapy and frontline CLL. The investigators who have been using synrotoclax in an investigational sense are also providing positive feedback on their experience. So we're very excited about the potential for our novel BCL2 inhibitor.

Aaron Rosenberg, CFO

And then with the QALZ, our brand name, the first indication that's been approved in the United States is in the relapsed refractory MCL setting. And that's a pretty narrow indication. We're very excited to get this differentiated medicine in the hands of prescribers and patients. There's significant unmet need in this relapsed and refractory MCL setting, and it's a great opportunity to gain experience. Obviously, the larger opportunity that you reference is with our zanabrutinib plus SONRO fixed-dose combination in the front line in CLL. That Celestial 301 study is fully enrolled. Obviously, the data will have to play out. So in the short term, we've talked about the opportunity being fairly immaterial in the very short run. Obviously, as we continue to get this in the marketplace, we'll serve those patients in the relapsed refractory MCL setting and look forward to the larger market opportunity. And as you said, we're really encouraged by the data as you think about a fixed-dose combination, the potential to have the kind of deep, durable responses that this combination could bring with what we hope is efficacy and a safety profile that's comparable to continuous-use Brukinza. Time will tell, right, across all, you know, as Brukinza has generated such a robust data set in the short, medium, and long term. And ultimately, as you think about Brukinza, you know, the differentiation in terms of efficacy in that Sequoia data that I mentioned, we had a really nice chart on this in our Q1 results is really from that year three to year six time period, where you really see Brukinza standing with significant and durable PFS across that time period. And when you look at the other in-class competition, as well as existing Venn-based fixed-dose treatments, that's typically where you see the drop-off. So we're really encouraged about our fixed-dose combination, look forward to bringing the initial data set, and we hope it will be an important solution for patients. In the meantime, Brukinza has demonstrated significant durability and really unprecedented durability in observing patients today. Cool. And switching gears to our ASCO data,

Lin Hai-Zha, Analyst — China Biotech Analyst

the CDK4 inhibitors, I think there are a lot of excitement about their early ORR, And we've also seen a very dose-dependent way of safety tolerability. Can you talk a little bit more about the dose selection? You chose 400 mg over 240 mg for the dosage. And how would you expect the ORR with mature follow-up? I'm aware of that for the CDK4 inhibitors. The longer the maturity, you're actually going to see an increase in ORR. How do you want to comment on the maturity data?

Mark Lanasa, Analyst — CMO

So the – thank you for the question. For CDK4, the maturity of the data that we presented at ASCO, the median time of follow-up or the median time on treatment was approximately nine months. Interestingly, we do observe late emerging responses. We had two patients that were relatively recently detected unconfirmed responses. So these were late emerging responses. Now, that said, I wouldn't want to create a notion that we think our response rate is going to continue to climb and climb and climb from there. We're really pleased with what we have seen in terms of the response rate. And as I mentioned before, we think that it is differentiated from what one would expect from the CDK4-6 inhibitors. and it gives us confidence to move into our Phase III study.

Lin Hai-Zha, Analyst — China Biotech Analyst

I do want to make sure that we talk about the tolerability profile. And we're talking about the CDK4-6 versus CDK4. I think naturally there is a tradeoff between the hemotoxicity versus the GI toxicity. Based on our communication with physicians, how should we think about this potential tradeoff with the CDK4-6 selected? and particularly what is the bar for GI toxicity to be considered as acceptable based on physician's feedback? And can you share a bit more on the mitigation tactics that we have been explored for the GI tox?

Mark Lanasa, Analyst — CMO

Great. Again, thank you for the question. There's really two components there. The first relates to the heme tox safety profile. So with CDK4-6 inhibitors, it turns out that the majority of the hematologic toxicity is driven by CDK6 inhibition, and indeed that was the core hypothesis of the molecule. By having greater 4 versus 6 selectivity, that we could drive deeper and more sustained inhibition of CDK4, which drives anti-tumor efficacy that is now reflected in the high response rate, while mitigating the associated hematologic toxicity. At the investor event that we had at ASCO, I shared our selectivity data, and indeed we have the most selective 4 versus 6 inhibitor with approximately 35-fold 4 versus 6 selectivity in a preclinical cellular assay. That has pulled through, in our view, based on mechanism, to an unprecedented heme tolerability profile that across 240 and 400 milligrams, we only had a single grade 3 event and no grade 3 heme tox events at 400 milligrams. You know, we have had the feedback sometimes that patients don't experience hematologic toxicity, but the reality is that heme tox is the leading cause of dose reductions for the 4-6 inhibitors, and therefore they are important. I also tried to make the point that heme tox also prohibits some combinations, and we think that there are a whole group of combinations that are available to us through having this a more favorable safety profile. Now, in terms of the patient experience, the GI tolerability is also very important. What we shared in our poster was that in the fasted state, our rate of any gray diarrhea approached 90%, and we had perhaps a 10% rate of grade two, grade three events. However, in a small cohort of patients who had co-administration of food, that that event rate dropped substantially to 50%, and importantly, all of those events were grade one. The feedback we've had from investigators is that grade one diarrhea is essentially very manageable. There are many successful medicines that have a moderate rate of grade one diarrhea, and that's straightforward for most oncologists to manage in their daily practice. So we're very pleased to mitigate those grade two, grade three events, which are the events that tend to lead to dose selection, but suffice to say, when we look at the cohorts of 240 and 400, the response rates were quite similar, but when we do our more detailed exposure response analysis, where we look at not just the dose level, but actually drug exposure, we found that 400 optimized our characteristics, both in terms of efficacy and safety. We have confidence given the favorable efficacy and safety profile that for those patients who do require a dose reduction, that they will be reducing to a very efficacious dose if they do require dose reduction in the phase three study. And importantly, the study is now active. We have taken that 400 milligram dose selection to global regulatory authorities who have essentially endorsed that choice and agree that 400 is an appropriate dose to take into a

Lin Hai-Zha, Analyst — China Biotech Analyst

registrational study. Yeah, that's very important to know, especially we've collected a lot of feedback saying that currently the regulators, they prefer, like, lower dosage versus higher

Mark Lanasa, Analyst — CMO

doses if the higher doses doesn't show meaningfully improvement. We're absolutely aligned with the feedback of FDA's Project Optimist to move towards the lowest efficacious dose, right? We think that it's really important in terms of the overall patient experience. We and others absolutely focus, and we focus our discussion primarily on efficacy, but when you look at what constitutes a successful medicine, the patient experience vis-a-vis tolerability is also extremely

Lin Hai-Zha, Analyst — China Biotech Analyst

important. Yeah, so a little brief follow-up on the medications. You mentioned the co-administration with food can effectively mitigate the GI toxicity. How are we integrating that into our

Mark Lanasa, Analyst — CMO

phase three protocols? So the phase three will require that patients take the drug with food. You know, there's a couple hour window and there's many medicines that are not, shall we say, problematic or burdensome to the patient or ability. Medical management of low grade diarrhea is quite straightforward using antidiarrheals. And that said, we continue to look to mitigate this further with, for example, in the phase one study, we're now enrolling a cohort that's going to take primary prophylaxis with antidiarrheals and understand that impact, that's something that we can look to integrate into the protocol if need be. Again, we're very comfortable with where we are, understanding that it's a small cohort and we'll be enrolling more patients to give us greater confidence in that initial observation. Yeah, great. And for the GPC-3,

Lin Hai-Zha, Analyst — China Biotech Analyst

You mentioned that it's kind of reached beyond your way beyond the go versus no go bar. And we've seen that this molecule was not highlighted as much as the other programs previously, but it was brought up more recently highlighting the very encouraging clinical profile where we see that the phase one data at ASCO show very nicely controlled safety profile overall with only a single-digit percentage of grade three TRAEs, and more particularly for 4.1BB-related liver toxicities, we've also seen very nice control. So what is the plan for the registrational trials in both the first-line and second-line plus?

Mark Lanasa, Analyst — CMO

Yeah, thank you. And we're extremely excited about our GPC3 by 41BB is where we have increasing confidence. I have increasing confidence that this will be a clinically a breakthrough molecule for patients with hepatocellular carcinoma. For context, at ASCO, the M-Brave 251 study was presented. In that study, the current standard of care, the control arm, delivered a response rate of 5%. And what we just demonstrated was that our molecule has a response rate of 30%. And importantly, it delivers a response rate of 30%, actually with a better safety profile than the currently available TKIs. So we think that this is really potentially a big step forward. There are other GPC3 targeting mechanisms, such as CAR T-cells or ADCs, but this is a patient population that tends to have substantial comorbidities related to liver cirrhosis, and frankly, those modalities are not well tolerated. So we really think that we are uniquely positioned in this later-line setting with a very safe and efficacious molecule. We intend to have development as monotherapy in a later-line setting. We received a question at the ASCO Investor event, well, what about a combination with We're considering that, but then we would be giving up this favorable safety profile that we have. But we also have already initiated a combination with tisilizumab or PD-1, along with bevacizumab to give us line of sight to a frontline opportunity, as well as ultimately also early stage for intermediate stage patients as well. Those cohorts are just now starting to enroll, but we're off to a good start, and we're very optimistic about not only the late-line registration opportunity, but the earlier lines as well.

Lin Hai-Zha, Analyst — China Biotech Analyst

Curious about the drug design of this by specific. We've seen other 4MBB-based bispecifics. I think a common tactic is to have differentiated binding affinity between the 4MBB versus the other target, usually having a lower affinity for 4MBB just to achieve conditional binding. So what is our strategy for this molecule?

Mark Lanasa, Analyst — CMO

Yeah, the idea is similar overall, that we wanted to have conditional T-cell activation really in the tumor microenvironment, not to have broad T-cell activation. So, indeed, the idea is that first what happens is through the high-affinity GPC3 anchor that it gets anchored in the molecule, and then you get local T-cell activation. It's important to highlight there are other features. We have a unique 4-1BB binder. We have made modifications to the constant change to improve the half-life of the molecule, and we're very excited about the data. We're very excited about the platform, so you all can expect to see other tuber-associated antigen by 4.1BB targeting bispecifics coming forward for us because we think that this might be an important platform technology where we can, again, improve responses with a favorable safety profile.

Lin Hai-Zha, Analyst — China Biotech Analyst

And you mentioned about the tri-specific antivirus, and I think there's no doubt that Lai seems to be very excited about that. And we've noticed that B1 Medicine, we are kind of a pioneer in the PD-1. This has been an extremely commercially successful product. But if we came to the PD-1 VGF field, And this recent collaboration is really like the first milestone event for B1 medicine to enter PD-1 VEGF. And we have the option to license this tri-specific. We know that the Phase I trial has recently been initiated. Can you share what are you looking at in this Phase I trial in order to treat the option? and what is your view on the overall survival benefits that we've seen from the ibanesimab and to share your perspective on what is our general plan for this trispecific?

Mark Lanasa, Analyst — CMO

Yeah, I think to start at the end of your question, we recognize the data that was recently presented at ASCO for ibanesimab, the Harmony 6 study is a positive study with overall survival benefits. Our view was twofold. So one is that it is now a highly competitive space, the PD-1 or PD-L1 by VEGF. We didn't want to enter late and end up with an undifferentiated molecule. We view CTLA-4 as a mechanism that has tended to have a positive effect on overall survival. So we saw the tri-specific as an opportunity to provide additional benefit with hopefully greater weight towards overall survival. The preclinical data, again, was very strong. This was an IND-ready molecule. The clinical trial applications are now submitted, and we anticipate to have the first patient dose this month. Again, it's a phase one molecule where we will have clear go-no-go criteria, and we'll be excited to see how this data unfolds.

Aaron Rosenberg, CFO

And I think, just to add, you know, I think this shows three elements of strategy in one deal. I think, first, as Mark said, you know, B1 is not going to chase the seventh, eighth, ninth asset in a crowded space. That doesn't support our mission. It doesn't support patients just to have a me-too medicine. I think it highlights our business development efforts to identify interesting science and to deploy our capital in a smart and efficient way to test the hypothesis embedded in that science. And finally, I think it showcases our global development superhighway capability where we will be able to take that potential medicine, explore, test the scientific hypothesis, and to the extent it hits, we'll move super fast to the extent it doesn't. That's why we have a prioritization criteria.

Lin Hai-Zha, Analyst — China Biotech Analyst

One last question. I do want to touch on our lung cancer strategy. I believe that our last significant trial in lung cancer was dated back to the TIGIT portfolio. And with discontinuation of EGFR CDAC program, what is the current strategy for lung cancer? We talk about the tri-specifics, And we have plenty of other great candidates. We have the bispecific ADCs or even trispecific ADCs that could be potentially targeting lung cancer. So just can you share a little bit more about the thoughts in lung cancer?

Mark Lanasa, Analyst — CMO

Yeah, so we are strongly committed to lung cancer. You will see more innovative molecules from us entering the lung cancer space. When you look at our portfolio to date, what you see are a group of molecules that capture the biologic heterogeneity of lung cancer. So we're not focused on any one target, but rather bringing benefit to multiple patient segments. We have high conviction in our PRMT5 inhibitor. We'll have our first disclosure for that molecule in the second half of the year. We're excited about our EGFR met-met tri-specific biologic, which is progressing well. And again, multiple other therapies, multiple ADCs in testing in lung cancer as well.

Lin Hai-Zha, Analyst — China Biotech Analyst

I think with that, we've reached the time. And, again, thank you all for the time, especially Mark, for the very insightful conversations. We're really looking forward to hear more updates about B1, particularly from the solid tumor pipeline. Thank you so much.

Mark Lanasa, Analyst — CMO

Thank you.