Kyntra Bio, Inc. (KYNB) Earnings Call Transcript & Summary

And good afternoon, everybody, and thank you for joining us for the second day of the 41st Annual Cowen Healthcare Conference. I'm Yaron Werber, biotech analyst here at Cowen with my colleague, Brendan Smith. And it's a great pleasure for us to moderate the fireside chat with FibroGen. Today, we have Enrique Conterno, who's the CEO; and Mike Tung, VP of Investor Relations and Strategy. Gentlemen, thanks so much for joining us. We appreciate it.

Thank you very much for the invitation, Yaron.

Absolutely. So Enrique, maybe the timing for this is good in a way, just given some of the news from yesterday, obviously, wasn't herbed our ways by chance. But maybe give us a little bit of a sense related to the news flow from yesterday, what you can share with us on the interaction with FDA or the next steps in the process?

Yes. Maybe -- I do appreciate the opportunity to be able to share. We had our earnings call yesterday. So this is an opportunity to basically maybe describe some of the events. And let me start with the extension that we had. As you know, last December, in the final stages of review, the FDA extended the review period of the roxadustat NDA by 3 months to review additional analysis of clinical data. And at that time, set a new PDUFA date of March 20, 2021. Yesterday, we were informed by the FDA that they plan to hold an advisory committee or an Adcom to review the NDA for roxadustat in the U.S. We have not received a confirmed date for this planned outcome. We were surprised by the request, I think in 3 separate occasions. The FDA let us know that they were not planning to hold an Adcom at that time, whether it was -- when the NDA filing was accepted during the mid-cycle review and then in the late cycle review. It is not unusual for the FDA to hold an Adcom for a first-in-class new molecular entity. And in fact, we shared last spring that we were preparing for -- very much for that possibility. So now I think for us, we are refocusing our efforts on resuming those activities. I'm very much looking forward now to presenting the comprehensive roxadustat data in that public saying. We continue to have confidence in the completeness of the NDA submission and the strength of the roxadustat data. And we're very much -- both FibroGen and AstraZeneca committed to working with the FDA to bring roxadustat to patients with an anemia CKD in the U.S. as soon as possible. So clearly, as you can appreciate and as we've mentioned this in the past, we are not in a position to discuss the detail of our FDA interactions, but I look forward to having discussion about this topic. And of course, I think also the broader agenda that FibroGen has.

Absolutely. So Enrique, just to set the stage a little bit, historically. My impression is that ESAs were originally submitted for approval 25 years ago to the Hematology division, and I believe ODAC probably reviewed them back then. About 13, 14 years ago, during the FDA's review of the safety issues of ESAs, remember, there was a -- I think it was 2007, there was a cardiorenal committee that look at dialysis and pre-dialysis in 2008, it was about a year later, ODAC reviewed relating to the safety issues of oncology. Roxa was filed to the Hematology division. Can you give us the history on that? And how did cardiorenal this time around get involved, the Cardiorenal division within the review?

Yes. I think it's a really good question. So let's take it step by step. First, I think, clearly, roxa was filed with the Hematology division. Keep in mind that the Hematology division that we're speaking of is part of the office of the ocean office. So this includes cardiology, hematology, endocrinology and nephrology which are all part of that division. There was a realignment where benign hematology basically was brought into in that office separately from the rest of oncology. So it is part of the same office, and it is that office and cardiorenal is -- it is part of that same office, right? In the past, when you're thinking about ODAC, the alignment of the FDA of the divisions to the office was different. Hematology was basically part of a different office. So that realignment occurred, if I remember correctly, maybe about 18 months ago. So it is not -- we don't view it as unusual for cardiorenal to be focused on the host in the advisory committee. And quite frankly, we view it as a positive for us. We think that we will have the appropriate expertise to make sure that the product is reviewed with -- through -- with nephrologists and cardiologists' inputs.

And so do you have a sense on how did cardiorenal get involved? Was there a request from hematology? Do they need to ask cardiorenal for help, and that's ultimately how an Adcom is called for by cardiorenal, just logistically, how does things even work between divisions?

Honestly, I don't know that question. But I do know that it is the office really, that is -- has discretion to call for the Adcom. And at this point in time, it's a cardiorenal Adcom. And we just look forward to presenting the data. But I don't know the -- how that decision was made by the FDA.

And have all the interactions so far, during the review process, been with hematology? Or was there some interaction with cardiorenal at some point, given this is a renal indication?

Yes. No, really, I think that review has been with the hematology division, we do not know, of course, the interaction within the agents itself.

Got it. And has there been any change in the reviewers at FDA side?

We're not commenting, as you know, on our FDA interactions or any type of details. I think at this point in time, I think our -- and keep in mind that these news are also -- we were informed yesterday, literally. So at this point in time, our focus is on basically preparing. As you can imagine, we need to look for any type of precedent here is what are some of the precedence we will do some work around that. But at the end, I think we know that an Adcom is an opportunity to basically showcase, I think, the strength of our data, and we continue to have confidence on the strength of the data of roxadustat across both DD and NDD.

And for a long time from your interaction with FDA, I think the comments to you were that FDA was not planning on calling an Adcom at that time. And that can always obviously change over time. Any sense -- it sounds like you're literally sort of on the 1-yard line, it was sort of the sense we're getting both from your comment and AstraZeneca's comments, when there was a last-minute request for more information, probably somewhere high up in the division. I imagine, at that point, it's probably the last review, sort of a higher up in the division. So any -- can you give us just chronologically maybe what happened that led to the, obviously, the PDUFA extension and now to the Adcom?

Yes. I think as you mentioned, we were in the -- very much in the final stages of our review. I think we had mentioned that we were in label negotiation back -- all the way back since maybe August, late August, early September. And we -- very late in the review, we were requested additional analysis, which basically, given the imminence of the PDUFA date, basically required a PDUFA extension. It is -- we've gone through those. We, of course, submitted the requested analysis. And at this stage, I think we were notified by the FDA that they are requesting an Adcom. It's difficult for us, as you can imagine, to speculate on the rationale for calling an Adcom. An Adcom is -- was very much a possibility throughout the review, but it's highly unusual at this stage in the process, right? So had you asked me a year ago, I would have said that was very much a possibility. In fact, we were very upfront that we were preparing for one. But -- and quite frankly, it is an opportunity for us to basically discuss the data in a public forum. The issue is really the timing, right, than the overall process.

I guess it's more of an issue. I mean, obviously, that could delay approval time lines, but is the issue more along the lines that now that PDUFA will lapse the March 20 PDUFA, by definition, is going to have to lapse just given the statue to give you almost 2 months' notice before a panel is called. The -- so is the next step for the FDA to give you a -- announce an Adcom and you go to an Adcom and thereafter, they'll finish their review or they're not going to finish the review, give you correspondence -- official correspondence and then have a panel, right?

No, I think a panelist can be held under an ongoing review. So I think, yes, I think the PDUFA date under this scenario would lapse, and the PDUFA date is March 20 of this year, so it's coming up quickly. And the FDA will probably notify us of the dates for the Adcom. And then I think post the Adcom being held, I think the FDA will basically make a decision. But there would not be a new PDUFA date given the PDUFA date can only be extended once.

One of the questions -- I'm sort of taking questions as they come along. On the question is, to the extent, in the best of your ability what you can comment on, what do you think might be discussed at an Adcom? What could be some of the topics that FDA and also you would want to air publicly during an Adcom?

I think during the Adcom, I think typically, broadly, you want to basically showcase the benefit risk profile of the product across both of DD indications, DD and NDD. And -- but it's difficult for us at this stage without receiving the formal notification and having a discussion -- a fuller discussion with the FDA for us to speculate right now on the focus of the Adcom. I think we will learn more of that as time goes by, and we engage with the FDA. And even at that point in time, I think we will have to make -- we will need to have a view of what is that we will be able to share at that point.

Has there been any more data requests since submitted the data, I presume around December 20?

Yes. We're not commenting on that. What I can say is that all analysis that were requested were submitted.

Okay. Okay. Understood. I mean is this a case where hematology just doesn't feel that they have the right expertise in the renal space to be able to review, and that's the reason that the they're calling an Adcom? Or is it by definition? If they were to call a hematology Adcom, it would be composed of hematologists, which is probably not best suited for this product. So by definition, they have to go through cardiorenal to convene an Adcom?

I think if you look at it logically and given the expertise in nephrology and importance -- the importance to get the clinical feedback from nephrologists, I do think that cardiorenal is not only a logical choice, but also the welcome choice, I think, in our view, in terms of holding this Adcom. So we view that not just a profit, but the opportunity to ensure that we have -- and the expert review basically with the comments from all the appropriate expert parties.

Yes. I recall from some of your previous comments and also from your partners, AstraZeneca, based on the totality of the data for roxa, you're fairly comfortable, optimistic that the data should support a broad label. And the impression we were all getting is that you're marching towards that sort of outcome. When we look at the totality of the data, there is much less questions, at least in our view, in dialysis, given the alignment with the regulatory agencies ahead of time, entity was admittedly, be at risk. The protocol wasn't agreed to, and it was a reasonable protocol, but there was ultimately a lot of crossover. There was -- the study was complicated. And the physical analysis was complicated. So when I think of the 2, we think dialysis is probably a huge unmet need. Non-dialysis, no product approved, maybe not quite as urgent and probably more complicated review process. Does that make sense, in your view, maybe is that something that might be discussed along the line?

Honestly, I think we feel highly confident about both DD and NDD. We think that the data, I think, supports -- the benefit risk profile, I think, supports both indications, the use of roxadustat, I think, across both populations. I know because we've discussed in the past, and I think I've been pretty clear in terms of what has been agreed with the FDA and what hasn't been agreed with FDA. I think that's known. And at this point in time, we're heading through to an Adcom, I think, so we'll have the opportunity to fully showcase. Keep in mind, I think, also, I think when it comes to NDD, yes, we conducted our studies against placebo, but we did have a pretty significant impact on the reduction of transfusions. And when you look at the hazard ratio, it was 0.26. So really, really significant benefits in terms of lowering risk of transfusions. We've also presented data from our clinical trials, the risk of transfusions dramatically increases for hemoglobin below 10 versus above 10, almost -- there's a 3 to 5x increase. So the opportunity for a product, for roxadustat, I think is very significant. Keep in mind that most of the NDD population is not treated. We've shared that maybe about 14%, 15% of the population that goes to dialysis receive ESAs in the 12 months prior to going on to dialysis, that's really -- for people that are very late-stage with chronic kidney disease, that's pretty low number. So I think the opportunity here is basically to be able to treat many more patients, so that patients can benefit. And then we think the roxa can play a very important role there. Yaron, I think you're on mute right now.

Yes. Thank you for that. The studies, I think yesterday, you mentioned on the call that the ASPEN and DENALI studies in the large -- well, we think in large dialysis clinics have completed enrollment in the dialysis setting. When -- is that data that you will share externally? Or is that data that was designed more to help those clinics understand about how to switch and how to incorporate roxa into their protocols?

I think both. We will -- we intend to share the data at an appropriate conference. But clearly, I think it is also allowing for us to understand roxadustat. I think the very specific settings are not -- yes, these are clinical trials, but in the very specific settings of dialysis or large dialysis organizations and thinking about the particular product also. It is important trials, and we are pleased that, that enrollment has concluded. And now I think we expect to report data in the second half of this year.

And so those are going to be essentially open-label studies that are going to looking at outcomes, pharmaco...

Yes. Yes, it's going to be looking at a number of factors. Clearly, the efficacy and safety of roxadustat was established by the global Phase III program, the pivotal Phase III programs, are known 3 programs in DD and 3 programs in NDD in terms of the submission to the FDA. And I think in this particular case, is just very specific trials adapted to the needs of the dialysis organizations to look at outcomes that they will be very much interested.

Okay. The -- when you think about one of the novelties of roxa is that there was an incident dialysis population, the prevalent dialysis population. And you haven't reported the data in incident dialysis. I mean obviously, presumably, you would expect -- you would ask for a broad label. I'm just trying to think about all the nuances during a review, discussion, the flexibility of dosing and dosing parameters, just parameters relating to switching from an ESA to roxa. And then there's a complexity of other companies in the space mentioned that they were in agreement with FDA to run an NDD study against an ESA, and there was an understanding within that context, those modulators will inherit an ESA-like black box. When I think of a drug like roxa, you have your own parameters around your studies. ESAs have their own black box and many -- in many ways because of cancer promotion data, which is not relevant to roxa. So as I think about all the topics think you think are going to be critical for you and FDA to align on to then write a label, what are the parameters are we missing that maybe I didn't kind of bring up?

Yes. You're asking me to speculate on the thinking of the FDA here. But I think in general, I think the rationale that we provided for and the discussion that we had with the FDA at that time. And the rationale for conducting the trials related to placebo was related to most patients are untreated in this population. By the way, placebo is a higher hurdle, right? And when you look at the overall results, we showed comparability when it comes to these outcomes in the population. So we feel good about our results. Now at the end, I think we need to go through the outcome, I'll be able to have a discussion for us to be able to fully answer, I think, the questions that you're asking.

Just remind us in pre-dialysis and maybe for both, the agreed-upon upper bound of the confidence interval, just remind us what you said publicly.

Yes. We -- what I said public is that there was no agreed-upon upper bound. I always commented, this was always a review issue with the FDA, meaning, at the end, the FDA needs to look at all of this data, and there's no established guidance, I think, in this particular therapeutic area. There is established guidance in diabetes when there is a particular upper bound of 1.8 to approve of product on 1.3 long-term to be able to -- for the probe to show and be able to exclude that risk of more than 30% potential increase. I think in our case, and that's not something that -- what we agree with the FDA, the agreement that we had was related to the trial that will be included in the analysis and the submission as well as the statistical methodology that would be used. Clearly, throughout the review and as part of our submission, we always do a number of sensitivity analysis with the FDA, and we included that as part of our package. But 1.3 was not agreed upon pre-defined agreement on upper bound with the FDA.

And you're talking about both dialysis and pre-dialysis? Or you're mentioning in pre-dialysis?

I'm speaking broadly, broadly. Yes.

Okay. Yes. And I think the discussion really has been even with some of your competitors more in the 1 point -- the 15% and the 25% sort of range between FDA and EMA?

Yes. Clearly, I think when you look at -- I cannot speak for the comments of our competitor, but in your question about NDD, I think it's pretty clearly -- we basically would meet that anyways. But -- and even though we were relative to placebo, which is a higher hurdle from a safety perspective. I -- you also spoke about the dialysis population and you may recall that we presented, in particular, we're very excited and continue to be very excited about the incident dialysis data, where we basically show the statistical significant reduction on both MACE and MACE+ outcomes in that population. And so we also think that, that's quite significant and quite important, given that, that's when the decision for a new anime treatment is made for patients that are started dialysis.

And what about with EMA? I think with EMA, if I -- my recollection is that there was more agreement and alignment. Can you maybe just discuss what you said publicly about that?

We haven't commented on EMA, I think Astellas is the sponsor for EMA not FibroGen. And FibroGen, we were the ones that submitted the NDA. That review is ongoing, and I think what we shared yesterday was that we expect the decision sometime around the middle of the year.

And that's from the CHMP initially?

Well, just yes, not just an opinion, but we are -- my comments about the beginning of the year is around approval.

Around approval? Okay, right. So we should even find out over the next maybe even 1 or 2 months really, but depending on the definition of -- from the CHMP. Okay. I -- Brendan, do you want to ask maybe [Audio Gap] and MDS?

Sure. Sure. Yes, I know you have a couple of other studies going on outside of the CKD anemia space. So can you kind of just give us a really quick update with the enrollment status is for the MDS study and CIA. And kind of just confirm when we're going to see data from each of these and what that would maybe look like?

Yes. I think CIA is fully enrolled, and we expect to have basically the readout for that in the second half of this year, that's a Phase II study. And assume this study is positive, we expect to start of the phase III trial in chemo-induced anemia. The opportunity is very significant, and we basically, from a scale perspective, magnitude perspective, the opportunity is almost comparable to the opportunity that we see across CKD anemia. In the case of MDS, this is a Phase III trial, which is ongoing. And we've shared that we expect to report data in the first half of next year. And clearly, I think it's very much an unmet medical need. And we feel that roxadustat can be an important treatment option in that setting. Of course, we need to wait for the Phase III results, but we are looking forward to concluding the trial as soon as possible.

Got it. So I mean, obviously, MDS is kind of exploded with competition more recently. So I guess, can you kind of give us just a sense of how you're approaching the commercial opportunity there? And where you really see roxa kind of fitting in versus some of the other options that are available?

Yes. I think there's been additional options that are available today. I think those options tend to have a narrower set of patients or indications, although they are pursuing studies that are broader. Keep in mind, in our studies, we include both R positive and R negative patients, and also patients that were -- regardless of failure to ESAs agents. So we feel that the roxadustat's approach basically covers a very significant amount of patients. So we could have broad applicability, of course, we need to look at the results. But the results so far that we've seen, I think, tend to indicate that we have a product that is effective, and we need to see the final Phase III results to fully understand the profile of the product. But we feel confident about our -- the potential utilization of roxadustat in this scene.

Okay. Great. And I know we just have a couple of minutes left. I want to ask 1 quick one on pamrevlumab. Obviously, you have studies in IPF, in pancreatic cancer, now DMD, or plan to start the non-ambulatory DMD pretty soon. So can you -- I guess, just maybe on IPF here because I think this is the one that gets a lot of attention for the drug itself. You're going to have these 2 different studies. Obviously, COVID is an issue here for these patients. But can you kind of give us an idea of what you're really hoping to see from that Phase III that would really kind of reinforce confidence that it's maybe a particular endpoint that you think is really most important and kind of what extensive improvement and maybe kind of your plans for the readout in trials?

Yes. So clearly, what we -- the best example, what we expected, we want to replicate the studies -- basically the results that we saw in Phase II. They showed a very significant affect size. When it comes to the FDA, I think the primary endpoint is forced viral capacity. So -- and the Phase II results looked at that and a very significant impact in that. Keep in mind that in the case of pamrevlumab, not only do we have great results when it comes to forced vital capacity, but also we were able to show through imaging, basically really improvements when it comes to fibrosis. So not only is the biology, really promising here, but clearly, we have clinical data in Phase II that is quite impressive. And we made literally very few changes in the Phase III program. So we feel that the program is -- the likelihood of technical success, we believe, is very high. We are trying to make sure that we execute as well as we can. COVID has been a pretty significant challenge when it comes to enrollment in these trials, just given the vulnerability of these patients. As we see now with the failure of the Galapagos trial, that has opened up a number of additional sites for us to be able to recruit sites in the past we did not have full access to. So we've already started that process contacting, and we've already added a number of sites. But also patients that were enrolled in those trials that might be eligible or could be eligible to enroll in the IPF, the ZEPHYRUS trials for pamrevlumab. So that's probably an opportunity for us to accelerate the enrollment. We've also commented on our expansion of sites throughout the world, but also geographically, including China. So we've basically kind of pulled a number of levers to basically improve enrollment, and we're seeing some of that.

Okay. Great. I think we're right up against time. And last questions from you, Yaron?

No. I think that warps it up. So Enrique and Mike, thanks so much for joining us. We really appreciate it.

Thank you very much, Yaron and Brendan.

Absolutely. Stay safe, and we'll be in touch.

Bye-bye.

Thank you.