Corbus Pharmaceuticals Holdings, Inc. (CRBP) Earnings Call Transcript & Summary

Hello, and welcome to Corbus Pharmaceuticals' September 8 lenabasum Phase III RESOLVE-1 Top Line Results Conference Call. [Operator Instructions] This conference is being recorded at the company's request, and will be available on the company's website following the end of the call. I would now like to turn the call over to your host, Ted Jenkins, Senior Director, Investor Relations and Corporate Communications. Please go ahead.

Thank you, and good morning, everyone. At this time, I'd like to remind our listeners that remarks made during this call may state management's intentions, hopes, beliefs, expectations or projections of the future. These are forward-looking statements that involve risks and uncertainties. Forward-looking statements on this call are made pursuant to the safe harbor provisions of the federal securities laws. These forward-looking statements are based on Corbus' current expectations and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from those contemplated by such forward-looking statements are discussed in the periodic reports Corbus files with the Securities and Exchange Commission. These documents are available in the Investors section of the company's website and on the Securities and Exchange Commission website. We encourage you to review these documents carefully. Today, we'll be discussing results from the analysis of our top line results from RESOLVE-1 Phase III study of lenabasum for treatment of systemic sclerosis. After our remarks, we'll open the call for Q&A. Joining me on the call are Dr. Yuval Cohen, our Chief Executive Officer; Dr. Barbara White, our Chief Medical Officer and Head of Research; Sean Moran, our Chief Financial Officer; and Craig Millian, our Chief Commercial Officer. With that, I will turn the call over to Yuval.

Thank you, Ted. Good morning, everyone. As we announced in this morning's press release, the RESOLVE-1 Phase III study, testing lenabasum in systemic sclerosis, did not show statistically significant differences in the primary or secondary endpoints when comparing lenabasum to placebo. Both were added to background drug therapy. As you can imagine, we are both surprised by and deeply disappointed with this top line data. Top line data from the RESOLVE-1 study continue to demonstrate lenabasum's positive safety profile. Lenabasum treatment was safe and well tolerated in the Phase III study, with no new safety signals observed. We have had top line data only for a few days, and we made the right decision to announce them quickly. We will be getting additional analyses to help us understand these results. In the meantime, I want to share some initial thoughts about our results with you. We were all surprised by the very high ACR CRISS score we saw in the control arm, which was placebo added to background drug therapy. The median ACR CRISS score in this arm was 0.887, which is higher than any ACR CRISS score for control arm in previous studies of systemic sclerosis that we are aware of. I will remind you that the maximum achievable ACR CRISS score is just 1. For the lenabasum 20-milligram twice-daily arm, the median ACR CRISS score was an equally high 0.888. We can begin to realize the challenge of trying to determine the effect of an experimental drug, with the control arm of the study is scoring so near the top of the scale. Our study was designed to include patients as currently treated in clinical practice. And to our knowledge, it is the first 52-week randomized, placebo-controlled Phase III study in diffuse cutaneous systemic sclerosis, in which the majority of patients, 84% to be precise, were indeed receiving background immunosuppressive drugs. In collaboration with our principal investigators and Steering Committee, we will interrogate our data to understand the higher-than-expected ACR CRISS score in the control arm, as well as to understand if there are groups will lenabasum offered potential clinical benefit. We plan to present this data at upcoming medical conferences. Once we have a fuller understanding of the data, we would like to engage the FDA to determine potential next steps in the clinical development program of lenabasum in systemic sclerosis. We remain committed to lenabasum and to our additional pipeline programs. We look forward to upcoming top line results from our study of lenabasum in patients with cystic fibrosis, and we have fully enrolled our Phase III in dermatomyositis. I will now turn to Dr. Barbara White, our Chief Medical Officer, Head of Research, to discuss these details further.

Thank you, Yuval. Good morning. To echo Yuval, we are all deeply disappointed and surprised by these results. I'd like to review the design of the RESOLVE-1 Phase III study with you. The trial was a multinational, randomized, placebo-controlled study, evaluating the efficacy and safety of lenabasum in systemic sclerosis, when tested as add-on to background treatment. This design took into consideration input from our principal investigators and other experts in the field. The eligibility criteria were very similar to those used in the Phase II study. This study deliberately enrolled subjects on their current background therapy, without significantly limiting background immunosuppressive use. This approach of allowing background immunosuppressive therapy was and still would be the right thing to do, because it allowed us to enter patients whose treatments represent current practice. The relevance of this design and decision was supported by the fact that 84% of patients were on background immunosuppressive therapy. The degree of improvement that was observed in the control arm in this study far exceeded what we expected based on our analyses of the literature, reports from other clinical studies and input from our principal investigators and other experts. It seems clear to us that this improvement in the control arm is because of the effect of background immunosuppressive therapy. This level of improvement was unexpected. Our principal investigators and our Steering Committee are all equally surprised. Dr. Rob Spiera, one of our principal investigators on RESOLVE-1, shared that immunosuppressive drugs alone, or in combination, are increasingly becoming the mainstay of treatment for patients with early diffuse cutaneous systemic sclerosis. However, to our knowledge, the impact of these drugs on disease has not previously been studied systematically and was underappreciated. The degree of improvement in the control arm was great enough to make it difficult to see any improvement when lenabasum was added as background therapy in this study. However, even preliminary analysis suggests that we may be able to discern patient characteristics and treatment characteristics that allow us to identify groups of patients in which the potential therapeutic benefit of lenabasum can be shown. We now have data that no one else has. Our RESOLVE-1 data set will provide us with unique understandings about relationships between patient characteristics, current treatment and outcome. We look forward to working with our principal investigators and Steering Committee on the design of a potential future study of lenabasum in systemic sclerosis. Although patients are improving more than previously recognized on background immunosuppressive therapy, it doesn't mean that these improvements are good enough. Chris Denton, our other Principal Investigator, shared that despite the unexpected magnitude of improvement provided by current immunosuppressive treatments, it is not enough. Patients are still suffering, and need new drugs that can provide additional improvement. Both Rob and Chris expressed excitement about the potential value of a non-immunosuppressive treatment for these patients such as lenabasum. They highlighted that the safety profile and tolerability of lenabasum make it very attractive for potential use in scleroderma patients. In particular, no new safety signals were observed for lenabasum in the study. Similar proportions of placebo-treated and lenabasum-treated subjects had at least 1 treatment-emergent adverse event. Serious adverse events occurred in 14.6% of subjects -- presented subjects in the control arm and 9.2% of subjects in the lenabasum 20-milligram arm. Severe adverse events, which are slightly different, occurred in 13% of subjects in the control arm and 5.8% of subjects in the lenabasum 20-milligram arm. Lenabasum was well-tolerated, and no subject who received -- who was receiving lenabasum withdrew from the study because of an AE related to study drug. No evidence of lenabasum-related immunosuppression or new safety signals for lenabasum were observed. In summary, this study had the unexpected finding of high improvement on background immunosuppressive therapy. Nonetheless, there remains need for additional treatments for this rare and serious disease. Our data set allows us to have unique insights about interactions between patient characteristics and usual treatments that are relevant to clinical trial design in SSc. We are optimistic that our interrogation of the data will provide clarity on patients who could potentially benefit from lenabasum. On behalf of the entire staff at Corbus, we are deeply grateful to and thank all those who made the RESOLVE-1 study possible. We are especially grateful to the people with systemic sclerosis, who participated in this study, and to our principal investigators, Dr. Robert Spiera and Dr. Christopher Denton, our other Steering Committee members, members of our Data Monitoring Committee, the site investigators and study staff at each site, who among them, provided advice and encouragement or performed the daily work of the study at the sites. Yuval, back to you.

Thank you, Barbara. Before we wrap up and take questions and answers, I just wanted to add a couple of more comments. One is, again, the study has generated an invaluable database, for 2 reasons. The one, we have a much better understanding of how these patients should be treated. And I don't think it's an exaggeration to say that this will have a very, very significant impact on how the tens of thousands of systemic sclerosis patients worldwide will now be treated and which standard of care they'll be put on. That in and of itself is a very, very worthy outcome for a clinical study. And we are immensely proud of that. The second thing is -- and again, it is very early on, but I have a very high degree of confidence that out of this data, we will emerge with a much better, clearer understanding of the contribution lenabasum could have to the standard of care, and how it could fit in this new paradigm that we will bring about. I remained very, very optimistic about lenabasum, about the potential of CB2 agonism and the potential for the endocannabinoid system across multiple indications, including systemic sclerosis. And I just want to echo what Barbara said, this has been a journey of over 3 years in the making with hundreds and hundreds of people participating. Both patients, physicians, our staff who have worked incredibly hard, I am so grateful to them. And I am so pleased that out of this study, something very positive will come out, and maybe more than just one thing. So with that, thank you, all of you for your time this morning. I wish we had the different news for you this morning. But nevertheless, we are excited about the next steps. We are excited about lenabasum, and we look forward to the future. I will now turn it back to the operator for any questions to our team.

[Operator Instructions] Our first question today is coming from Brian Abrahams from RBC Capital Markets.

Sorry for the outcome but clearly, a very robust set of data that can hopefully advance the field going forward. I guess, first off, the CRISS primary endpoint, I know was a median. Are there any other ways to analyze CRISS, either through a threshold effect, a mean or spread, that might be able to better discern a treatment effect, given the high placebo rates on median? Just wondering if you've seen any signals on those types of analyses?

Brian, this is Barbara. Thank you for the question. We, certainly, have already looked at those things and looked at other aspects. And the answer is, no, we don't see it there in the ACR CRISS, and the outcomes are really quite similar across the ACR CRISS in the secondaries. I do think it is because we saw, without exaggeration, what I might consider, this is unprecedented improvement in these people with background therapy. And when they are clustered together, different therapies, different baseline characteristics, different characteristics of the drugs and how long they've been on the drugs, those kinds of things, it's just not possible for us, in aggregate, to see the improvement. I do also remain quite optimistic that we will be able, with this data set, to understand enough to allow us to place lenabasum in where it can provide benefit because there still is great need for treatment of these patients. We do have much to learn, and we will do this with our principal investigators and our Steering Committee as we interrogate this database. But I do also remain optimistic that we will see clear signals of efficacy when the data are cased apart.

That's really helpful. And maybe just a follow up to that, Barbara. Just wondering if you could talk a little bit more about the types of subgroups that you may be looking at, what you would need to observe to warrant continued development in scleroderma? And any hints that you may have seen thus far? Obviously, I know the data is very fresh.

I think -- while I would love to share our hints with you, and where we think we are, I think it's too premature. We really need to have further time to analyze these, discuss these, review them with our experts, our Steering Committee, our principal investigators and be very certain about them. I wouldn't want to be premature on that. We will disclose the data in much more detail at upcoming medical meetings. And we will continue to publish results, and we will make these data available. We also, again, trying not to overstate it, but I think the importance of these data will be very big when it comes to allowing physicians to make choices about what treatments they may or may not want to put particular patients on. And I think that it's a great opportunity for us to contribute to the field. And that's the one aspect of the study that makes us happy.

Got it. One more quick one, if I could, then I'll hop back in the queue. It did look like the severe adverse events were lower off the lenabasum arm versus placebo. And I guess, I was wondering if that might suggest any underlying immunosuppressive steering effect that you may be seeing such that this could provide a safer alternative for systemic sclerosis patients?

Well, I'm glad you speculated on that, not me, but I can't say that. I'm simply that we are pleased that we continued to see a very acceptable safety profile. This is echoed by sentiments from our principal investigators and the Steering Committee. These are sick patients. They're [indiscernible] and background treatments, including immunosuppresses and anything that can be done not to greatly increase burden, just if treatments themselves would be very helpful to them. And so we're pleased that the safety profile continues to be quite favorable in this group of patients in this study.

Our next question today is coming from Maury Raycroft from Jefferies.

And I'm sorry to hear about the news today. First question is just on the use of background immunosuppressives in RESOLVE-1. I guess, how does that compare to your dermatomyositis study? And can you talk about key evidence or new understanding from RESOLVE-1 that gives you insight into how the DM or other studies could play out?

Maury, thank you for the question. Patients with dermatomyositis is a related disease, it is a different disease. Those patients, because they are also still, are treated with background immunosuppressants. In the past, corticosteroids, we consider the mainstay, large dose, high doses of corticosteroids. And then if they didn't respond, switch over to additional immunosuppression. We will see what we get when the study we published in abstract form in American College of Rheumatology, the background characteristics of these patients. And indeed, they are also heavily treated with immunosuppressants. That in and of itself doesn't mean we will see exactly the same effect in the dermatomyositis study. It's not clear, to date, at least, we can't find in the literature or have that insight from our Steering Committee that one, immunosuppressive is better than the other or that there are certain characteristics that make a difference, or even that they are terribly effective. So I think the results of the DM study will need to await top line data. But again, it's true, the patients are heavily treated, as our most patients with systemic autoimmune diseases in nearly all cases. What's different about this one was that I think it has been really underappreciated, that the patients were receiving some significant benefit. It doesn't mean it was enough, but indeed, what the physicians were doing was helping and is helping the patients that they take care of. That's good news.

Got it. That's helpful. And just wondering if you've done any preliminary check into blood biomarkers? And do you have a sense of whether the drug is having a biological effect that would benefit patients with SSc or even the other diseases, too?

We don't have any of the biomarker data available to us yet. These are just top line news that came in. As in the next 2 weeks, we actually -- as you may know, when you get study data results, they come in batches. First, you get the top line, and then you get the rest of the story. And you can also do a further analysis to interrogate the data. We have just gotten the top line data. We don't have the rest of the planned analyses, and it will inform us, as a company, about the full extent of what went on in the study as well are other interrogations, in collaboration with experts in the field.

Got it. And last quick question. You mentioned potential for another future study in SSc. Do you have an idea of what that study would look like? And any views on timing for when that could be revealed and initiated?