I'm Paul Choi, and I cover this mid-cap biotech sector here at Goldman, and it's my pleasure to welcome FibroGen to this session. Maybe to kick it off, I think we'll provide a brief overview of FGEN, your key clinical programs, and maybe, you know, to talk what makes you maybe most excited about what's coming up here in the near term.
Yeah. Thanks, Paul. 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.
We're really excited about both of those opportunities. Clearly, a high bar in pancreatic cancer, but if you can show, you know, a clinically meaningful, you know, benefit of, you know, 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. You know, 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 2 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 gonna be starting a phase 1 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, you know, with a strong balance sheet and then with a very attractive business in China, in collaboration with AZ, you know, 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, you know, continue to be really, really... growth, volume growth, in particular, continues to be really impressive in China there. So- and your sales were up about 26%, if I recall correctly-
Mm-hmm
... year over year. So, you know, how do you think about this, the momentum here? What, you know, 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?
Yeah, thanks. It's a really important question. You know, roxadustat, a significant generator of revenue for FibroGen. It's a profitable business for us in China. So, you know, there aren't a whole lot of biotech companies like FibroGen that have, you know, revenue-generating, a profitable business in an important market like China, upcoming catalysts, 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, you know, we did $284 million in 2023 top line revenue. We've guided to $300 million-$340 million in top line revenue for 2024, meaningful volume growth that you referenced and meaningful net sales growth.
So what's upcoming 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. You know, if this were the U.S., and we had a composition of matter patent expire first 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, you know, 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, you know, 90%-95% of the value eroded within the first 12 months. That's not the way the China market's working today.
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 first 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, you know, in the spring, it could be in the fall, and it ultimately depends upon when the, when the government ultimately includes roxadustat as part of their, VBP, program. And so we're gonna 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 on 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. Yeah, current standard of care are 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 3 times 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 RDL, 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, you know, 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'll be a really important incremental opportunity for us.
Okay, great. Can you maybe just remind us in terms of calendar mechanics, you know, when does the decision need to come by for inclusion in the next round of NRDL pricing versus the following calendar year?
Yeah, so I think that the decision would 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, you know, opportunity, I think for Roxa, is just thinking about, like, MDS and anemia there. That'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 know, you saw some better responses in certain subsets of patients and maybe where the opportunity set lies there for-
Yeah
... for an oral?
No, it's a really important opportunity that we're, you know, paying a lot of attention to. You think about the MDS market with luspatercept, and, you know, they've guided to what? $1.3 billion-$1.4 billion for this year in the US alone. And then imetelstat from Geron that was approved most recently.
Just recently.
And so, and then what's their market cap? $2.5 billion, primarily due to this one asset. And so, there is 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 will—it 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 two units over the previous eight weeks prior to entry into the trial.
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 eight-week period of time within that 26-week trial. That was well-received at ASH. A number of thought leaders are very excited about the opportunity. So, we got the rights back from, for roxadustat in the former AZ territories, not China, because that collaboration still is ongoing and very, 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 hemonc presence, to do another phase 3 trial in a patient population with a higher transfusion burden at baseline.
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. Three times a week oral option relative to an every three or every four-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.
Yeah. And maybe just one more before I move on, and this would potentially be in a ring positive and negative population.
It would be.
Okay.
That's correct.
Okay, great. Super interesting. Maybe turning to pembrolizumab, you mentioned earlier you have two data sets coming up here-
Mm-hmm
... in 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.
Yeah. 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 one, 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 two, 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 4-6-week period of time, where the statistical monitoring committee was doing the analysis to determine whether or not the pamrevlumab arm graduated from stage one to stage two, there were 38 additional patients enrolled in the pamrevlumab arm, so 213 patients in total in pamrevlumab, 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-
The path
... from stage one to stage two, 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 not even sure you guys even have it in your model, Paul, with any sort of a probability associated with it. But we know it's... 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 six cycles of pamrevlumab plus standard of care chemo, compared to six cycles of chemo by itself.
Mm-hmm.
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. 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 wasn't anything associated with the postponement of the trial. It's just that, as we followed 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 be for on the regulatory front?
Yeah.
This is kind of uncharted territory, just given the lack of therapeutic options-
Yeah
... you know, relative to historical, the 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 looks like-
... It's really important, 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, you know, innovation and benefit over the years. But it's been, you know, a number of years since there's been really any meaningful innovation in the pancreatic cancer area. And so both these trials, 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, is that these are both registration-registration quality trials. And-
I'm sorry, pre-IND?
I'm sorry, pre-BLA.
Okay.
Sorry.
Yeah.
These are both registration quality trials, and we would expect to move toward a BLA filing, based upon the results.
Okay. Okay, great. Okay, maybe turning to elsewhere in the pipeline and talking about FG-3246 here.
Mm-hmm.
You know, I think this is a target area that's, you know, gotten a fair amount of interest recently.
Yeah.
So can you maybe just remind us what CD46 does? Kind of-
Yeah
... maybe a brief overview of the landscape.
You bet.
And then, just sort of the background on how you acquired this, the asset through Fortis.
You bet, yeah. So I think the initial excitement was associated with the fact that this is an antibody-drug conjugate, right?
Yeah.
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, you know, 13 months or so. Fortis ran the original monotherapy trial, which was post ARSI, pre-chemo, and that's data that was released, you know, a couple of months ago. But it's a... 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.
Of the technologies.
Of the technology.
Yeah.
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's active based upon the data that has been generated and presented to date, the PSA 50 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 it seems like that the investment community looks at PSA 50 and tries to compare across programs. What we wanna make sure that people understand is that we have a really robust RPFS signal of 8.7 months.
When you compare that to other programs that are in as 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 one ARSI and prior to chemotherapy, that 8.7 months of rPFS is very competitive, and that's what we're really excited about. Then recently at ASCO last week, Rahul Aggarwal from UCSF, who's the principal investigator of the investigator-sponsored trial of a combination therapy of CD46 ADC in combination with enzalutamide, did release also some preliminary rPFS data, 10.2 months in combination with enzalutamide, of 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.
That's what's leading us to the next catalyst associated with our CD46 ADC: an upcoming interaction with the FDA, which we'll be scheduling here in the very near future. That will get informed in our phase 2/3 design, which we are proposing. Then there'll be a manuscript on the monotherapy trial, hopefully published sometime between now and the end of the year, and then a phase 2 start for the monotherapy phase 2/3 trial as well. Our proposal, you know, going into the FDA interaction will be a seamless phase 2/3 trial, where we will investigate FG-3246 with two different doses in the monotherapy design, again, post ARSI, pre-chemotherapy.
And then based upon the results, have that segue into a phase 3 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 gonna do as part of that phase 2 program design is treat everybody with the PET 46 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 PSA 50, 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, as determined by the PET 46 biomarker, and 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 seamless phase 2 program that you've described here, is that maybe, in your mind, the fastest route to market here, potentially for FG-3246? Or do you think about maybe prioritizing the combination program with enzalutamide-
Yeah.
-e- expanding?
It's an important question, and one that we, we talk about on a fairly regular basis. The reason that we're proceeding so rapidly with the monotherapy design is that's the, 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 2 portion of that trial is starting. Rahul Aggarwal at 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 2 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 2 start, and then have the flexibility to determine what we think it makes the most sense. You know, do we potentially add, you know, an arm down the road, in a combination therapy approach to the monotherapy trial? Is it 2 separate programs, or do we prioritize 1 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've mentioned from the IST out of UCSF, obviously very prominent, you know, oncologists in the field-
Mm-hmm
... of prostate cancer, but maybe, you know, just how do you think about developing a larger or more robust data set on the combination approach, you know, that could potentially support, you know, 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 halfway through, so he's transitioned from the escalation phase now to the expansion phase at 2.1 mg/kg. And so, you know, 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 PET 46 as well, so we'll be able to determine if, in fact, there is a correlation with CD46 expression and the combination results. And again, it's important also to state that enzalutamide upregulates the expression of CD46 on prostate cancer cells, and so that's the hypothesis of why the combination approach. Based upon the 10.2 months of rPFS, it seems like, you know, there could be something there.
Okay. And would you need possibly multi-center data versus just a single center?
Uh, well-
Or does that not matter?
... I think, yeah, we don't believe that this phase 1/2 that Rahul is doing is registration quality. It's just not large enough.
Okay.
But it would allow us to then expand into a broader program that would be multi-site and potentially multi-country as well.
Okay, great. I want to turn maybe towards another asset in your pipeline, FG-3175, and you know, you've just cleared that. And so maybe can you describe again, sort of what's the rationale here for targeting galectin? And then just sort of what the opportunity set broadly is in terms of solid tumors.
Sure. So it's 3165 is the anti-galectin antibody.
Thirty-one seventy-five.
Yeah, 3175 is our anti-CCR8 antibody. So yeah, so the FDA recently cleared the IND. We're going to be studying it in 6 different tumor types as part of the phase 1 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, you know, adds a bit of credence as well to both the Gal-9 approach as well as the CCR8 approach. We're gonna be studying it in head and neck cancer, ovarian, pancreatic, gastric, gastroesophageal. So about 6 tumors we're gonna take it into the phase 1 program. And then we'll see the...
What kind of responses 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. 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, you know, we're excited about that, and we've stated publicly that we would expect to start the phase one 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.
Mm-hmm.
I guess just in terms of clinical plans, can you just remind us, you know, do you drive it? Do you do it in conjunction with Regeneron?
Yeah.
Then, you know, what could potentially the economics down the road look like for these programs?
Yeah, so we drive it. They're just. They supply the PD-1, and that's in essence 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. Are there any questions in the room? Please feel free to raise your hand or shoot me an email at paul.k.choi@gs.com. But in the meantime, maybe just continue with this and, you know, thinking about your R&D cadence, you know, which has definitely picked up in the wake of the, you know, since the pamrevlumab phase 3 you had previously a year ago, a year plus ago.
Mm-hmm.
And so just as you think about your R&D productivity, you know, you definitely made a heavier pivot, clearly, to oncology here. So as you think about the shape of the company, saying maybe over the next few years, do you end up... You know, how much, you know, does an oncology life figure in terms of, you know, what FGEN looks like over the next few years?
Yes, it's another thing that we spend a lot of time speaking about internally. And then I'll highlight the R&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 we'll 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, you know, 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, you know, 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 FG-3246 and then the Gal9 impending phase 1 start between now and the end of the year. And so that would be...
We would refocus, obviously, focused on oncology, but we would be more narrowly focused on the phase one and phase two opportunities.
Okay, great. In terms of the runway that you guys have talked about, maybe can you just remind us, takes you and, you know, knock on wood, you know, clinical capital plans would be to support commercialization or-
Yeah, 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, you know, either depending on success for Pamrevlumab or...
Yeah, so we, 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. 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 FG-3246 ADC for prostate cancer, as well as the Gal9 potential start in phase 1, and both of those scenarios have runway into 2026.
Okay. You've been obviously active over the last year in terms of BD activity, in terms of in-licensing the Fortis ADC, excuse me, partnering with Regeneron in terms of the PD-1. And maybe just, you know, I guess, as you think about partnering and BD, broadly speaking, you know, what would you think about as probably the next opportunity there? Would it be commercializing pancreatic ex-US, as you kind of mentioned here? Or would you want to think about partnering on some of the earlier stage oncology assets?
Yeah, 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, you know, with a positive PDAC, you know, 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 gonna 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 just end it on that note. Thank you very much.