Good morning, everyone, and welcome back to day two of Oppenheimer's 36th annual healthcare conference. I'm Jeff Jones, one of the biotech analysts on the team here, and I am delighted to welcome Adi Mor, CEO of Chemomab Therapeutics, to give us an update on their story. Adi, I will hand it off to you.
Thank you very much, Jeff. My pleasure to be here today and presenting Chemomab at the Oppenheimer conference. Just before I start, please note I'll be making forward-looking statements, so please refer to the risk factors in our SEC filings. Chemomab is a clinical stage company developing novel treatments in inflammatory and fibrotic diseases. Our lead asset, nebokitug, is a first-in-class monoclonal antibody that targets CCL24, a key factor of inflammation and fibrosis across multiple indications. We are targeting rare diseases with large commercial potential and high unmet medical need, including primarily primary sclerosing cholangitis, or PSC, a rare liver fibrotic disease of the bile duct, for which we have completed successfully a phase II clinical study, and also systemic sclerosis, or SSc, for which we have a phase II ready program.
Over the years, we have generated a very comprehensive set of preclinical and clinical data showing nebokitug's strong interference in inflammation and fibrosis in the liver, in the skin, and in the lung. Nebokitug showed clinical proof of concept for the first time in a phase II clinical study in primary sclerosing cholangitis, following both 15 and 48 weeks of treatment. These results not only pave the way towards a single pivotal study for approval in PSC, but it also further validates CCL24 as a target in inflammation and fibrosis, and therefore support advancing nebokitug into additional indications in fibrosis and inflammation, for example, systemic sclerosis. Based on the very strong anti-inflammatory and anti-fibrotic activity of nebokitug that we've shown over the years, we are considering nebokitug to serve as a pipeline in a drug and see great potential in its disease-modifying activities across multiple indications.
Looking ahead, nebokitug is now positioned as a phase III ready program in PSC, which we aim to start together with a partner. With its Orphan Drug Designation from both the EMA and the FDA, nebokitug is also phase II ready in systemic sclerosis as well. A couple of words about the target itself. CCL24 is a soluble protein, belongs to a subfamily of cytokines, and the uniqueness of this target relies on the fact that it is able to enhance simultaneously and directly the two main pathways that eventually leads to this abnormal fibrosis that we are seeing. On the one hand, CCL24 is a key regulator of the type two immune response, and at the same time, it directly activate the fibroblasts. Controlling these two pathways, that's what led CCL24 to play such a significant role in advancing inflammation and fibrosis.
Based on the data that we've generated over the years, we have generated nebokitug, a neutralizing antibody to CCL24 that was indeed shown to be able to attenuate significantly both inflammation and fibrosis across multiple potential indications. Let's focus on primary sclerosing cholangitis. First of all, maybe a few words on the disease itself. PSC is a rare liver fibrotic disease. It's characterized by obstructive damage to the bile duct that eventually leads to inflammation and fibrosis and end-stage liver disease. Unfortunately, to date, there are no FDA-approved drugs for primary sclerosing cholangitis, and actually, the only treatment with curative potential that is out there is liver transplant. Even there, we can see recurrence of the disease in many of the patients. There are approximately 70,000 PSC patients in the seven major markets.
The expectations is that it's going to be even higher than that once an approved drug is out there, and we are looking at a potential market that exceeds-- may exceed $1 billion of revenues. We are facing a very unique competitive landscape, I would say, because nebokitug is the only drug in development today, in late-stage development, that suggests clear disease modification, inhibiting both inflammation and fibrosis, meaning it is able potentially to stop disease progression. This is unlike many of the other drugs that are in development that are mainly focusing on bile acid metabolism, improvement of symptoms like pruritus, for example, symptoms that are very much related to the disease but do not eventually change the trajectory of the disease.
We believe that once nebokitug enters into a phase III, it could be the first approved disease-modifying drug in this terrible disease. Maybe we take a look on our recent phase II clinical data in PSC, and maybe starting by presenting the design of the study. We have randomized 76 patients with PSC into this study, divided between threee groups. We have two dose arms of nebokitug, 10 and 20 milligram per kilogram versus placebo. Patients were treated for 15 weeks in this double-blind period, and then offered to join an open-label extension up to 48 weeks of treatment. The primary endpoint is safety and tolerability. Secondary endpoint is composed from a variety of markers that represent disease progression. First and foremost, liver stiffness and ELF, but also important to look at the broad picture.
We looked at the other fibrotic biomarkers like ProC3 and pruritus, and inflammatory cytokines, liver enzymes, et cetera, et cetera. Important to mention that we predefined in our analysis plan, looking at all patients that completed the study, but also specifically looking at patients with moderate to advanced fibrosis. This is the target population of this drug. We believe that patients that would have higher levels of inflammation and fibrosis in this study could benefit most from nebokitug within the time frame of this study. Overall, the study met both its primary and secondary endpoint, the drug appears to be safe and well-tolerated in patients with primary sclerosing cholangitis. In addition, we have seen clear improvement across all of the inflammatory and fibrotic markers that we have evaluated in this study. We have two take-home messages from this phase II clinical study.
The first one is the dose. The 20 milligram per kilogram is the selected dose to move forward with towards phase III, based on safety and activity data. Second, we are looking at patients with moderate to advanced disease. As expected, they are the ones that have shown more prominent results in the duration of the study, and this is the patient population that we are planning to enrich or to focus on in our phase III clinical study. Few examples to the clinical data. Looking at liver stiffness, maybe one of the most validated methods that are used by clinicians to date in patients with PSC. We are seeing improvement in patients treated with nebokitug after 15 weeks in all patients, but it even becomes statistically significant and much more prominent in patients that started the study in a moderate to advanced pattern.
In addition to that, when we are looking at the ELF score, a composite biomarker that represents three biomarkers of inflammation and fibrosis. Here as well, we were able to see that patients with moderate to advanced disease, to start with, that were treated with a higher dose of 20 milligram per kilogram, were able to show an absolute improvement of 0.13 in their ELF score, which is a very, very successful results in this study. Looking also at other parameters of fibrotic, specifically, TIMP-1, PIIINP, ProC3, TGF-beta. Once again, you can see the very clear attenuation of these parameters, seen more extensively in patients with moderate to advanced disease and with the 20 milligram per kilogram dose.
When we're looking on the inflammatory pattern, biomarkers like IL-6, IL-18, CD14, and others, were all shown to be reduced dose-dependently following treatment with nebokitug for 15 weeks. Overall, again, looking at the broad picture, we're not just looking at biomarkers like ELF and liver stiffness that have definitely shown improvement and are very consistent with reductions in clinical events, in disease progression. Across the board, all of the biomarkers of inflammation and fibrosis that we have tested in this study that are relevant to PSC, were shown to be reduced following only 15 weeks of treatment. As I've mentioned, the second stage of the study included an open-label extension. 93% of the eligible patients selected to continue into the open-label extension, meaning getting treatment for an additional 33 weeks.
This is a very high % of acceptance, and this, we believe, shows how compliant the patients were to the drug. The goal of the open-label extension was to evaluate the safety of the drug for a longer duration of treatment, but also looking at the durability of effect after a longer period of time. As we all know, PSC is a disease that takes long to progress. We were very excited to see the data of the 48 weeks following treatment. First of all, the drug continues to be safe and well-tolerated, looking at both of the doses, 10 or 20 mg per kg, after 48 weeks of treatment. In addition, we have seen continued improvement in biomarkers that represent disease progression, ELF-related components, ProC3, et cetera. All of those showed absolute reduction following 48 weeks of treatment.
We've also evaluated clinical events in this study. Although the study was not powered for that, it was important for us to see whether the patients treated with nebokitug are suffering from clinical events that eventually will be the primary endpoint in our phase III study, we have seen a much more limited percentage of events compared to historical control, I will show the data in a second. Going briefly over the data, starting with the ELF score. As you can see, when we are looking at all patients, we are seeing kind of a stable pattern of ELF with a 20 mg per kg.
When we are looking specifically at the key population that can show change in this study, you can see an absolute reduction of -0.4 in patients with moderate to advanced disease treated with a 20 milligram per kilogram. Other parameters like ProC3, TIMP-1, PIIINP are all showing the same trend: reduction, continued reduction, and improvement after 48 weeks of treatment, which further strengthen the anti-inflammatory and anti-fibrotic activity of the drug over time. The two key parameters that have the most validated or referenced to clinical events are liver stiffness measurements and the ELF score.
In both cases, we have seen that patients that were treated with nebokitug, and especially the 20 milligram per kilogram dose, showed reductions in LSM and in ELF that support reduction in clinical events, meaning that threshold that we have seen nebokitug to be, to show an effect in, is the threshold that shows that we are expecting to also see less clinical events over time. This, of course, is very de-risking for the phase III anticipated program. As I've mentioned, the phase III is going to focus on clinical events, so we did have the opportunity to look how many clinical events were in our study. We have seen 4.8% of the patients that were treated for 48 weeks have shown a clinical event that is related to PSC.
If we are comparing it to a matching population from a previous historical study, we can see that resulted in almost a 26% of the patients showing clinical events. It's an 80% less events after 1 year of treatment with nebokitug treatment versus historical data. Chemomab has aligned with the FDA on the design for a phase III for a full approval. We're looking at a single study that could provide full approval for nebokitug for patients with primary sclerosing cholangitis. This study, as mentioned, is going to be based on a composite of clinical events, or there are going to be numerous outcomes that we are going to evaluate: ascending cholangitis, strictures that require intervention, portal hypertension, hepatic decompensation, MELD score above 15, liver transplant, and death.
The study is going to look at patients that will receive placebo versus nebokitug, and the time for first event is going to be the primary endpoint of this study. We are planning to also include an interim analysis into the study, so in case we will be able to show a very massive improvement, maybe similar to what we have seen initially in the phase II. Following treatment with the drug, we can then file for an earlier BLA in our phase III clinical study. Beyond PSC, as I've mentioned, we do see the great potential of nebokitug in additional indication as that involves inflammation and fibrosis. One of them is systemic sclerosis. Like PSC, we're talking about a rare disease, only in this case, it's an inflammatory rheumatoid disease that primarily affects women.
The disease involves inflammation and fibrosis in the skin, vasculature, and additional internal organs. The main cause of death in these patients, in these mainly women, is actually lung damage, due to fibrosis at the end of the day. Although there are two approved drugs for treating specifically the lung disease associated with systemic sclerosis, there are currently no disease-modifying drugs in the market. We're talking about a market that includes almost 180,000 patients in the seven major markets, and a commercial opportunity that exceeds $1.5 billion. We have done a lot of research in systemic sclerosis over the years.
First of all, a very comprehensive set of preclinical data showing that CCL24 itself is significantly elevated in the skin of systemic sclerosis patients as compared to healthy skin, as you can see in the left hand of this slide. We're also able to show that CCL24 actually predicts mortality in patients with systemic sclerosis. In addition to that, maybe focusing specifically on the lung disease, because this is the number one cause of death in these patients, not only that we were able to see the CCL24 is elevated in patients that are suffering from ILD, but CCL24 was also found to be predictive for the deterioration in ILD, meaning deterioration in forced vital capacity. Clear connection between the target and all of the pathologies that are related to systemic sclerosis at the end of the day.
In addition, we have done a lot of work with nebokitug itself. For clinically, we have shown CCL24 to block inflammation, fibrosis, and vasculopathy in the skin and the lung in these patients, kind of all the three key pathologies that are involved in the disease. The changes that we've seen in our phase II in PSC very much translate and are relevant to systemic sclerosis as well. Changes in ELF, in ProC3, inflammatory cytokines, TIMP-1, P3NP, and others, all of those were observed in the phase II study in PSC, further reinforce, I would say, the therapeutic potential of nebokitug in systemic sclerosis and strengthen the probability of success in a phase II study in this indication.
Maybe just to summarize, with its unique dual anti-fibrotic, anti-inflammatory mechanism, nebokitug represents a breakthrough, or a potential for a breakthrough, with application to PSC as well as to additional indications, including systemic sclerosis. The positive phase II readout in PSC paves the way towards a single phase III for registration in PSC, and further validates, as I've mentioned, the broad anti-inflammatory and anti-fibrotic activity of the drug in other indications as well. We are currently advancing discussions with partner in order to support the initiation of our phase III clinical study in PSC, and at the same time, also advancing nebokitug into other indications like systemic sclerosis. I'd like to thank you all for your time and attention. If there are any questions, I'm more than happy to answer.
Wonderful. Thank you very much, Adi. I guess, just one clarification on the PSC market. You mentioned about 70,000 patients, these and then when you look at nebokitug in your phase two trial, there's obviously a stronger signal in patients with moderate to advanced disease. What portion of those 70,000 patients do you think are, at any time, really have a moderate to advanced disease? What portion are the most likely to be candidates for nebokitug?
There are about 50% of the patients would have the, I would say, F2, F3, maybe F4A type of disease, moderate to advanced. By the way, that was also 50% of our study population as well. I do wanna emphasise that it's not necessarily that the label for that we will receive at the end of the day would be only for moderate of disease patients. This is just the ability for Chemomab to have a clinical study in a suitable or relevant timeframe in order to show the anti-inflammatory and anti-fibrotic activity of the drug.
We do believe that, you know, this could also prevent the progression of patients with mild disease, but obviously, that would require a much longer period to assess, and that's why we would like to enrich the patients in the phase III to having a more advanced disease.
For the phase III trial, you wouldn't exclude patients with more mild disease, but you would enrich for those with moderate to advanced?
Ideally, we would look mainly on a population that will show some kind of above a threshold of ELF, and/or LSM for the inclusion criteria in the phase III. As mentioned, based on the discussion with the FDA, it's not, necessarily, I mean, that the label will be strict only to moderate to advanced. The $1 billion revenues that I've indicated, by the way, these are conservative assumptions that were done only on the moderate to advanced population, but we do believe that this could be much broader than that as well.
In thinking about the phase III, I know you've done a lot of work to think about design and sites and things like that, and have had really in-depth discussions with the FDA and EMA. Do you have a feel for what the cost of that trial would be? How much money do you need to be able to complete it?
This is something that we have not disclosed to date. Obviously, we think we can definitely leverage all of our capabilities and relationship and unmet need in order to expedite the recruitment, and this would save cost at the, at the end of the day. One of the reasons that we would like to partner on this study is in order to be able to be more cost effective, I would say, and get more value to our shareholders in terms of less required equity-related financing.
Yeah. Well, and, you know, given it's a rare disease and this is a long trial, you know, it's a complex, large trial to run. For a small company, having a partner at the table is certainly an advantage.
Yes.
If we look, you know, in your partnering discussions, I know you've talked about a variety of flavors of, types of deals, being it in terms of, a single indication or territories and things like that. I guess, you know, what is the most attractive option for you? What would you like to see in a partnership?
... I guess what we're looking for in a partner beyond, of course, the financial commitment is also the expertise in the field, its ability to support future commercialization, et cetera, et cetera. That's obviously something that could be done with a global partner, but could also be done if we're looking for a territory from a, you know, with more regional type of partners. So that's I mean, in our, you know, basket of evaluations, as we are evaluating the options that are currently on the table from partners, this is the experience in the field, the commercial capabilities of the partner is definitely something that we are taking into consideration.
Okay. You know, you're obviously phase II ready for SSc. As you noted, most of the mortality for SSc is on the ILD side. As you think about a phase II design, do you think, you know, a trial specifically focused on the SSc-ILD, or would you prefer a broader SSc trial looking at ILD as one of the outcomes, versus skin effects and things like that? As you noted, CCL24 is elevated in the skin of these patients, so how... So I guess, to simplify the question, would an SSc trial, in your mind, be more focused on the single indication of ILD, or would it be broader to look, more holistically at the impact across SSc morbidity?
I believe that given the mechanism of action of nebokitug, the fact that we have seen it to be, and the expression of the target, and the downstream activity of the target, and of course, the inhibition of the antibody to be involved in the skin, in the lung, in the vasculature, which is also a key component of worsening of the disease. The fact that it is able to interfere with both inflammation and fibrosis, kind of pave the way for us to evaluate a broader evaluation of its activity and not just ILD. It's too soon to say exactly how the design would look. This is obviously something that is still within discussions. I believe that if we would like to get the maximum out of the potential of nebokitug, we should look beyond only lung.
All right. Obviously, you've been having discussions with partners about the path forward, I guess, there's obviously more data on PSC. ILD is perhaps, or SSc-ILD might be a larger indication or, you know, there's certainly more data around it commercially. I guess, where do you see the most interest from partners, Maybe what's the, Where do you see pushback?
The, the interest, mainly goes into the phase III in PSC, because this is obviously the quickest way to the market, right? Because we are already there. We have proof of concept in the phase II, and with the single phase III, we can get this towards registration. Having said that, I should emphasize the fact that there is also interest in systemic sclerosis, and even beyond systemic sclerosis, in other indications where CCL24 was found to be very relevant. In some of the discussions that we are having, it is the opportunity is being evaluated as a very broadly, and not just per indication specifically.
Okay. You know, what kind of pushback do you get from partners?
You know, the fact that the CCL24 is a novel target, I think that all of the parties that we've been in touch with over the years were waiting for clinical proof of concept to see how it works in a clinical study. I think it's very clear to everyone that the drug is effective and is reducing inflammation and fibrosis. Obviously, the phase III in PSC is a bit different than the phase II. We're not looking at biomarkers, we're looking at clinical events, we've shown some evidence to that in our phase II clinical study. There is also data, as natural history data, that supports the translation from MRE liver stiffness into clinical events.
Nonetheless, obviously, you know, at indications where the phase II and the phase III are exactly the same, sometimes it's easier to evaluate the risk of the phase III.
Okay. Makes sense. I guess just to close out with the last question, although you haven't announced year-end numbers, just, as far as what you've reported, in terms of cash today and what that supports?
We reported in our last earnings, we had about $20.8 million. That money should take us through the end of 2026. It will support activities or preparation, I should say, is for the phase III, and mainly CMC-related preparations, including the manufacturing of clinical materials for the phase III. It will also include additional interactions with regulators, FDA, EMAs, and others. The company does have runway until the end of 2026.
All right. Fantastic. Well, I think we are essentially up on time. Adi, it's always a pleasure. Great story and data getting you guys prepared for phase III. Thank you very much. I hope you have some great meetings today.
Thank you so much. Always a pleasure, Jeff.