Edited Transcript of CRBP earnings conference call or presentation 9-May-19 12:30pm GMT

Thomson Reuters StreetEvents - finance.yahoo.com Posted 6 years ago
. Operator?" data-reactid="82">With that, I'd like to turn it over to the operator for any questions from our audience today. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions)

Our first question today is from Brian Abrahams of RBC Capital Market.

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Unidentified Analyst, [2]

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Hey, guys, this is [Owen] on for Brian. A couple questions on CRISS. First question, I'm wondering if you could talk a little bit more about how the endpoint weights the different aspects that go into it, all of the secondaries, and what sort of profile you would need to show in those secondaries to sort of validate the primary CRISS outcome?

And then secondly, are you planning on looking at the median again? And if so, are there are additional analyses you think you might conduct that would perhaps demonstrate the effect of lena on organ involvement, like looking at the percentage of patients in each group that had 0 CRISS scores, or something of that nature? Thanks.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [3]

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Thanks, Owen. Barbara, I'm going to turn that over to you.

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [4]

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Thank you, Owen, for that question. Let me start with your question about the weighting of the CRISS score. The formula is published, and it's daunting when you look it. The reality is that the change from baseline -- let me pause. Everything is a change from baseline, so there is no ACR CRISS score when the patient's started. Thereafter, you calculate it. MRSS weighs most heavily, but the others all contribute. So this is not simply mRSS with bells and whistles, this is a real composite outcome that includes a variety of core items, all of which are clinically relevant in the assessment of scleroderma patients.

So the patient global assessment; the patient assessment of function with the HAQ-DI; the forced vital capacity percent predicted, which is a lung performance measure; and the physician global assessment of health all contribute. We believe that is -- their contributions to this composite make this an outcome that better reflects the totality of change in disease status in patients with SSc. We believe it is better for a primary look for a drug that's going to go after an indication for treatment of scleroderma to look broadly rather than just look at skin.

So the way the actual formula works, and if you were to play with it, you would find that it's highly unlikely, at least in my opinion, that one would see a difference in ACR CRISS scores without a difference in multiple of these composite outcomes. That's just the way it works. So I think that our -- I know that our expectation is that we will see improvement versus placebo in essentially all these outcomes. Some may not achieve statistical significance, but that's not necessary. I believe that the regulators will look at the totality of the data, as they have promised to do, and that will include looking not only at the composite score, but certainly and importantly at changes, directional changes, in each of the core set items. All of those would support efficacy of the compound.

In terms of subset analysis, certainly we'll do those. Those are very important in supporting the primary efficacy outcome. There would be subsets based upon what might be considered minimally important differences. There would be subsets based on geography, different disease characteristics, all kinds of things. There would be multiple analyses that are done.

I do want to say that, importantly, the ACR CRISS score itself has an initial step of scoring in which people who develop new severe organ involvement are given a CRISS score of 0. That is new severe or worsening interstitial lung disease, pulmonary artery hypertension, renal crisis or congestive heart failure. Those will be reported to the regulators as part of the ACR CRISS score. So they will have that very important subset of the scoring available to them.

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Operator [5]

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The next question is from Maury Raycroft of Jefferies.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [6]

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I had a question on the endpoint change, too. So you've mentioned that it's not going to change the size or the length of the study, but I'm just wondering if there's any other actionable items that need to be implemented with the study that require some protocol modifications?

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [7]

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Thanks, Maury. Barbara, it's back to you.

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [8]

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Yes, thank you, Maury. First of all, the statistical analysis plan needs to be changed. That's not part of the protocol, but that's the most important change that needs to happen. There are some minor changes to the protocol that need to be done to accomplish this. First of all, we have to write the changes in. So you've got to do that in your protocol. And we will also ask, at the end of the study, questions of the patients and physicians to see if they believe they have improved during the study. This is -- this adds to our ability to validate the CRISS score further. We believe that there's significant validation of it already; it's just augmented. So there'll be a single question added at the end of the study. So the changes are really pretty perfunctory.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [9]

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Got it. That's helpful. And then I had a question on 4001. So with the minimal displacement of a CB1 PET ligand from the brain, which I think has been shown before, do you think in the absence of the PET ligand, would 4001 still show any activity in the brain?

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [10]

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Barbara?

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [11]

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I think that that certainly needs to be tested. It is our assumption that it will not. At the same time -- and those are important things to show. That's an important aspect of the safety. There is a tremendous amount of preclinical data and even some clinical data with rimonabant that suggests that a CB1 inverse agonist such as 4001 that does not have significant blood-brain barrier penetration would provide -- has the potential to provide clinical benefit in diseases with liver inflammation and fibrosis such as NASH. I think it's an essential question, because I think safety is the first hurdle for this compound. So it is very important for us to explore in humans, to -- which is where it counts, what looks like blood-brain barrier penetration, and importantly, the safety profile. So that's what we will do in the early studies.

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Operator [12]

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(Operator Instructions)

Our next question is from Leland Gershell of Oppenheimer & Co.

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Leland James Gershell, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [13]

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First question, on the RESOLVE trial, again with the change to the CRISS primary endpoint. And I know the SAP is still being finalized and to be submitted, but wondering if you could share with us any changes in the powering of the study based on the change in the endpoint, given the prior data that was seen with lenabasum? Thanks.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [14]

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Good morning, Leland. Barbara, it's you again.

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [15]

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Thank you, Yuval. Leland, our power calculations indicate that we are still very well powered with ACR CRISS as the primary efficacy outcome, and it's -- if there's a trend, we're probably better powered. We expect to see a significant treatment effect, that the size of the treatment effect should be pretty significant, and that -- accounting for that. And I forgot to say, of course it will be an analysis based on median, and will be ranked from -- it will be reported as median. The analysis will be done based on ranked data, an MMRM of ranked data. But accounting for those things, we're certainly still well powered, perhaps better powered.

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Leland James Gershell, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [16]

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Okay, that's helpful. And then a question on the CF program. Given the design of the study, the primary endpoint, the unmet need, wanted to hear if you may have any updated thoughts with regard to entering into an accelerated approval pathway based on the upcoming data, what the data might need to show, if that could be a possibility.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [17]

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Barbara?

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [18]

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So -- yes. For all of the studies that we have, based on the strength of the data, we would discuss with the regulators the opportunities to have -- to speed time to approval. Whether it's CF or SSc or DM, we would do the same for all of them.

It is a very clear unmet need. Pulmonary exacerbations account for about half the loss of lung function in patients with CF. It causes significant morbidity and contributes to long-term mortality, need for lung transplantations. It is a very clinically relevant outcome that we're going after. So again, we would, if we saw appropriately robust data, have that discussion with the regulators.

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Leland James Gershell, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [19]

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Okay, thanks. And then on my question, just on the business development side, if you could share any further color on your discussions that you may be having with potential partners or licensers who are -- may be either Pacific Rim or other geographies that you may be having? Thanks.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [20]

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Leland, could you just repeat that? I'm sorry, I lost you for a second there.

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Leland James Gershell, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [21]

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Oh, just wanted to ask about any color you could provide on your discussions as you advance in OUS commercial opportunities for lenabasum. Obviously with Kaken having been secured, and I think you had mentioned in the past you're continuing to look, of course, at additional opportunities, if you could just share any thoughts as to where we might see the next deals occurring, if they could be this year as well.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [22]

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Sure. So obviously I have to be very careful as I answer this, but I think we have mentioned many times in the past that Japan is one of several territories, primarily in Asia, that really don't make any sense for us to try and commercialize ourselves. I think the other 2 territories that come to mind other than Japan will be its sort of immediate neighbors, South Korea and China. So I think those 2 are very logical to look at next. They're major economies, and again, would fit into the pattern of the same logic as Japan. But they're economies where it really doesn't make sense for us to be.

So we look forward -- these things are obviously very, very difficult, especially from the outside, to try and guess in terms of timing, but it's something that we have been really committing a lot of thought and effort to. And I think we were really very, very encouraged by the quality, the interest that we had in Japan, and we are cautiously optimistic that we will have the same experience in those 2 territories.

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Operator [23]

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The next question is from George Zavoico of B. Riley FBR.

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George B. Zavoico, B. Riley FBR, Inc., Research Division - Analyst [24]

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First question I have is regarding the RESOLVE also, the change in the endpoint. It's not typical that in the middle of a trial that an endpoint changes. I just would like to know how that came about, especially since the CRISS score was the primary in the second -- in the Phase II trial. Was this something that you changed your mind about in the beginning, or was this something you wanted from the very beginning of the RESOLVE trial?

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [25]

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Good morning, George. Again, I'm going to turn it over to Barbara to give you all of that background.

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [26]

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Good morning, George, and thanks for the question. As you said, the ACR CRISS score was the primary efficacy outcome in our Phase II study, which was short and relatively small. At the same time, we felt that it gave indication of the potential for clinical benefit. And that's why we chose it in the first place. Use in the Phase II allowed us to become more familiar with it. We did approach the FDA initially in our end-of-Phase-II meeting with our thought of using the ACR CRISS score as the primary efficacy outcome in this Phase III study, so our thoughts that it would be a reasonable primary efficacy outcome are not new. They go back a long time.

After discussions at that first meeting with the FDA, based on their advice, we changed to change in mRSS. Thereafter, there have been a number of things that have changed or have become more apparent.

First, there's additional data that helped validate the ACR CRISS and its usefulness as a clinically relevant outcome in studies in systemic sclerosis. There have been some reasonably high-profile failures to show treatment effect with change in mRSS, but the same studies did show treatment effect with ACR CRISS. There has been a shift in opinion of multiple key opinion leaders around the globe, thinking that ACR CRISS score may better reflect the totality of what happens to the patient when you are looking for an indication of treatment of systemic sclerosis. So if that's the goal of the clinical study, it perhaps is a better efficacy outcome to reflect effect benefit to the patient than just change in skin score, although again, that remains very important to outcome. We had advice from our steering committee, which is an international group of experts that -- who felt that we should make this change. So with all of that, and acknowledging that it is unusual, we then went forward and had the discussion with the FDA. And again, we've announced the results that following that meeting, we decided to make this change.

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George B. Zavoico, B. Riley FBR, Inc., Research Division - Analyst [27]

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I'm also wondering whether -- well, thank you for that. I'm also wondering whether it positions you to approach a much broader systemic sclerosis population, because the RESOLVE really focuses on diffuse cutaneous systemic sclerosis, which I presume means more skin involvement than organ involvement. So is that one of the goals as well?

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [28]

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Let me start, George, with a bit of background information, then address the question. Diffuse cutaneous systemic sclerosis, patients who carry that diagnosis have more widespread body involvement, skin involvement. Patients with limited cutaneous systemic sclerosis also can have significant skin involvement; it just doesn't extend above the elbows, knees or on the truck. Both groups have significant internal organ involvement. Internal organ involvement is a major cause of death. Skin involvement is a major cause of morbidity. Lots and lots of signs and symptoms and effects on quality of life.

I believe that the use of the ACR CRISS score better reflects, again, the totality of what happens to the patients. It will provide the physicians and the people with scleroderma with information on a number of outcomes that will be important to them. Yes, skin; it's very important, but also function, global assessment of health and lung function. I believe that having these data available will be useful in allowing physicians to best estimate its usefulness, the usefulness of lenabasum in the patients with scleroderma. So yes, it provides more opportunity for them to have data that they'll want to see.

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George B. Zavoico, B. Riley FBR, Inc., Research Division - Analyst [29]

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Okay, thank you for that. And I have a question on 4001. So this is an inverse agonist, and it appears that you've designed it to be an inverse agonist rather than as an antagonist. And you probably did that for a reason. Is there some level of constitutive activity that an inverse agonist, you think, would be more effective than a simple antagonist?

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [30]

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George -- Yuval, is it okay if I go ahead? Sorry.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [31]

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By all means, please do.

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [32]

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Yes. So George, again, thank you for that. And I agree with what you're implying; there would be reason to theoretically think that an inverse agonist might have more activity than a neutral antagonist. And these compounds came to us from our acquisition of the Jenrin library, and indeed, that's what the medicinal chemist there had in mind. And we're delighted that it is an inverse agonist, and we look forward to taking it into the clinic at the end of the year, quickly moving through our Phase I testing and then moving on to Phase II testing in collaboration with the NIH.

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George B. Zavoico, B. Riley FBR, Inc., Research Division - Analyst [33]

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Yes, thanks for that. It puts in, for NASH, an entirely new approach, which certainly makes that field a lot more interesting. So thank you for that, and good luck with 4001.

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Barbara White, Corbus Pharmaceuticals Holdings, Inc. - Chief Medical Officer [34]

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Thank you, George.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [35]

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And George, if I can just butt in, on your very last comment here, I couldn't agree more, except I do want to remind everyone that there is, in fact, a competitor or a peer that is placing a bet in NASH on the same mechanism of action but using a different way of achieving the same result. This will be Janssen, with their collaboration with Bird Rock Bio, that, just like CRB-4001, are out to neutralize or reverse the CB1 receptor in the liver.

But there are some very important differences between our compound and their compound. CRB-4001 is a daily oral small molecule. Their compound is an injectable once-a-month monoclonal antibody that acts as an antagonist. What we share in common is a very, very different approach but a common goal of keeping our respective drugs out of the brain. Again, we achieve this by chemical modification to a small molecule; they achieve this by having a monoclonal antibody.

So I think what's interesting, George, going back to your comment, is this is a completely novel approach to targeting inflammation and fibrosis in the liver, but so far, it's an N=2, and one of those, of course, is one of the world's largest and probably one of the most innovative pharmaceutical companies. So we look at that as a very, very interesting endorsement of the potential for this pathway.

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Operator [36]

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There are no further questions at this time, so this will conclude today's conference. You may disconnect your lines. Thank you for your participation.

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Yuval Cohen, Corbus Pharmaceuticals Holdings, Inc. - CEO & Director [37]

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Thank you, everyone. Take care. Have a wonderful day.

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