Good afternoon, everyone, and thank you for joining the 2025 HC Wainwright 27th Annual Global Investment Conference. I'm Dr. Jade Montgomery, an Associate Biotech Research Analyst at the firm, and I'd like you to please join me in welcoming Dr. Marc Hertz, CEO of GRI Bio. Marc.
Thank you so much. I'm thrilled to be here and look forward to presenting GRI Bio, our programs, and to give an update on our clinical studies and upcoming milestones. I will be making forward-looking statements, so please refer to our SEC filings and our website at gribio.com. GRI Bio is a clinical-stage biotech company advancing a pipeline of NKT cell modulators for the treatment of inflammatory, fibrotic, and autoimmune diseases. Our programs are small molecules, but they act like a cell therapy in that they are regulating the activity of a critical lymphocyte in NKT cell, both turning on or off different subsets of NKT cells. We're initially focused on idiopathic pulmonary fibrosis and systemic lupus erythematosus. We have a focused pipeline. Our lead program is GRI-0621. This is currently in a Phase 2A IPF study. We'll have top-line data reading out from this study later this month.
We have a second clinical-stage asset, or soon to be clinical-stage, GRI-0803, initially focused on systemic lupus erythematosus, and we'll be advancing that through its IND and Phase 1 program next year. In addition to these two programs, we have additional clinical-stage assets ready for development with additional funding or partnering and a pipeline of about 500 proprietary compounds to help fuel our growth for years to come. I just want to take a second to give a little bit of an overview of our technology and its role in the immune system. We're developing a novel immune mechanism to regulate the adaptive innate immune axis and reset dysfunctional immune responses. That's kind of a mouthful. What do I actually mean by that? There are two main arms of our immune systems: the adaptive immune system and the innate immune system.
You know, we generally think of these as being independent of each other, but they're not really independent. There's a lot of crosstalk between the two. Often in diseases like IPF and other fibrotic indications, you see an initial dysregulation of the adaptive immune system, but over time, the innate immune system seems to play a bigger and bigger role. What we've discovered is that NKT cells, these very special innate-like T cells, really have the ability to interact, recruit, and activate cells of both arms of the immune system and have the ability to mediate this crosstalk between the two arms of the immune system. We see this as potentially a more selective approach to immunomodulation than trying to sequester or down-regulate any single, you know, molecule or cell systemically throughout the body. This is some data, some translational data from patients.
On the left, I'm showing IPF patients with lung fibrosis and increased levels of NKT cells in the bowel fluid from their lungs. On the right, I'm showing samples from systemic lupus patients with kidney fibrosis, showing again elevated levels of NKT cells in the PBMCs from these patients. In the middle, similar data from MAF patients with liver fibrosis, where here we're able to segment the patients by their level of fibrosis or their level of steatosis or ballooning, their NAS scores, or even gross pathology, and show that as disease is progressing, as fibrosis is worsening in these patients, the levels of NKT cells are increasing. Some similar work like that has been done in IPF patients, showing that the levels of NKT cells are a strong predictor of progressive IPF or a progressive course of disease for these patients.
If we think of how this works, NKT cells are some of the first cells recruited in the body's normal healing response to injury. They recruit many of the other cells involved in this process, but as injury becomes prolonged or repeated, that drives the normal healing response towards a fibrotic response. What I'm showing at the top is a pathway that goes from NKT cells through a molecule called TGF beta, which is a really critical protein in the body that drives fibroblast differentiation into myofibroblasts, excess extracellular matrix deposition, and fibrosis. Most drugs in development for fibrosis, one way or another, target either, you know, disruption or dysregulation of this important protein. It's not the only way to drive myofibroblast activation.
I'm showing at the bottom a path through IL-13, which can also drive that differentiation of myofibroblasts and development of fibrosis that's also impacted by NKT cell activity. Our solution to this is our lead program called GRI-0621. As I mentioned, it's in a Phase 2A biomarker study for IPF. We completed enrollment a little more than last quarter ago. I have top-line data later this month. We reported positive interim data after two and six weeks of therapy and are moving this forward in IPF. This is just kind of a summary of some of the preclinical data that we've done. We've probably looked at this molecule in a dozen different models of fibrosis from, you know, liver fibrosis, kidney fibrosis, lung fibrosis, obviously.
This is a standard model of pulmonary fibrosis, the bleomycin model, a treatment model, and just showing that in the left column, GRI-0621 alone, compared to nintedanib or in combination with nintedanib, outperforms nintedanib really across the board from, you know, really early drivers of this response, you know, inflammation, lung injury, activation of the inflammasome, to kind of middle drivers of that fibrotic cascade, things like CCL3, IL-13, and TGF beta production, but also, you know, quite late stage things like hydroxyproline, S-alpha SMA, which is a marker for activated myofibroblasts, or even the deposition of extracellular matrix, things like the Ashcroft score. I'll just show this one data slide from that model. This is the histology from the lungs of these animals. On the far left are the sham animals that don't develop any fibrosis. Left of middle would be the control.
These animals develop significant fibrosis in their lungs. Right of the middle is with treatment with GRI-0621, showing really reduction, a pretty, pretty significant reduction in fibrosis. On the far right, nintedanib alone. Again, not just from those studies, but, you know, probably, like I say, a dozen different models of fibrosis, treatment with 0621 inhibits the activity of dNKT cells. We've been able to show in pulmonary fibrosis, liver fibrosis, other forms of fibrosis, it really shuts down this cascade that I outlined in the earlier slide. A little bit more about IPF. This is a rare chronic progressive pulmonary disease with abnormal scarring in the lungs that really blocks the ability for oxygen to enter the bloodstream. In the middle, I'm showing the average patient's journey. The average age of onset is in the mid-60s to 70s. It's a very aggressive disease.
Median survival is about two to three years from diagnosis. Unfortunately, only about 20% of patients survive five years. There is no curative therapy at this point. Really, lung transplantation is the only thing that can change this course of disease. Unfortunately, not many patients are able to get a lung transplant. There are two approved drugs for IPF. They slow the decline in lung function, but they do not significantly change the mortality outcome. Median survival remains around that, you know, three-year mark. They have some significant side effects that impact their compliance. Despite these challenges, they still sell around $4 billion a year to this market. There is clearly a high unmet need for drugs that do more than just slow the decline in lung function for these patients. A little bit more about GRI-0621. It's a once-a-day oral formulation of a topically approved dermatology product.
It's approved as a topical. It's never been approved as an oral for any indications. Yet it has been evaluated as an oral in over 1,700 patients dosed for up to 52 weeks. There is a lot of human safety data for this molecule as an oral formulation. A significant amount of safety data when you consider this is an early Phase 2 for an orphan indication. A little bit more about our Phase 2 study that we're recruiting, or we recruited 36 patients, two-to-one randomization. They can be on background therapy. If they're taking one of the two approved drugs, nintedanib or pirfenidone, they can stay on those drugs, no problem. We're looking at a 4.5 milligram dose compared to standard of care. We did an interim analysis after two weeks and six weeks. Reported serum biomarker data. I'll show a little bit of that on the coming slides.
Primary endpoints are safety, but we are also looking at lung function tests, these serum biomarkers that I mentioned, really about a dozen of them, very carefully looking at a number of things. Differential gene expression and very, very detailed flow cytometry. I'm pretty sure this is about as much detailed assessment of these patients over a 12-week trial that's been done to date. A little bit about these serum biomarkers, and I just want to explain a little bit of what we're really looking at. Fibrosis, by definition, is the accumulation of excess extracellular matrix, which is primarily composed of collagen. You can look at these serum biomarkers of collagen formation and degradation and get a really strong sense of what's going on in these patients, and often at a time point much earlier than you could look at other traditional fibrotic endpoints.
In a healthy individual, collagen synthesis and collagen degradation is always going on. There's always remodeling. It's just that it's in balance. It's kind of like bone, if you're familiar with that field. There's always bone resorption and formation going on, but it's just in balance. There is this concept of something called the remodeling rate, which basically looks at the ratio of collagen formation to degradation. It allows you to determine if net there is more collagen synthesis relative to degradation, tilting this balance towards fibrogenesis or the worsening of fibrosis, or shifting it to more degradation relative to synthesis, shifting that remodeling rate towards fibrolysis or the resolution of fibrosis. What we were able to show, this is looking at one species of collagen. This is type III collagen.
We showed a pretty pronounced decrease in the synthesis of collagen, looking at ProC3, an increase in the degradation of collagen, looking at C3M, and importantly, an increase in cross-linked type III collagen. This collagen is really only found in fibrotic tissue. That is a direct example of resolution of fibrosis by breaking down cross-linked type III collagen. In the little fancy balance figure there, we're showing again the shifting towards a more fibrolytic or resolution of fibrosis profile. We showed this across collagen species that we looked at. Here is type III, type VI, and type IV collagen. Type IV collagen is a little bit unique. It is the major component of what's called the alveolar basement membrane. Destruction of the alveolar basement membrane is a hallmark in idiopathic pulmonary fibrosis (IPF). Repair of the basement membrane is a critical step in inducing a healing response to lung injury.
What we were able to show by the changes in type IV collagen is that it appears that we were inducing a repair mechanism of the basement membrane, which is a good signal that potentially we are inducing a lung repair mechanism, which would be absolutely fantastic for these patients. I hinted at this earlier. We're doing a very, very extensive amount of biomarker analysis in this study. The primary endpoint is, of course, safety, but that doesn't mean we don't want to look at clinical efficacy endpoints as well. We are looking at lung function, but this is a study on the smaller side. Typically, you would be looking at lung function in longer studies, longer than 12 weeks, to really see something there.
To kind of build upon that data, things like the serum biomarkers, like the flow cytometry, like the differential gene expression, they can all help support each other. For example, if we see changes in collagen degradation, we might predict that we should see changes in the NMPs in terms of the gene expression that are important in driving that process. The hope is that by doing all of this work, we can develop an extremely strong pharmacodynamic profile of this drug in these patients to really help us design an efficient next study. If our current Phase 2A is successful, the next study would be a Phase 2B potentially pivotal study. This is just a snapshot of some of our peers, really just highlighting that M&A has been very active in this space. That gives us a lot of optionality in terms of how we move forward.
I think what differentiates us from some of the peers here is really going after core biology that we believe is critical in driving these chronic inflammatory, fibrotic, and autoimmune indications. Just briefly, I wanted to touch on the second asset, GRI-0803, that's soon ready for clinical studies. This is a little bit different than GRI-0621, which is an inhibitor of type 1 NKT cells, whereas this is an activator of type 2 diverse NKT (dNKT) cells that represent more of a regulatory T cell population that you want to turn on and activate in different therapeutic settings. I'll show just a little bit of data. This is from the NZBWF1 model. These animals spontaneously develop a lupus-like disease.
On the left, I'm showing some histology showing a decrease in the inflammation after treatment, a restoration of kind of the normal glomerular anatomy in these animals, and a reduction in the deposition of collagen and fibrosis. On the right, I'm showing some different graphs of a decrease in anti-double-stranded DNA antibodies, improved overall survival, and importantly, improvement in proteinuria and proteinuria-free survival. This is one of the more serious complications, the more frequent complications that these patients might encounter. I should mention for lupus, this is again a disease where there's a high unmet need. A lot of work has been done in the field, but unfortunately, only two drugs, I believe, have been approved in the lupus space in the last 50 years. There's really a need for some new therapies. Current treatment is really centered around immunosuppressives that have room for improvement. That was it.
I have about three minutes to spare. In summary, I think we're in an exciting time for the company. We believe that we present an opportunity to create a lot of value for our shareholders, but also new treatments for patients and their caregivers. We believe we're addressing a biology that's really core to driving these diseases. We have a pipeline that will allow us to continue to grow organically for years to come. Thank you so much.
Yep.
Thanks.
Does anyone have any questions?