I'd like to welcome everybody back to the H.C. Wainwright 28th Annual Global Investment Conference. My name is Andres Maldonado, and it's my pleasure to welcome you here. Our next fireside chat today will be with NovaBridge, and it's my pleasure today to welcome Srishti Gupta, the CEO of NovaBridge. Thank you and welcome.
Andres, thank you so much for having me.
To start off, for investors newer to NovaBridge, walk us through the company today, the lead programs, and how you think about the broader strategy.
Thanks for the question, and thank you everyone for joining us. The value proposition of NovaBridge is to combine three things. One is preferential and differential sourcing, predominantly in Asia, on assets that are later stage, that have been tested in phase I, phase II studies, with a clinical development team in the U.S., and a company that's Nasdaq listed, and a capital allocation framework that brings flexibility, so that every asset that becomes a therapeutic for patients follows the best pathway for that to become a therapeutic for patients. Our two lead programs we're using to demonstrate this story, one is givastomig, which is a claudin 18.2 4-1BB conditional activation bispecific being developed for frontline gastric cancer. The second is a program that's within Visara, but the lead program is VIS-101, which is also a bispecific VEGF Ang2, which is being developed for neovascular AMD.
We're trying to do with NovaBridge is say we have access to assets that can become differential therapeutics for patients around the world. We have a clinical team that can help continue to advance and de-risk them, and we want to do this repeatedly, over and over again. We're focusing right now on givastomig and VIS-101, but our model is that we'll do this again and again as we continue to engage with companies that are in later stages with their programs.
Wonderful. Thank you for that overview. A lot to unpack here. Very exciting clinical pipeline program and a very unique strategy. I guess to start, let's dive a little deeper into the pipeline. Starting, I guess, with givastomig, what do you think investors underappreciate about the program? If you can review what you've done to date with that program.
Givastomig, as I mentioned, is a bispecific claudin 18.2 4-1BB, which is conditionally activated in the tumor setting. What's really interesting about this molecule is that it actually has the ability to work on low expressers of claudin. A lot of people in the claudin space are chasing the high claudin expressers, but the 4-1BB with the affinity of givastomig, helps it conditionally activate within a very localized tumor setting. We could access, in our phase I trial, we've seen that there's activity with givastomig at claudin levels down to one with a CPS score of one. We're, in some ways, thinking about being able to be relevant in an addressable market that's twice as much as what the claudin molecules that are in market are today.
Let's talk a little bit about, as you move towards the phase III, talk a little bit about how you ended up thinking about the dose cohorts between the 8 milligram dose cohort and the 12. What can we expect in terms of that dosing schedule and regimen there?
The givastomig story is very fascinating from the standpoint of its clinical development. We had phase I data that we took with 17 patients, that came out at ESMO GI about a year ago, July 2025. We took that data to the FDA to discuss the programs to move forward to phase II, and get any feedback from them. We were pleasantly surprised that the FDA said that we actually could be on track for running a phase III program. The phase I program is run on two doses, both 8 and 12 mg. To your question, we actually see activity at both 8 and 12 mg in terms of both response rate as well as improvements in median PFS compared to standard of care.
As we move forward and we finalize with the FDA for dose selection, I think we're going to be balancing a handful of factors. Efficacy is obviously only one of them. Safety, tolerability are going to be the other pieces of that. As the data continues to mature, we're in conversations with the FDA, and we'll narrow down on the dosing for the phase III.
Compared to historical programs that targeted claudin 18.2, what's interesting about givastomig is the activity that we've seen in the lower expressing patients. Can you maybe walk us through what's driving that, and what that translates to in terms of greater market?
Sure. As I mentioned, by design, this bispecific has one head that's claudin 18.2 binding and the other which is the 4-1BB conditional activation. We don't actually see a lot of the toxicity that you normally see with 4-1BB because it's only conditionally activated when the 18.2 is also binding. But the combination of those two acting within the tumor where there is immune infiltrate, activates the standard of care, which includes the checkpoint inhibitor and the chemotherapy, and you see a very localized response within the tumor setting. The binding site now, the claudin 18.2, we think is what drives us our ability to get to claudin levels that are much, much lower than the standards out there. I think the current standards are 74% and higher, and we can actually see activity in the low claudin between 1% and 74%.
We actually saw in our monotherapy study that was done prior to the phase I activity, that was 11+ , in terms of claudin levels. With that, we are probably able to, in HER2 negative patients, we are probably talking about doubling the number of addressable patients with the low claudin expressers.
Great. As you mentioned prior, you will have an update at ESMO. What should investors focus on, whether it be focused on PFS OS? Anything to read through for the higher dose cohort?
Our ESMO, which is at the end of October, we submitted an abstract, which was our June data, and our poster actually will be our August data cut. Our most recent data cut will be at our poster. If you are at ESMO, please come visit us and you can see the most recent data. I think in addition to the data maturing and seeing the evolution of both the response rate and the median PFS, I think pay attention to the durability and the duration of response.
Great. Moving on to maybe taking a more holistic view of the program. The FDA had previously given you guidance around an accelerated approval pathway. I guess, to the audience today, what can you say about the level of benefit you believe that gives you in terms of designing the phase III study and really defining those bars in the sand for efficacy, safety, and just overall design of the study?
It's a great question. I think as we're thinking about this, the current comparator for us is the standard of care, which is PD-1 chemo, so immuno chemotherapy. We have already seen in our I-B data, overall response rates, median PFS, that's significant improvement over the standard of care. We also see that the safety and tolerability is comparable to the standard of care. As we look forward to the phase III, and given the feedback from the FDA, I think we're highly confident that we should be able to meet the endpoints that would be a successful registration trial.
Great, and I'd like to note, this is not just a gastric cancer story. You're developing givastomig in both pancreatic and biliary tract cancers. I guess the question remains, what do you need to see to become convinced that the claudin 18.2 platform is not just a gastric cancer play?
It's a great question, Andres. I think for us, the gastric cancer play is the entry point into the space, with the conditional 4-1BB activation. Gastric tumors have immune infiltrate, so you can see the MOA sort of playing out, in real time with gastric cancer. I think the real test for us will be pancreatic cancer. We're currently enrolling cohorts for both PDAC as well as BTC, and we're looking forward to seeing how those results and those patients respond over the next year, so that we can actually continue to advance this in a range of gastric solid tumors.
Great. Very helpful. So, you opened the fireside by describing NovaBridge as a company that can develop, partner, and separately finance assets, depending upon the opportunity out ex-U.S. This is a very unique angle. Before I think we start diving into the second asset, VIS-101, which is the product of your efforts on this front, I guess, can you describe this strategy, which is very unique and very promising and exciting?
Thanks for the question. I think fundamentally we believe that innovation is not the challenge. Extraordinary science is out there, but the challenge remains the path to patient. When I was recently in China, I was struck by the number of companies out there that actually have meaningful phase I, phase II data. We have already put a range of therapeutics into human beings, yet not all of those companies will have the ability to advance those therapeutics to patients in any market, either that be in China or ex-China or around the world. Partly that is just the lack of strategic partnership, that is the lack of financing, that is the lack of access to these other areas. When I think a little bit about where NovaBridge fits in this, there is almost a pile-up out there of things that have been tested in humans.
They have made it already through animal models, they have made it into human beings, and they are stuck before they can actually compete in the market on their way to being patients. For NovaBridge, we are really focused right now in the near term on looking for companies that have generated that level of meaningful phase I, phase II data in areas that we think we can have an MOA that is established, so the risk is kind of de-risked, that there is clear differentiation, and there is a clear unmet need. Of course, our current capital is being devoted to givastomig and the Visara program, so the threshold is high for us to be thinking about bringing in new assets.
But as we look at new programs, we are definitely focused on things that have an established MOA that can be clearly differentiated in different markets, and the data has been de-risked, and we think we can take it on board and continue its clinical development program.
Maybe a fun follow-on question to that is, as you have been overturning all these rocks ex-U.S. in terms of products, are you seeing maybe a class of modality that is completely under the radar in your eyes? As much as you can tell us, at least, where is the disconnect to where the excitement is in the U.S. versus the development in China?
It's a really interesting question. I think the word that I want to pick up that you highlighted is actually U.S. I think oftentimes our lens and our focus for drug development has been the U.S. regulatory market and the U.S. commercial market. I spent about 15 years of my career so far living and working in Europe. I see that the interesting thing about the healthcare systems with the national reimbursement is that the bar and the access is very different. When we think about differentiation, of course, clinical efficacy is table stakes, and you want things to be working in human beings and patients and having meaningful improvements in their lives. But I think differentiation can also be really contextual. Can you develop it? Can it be integrated into a healthcare system? Is there someone willing to pay for it?
As we're looking forward into different areas, I think we're trying to uncover potentially pathways for drugs to maybe bypass the U.S. market and go directly into Europe, and rest of world market patients. Because right now, I think the complexities of both those healthcare systems, as well as structural issues created by the MFN policy, have made it actually quite challenging for innovation to reach patients in those settings. I think another area that we're very excited about, which has been long underserved, is women's health. Are there mechanisms of action, and in monoclonal antibodies for endometriosis, in the kisspeptin programs for PCOS, can we start to see the NK receptor for VMS? There is actually a lot of innovation happening in the Asia and the APAC region.
We'd love to be able to work with some of those companies to help them bring and find a strategic pathway forward on them.
Just to be clear, in a therapeutic modality and therapeutic tissue type agnostic manner, correct?
Yeah.
Great. So I guess turning to the first effort from this, I guess, hub and spoke model that you guys are bridging. The bridging model, I should say. Turning to VIS-101, Visara's VIS-101, I guess, can you talk to us about what you guys saw in VIS-101 in terms of it being truly differentiated in the therapeutic lens of wet AMD there?
Perfect. VIS-101 is a purpose-designed peptide body. It has two binding sites for VEGF and two binding sites for Ang2. That's where the efficacy comes from. The double binding sites, and we can see we want to be at least at parity with the standard of care in neovascular AMD. Where the design piece of it comes from is the engineering, which is its valency and its molecular weight. So it's a high molecular weight compound, which we actually see drives its durability. So, the phase II trial was designed to look at retreatment rates at weeks 20, 24, and 28. Week 20 would sort of be parity with standard of care. What we're actually seeing is that at weeks 24 and 28, the need for retreatment is in the 50%-60%. We're sort of seeing the freedom from need for retreatment.
That's what's actually driving the differentiation for us. The efficacy, again, is table stakes. Differentiation is going to come from the durability. That's the lead program for Visara. Visara is a majority-owned subsidiary of NovaBridge.
Next question would be, what would you want to see in the phase II-B to establish that advantage convincingly from that efficacy lens?
Our phase II-A was quite a small study. It was 17 patients. We saw both the best-corrected visual acuity improvements, CST improvements, and the durability. We are scaling up the phase II-B in conjunction with our partner, Everest Medicines in China. We have a 100-patient trigger to start the phase III, and we are well on our way to enrolling and continuing the phase II-B. It is scale, and it is similar results at scale.
Early days, but talk to us about some of the conversations you are having in terms of the phase III design, in terms of how you are potentially balancing the visual and autonomical efficacy against the goal of extending treatment intervals.
It is a great question. As we are thinking about the phase III design, I think, we want to be versus faricimab with standard of care. We are probably going to do the two clock, the trial, sort of the standard, the double trial. I think what we are looking to do is we actually do not have to make a trade-off between efficacy and durability. The efficacy will come because we have the two binding sites, and then the durability is going to come through the trial design. We will check at retreatment. We will check for retreatment rates at the various week 20, week 24. It is a loading dose three dose initiation loading, and then we will follow the patients, and we will look for the need for retreatment.
From a strategic perspective, obviously the focus for Visara is VIS-101. Are you also thinking about expanding the kind of platform there? What ultimately drives Visara becoming either a standalone single asset or a multi-asset partner?
What I love about the Visara story is that we found an anchor asset with VIS-101, then we built a great team around it. We brought in a board that was experienced in ophthalmology. We brought in a very specialized CMO that was specialized in ophthalmology and a CEO that's done three IPOs in the ophthalmology space. Given that we now have a great asset as an anchor and a great team, we said to ourselves, "Look, if we're building a company for longevity, what should we think about?" In addition to the back-of-the-eye asset with the neovascular AMD, we're really thinking about expanding to some front-of-the-eye assets, also where we see the clear differentiation in terms of patients. VIS-102 is a program we're initiating, which is for neurotrophic keratitis.
And one of the big differentiators that we've been able to identify is that the current standard of care, OXERVATE, requires cold chain. If we're looking to be able to find a molecule and develop a molecule that has the same level, if not better levels of efficacy, but can actually be distinguished for patients and their families by not requiring that level of complexity of having to monitor or manage a cold chain. I don't know if you know anything about NK, but you have to put almost eight drops in your eyes eight times a day. To have to think about being near a refrigerator or a cooler for eight times a day drops, it's quite a hassle for patients.
Great. As we're coming up on time, I think it would be great to just quickly summarize where you see the vision over the next 12 to 18 months. Where should investors be focusing on specifically across the pipeline?
Thanks, Andres. I think right now we really want to make sure that givastomig and Visara's programs are well on their way to getting to patients. That's the number one reason we exist is to make sure that we're improving patients' lives. To be able to be first in best in class in gastric cancer for patients especially who have no other options, especially the low claudin 18.2 and PD-1 negative , the low patients. We'd love to make sure that that program is on track and getting to patients as soon as possible. Visara has a range of differentiated ophthalmological programs, which we'd love to make sure get to be well on their way. Then I think we owe the market the repeatability. We want to do this, and then we want to do it again.
Stay tuned as you see where we take our two programs, and then we'll see what's coming up next.
Great. On behalf of myself and the whole H.C. Wainwright family, thank you so much, Dr. Gupta, for joining us today.
Thank you.
We look forward to future updates and congrats on all the progress thus far.
Thank you, Andres. Thank you for having us.