As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Barbara Lindheim. Thank you, and you may begin.
Thank you. Good morning, and welcome to the Chemomab Phase II SPRING Trial Results Conference Call. Thank you for attending. I am Barbara Lindheim, Consulting Vice President of Strategic Communications and Investor & Public Relations at Chemomab. Before turning the call over to Adi Mor, our Co-Founder, Chief Executive Officer, and Chief Scientific Officer, please take note of our forward-looking statement. Today's call may contain forward-looking statements, which may be identified by words such as may, could, will, expect, intend, plan, and other similar words and expressions. All forward-looking statements made today are based on management's current expectations, assumptions, and beliefs about our business and the environment in which we operate. These statements are subject to risks and uncertainties that could cause our actual results to materially differ from those expressed or implied on today's call.
Listeners should not place undue reliance on forward-looking statements and are encouraged to review our SPRING data press release that we issued this morning together with our SEC filings for a more complete discussion of factors that could cause our actual results to differ materially from those expressed or implied in forward-looking statements. You can read a comprehensive list of those factors under the heading Risk Factors contained in our annual report on Form 20-F, together with factors under similar headings in the other reports and materials we file with the SEC. Except as required by federal securities laws, Chemomab does not undertake to publicly update or revise any forward-looking statements subsequent to the date made as a result of new information, future events, changing circumstances, or for any other reason. Let me now turn the call over to Adi.
Thank you, and good morning. Welcome to the Chemomab Conference Call to discuss the top-line results from our CM-101 PSC phase II trial. You should refer to the press release we issued this morning and the presentation we will be posting on our website after this call. With me today, our CFO, Sigal Fattal; our Chief Medical Officer, Matt Frankel; and our Senior Vice President for Global Clinical Operations, Jack Lawler. This is a great day for Chemomab, and we believe potentially for the many patients worldwide battling debilitating and deadly fibro-inflammatory disorders like PSC. The results of the SPRING trial were very positive and a major milestone for Chemomab, exceeding our high expectations and providing the first substantial proof of concept for CM-101, our first-in-class CCL24 neutralizing antibody.
We also announced a $10 million PIPE this morning that will provide us all the resources we need to achieve our expected catalyst, finishing the open-label extension portion of the SPRING study, meeting the FDA to delineate our path forward and preparing for the phase III trial we hope to initiate before the end of 2025. These funds also extend our runway through early 2026. We were pleased to welcome several important new investors in this financing who joined long-term supporters of Chemomab to provide us the resources needed to go beyond our expected catalyst, providing us flexibility to get a jumpstart on laying the foundation for phase III while assessing all our strategic options for ensuring that resources are available to advance our program. Now let's turn to today's focus, the exciting results of the SPRING study.
The top-line results presented today are very promising as the study met both its primary endpoint, being safety, as well as its secondary endpoints that include improvements across multiple aspects of PSC: inflammation, fibrosis, and even cholestasis. We saw broad and consistent activity of the drug, especially with the high dose of 20 mg/kg, and even more so in patients with moderate to advanced disease. We believe these broad and consistent positive results provide a very strong foundation for advancing CM-101 in PSC and potentially in other inflammatory and fibrotic conditions, and provide the first clinical proof of concept for CM-101. Next slide, please. For those new to the field, PSC is a rare chronic liver disease in which the bile ducts inside and outside the liver become inflamed and scarred and eventually narrowed or blocked.
When this happens, bile acid builds up in the liver and causes further liver damage. This damage results in end-stage liver disease, the need for liver transplantation, and liver cancer, which causes half the deaths seen in PSC patients. This terrible disease affects mainly men, and about 70% of patients also have inflammatory bowel disease. Unfortunately, there are no FDA-approved drugs. The only treatment with curative potential is liver transplant, and even there, we see high recurrence of the disease of about 20% of the patients developing PSC in their transplanted organ.
In terms of the market, it's a serious unmet medical need with approximately 80,000 patients estimated in the seven major markets and a commercial opportunity that is estimated to exceed $1 billion. Next slide, please. The SPRING trial randomized about 70 patients divided between three arms: two doses of CM-101, 10 and 20 mcg, versus placebo. Patients were treated via an IV infusion once every three weeks for a total duration of 15 weeks, and this is the double-blind part of the study that we will be reporting today.
In addition, patients were offered the opportunity to join the open-label extension part of the study that provides all participants an additional 33 weeks of treatment with CM-101. I'm pleased to note that more than 90% of all eligible patients have elected to join the open-label extension. This is clearly a statement for their desire and need for effective therapies. It also highlights how IV administration is not a barrier for these patients, and we will be reporting data from the open-label extension in the beginning of 2025. Inclusion criteria in this study included patients diagnosed with large duct PSC and also having elevated levels of alkaline phosphatase.
In addition, we allowed patients with stable IBD as well as stable treatment with UDCA, a treatment that is used by many patients despite its general lack of efficacy, but it was still allowed as long as the patients were stable. The primary endpoint in this study was safety and tolerability. Secondary endpoints included a variety of measurements that represent PSC progression, including liver stiffness, ELF score, fibrotic markers, pruritus, bilirubin, liver enzymes, etc. The study aimed to evaluate the activity of CM-101 on all double-blind completers, meaning all patients that completed 15 weeks of treatment, and also in a population that has moderate to advanced disease at baseline.
Those are patients that are more likely to show disease progression and possible treatment effects in a relatively short time of 15 weeks. I should also mention that this moderate to advanced subgroup includes approximately half of the patients in this study and also represents about 50% of the general PSC population. I will now hand the floor over to Matt to present the safety data. Matt?
Thanks, Adi. 76 patients were randomized and treated. They will be presented as the safety population analysis. We will be presenting activity results based on the double-blind completer population, a pre-specified analysis set. Those are patients who received all five doses and had the ELF and alkaline phosphatase endpoints at the completion of the double-blind portion of the study. Next slide, please. When we look at the patient demographics, we see a population generally representative of patients with PSC in recent clinical trials. There are slight variations among the three arms. However, overall, they appear quite comparable.
Similarly, on the next slide, the baseline labs and other assessments vary slightly and are comparable. Next slide, please. It's my pleasure to report the overall CM-101 appeared quite safe and well tolerated in the SPRING trial, achieving the primary study endpoint. First, there were no deaths. There were three serious adverse events. One patient in the placebo arm had a Crohn's exacerbation. In the 10 mg/kg CM-101 arm, one patient had an ulcerative colitis exacerbation, and one patient was hospitalized for an elective cholecystectomy secondary to polyps noted during their screening.
All these events resolved, and the patients remained on study. Notably, there were no SAEs reported in the 20 mcg arm. As far as the six patients discontinued due to their adverse events: one in the placebo arm, three in the 10 mcg arm, and two in the 20 mcg arm. In the placebo arm, a patient had a mild hypersensitivity reaction during the first infusion. In the 10 mcg dose arm, one patient had worsening of their shoulder osteoarthritis. One patient had a rise in their GGT reported as mild at visit two, and another had a reduction in their white blood cell count reported as mild, also at visit two. In the high-dose arm, one patient experienced a moderate hypersensitivity reaction at visit two, and another had a non-cardiac chest pain reported as moderate at visit two.
None of these adverse events were considered life-threatening and all resolved. We have captured, next slide, please. We have captured the adverse events that occurred in 10% or more in any one arm, and they are listed here. Two of the top three are commonly associated with PSC. The rest occurred in very few patients. There were no obvious patterns. These data have been reviewed by our DMC, our Data Monitoring Committee, and also several key thought leaders who agree that we have achieved our primary endpoint of safety and tolerability. Let me turn it back to you, Adi.
Thank you. Now let's turn over to present the activity data, and maybe starting from the PK profile of the drug. In the trial, CM-101 demonstrated a clear dose-dependent increase of the level of CM-101 in the blood between the 10 and the 20 mg/kg arms. In addition, we also saw a strong correlation between target engagement and PK. The PK target engagement profiles are very consistent with what we expected and with what we've seen in previous studies.
Next slide, please. The effects of CM-101 were seen across multiple parameters and will go one by one, both in all patients' populations that completed the study as well as in the pre-specified subpopulation of patients that started the study with a more moderate to advanced disease. This population was selected based on a well-accepted predefined cutoff of 8.7 kilopascal using liver elastography, also known as FibroScan. So transient elastography is an ultrasound-based method that evaluates liver stiffness and is commonly used in liver fibrosis and specifically in PSC.
The validity of liver stiffness as an important marker of disease progression, specifically in PSC, has been demonstrated over the years and even received further validation when the data from the large FICUS longitudinal study presented at EASL 2024 strongly validated the prognostic value of transient elastography in hundreds of PSC patients. Understanding the importance and value of elastography and its likelihood to use an endpoint in phase III clinical trials going forward, it was very exciting to see that both doses of CM-101 improved liver stiffness relative to placebo at week 15, with a statistically significant improvement even achieved in patients with moderate to advanced disease.
This is the first time that an investigational drug for treatment of PSC demonstrated such significant improvement, even statistically significant again, in liver stiffness in a relatively short study. Next slide, please. Let's turn to ELF. The ELF score is a well-validated prognostic marker of liver disease severity and liver-related clinical outcomes in patients with advanced fibrosis, including even transplant-free survival in PSC. As you can see here, patients treated with a 20 mg/kg dose of CM-101 with moderate to advanced disease showed a clear and rapid improvement in ELF relative to placebo, starting as soon as six weeks post-treatment and staying quite consistent until the end of the study.
In addition, all patients treated with a 20 mcg of CM-101 showed that changes in ELF score remained consistently below the 0.19 threshold. This is a recognized threshold for predicting long-term PSC-related clinical events. It's also worth noting that when looking at the entire population of the study, not just the more advanced patients, including the patients with the earlier stage disease, the 20 mg/kg showed a mild improvement over time in ELF score compared to placebo, and once again, none of the patients in the 20 mg/kg group got above the 0.19 cutoff, so a very positive outcome for ELF score.
Next slide, please. Similarly, for PRO-C3, another widely recognized marker of active fibrogenesis, both the 10 and the 20 mcg cohorts showed decreases in PRO-C3 compared to an increase in placebo in patients with moderate to advanced disease. We've also seen improvement in PRO-C3 levels in the entire study population, but to a lesser extent. Next slide, please. Another set of super exciting data seen in this study is related to pruritus or itch. Patients with PSC often experience pruritus as a major symptom of their disease, and this is considered one of the most disturbing symptoms reported by patients.
The study results demonstrated that pruritus is improved in CM-101-treated patients, both in the 10 and 20 mg/kg doses at week 15, and this is compared to a slight increase in placebo patients. Over time, treatment with CM-101 demonstrated benefits as early as six weeks after treatment started and even reached statistically significant reduction relative to placebo at week 15. This is an especially intriguing and positive finding since unlike some of the other PSC studies, our study was not enriched for pruritus. So these results actually suggest that beyond the anti-inflammatory and antifibrotic activity, CM-101 is also affecting the cholestatic pathology of the disease. Next slide, please. Bilirubin is probably the most well-recognized marker that represents biliary disease progression.
The fact that we've seen a dose-dependent improvement that reached even up to a 30% decrease in the more advanced disease population surely reinforced the possible effects of CM-101 on reducing biliary disease, even in this relatively short study, and these findings were especially impressive to the KOLs and the experts in the field. This is something that is rarely being seen in such a short period of time. Next slide, please. The evaluation of the impact of treatment with CM-101 on liver enzymes, including ALP, ALT, AST, and GGT, further reinforces the evidence of the activity of the 20 mg/kg dose across all patients, and even more so in the moderate to advanced patient population.
The consistent pattern that we are seeing here of improvement across all key liver function tests may be indicative for the overall improved liver health we believe we're seeing in PSC patients treated with CM-101. Next slide, please. Finally, yet more evidence for the activity of CM-101 is demonstrated by evaluation of its impact on levels of inflammatory cytokines. Results show that both IL-6 and TGF-β1, two cytokines that are known to be highly involved in inflammation and fibrosis, were decreased in CM-101-treated patients compared to placebo.
This decrease was even more pronounced and statistically significant in the moderate to advanced patient population with more advanced fibrotic disease. So to summarize, the results from the spring study, as you've seen, are super exciting for Chemomab and for the entire field. Feedback we've received from all the PSC experts who got an advanced look at the data under confidentiality. In this study, we established for the first time clinical proof of concept for CM-101 in PSC. We've seen that beyond being safe, CM-101 is interfering with the three core pathologies involved in the disease: inflammation, fibrosis, and even cholestasis.
This is a consistent and sustained way that may reflect well what we will see in a larger, longer-term study. As to next steps, based on these positive findings, we will be preparing for an end-of-phase II meeting with the FDA later this year to discuss the data and a potential registration of trial design. We look forward also to the completion of our open-label extension portion of the trial in early 2025, which we expect to provide additional insights and even expand or reinforce the data that's seen so far. In addition, this study clearly added substantial evidence to the role of CCL24 in fibrotic diseases.
We have seen clinical evidence validating the novel mechanism of action of CM-101 that is also very relevant to other diseases that involve inflammation and fibrosis and for which we have extensive preclinical data like systemic sclerosis. Finally, as I noted, we will continue discussion with the potential strategic partners who have expressed significant interest in our CM-101 programs and have also been awaiting for the data. I also want to thank the PSC patients and advocates, the many investigators and institutions that enabled us to complete the SPRING study six months ahead of schedule, and our amazing team at Chemomab who have worked around the clock to bring this critical part of the SPRING trial to a successful close. Operator, we can now open the floor for questions. Thank you.
Thank you. We will now be conducting a question-and-answer session. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for questions. The first question is from Michael Okunewitch with Maxim Group. Please go ahead.
Hey there. Good morning. Thank you for taking my question and congratulations on the fantastic data.
Thank you.
I guess to start off, just looking at the liver stiffness data, right? You hit the P-value in the moderate to advanced, but the results do look generally comparable in the study population as well. Do you think this is just a factor of fewer patients being needed for that subgroup and that a larger powered study would likely hit a P-value?
So I can start by saying that given the fact that it's only 15 weeks of treatment and the fact that we've seen such positive results, both as you've mentioned in all patients, but more so reaching statistically significant in patients with more advanced disease, clearly shows the effect of CM-101 in PSC on liver fibrosis, and we do expect that a longer duration of time may be able to yield the same extent of improvement also in patients with milder disease. It is reasonable to assume that the fact that we've seen that only after 15 weeks of treatment and reached statistically significant in the more advanced patient population is because those are more active patients, and longer duration of treatment may yield to same or to similar extent of activity even on the milder patients.
All right. Thank you for that. And then in terms of pruritus, right? Were you expecting to see an impact on pruritus, and then is this something that you would seek to prove in a phase III to potentially help with competitive positioning and adoption, given that that is such a significant side effect of these liver diseases?
Matt, would you like to address that?
Absolutely. First of all, we did not specifically enhance for patients who had severe itch or moderate to severe. This was open to all patients, particularly because their patients really expressed their itch at various points in progression. We felt that that wasn't a way forward for us at that point, and we were delighted to see the separation. As far as moving forward, the beauty of our mechanism of action is that it really seems to impact the fibrosis as well as the inflammation, and so we believe that we will have an impact not just on itch, but the progression more broadly.
As we go forward, we will certainly enroll the patients with itch. On the other hand, we believe that there is a way forward to really include all patients who are going to continue to suffer and potentially reverse or slow down or halt that disease. So we think that there's a way forward for less pruritus.
All right. Thank you. And then one last one, and I'll hop back into the queue. I just want to see if you have an idea of what sort of length of the study the FDA would want for a phase III. Is that expecting to be something like a six month primary? Just any more color you can provide would be helpful.
Yeah.
[crosstalk]
Based on. [audio distortion] Yeah. So accelerated approval is based on a surrogate, a marker, and that is reasonably likely to show improvements on the long-term outcomes. So we know that the FDA is moving away from biopsies, and we're excited about that. So we imagine that a one-year study would be a viable way forward, and then a confirmatory study subsequent after the regulatory approval.
All right. Thank you very much. Once again, congratulations on the data.
Thank you.
Thank you. The next question comes from Jeff Jones with Oppenheimer. Please go ahead.
Good morning, guys. And as well, congratulations on the data. It's a fantastic result. A couple of questions from us. Adi, you mentioned the target engagement at the 20-mg dose being as expected. Just wondering what that looked like in this population, given you do appear to be seeing a dose effect and obviously topped out at that 20-mg dose, and so how that impacts your thinking about potentially higher doses.
Yes, absolutely. So we have seen, as mentioned, that those proportional increase, both in the pharmacokinetic profile and similarly to that and correlative to that, also in target engagement. It seems like we have reached very high levels of target engagement in the 20 mg/kg, which can definitely explain the changes that we're seeing, the dose-related changes that we're seeing in terms of activity. And again, I recall it's only 15 weeks of treatment, so perhaps longer treatment will also result in additional activity from the 10 mg/kg. But as of now, the 20 mg/kg achieves very high saturation, very high target engagement, and together with the great activity and the very good safety that we've seen, which is quite comparable between the groups, we believe that we have a dose potentially moving forward.
Right. Appreciate that. Following on the discussion of phase III studies, and as we've recently heard from others in the space, that the FDA appears to be moving away from biopsy, which is great news for, I think, everyone in the space and certainly patients. Given you've seen nice results both for ELF and FibroScan, what are your thoughts on what you might propose for pivotal endpoints here?
Matt?
Yeah. I think, as you just highlighted, based on our really exciting data in both of those, in the liver stiffness as well as the ELF, it makes perfect sense for us to move forward with that as a co-primary and focus to really ensure that we can do this as efficiently and effectively as possible and not do things that the patients are used to doing, and also enabling the physicians to manage the patients they used to manage them. Absolutely, it's the way that we plan on going forward and proposing to the FDA.
Okay. And then you've reported previously on some clinical data with a sub-Q formulation. What's the status of that formulation, and could that be an option for your phase III?
So we will be continuing with the IV into the phase III. And again, we didn't see any barrier with that. You can see that even by the fact that the majority of the SPRING patients elected to continue into the open-label extension with the IV dosing. Having said that, we do have a sub-Q formulation. We're continuing to explore the feasibility of the sub-Q formulation with some additional development work. There are several emerging technologies that make the ability to use sub-Q formulation even with higher dose or higher volume type of therapies. So we are certain that we can overcome a potential challenge of volume and continue with sub-Q in the future. But as mentioned, at the moment, we are continuing with the IV.
Okay. Great. Thank you, guys, very much.
Thank you.
Thank you.
Thank you. The next question comes from Jason Wittes with Roth MKM. Please go ahead.
Hi. Thanks, [audio distortion] congratulations. Great data. In terms of trial design, do you have a sense now that you see this data, how big a trial in terms of patients you might need? And I don't know if you can also comment on timelines or on the amount of the time of the extension for the, sorry, the length of time for the study, or are you going to wait and see what the extension looks like? Thank you.
Yeah.
Thank you. So basically.
Go ahead. Go ahead. Sorry. I'll start and please finish up. The data really is quite encouraging, and based on that, we're still understanding our effect size to ensure that we have the right patient population associated with that. We do believe that based on historic numbers, that somewhere in the range of 300-400 patients will be necessary. We also plan on a one year accelerated approval design followed by confirmatory studies after the regulatory approval.
Okay. Great. And sorry. Thank you. In terms of—you said you're still deciding on the patient population. I know this was a smaller study, and it hasn't gone all the way. I think it was a question asked at the beginning about this. On liver stiffness, you did get significance on the monitored advanced patients, less so on the entire population. Is that what you're talking about when you weren't talking about deciding on what population to target here?
Yes, exactly. We're still doing some internal analyses and running the sensitivities because, as you highlight, this is a progressive disease, and there's absolutely no reason, and it's going to be a chronic therapy. So it really behooves us and the broader organization to make sure that we've got the right patients in, and we will certainly enroll those that we believe that will be able to impact over their lives as well as within a reasonable time within the study.
Okay. Great. And then I guess this trial was initially powered on the secondary endpoints. I noticed on some of the data points, there was at least one data point where on the secondary data point where the 10-milligram dose hit significance, the 20-milligram didn't. I assume that's simply due to the low numbers of patients in this trial, and we'll see what happens with the extension.
Yes. I mean, the fact is that although the study was not powered to detect efficacy, we have seen efficacy on so many parameters. That's even more exciting. Yes, you are correct. On one of the markers, we have seen statistical significance in the 10. The 20 did show a very similar extent. It's just that the baseline level started from a slightly lower level. However, nonetheless, the effect that we're seeing with the 20 mg per kg is so consistent overall, the entire parameters evaluated in the study, all parameters evaluated in the study, actually. So we feel very confident on the activity of the 20 mg per kg after 15 months.
Great. Oh, sorry. Great. Congrats on great data. I'll jump back into you.
Thank you.
Thank you. A reminder to all participants, if you would like to ask a question, please press star one on your telephone keypad. The next question is a follow-up question from Michael Okunewitch with Maxim Group. Please go ahead.
Hey, thank you. Just one more quick one from me. When it comes to strategic partnering, are you thinking something related to PSC as an indication, or are you taking this as a proof of concept that could kind of open up partnership opportunities across the broad range of fibroinflammatory disorders that CM-101 could potentially address?
I would say that we're very pleased from the great interest that we are getting from strategics regarding CM-101 in PSC and overall after proving the mechanism of action in fibrosis and inflammation. It definitely opens up the potential for additional indications. So overall, the plan is to evaluate the opportunities and pursue whatever is the best option for the company moving forward. We do see the potential as well as other parties in CM-101 in liver diseases in general, in PSC in specific, and also in other fibrotic and inflammatory diseases for which we have a very strong scientific set of evidence.
All right. Thank you very much.
Thank you.
Thank you. A reminder to all the participants, you may press star one to ask a question. There are no further questions at this time. I would like to turn the floor back over to Dr. Mor for closing comments.
Thank you. So just to say, this is a great day for Chemomab and potentially for patients with PSC. Very exciting days ahead of us. I would like to thank everyone very much for your time and attention today.
Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.