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

Okay. We'll continue with our next session. I'm Paul Choi, and I cover the SMID cap biotech sector here at Goldman, and it's my pleasure to welcome FibroGen to this session. Maybe to kick it off, we'll provide a brief overview of FGEN your key clinical programs and maybe to -- what makes you maybe most excited about what's coming up here in the near term?

Yes. Thanks, Paul, and thanks for having us. I'm also joined by Deyaa Adib, who is our Chief Medical Officer, Deyaa joined us a few months ago. So happy to answer any questions as well after the session that anybody may have. So we have a number of exciting things happening at FibroGen. And the most near-term catalysts are the two readouts we have upcoming with -- for pamrevlumab in pancreatic cancer, one in metastatic pancreatic cancer, that's actually part of the Precision Promise platform trial that's sponsored by the Pancreatic Cancer Action Network, and we've guided to a mid-2024 top line OS result. The second one is the locally advanced unresectable pancreatic cancer trial, that's a FibroGen-sponsored trial that we've guided to the third quarter in terms of top line results. And so we're really excited about both of those opportunities. Clearly, a high bar in pancreatic cancer. But if you can show a clinically meaningful benefit of even 4, 6, 8 weeks on top of standard of care chemotherapy, we think that, that could create a really important advance for patients and a meaningful opportunity for FibroGen and our stakeholders as well. So that's the most near-term catalyst. We're excited about our CD46 targeted ADC for prostate cancer. We'll talk about the data that we've released on that program in both a monotherapy trial as well as a combination with enzalutamide trial. The next catalyst associated with that will be some upcoming regulatory interactions, hopefully, a manuscript that further articulates the monotherapy results and then a planned Phase II start in a monotherapy trial in the second half of this year. And then we also just recently received clearance of an IND from the FDA for our anti-Gal9 antibody, FG-3165. And we're going to be starting a Phase I trial in the coming months for that particular asset in a number of different solid tumors, and we can talk more about that as well. So a number of upcoming catalysts that we're really excited about. And clearly, with a strong balance sheet and then with a very attractive business in China in collaboration with AZ, with roxadustat for anemia associated with CKD, a lot of good things happening.

Okay. Great. Let's actually start with the commercial piece of it with Evrenzo or roxadustat in China. Your growth and volume continue to be really, really growth -- volume growth in particular continues to be really impressive in China there. And your sales were up about 26%, if I recall correctly, year-over-year. How do you think about the momentum here? What's driving the momentum and the growth and share gains that you've been posting this quarter? And how should maybe investors think about the intermediate to longer-term trajectory?

Yes, thanks. It's a really important question. Roxadustat a significant generator of revenue for FibroGen. It's a profitable business for us in China. So there aren't a whole lot of biotech companies like FibroGen that have revenue generating a profitable business in an important market like China, upcoming catalysts, we're late-stage in pancreatic cancer and then some really interesting near-term or early-stage opportunities from a pipeline perspective. In terms of roxadustat in China, we did $284 million in 2023 top line revenue, we've guided to $300 million to $340 million in top line revenue for 2024, meaningful volume growth that you referenced and meaningful net sales growth. So what's coming with roxadustat is we did just last week, the composition of matter patent has expired for roxadustat. We don't expect any near-term impact. If this were the U.S. and we had a composition of matter patent expire 1st of June, we'd probably immediately start to see generic erosions. There'd be generic products that would be approved immediately after the patent expiration and then distribution and impact in the U.S. market. In fact, in the U.S., it's not atypical for a small molecule like roxadustat to see 90% to 95% of the value you wrote it within the first 12 months. That's not the way the China market is working today. And so there are generic roxadustat filings that are under review by the CDE. We don't know the status of those. We don't know if and when they'll be approved. What we do know is that if you look at the typical China market from a generic perspective is you don't see that rapid erosion. Once the fourth generic is approved, the government has the opportunity to call for, in essence, a national tender, this volume-based purchasing or VBP dynamic that is in play in China. Even then, it's very typical for the originator to maintain a meaningful amount of net revenue in China for several years. We're partnered with AZ in China. We don't believe we can be partnered with a better multinational than AZ. They have a number of brands that are impacted by volume-based purchasing and those brands continue to contribute significant revenue for AZ in the China market. And so we don't know exactly when the impact for VBP will occur in 2025. It could be in the spring, it could be in the fall, and it ultimately depends upon when the government ultimately includes roxadustat as part of their VBP program. And so we're going to continue to invest from a commercialization perspective to drive the CKD revenue. And then obviously, we've got the CIA indication, the chemo-induced anemia indication that's under review by the CDE, and we expect an approval decision sometime in the second half of the year.

Okay. Maybe touching on CIA. Just again, you said your decision could potentially come, but there are also a couple of second derivative factors coming in, including potential inclusion, the NRDL. And so maybe just starting with the indication itself. Can you maybe just remind us how -- what sort of current standard of care is there? And what's sort of the opportunity for roxa to penetrate CIA in China...

Sure. Yes, current standard of care or the ESAs, the erythropoiesis-stimulating agents. Blood transfusions are very uncommon in China just because of the difficult dynamics associated with transfusions. And so we're really excited about the opportunity for an oral 3x a week opportunity or option for clinicians. And so it's not going to be as large of an opportunity as the anemia of CKD in terms of the patient population, but it's still a meaningful incremental opportunity for roxadustat. What we've seen in the clinical trial is patients are typically on a higher dose for chemo-induced anemia than they are for anemia associated with chronic kidney disease. So even though the patient population isn't as large, you still have an opportunity on a per patient basis to drive a substantial incremental revenue. What we also see with respect to the CIA indication is until we are able to achieve status in NRDL, it will be a cash pay market until then. Oncology in China from a cash perspective is still a very attractive market. And so we would expect that once the product is approved, to have fairly rapid adoption that the teams have both the AZ and the FibroGen teams have in place a really robust launch plan. And if they can replicate the kind of launch trajectory that we've seen in China for anemia of CKD with the chemo-induced anemia opportunity once we -- if and when we get approval, again, it will be a really important incremental opportunity for us.

Okay. Great. Can you maybe just remind us in terms of calendar mechanics, when does the decision need to come by for inclusion in the next round of NRDL pricing versus the following calendar?

Yes. So I think that the decision will have to come in the next few months in order for us to then be included for the potential for NRDL in 2025. If it doesn't, if we don't get the approval in the next few months, then it would be likely that we would be included in the 2026 NRDL.

Okay. Great. One more opportunity, I think, for roxa just thinking about is like MDS anemia there. It's something that doesn't get discussed a lot, but you have run some clinicals there. And can you maybe just remind us briefly, you saw some better responses in certain subsets of patients and maybe where the opportunity set lies there for an oral therapy.

No, it's a really important opportunity that we're paying a lot of attention to. You think about the MDS market with luspatercept and they've guided to, what, $1.3 billion, $1.4 billion for this year in the U.S. alone. And then imetelstat from Geron that was approved most recently. And so -- and then what's their market cap, $2.5 billion, primarily due to this one asset. And so there's still -- we still believe that there is a substantial clinical unmet need. Luspatercept as best we can tell, works on about half of the patients and imetelstat remains to be seen what the uptake will be for that particular product, but we are excited about the opportunity for roxadustat. So just to refresh the clinical data. In May of last year, we released top line results in anemia associated with low-risk MDS, where we showed a numerical advantage but not a statistical advantage relative to placebo in terms of transfusion independence. When we went back and did a number of different data cuts that lack of statistical significance was driven by the high response in the placebo population. And so as we then did additional subgroup analysis, and this was data that was presented at ASH in December, if you just look at that cohort, which is a meaningful cohort, both in terms of size and in terms of the unmet need from a clinical perspective, that cohort that had a high transfusion burden at baseline, so at least 2 units over the previous 8 weeks prior to entry into the trial. And you look at that subgroup of transfusion independence for roxadustat versus placebo. We showed a meaningful difference, about a threefold difference in transfusion independence over a 56-day period or 8-week period of time within that 26-week trial. That was well received at ASH. The number of thought leaders are very excited about the opportunity. And so we got the rights back for roxadustat in the former AZ territories, not China because that collaboration still is ongoing and very healthy. But in the ex-China AZ territories, which primarily includes the U.S., we now have the rights back. We've started outreach to companies who would have the interest given their Hem/Onc presence to do another Phase III trial in a patient population with a higher transfusion burden at baseline. And if we could replicate the results that we saw in the subgroup analysis, we think it would be a meaningful alternative or addition to the armamentarium associated with anemia and MDS, 3x a week oral option relative to an every 3- or every 4-week IV infusion, which is what you have with luspatercept or imetelstat. So we're excited about that potential opportunity, and we continue the outreach on that.

And maybe just one more before I move on. And this would potentially be in a ring positive and negative population...

It would be. That's correct.

Okay. Great. Super Interesting. Maybe turning to pamrevlumab. You mentioned earlier, you have 2 data sets coming up here near term, both LAPIS and LAPC. Can you maybe remind us what you've seen so far from both studies on a blinded basis to the degree you can talk about it? And just maybe sort of what the blinded data to date has shown us.

Yes. So we can't really talk about what blinded data we've seen. What we can say is that in the metastatic trial, which is being run by the Pancreatic Cancer Action Network, we did disclose a few months ago that based upon analysis on the first 100 patients, which was part of the prespecified design in stage 1, you treat 100 patients with pamrevlumab on top of Gem/ABRAXANE and then you compare that to Gem/ABRAXANE by itself. The statistical monitoring committee looked at the first 100 patients and made the determination that pamrevlumab graduated to stage 2, meaning that it had exceeded the 35% threshold of -- at least a 35% chance of showing a positive overall survival benefit by the end of the trial, so with subsequent patient enrollment. So that's the one data point that we do know. And so we know we've got at least a 35% chance of showing a positive OS benefit. What that then led to is an additional 75 patients that were enrolled in the second stage of that trial. We also know that in that kind of 4- to 6-week period of time where the statistical monitoring committee was doing the analysis to determine whether or not the PAM arm graduated from stage 1 to stage 2. There were 38 additional patients enrolled in the pamrevlumab arm. So 213 patients in total in PAM plus Gem/ABRAXANE to be then compared with Gem/ABRAXANE by itself. We're expecting that top line OS data in the middle part of this year. So we're really close to seeing that data set. But again, we haven't seen any blinded data. We just know that we graduated from stage 1 to stage 2, which is a pretty exciting opportunity. I think a lot of people aren't giving pamrevlumab much opportunity or much credit in the metastatic patient population. I mean, I'm even sure you guys even have it in your model, Paul, with any sort of probability associated with it. But we know there's at least a 35% chance. And so we'll see that data here shortly. The second trial we have is in the locally advanced patient population. And we enrolled 284 patients in that trial, placebo-controlled, double-blind, about 50% of patients on pamrevlumab plus either GEM/ABRAXANE or FOLFIRINOX to then be compared to Gem/ABRAXANE or FOLFIRINOX standard of care chemo. The way that, that trial was designed, it's a neoadjuvant design, which means that patients got 6 cycles of pamrevlumab plus standard of care chemo compared to 6 cycles of chemo by itself. Patients were then assessed for surgical resection, either underwent resection or they did not. And then they're followed out until we accrue the requisite number of OS events that hit the prespecified power calculation. We -- as you know, we guided originally to Q1 for top line results, then we changed it to Q2. Now we've guided to Q3. The reason is just because the OS rate slowed down. There was -- anything associated with the postponement of the trial assisted as we follow the patients that number of OS events that we were accruing slowed down quite significantly, but we can say now that based upon the OS events that have been accumulated that we will see top line results in the third quarter.

Okay. Great. Maybe just staying on the topic, like assuming clinical success here, what would sort of potential next steps would be on the regulatory front. This is kind of -- on China territory just given the lack of therapeutic options relative to historical chemo options that you've described in the control arm here. So what is sort of like your potential next step...

No, that's it's really a really important question. The bar is low from a clinical perspective just because of how significant the unmet need is and the fact that there's been some incremental innovation and benefit over the years, but it's been a number of years since there's been really any meaningful innovation in the pancreatic cancer area. And so both these trials are registrational quality trials, and we would, therefore, strongly believe that should one or both of them show the kind of clinical benefit that we think would be meaningful as well as obviously on the statistical side that we would be able to move toward a BLA filing. Clearly, we'd have a pre-IND meeting with the FDA that we would schedule. They would give us guidance. But the anticipation is that these are both registration quality trials.

I'm sorry, pre-IND?

I'm sorry, pre-BLA. Sorry. These are both registration quality trials, and we would expect to move toward a BLA filing based upon the results.

Okay. Great. Okay. Maybe turning to elsewhere in the pipeline and talking about 3246 here. I think this is a target area that's gotten a fair amount of interest recently. So can you maybe just remind us what CD46 does kind of -- maybe a brief overview of the landscape? And then just sort of the background on how you acquired this assets through Fortis.

Yes. So I think the initial excitement was associated with the fact that this is an antibody drug conjugate, right? And we were excited about that part of it, but we were also excited about the target itself. So we acquired the asset. We licensed it from Fortis Therapeutics in May of last year, so we've had it roughly 13 months or so. Fortis ran the original monotherapy trial, which was post ARSI pre-chemo. And that's data that was released a couple of months ago. But it's -- the target is CD46. CD46 is expressed on the surface of prostate cancer, colorectal cancer, lung cancer. And so it's a target that extends beyond prostate cancer, but we're looking at it most specifically in the near term in prostate cancer. And again, it has the standard linker and MMAE payload associated with the ADC. So we don't believe that there's really much risk associated with that.

On the technology side.

The technology, we believe that the unique part of our program or the potential differentiator is the fact that it targets CD46, and it's not another PSMA-targeted approach. We do know the target is active based upon the data that has been generated and presented to date, the PSA50 data, but most importantly, the radiographic progression-free survival data that we disclosed in the monotherapy trial, where we had 8.7 months of rPFS. And it's hard to find, I think, another clinical program in early stage like ours is that has rPFS data. So a tip patient -- it seems like that the investment community looks at PSA50 and tries to compare across programs. What we want to make sure that people understand this is that we have a really robust rPFS signal of 8.7 months. And when you compare that to other programs, that are in a similar as apples-to-apples as you can get that are in a similar part of the continuum of prostate cancer, which is post at least 1 ARSI and prior to chemotherapy. That 8.7 months of rPFS is very competitive, and that's what we're really excited about. And then recently at ASCO last week, Rahul Aggarwal from UCSF, who is the principal investigator of the investigator-sponsored trial, a combination therapy, CD -- or ADC -- or CD46 ADC in combination with enzalutamide did release also some preliminary rPFS data 10.2 months in combination with enzalutamide progression-free survival. So again, another very positive data point that tells us that the target is active. And that's what we care most about. And so that's what's leading us to than the next catalyst associated with our CD46 ADC, our -- an upcoming interaction with the FDA, which we'll be scheduling here in the very near future. That will get informed in our Phase II/III design, which we are proposing. Then there'll be a manuscript on the monotherapy trial, hopefully, public time between now and the end of the year. And then a Phase II start for the monotherapy Phase II/III trial as well. Our proposal going into the FDA interaction will be a seamless Phase II/III trial, where we will investigate FG-3246 in -- with 2 different doses in the monotherapy design, again, post ARSI pre-chemotherapy. And then based upon the results to have that segue into a Phase III program. I think it's also important to highlight the fact that -- we do have a PET agent in addition to the ADC, and it targets the same antibody backbone as well. And so what we're also going to do as part of that Phase II program design is treat everybody with the PET46 diagnostic, treat everybody with the ADC and then do a correlation analysis as we go through time because it's an open-label trial. And we'll be able to just look at PSA50, we'll be able to look at PFS, ORR data as it accumulates and be able to do a correlation analysis between the expression of CD46 and as determined by the PET46 biomarker in response to the drug.

Okay, great. A lot to go through there. Maybe starting with the monotherapy development. Is that, in your mind, maybe the fastest -- the Phase II program -- the seamless Phase II program that you've described here? Is that maybe in your mind, the fastest route to market here potentially for 3246? Or do you think about maybe prioritizing the combination program with enzalutamide [indiscernible]?

Yes, it's an important question and one that we talk about on a fairly regular basis. The reason that we're proceeding so rapidly with the monotherapy design is that that's the most mature data that we have with respect to the program. The 10.2 months of rPFS for the combination trial with enzalutamide is a really fresh data point for us. The Phase II portion of that trial is starting Rahul Aggarwal, UCSF is the PI for that. Again, it's an IST 2.1 milligrams per kilogram is the dose that he has selected to take into then the Phase II portion in combination with 160 milligrams of enzalutamide twice a day. And so we'll continue to evaluate that data as we then advance toward the Phase II start and then have the flexibility to determine what we think it makes the most sense. Do we potentially add an arm down the road in a combination therapy approach to monotherapy trial? Is it two separate programs? Or do we prioritize one versus the other, but it's good that we've got the flexibility and the optionality associated with that.

Maybe a follow-up to that is the data that you mentioned from the IST out of UCSF. Obviously, very prominent oncologists in the field of prostate cancer, but maybe just how do you think about developing a larger or more robust data set on the combination approach that could potentially support, I think, regulatory sign-off here versus just the UCSF data to date so far?

You bet. So we'll see. The plan is to enroll 36 patients in total, he's a little bit more than half way through, so he's transitioned from the escalation phase now to the expansion phase at 2.1 mgs per kg. And so depending upon the enrollment rate, we think that by the end of this year, we'll have the ability to see a much more mature data set. He's also treating those patients with PET46 as well. So we'll be able to determine if, in fact, there is a correlation with CD46 expression and the combination results. I think it's important to also to state that enzalutamide upregulates expression of CD46 on prostate cancer cells. And so that's the hypothesis of why the combination approach. And based upon the 10.2 months of rPFS, it seems like there could be something there.

Okay. And would you need possibly multicenter data versus just a single center, or it doesn't matter -- or not matter?

Well, we don't believe that this Phase I/II that Rahul is doing is registration quality. It's just not large enough, but it would allow us to then expand into a broader program that would be multisite, potentially multi-country as well.

Okay. Great. I want to turn maybe towards another asset in your pipeline, 3175. And you've just cleared that. And so maybe can you describe, again, sort of what's the rationale here for targeting Galectin-9. And then just sort of what the opportunity set broadly is in terms of the solid tumor.

Sure. So it's 3165 is the Galectin-9 antibody and 3175 is our anti-CCR8 antibody. So yes, so the FDA recently cleared the IND. We're going to be studying it in 6 different tumor types as part of the Phase I program. Initially, it will be monotherapy. And then subsequent to that, it will be in combination with LIBTAYO. So we've got a supply agreement with Regeneron that we recently announced as well, which I think adds a bit of credence as well to the both the Gal9 approach as well as the CCR8 approach. We're going to be studying it in head and neck cancer, ovarian, pancreatic, gastric, gastroesophageal. So about 6 tumors, we're going to take it into the Phase I program. And then we'll see what kind of response is we get, both the monotherapy as well as in combination therapy. PureTech has formed a company under their umbrella called Gallop Oncology to advance their anti-Gal9 antibodies. That's the only other one that's in the clinic. They've shown some interesting results in both hematologic malignancies as well as in head and neck cancer, that's small numbers, but at least it's encouraging to give us some confidence that the target targeting Galectin-9 is a good approach. And so we're excited about that, and we've stated publicly that we would expect to start the Phase I program between now and the end of the year.

Okay. Maybe just in terms of the Regeneron partnership, you mentioned the LIBTAYO, the PD-1 supply agreement. And I guess just in terms of clinical plans, can you just remind us, do you drive it? Do you do it in conjunction with Regeneron? And then what could potentially the economics down the road look like for these programs?

Yes. So we drive it. They're just -- they supply the PD-1, and that's an instance of what it is. They own data that's generated as part of their asset. We own data that's generated as part of our anti-Gal9 approach as well as the anti-CCR8 antibody. So there really are no economics associated with it. But we're excited to be able to see not only the results of our Gal9 antibody by itself, but also in combination with the PD-1.

Okay. If there are any questions in the room, please feel free to raise your hand or shoot me an e-mail at [email protected]. But in the meantime maybe just continue with this and thinking about your R&D cadence, which has definitely picked up in the wake of the -- since the pamrevlumab Phase III previously a year ago -- a year plus ago. And so just as you think about your R&D productivity, you definitely made a heavier pivot clearly to oncology here. So as you think about the shape of the company and maybe over the next few years, do you want to -- how much does an oncology like figure in terms of what FGEN look like over the next few years?

Yes. It's another thing that we spend a lot of time speaking about internally. And I'll highlight the D part because we don't have any active research programs ongoing. We've said we believe that our best approach is to not only progress what we currently have in our pipeline, but then to also continue to look for exciting opportunities externally. And so if you think about the pancreatic cancer trials that will read out, if one or both of them is positive, that clearly takes us in one direction. We would plan on commercializing on our own. In the U.S., we don't think that, that's a significant lift given the concentrated nature of clinicians that treat pancreatic cancer as well as the significant unmet need. We would then search for an ex-U.S. partner. If pamrevlumab doesn't hit then we would look to a restructuring of the organization because we wouldn't obviously be progressing toward a filing for pancreatic cancer but we would have some really exciting opportunities in both the early as well as the mid-stage to have an ADC focused on metastatic castration-resistant prostate cancer with a couple of different shots on goal, both in terms of a monotherapy as well as a combination therapy approach as well as the fact that CD46 is expressed in other tumors such as colorectal, we're really excited about 3246 and then the Gal9 impending Phase I start between now and the end of the year. And so that would be -- then we would refocus -- patients, so obviously focused on oncology. But we would be more narrowly focused on the Phase I and Phase II opportunities.

Okay. Great. In terms of the that [indiscernible] you guys have talked about, maybe can you just remind us [indiscernible] takes you and knock on wood, clinical [indiscernible] capital plans would be to support commercialization or [indiscernible]

Yes. So we announced for our Q1 earnings that we had $214.7 million in cash, accounts receivable investments at the end of the first quarter, and we reaffirmed a cash runway into 2026.

Okay. And then just sort of what the strategy might look like post either depending on success for pamrevlumab or [indiscernible]?

Yes. So we've got kind of a pivot, as you can imagine, based upon the binary nature of the readouts in pancreatic cancer. And so in either case, we would see a cash runway into 2026. There would be on the positive side, obviously, a focus of investment resources not only on the early and mid-stage program, but then also in preparation for a BLA filing. Now we've got the infrastructure pretty much already in place in order to accomplish that. In a negative pancreatic cancer scenario reduction in the number of people within FibroGen. And then obviously, we'd be able to take the investments and focus on the 3246 ADC from prostate cancer as well as the Gal9 potential start in Phase I. And both of those scenarios have runway into 2026.

Okay. You've been obviously active over the last year in terms of PD activity in terms of -- in-licensing the Fortis ADC, excuse me, partnering with Regeneron in terms of the PD-1. And maybe just, I guess, as you think about partnering and PD broadly speaking, what would you think about as probably the next opportunity there? Would it be commercializing pancreatic ex-U.S. as you kind of mentioned here? Or would you want to think about partnering on some of the earlier-stage oncology assets?

Yes, it's a good question. So I think in the near term, positive pancreatic cancer data ex-U.S. partner, continue to look for a partner for anemia associated with low-risk MDS in the U.S. for roxadustat and then investigate potential partnering opportunities for the earlier-stage pipeline. But with a positive PDAC, I think we'd have, hopefully, capital raising opportunities and some additional bandwidth to not only prosecute our internal portfolio, but to perhaps also look for some additional opportunities as well. We think we've got enough on our plate though in the near term that we're not going to necessarily rely on any sort of inbound opportunities from an asset or a business development perspective.

Okay. Great. We're coming up on time. So I think we'll end it on that note. Well, thank you very much.

Thanks...