Great. I think we'll continue with our afternoon session. Again, my name is Andres Y. Maldonado. I'm a Senior Biotech Analyst here at H.C. Wainwright & Co., and I'd like to welcome everybody back to the H.C. Wainwright BioConnect Conference. Our next presenters are NovaBridge Biosciences, and from the company, we have Sean Fu, CEO, and Phillip Dennis, Chief Medical Officer. Welcome. It's a pleasure to have you guys today.
Thank you.
Thank you.
A great place to start off will always be for those, less familiar with the NovaBridge story, could you give us a brief overview and walk us through the company's current strategy of moving your assets forward?
Yeah. Thanks, Andres Maldonado. It's always good to come back to HCW and have wonderful conversations with you and other investors. NovaBridge is a company that I think it's quite unique compared to some other biotech companies at the conference in the sense that we believe we can create value by doing a platform-based development. There are three things we have conviction in. One is that we see the rise of innovations coming out of Asia, in particular China. This is not a one, two assets phenomenon. I think it is more fundamental. It is a wave of growth powered by investment in the last five, maybe 10, 15 years, you're going to see the dividend from that investment in terms of molecules, both in terms of numbers and in quality. We started to see a lot of that.
I believe that'll continue. That's point number one. Second thing that we believe is that those molecules, the value can enhance tremendously if you develop these China-based or Asian-based molecule into a U.S.-based product. Those are very different concepts, where the molecule coming from and where the value of the molecule is being evaluated. Think about the Summit Therapeutics way back 2022, right? They licensed a cadonilimab bispecific. In that same week, the company value increased 350%. There's no clinical data generated. It really is just to put the molecule in the right hands and has the potential to create a value in a much more significant market, commercial opportunity.
Those are the two things we believe in and how we do that, we have a very strong on-the-ground access to China biotech ecosystems, give us a front row seats in terms of what are the good molecules, what are the credible teams, and where and when those readouts are going to come from. We can pick the right molecules in a capital-efficient way. We can give you some more examples along the investments efficiency side. The next thing we do is leverage another capability which is translational clinical development. We're not flipping assets, you're licensing and you sell. We want to develop it, like I said, to make it a U.S.-based, EU, Japan-oriented product. We have translational clinical development capabilities. When you combine those two, it's very powerful.
Very few companies have a strong fundamental historical access to the China ecosystem or Asian ecosystem through our partnership, our investor networks, and ability to run translational clinical development in U.S. Under those business models, and we've built two verticals, oncology and ophthalmology. Right? Oncology and ophthalmology. The oncology, we have a lead asset called givastomig. This is a claudin 18.2 4-1BB bispecific antibody. We are positioned this asset as a bolt on to the current standard of care in frontline metastatic gastric cancer. This has potential in other cancers as well, as long as cancer cell express or overexpress claudin 18.2. The first indication we go after is frontline gastric cancer. This asset is phase III-ready.
We're working with FDA to finalize the pivotal study design. We see this asset to go into phase III clinical study as early as 4th quarter of this year. In the ophthalmology vertical, we have VIS-101 as our lead asset. This is a bispecific biologics going after VEGF-A and Ang-2, two proven targets in the wet AMD DME indications. This molecule is in phase II-B clinical study. We expect the first patient enrollments happening 2nd half of this year. This molecule differentiate itself against some other competitor in this space in its durability. Patient can last on this phase II study demonstrate the patient can continue to benefit from this molecule up to 24 weeks between doses. That's best in class.
Vabysmo, give you an example, current market leader is 50% of the patient benefit up to 16 weeks, right? We're going to 24 weeks. It's 50% longer. Just give you a high-level overview of what do we do in terms of business model, and what are the leading molecules that we're actively developing right now.
Great. That was great. That, so helpful. I guess starting with givastomig, it would be great if you could walk us through not only some of the mechanistic rationale of the program, but help us tie that mechanism to the most updated data, which showed strong response rates, 16.9 month PFS at 8 mgs per kg with nivolumab and FOLFOX. I guess what should we understand mechanistically and clinically moving forward there?
Thanks. I, the way that I would start is let's look at the structure. I'll call it Jiva. That's our nickname for it, and it's easier. two syllables. Jiva, it's structurally unique. What do I mean by that? I mean that the affinity for claudin 18.2 is very avid. It's so avid that we can extend the activity of Jiva to a minimal threshold of claudin expression in gastric cancer. What do I mean by that? Meaning pathologists can only feasibly look at one cell out of 100 with very faint staining, 1+ or greater. That's our threshold in our entire clinical development plan. one feature of Jiva is the claudin 18.2 affinity. The second is we've mutated the Fc portion of the molecule. What does that do? That takes away ADCC and CDC activity.
Why is that important? The lead asset in the class is a monoclonal antibody called zolbetuximab that in its phase III studies had a very high incidence of nausea and vomiting, especially severe nausea and vomiting that is likely related to that ADCC and CDC activity. That's how it works. We've mutated, we've eliminated that. Finally, we activate T cells not via a signal 1 or what really kind of brute force mechanism such as CD3, we use signal two. We have 4 scFv fragments that bind to 4-1BB on T cells adjacent to the ligand binding site. What this does, this leads to highly regulated T cell activation. What does this mean functionally and physiologically? What this means is that givastomig binds to claudin 18.2 in gastric cancers with a very high affinity.
Because it's so tightly bound and there's no possibility for systemic activation of T cells, all the T cells that are regulated are in the tumor microenvironment. What does that look like? If we think about the monotherapy data with givastomig, the monotherapy data told us again that we could get very low in levels of claudin 18.2 expression, but we had activity in highly pretreated patients, third line and beyond. We had an objective response rate of 18%. What's even more impressive is we had a grade 3 incidence of adverse events of 33%. We took those two features, and we said, "We know that frontline gastric cancer patients need more than what's available, more than just IO chemo." We hypothesized based on all the features that I described, that we could successfully add Jiva to the standard of care of IO chemo.
What we've seen in our data, again, you know, single-arm study in a cross-trial comparison with all the weaknesses involved with that, we have a profound improvement over the phase III studies in terms of objective response rates and in terms of median PFS. We have a very favorable toxicity profile.
Great. Taking that into consideration, you know, maybe one question on a little bit of the historical context that you can help us with. You know, recent, you know, history of promising single-arm, you know, gastric cancer datasets, you know, have failed to translate into randomized studies. What lessons are you applying to design your next, you know, givastomig trial? Historically, how have they influenced trial design moving forward?
I'd make a couple of comments. The first thing that's impressed me, I've been doing drug development literally since 1995, either as an academic or someone in industry. I can tell you it's the consistency of data. We presented our data, our first dataset was a dose escalation in the combination with givastomig, nivolumab, and a chemo regimen called FOLFOX, in our dose escalation. Since then, we've enrolled approximately 50 more patients, actually more than 50 into this study. The data is extraordinarily consistent in terms of the objective response rates. The PFS effect, if anything, the PFS is improving over time, our data is very consistent if we look at subgroups such as claudin expression, high and low, we look at PD-L1 expression above and below thresholds like 1%. The data is very consistent.
The second thing, it's not only consistent, it is far superior to the phase III data that is accepted and was used for the approval of nivolumab plus FOLFOX. The second part of this in terms of our study, our registrational study, which again we have the potential to launch by the end of the year, is a very simple and elegant design, right? The whole premise here is we're adding to the standard of care. While we haven't, you know, publicly announced what the design is, it's easy to imagine if you're adding something to the standard of care, the comparison would be the standard of care. I think we have a very simple and elegant design. The two things that are really notable are the fact that we've actually taken our data to the FDA.
We've taken our phase I data. We have an ongoing phase II study. We took that design, we took our phase I data, we spoke to the FDA, we asked a very simple question, "Are there pathways for accelerated approval for givastomig in frontline gastric cancer?" They said an unequivocal yes. Not only did they say yes, they gave us really precise benchmarks to meet for those accelerated approval pathways, and those benchmarks, we far surpassed them in our single-arm study. We have great confidence.
The final thing I'll mention in terms of the, you know, this potential for a phase III study is the fact that if we look at the competitors and where they are in terms of phase III studies, we look at our possibility for a very lean, mean study that can deliver on accelerated approval pathways. If we deliver, we have the potential to actually leapfrog the phase IIIs that are already ongoing. It's in a very exciting time for givastomig and its development.
I guess maybe circling back to a few earlier comments about the broad activity you've seen in these gastric cancer patients. Obviously, we're always trying to, yeah, kind of size up the market and how many more patients you can garner using this unique mechanism. One question we had is, you know, mechanistically, you know, how low can, you know, 18.2 expression go while still preserving a meaningful, you know, 4-1BB, you know, localization and clinical benefit? I guess just at a broad level, how many more patients does that afford you over maybe zolbetuximab?
The most straightforward answer is our clinical development program is entirely predicated on a cut of 1% of cells, 1+ or greater intensity for claudin 18.2 staining. Zolbetuximab's development is predicated entirely on a cutoff of 75% of cells, 2+ or greater. This is true for their ongoing phase III called LUCERNA. If the question is how low can you go, we can clearly get down to 1%. We have looked at our data in detail by subdividing patients into even groups of 3 or 4 or 5 to say, "Is there a decrement of activity as you go from, let's say, the top third of patients based on claudin versus the middle third versus the lower third?" We don't see much of a fall off.
We see, if anything, it's very, very small, and even then, we probably don't have enough patients to make a firm decision. That leaves a fundamental question, which is really exciting, very bold, which is, if you look at the distribution of claudin expression in gastric cancer, approximately 25%-35% are negative, meaning less than 1%. It is a natural extension, and this is, you know, this is what Daiichi thought about with Enhertu , right? If you have very strong data, what about very low levels of expression? I think that there is arguably a biologically plausible hypothesis that givastomig might have activity in those 25%-30% of patients that are, "claudin negative" or less than 1%, because we know that IHC is fraught with sampling error, right?
Any IHC-based test has heterogeneity invariably associated with it. It's something that we are considering. We haven't embarked upon it yet, I think that that's something that we're thinking about very strongly because we don't wanna leave givastomig's benefit on the table for 25%-30% of patients who currently wouldn't qualify.
Great. Maybe turning to some commentary on the safety profile and expectations for safety moving forward. Obviously, you know, gastritis has emerged, you know, as a distinct safety signal, which is par for the course for a lot of these patients. You know, management has also suggested, you know, it may be associated with, you know, management of those symptoms with better outcomes. Through that lens, how are you viewing gastritis as a manageable on-target toxicity, and more importantly, as a potential maybe pharmacodynamic marker?
I'll start with the overall picture, which is if we look at our toxicity profile compared to CheckMate 649, which is the phase III study that led to the approval of nivolumab plus FOLFOX. Our phase I study is an addition of givastomig to that regimen. If you look at categories of AEs, treatment-related adverse events, all grade or greater than or equal to grade 3, we're very similar in incidence, virtually identical. If you hone down into immune-related adverse events, overall, there is absolutely no difference with nivolumab plus FOLFOX.
The history of gastritis is interesting because as we did our phase I study and as the data emerged over time, we noticed that for a subset of patients, after several months on treatment, typically after a tumor response occurred, patients would develop a mild gastritis that would lead to treatment interruption and would lead to routine kind of management for nausea, vomiting, things like this. As time went on, we saw a very small subset of that subset develop more severe toxicity. What we noticed is that the patients who developed any grade gastritis, including those that developed grade 3, which very small minority, actually had improved outcomes in terms of ORR, PFS, and OS.
We're trying to discern what's the basis for this correlation, but we are viewing it as a pharmacodynamic marker that, you know, one could easily ask a question, does every patient who develops a vigorous anti-tumor response? Look at these signals. We've already started recruitment, patients have already been treated in both the pancreatic and biliary tract cohorts. I'll mention that the bar for biliary tract cancer is even lower. The objective response rate there with IO chemo is 27%, we'll be able to discern signals in both of these tumor types in the next 12 months.
Great. In the next few minutes, just kind of wrapping everything together, Sean, you started off saying the promise of NovaBridge and the way it forms a bridge between, you know, overseas assets and value for investors here. I guess one of the first candidates in that hub and spoke model is the, you know, VIS-101, where the phase II, you know, wet AMD study showed, you know, rapid BCVA gains, you know, CST reductions. I guess briefly, you know, what is the single most important question essentially the phase II ultimately needs to answer to establish it as a meaningful and differentiated product for the product and just for the strategy of the hub and spoke model there?
Yeah. You asked two very good questions. One specific about VIS-101, what we try to accomplish building on the phase II-A data in the upcoming phase II-B. There are really two things we want to accomplish, one is to pick the dose for phase III, right? We're gonna evaluate several dose candidates and even variabilities, variations of the current formulation. That's ongoing. The second thing is potentially more important is that we wanted to repeat the phase II-A data in a randomized study with more patients. Establish the competitive advantage, as I mentioned earlier, with more robust clinical data. Those are the two things we wanted to do, we want to do it in a very efficient way.
Second half of this year, first patient in phase II-B, Position data readout early next year, so the asset is phase III-ready. The second question, Andres Maldonado, you ask is essentially about how do we think about resource allocation across different priorities. We have 2 core assets right now, and both are very exciting opportunities. givastomig, Phillip Dennis gave you a lot of latest updates, and we touched upon VIS-101. A words on the hub and spoke model. This is something that we are developing that is sort of unique to us, not many biotech companies are doing. We see this as a necessary infrastructure when it comes to efficiently sourcing assets and developing and creating value according to our business model.
It gave us flexibility to quickly launch some of those SubCos and support these SubCos going forward once you have clinical data to support further development, like what we are doing with the VIS-101, the ophthalmology asset, like what we are going to do with the oncology assets. How do we think about the resource allocation on the ongoing basis? That require us to go back to the basics. We make decision in that sense, not different from any other biotech company. We look at the clinical data, we look at the regulatory pathway, competitive strength, and the milestone dates for data to readouts, capital efficiency, and in many cases also commercial opportunities. Right now we are very laser-focused on getting givastomig ready for phase III, getting VIS-101 ready for phase II-B, and things like what is the pivotal study gonna look like for givastomig?
Working with FDA to clarify what is the study gonna look like, patient number, inclusion, exclusion criteria, choices of a statistical analysis methods. Regardless of how we're gonna develop this asset forward internally or with a partner, these are the things we need to understand, and those are the focus that we're working on right now.
Great. I think that's all the time we have left. I wanna thank Sean and Phillip for joining us, and we look forward to congrats on all the progress thus far, and we look forward to future updates.
It's always a pleasure. Thank you