Good day, everyone. Thank you for joining the 23rd Annual Needham Healthcare Conference. My name is Joey Stringer, and I'm one of the Biotech Analysts at Needham & Company. It's my pleasure to introduce our next presenting company, FibroGen. Joining us today from the company is CEO Thane Wettig. For those of you joining on the webcast, if you want to ask a question, please do so at any time. You can submit a question using the chat box at the bottom of your screen. So with that, we'll get started. I'll turn it over to Thane for the presentation.
Yeah. Hey, thanks, Joey. I appreciate the time, and, good afternoon, everybody. Just as a bit of background, I'm Thane Wettig, the CEO of FibroGen. I joined FibroGen about four years ago as the, Chief Commercial Officer, and then was appointed the interim CEO, in July of last year, and then the permanent CEO and a Director in October of last year. Prior to joining FibroGen, I spent a couple of years at Intarcia Therapeutics, which was a private pre-commercial biotech based in Boston, working on a drug device combination product for type 2 diabetes. And then prior to that, I spent about 28 years at Eli Lilly, the last half of that, period of time in, exclusively focused on Lilly's diabetes business. So pleased to have the opportunity to present an update on, FibroGen, this afternoon.
The forward-looking statement is included as part of the presentation, and we'll go right into the content. We'll start with just a general overview, and then I'm gonna dive into our latest stage asset, pamrevlumab, which is under investigation in pancreatic cancer. And then I'll touch on our antibody drug conjugate, which is in development for metastatic castration-resistant prostate cancer. And then I'll touch on roxadustat, which is our in-market asset. So at a high level, we're really encouraged and excited about the upcoming readouts that we have for pamrevlumab in pancreatic cancer. There are two of them that we anticipate reading out this quarter, one being in the metastatic patient population as part of the Pancreatic Cancer Action Network Precision Promise platform design.
The other one, which is a FibroGen-sponsored trial in the locally advanced patient population. Again, thinking about pancreatic cancer, the significant unmet need and the sizable commercial opportunity, we're really excited to see that data yet this quarter. With roxadustat, we have growing revenue and cash flows coming from the business, not only in China, where we have a close collaboration with AstraZeneca, but also in Japan and Europe and many other countries where Astellas handles commercialization. We also, in the middle part of this year, expect an approval decision for the chemotherapy-induced anemia indication. And we also have recently regained rights to roxadustat in what was the former AstraZeneca territories, which primarily includes the U.S..
And we'll talk a little bit about what we think is an exciting opportunity in anemia of a low-risk myelodysplastic syndrome patient population that we're looking at right now as well. We do have what we believe is an exciting early-stage oncology pipeline. The most advanced is our CD46-targeted ADC for mCRPC. We released additional data from the phase I monotherapy trial last week, and we'll touch on that. We also expect to file in the coming weeks an IND for a Galectin-9 targeted monoclonal antibody, and then in 2025 would expect to file an IND for a CCR8 targeted monoclonal antibody. And then finally, we have a strong balance sheet.
We announced, as part of our Q4 earnings call, $248 million in cash, cash equivalents, and accounts receivable as of the end of the year, and reiterated the fact that we believe we have sufficient funds to continue us into 2026. So, and to touch on initially, pamrevlumab to begin with, it is a first-in-class connective tissue growth factor targeting antibody that's in late-stage development for pancreatic cancer, a novel differentiated anti-tumor MOA, where in vivo we have shown an increase in survival, promotion of tumor cell apoptosis, a reduced proliferation of tumor cells, and decreased tumor vascularization.
We also have data in early-stage clinical trials in both a metastatic patient population as well as a locally advanced patient population, and we'll go into that data in a moment. Then finally, there's no doubt that if we are able to show incremental OS benefits in either the locally advanced patient population or the metastatic patient population, that given the unmet need and the lack of real advance with this particular tumor over the last 20 or 25 years, that if we can show, you know, a clinically meaningful impact on overall survival, it represents a sizable commercial opportunity. There's no doubt that pancreatic cancer is in significant need of novel targets and additional treatment options.
You all know the, I'm sure, the statistics, but if you think about a five-year disease-free survival in pancreatic cancer of only 12.5%, and in the metastatic patients, about 3%, it represents just an unbelievable opportunity to bring forward an incremental advance. No, as I said earlier, no major therapeutic advances in quite some time. The standard of care is chemotherapy with gemcitabine on top of, in addition to nab-paclitaxel, or modified FOLFIRINOX. The IOs have shown limited improvements, despite the fact that there have been many shots on goal with the IOs in pancreatic cancer. And so, you know, we're really excited to be able to bring forward this particular approach, and we'll see data shortly.
In one of the important trials that was done a number of years ago, we looked at a patient population which was heavily metastatic in nature. There were 75 patients, 66 of the patients had metastatic disease. The other nine patients had locally advanced disease, and we saw a clear exposure-related increase in survival in this particular trial. If you take a look at the curve on the right, there was a median threshold analysis that was done post-hoc, which looked at of the 75 patients, 38 of them had an exposure of greater than 150 micrograms per ml of pamrevlumab at trough. 37 had less than 150 micrograms per ml at trough.
When you separated those two patient populations out, there was a 2x median survival in the patients above the median threshold as opposed to below the median threshold, and more than a 3x one-year survival benefit, 37%, in the patients with the higher level of pamrevlumab versus the lower level of pamrevlumab. So that gave us some confidence that there was a clinical activity with pamrevlumab in this particular patient population. Another trial that was done, a phase II trial in the locally advanced patient population, looked at resectability. It also showed that in patients treated with pamrevlumab versus standard of care alone, that the pamrevlumab patient population also had a much higher rate of resection relative to the chemotherapy arm.
And so again, that gave us the confidence to take this program into a phase III design, where it's now in two particular specific trials for pancreatic cancer. This is a comparison and a contrast of those two trials. The metastatic pancreatic cancer trial on the left, which is being conducted by the Pancreatic Cancer Action Network as part of their Precision Promise program, the one on the right, which is the FibroGen-sponsored program in the locally advanced pancreatic cancer population. Together, these two populations of pancreatic cancer patients who are diagnosed annually in the United States. A key similarity between these two patient populations is that the primary endpoint is overall survival in both. There are some key differences, however.
In the metastatic patient population, or the metastatic trial, the pam dosing in the active arm is unlimited 28-day treatment cycles until either disease progression or discontinuation, whereas in the locally advanced trial, it's six 28-day treatment cycles of neoadjuvant therapy, and then patients were assessed for resection at that point in time. In addition, the trial completion trigger for the metastatic trial is time-based, 12 months after our last patient in, we'll go into that in more detail in a moment, whereas the locally advanced trial is event-based. We enrolled 284 patients across 100 sites globally, and we're looking for 233 OS benefit or 233 OS events. We're at the flat part of that OS curve right now.
We had originally guided to a top-line readout in the locally advanced trial of Q1, but based upon the current accrual of OS events, we revised that guidance to read out in the second quarter of this year, which is this quarter, which is the same as we expect to then read out for the metastatic trial as well. Wanted to briefly touch on the design of the Precision Promise trial, which is an adaptive multi-arm registrational trial in metastatic patients. This is a schematic of the overall Precision Promise design. Pay closest attention to the top two bars, because that represents the pamrevlumab arm.
But the way the trial was designed is that 50 patients were enrolled, and after that 50th patient was enrolled, up to the 100th patient, there was then a monthly analysis for futility and probability of success by a statistical monitoring committee. And so with pamrevlumab, after that 50th patient up until the 100th patient, there was almost an ongoing or perpetual futility and POS analysis.
There was then the final analysis after the 100th patient was enrolled to determine whether pamrevlumab would graduate from Stage 1 to Stage 2 of the trial, based upon a pre-specified, probability of success threshold of at least 35%, meaning that if pamrevlumab did graduate from Stage 1 to Stage 2, it had to show at least a 35% probability of showing a positive OS benefit at the end of the trial or after a subsequent 75 patients were enrolled. We announced in January, that in fact, the pamrevlumab arm did graduate from Stage 1 to Stage 2, so it had achieved that pre-specified threshold of at least a 35% probability of a positive OS benefit at the end of the trial, and 75 patients were subsequently enrolled.
Pamrevlumab in the Precision Promise trial was on top of gemcitabine and nab-paclitaxel, and so the comparison that we will have at the end of, once the analysis is complete and released, it will be pamrevlumab on top of gem nab-paclitaxel compared to Gem nab-paclitaxel alone. A couple of additional points as it relates to the conduct of the study. In that period of time, which was about a 4-6-week analysis period after the 100th patient was enrolled, there were an additional 70, or an additional 38 patients that were enrolled on the pamrevlumab arm, and so those 38 patients didn't count in that first 100-patient analysis. They also didn't count toward the additional 75 patients that were enrolled.
So when the OS data is released, it will be on 213 patients in the pamrevlumab plus Gemcitabine nab-paclitaxel arm, and that will be compared to then just the standard of care gem nab-paclitaxel arm. A couple of things that we don't know about the trial. We don't know if in achieving that threshold of at least 35%, was it 40% or was it 60%? We also don't know if pamrevlumab graduated in both the first-line metastatic patient population and/or the second-line metastatic patient population. So those will be really important pieces of the analysis that will come out later this quarter. If pamrevlumab did graduate in both the first-line and the second-line setting, then of the subsequent 75 patients that were enrolled, there would be both first-line and second-line patients enrolled in that subsequent 75 patients.
What we also don't know is the degree of... We don't know the threshold that was achieved in the first-line setting versus the second-line setting. And so if the first-line patient population had a greater achievement of probability of success than the second-line setting, there would then be a commensurate number of patients in the second stage that would be enrolled relative to the second-line metastatic patient population. So it's all a part of this adaptive design trial to give the active treatment arm the best chance of success as possible. But we're again really encouraged that pamrevlumab graduated from Stage 1 to Stage 2, and we'll see the results later this quarter.
Then just quickly on the LAPIS study, there are two treatment arms in this particular trial in the locally advanced patient population. Arm A, which is pamrevlumab plus Gemcitabine nab-paclitaxel or FOLFIRINOX, then compared to chemotherapy alone. Patients were then determined if they were eligible for surgical exploration or not. If they were eligible for surgical exploration, they would undergo surgery and either achieve a successful resection or not. So that will also be an important part of the analysis of the locally advanced trial, is not only the OS result, but also then the stratification for those patients that were either eligible or not for surgical resection.
As it relates to then the commercial opportunity, there's a sizable opportunity just in the US alone, if in fact, we're able to demonstrate a positive OS benefit. And when we've tested different profiles with KOLs as well as with clinicians, what we hear back is if we're able to demonstrate even a two or three-month improvement in overall survival in the metastatic patient population, that would be viewed as very clinically meaningful and represent then a sizable commercial opportunity. So again, results later this quarter in both the locally advanced trial as well as in the metastatic trial. Now I'd like to turn to our CD46-targeted antibody-drug conjugate for metastatic castration-resistant prostate cancer. So FG-3246, or formerly known as 446, we in-licensed this program from Fortis Therapeutics last May.
Fortis had done the initial development work in close collaboration with UCSF, but we believe it has a first-in-class potential. It binds a unique epitope on CD46 that's preferentially expressed in tumor cells. The ADC is composed of the anti-CD46 monoclonal antibody YS5, which is conjugated to an MMAE payload via a cleavable linker. We have demonstrated efficacy against CD46-expressing tumors in both the preclinical and the clinical setting. A little bit of background on how the target was identified, because I think it's important to really articulate this as a potential unique differentiator of this particular ADC relative to some other approaches, you know, which may target B7-H3 or may target PSMA.
So an investigator at UCSF, Ben Liu, took a target-agnostic approach to identifying antibodies that bind specifically to prostate tumor cells with minimal binding to normal tissue. The antibody phage display approach utilized a panning on both cell lines and tissue samples and was designed to enrich for antibodies that specifically bind to tumor cells and internalize upon target binding. One of the candidates that had a compelling profile of tumor-specific binding and rapid internalization was subsequently de-orphaned, with CD46 identified as the target antigen. CD46 acts as a negative regulator of complement activity to protect cells from complement damage. While CD46 RNA is broadly expressed, it demonstrates a much more restricted expression profile at the protein level. CD46 tumor-restricted expression was confirmed by IHC for both the UCSF-discovered antibodies as well as a commercially available polyclonal antibody.
The YS5 is an optimized, fully humanized monoclonal antibody against CD46 that binds with a nanomolar affinity, internalizes rapidly upon target binding, and it is the targeting moiety for both the MMAE-linked FG-3246 ADC, and the CD46 targeted PET 46 biomarker. And so both of those are important as a part of this program. So, in a preclinical setting, FG-3246 demonstrated efficacy against CD46-expressing tumors, as seen on the graph below. And then the PET 46 zirconium-89 biomarker also demonstrated the specific uptake in CD46-positive tumors, in a tumor imaging study as well. So again, both of these pieces we think form a really important part of the story for our approach in this particular tumor setting.
As I said earlier, we did release updated information on the phase I monotherapy trial, which had initial disclosure at ASCO in 2022. And in 2022 ASCO, there was a PSA50 measure and ORR measure as well. We updated that now to include a median RPFS result, as well as a median tumor duration of response result, which you see here. And so, again, we think that this clearly signifies as a very important clinical activity with respect to 3246. We've seen a median RPFS of 8.7 months, PSA50 decline of a PSA50 decline by at least 50% of 36%, an ORR of 20%, and a median tumor duration of 7.5 months.
Now, to put this in a bit of perspective, the previous PSA50 result that was released at ASCO was higher than this. And so we've received a number of questions as it relates to why do we believe that the PSA result came down? We wanted to make sure that we re-emphasized that this was in an all-comers population, it was biomarker unselected, and these patients had a median of 5 prior lines of therapy. And we now have an important median RPFS result to look at.
And so while PSA is a gold standard way of measuring, via a biomarker, a clinical activity, we think the most important marker associated with the treatment of metastatic castration-resistant prostate cancer is survival, and in this case, a measure of radiographic progression-free survival across the entire efficacy cohort of 40 patients. We're really encouraged about the 8.7 months of RPFS at the dose escalation cohort level of 1.2 mg per kg. This is really forming the basis of us then taking this program forward, scheduling an interaction upcoming with the FDA to talk about the path forward.
Some additional activities ongoing and planned for FG-3246 are as follows: First, there is an active phase I trial, FG-3246, in combination with enzalutamide in patients with mCRPC that's being done by Rahul Aggarwal at UCSF. Interim results are expected in the middle part of this year. There has also been an abstract accepted for a poster presentation at ASCO in a couple of months that Rahul will present. In addition to that, there's a PET 46 imaging development study also ongoing at UCSF, with an expected readout later this year. We're also then starting to put plans together that we will share with the FDA for their feedback.
and our current thinking is to do an open-label dose optimization study in patients in the pre-chemo setting with mCRPC, where we will also look at imaging for CD46 expression in this patient population. And what we believe that that will allow us to do is, as that data is generated, we'll be able to look at a retrospective analysis of the correlation of CD46 expression or PET positivity and response to the drug, that that would, we believe, allow us to then enrich that that phase III patient population to ensure that we've got a targeted approach to achieve the best result possible as we advance the program. So again, initial thinking, meeting planned with the FDA to discuss the totality of the forward-looking development plan.
So in summary, as it relates to 3246, we think we've got a novel mechanism of action with a first-in-class opportunity against a novel targeted approach with an MMAE payload with a complementary biomarker diagnostic. We've seen encouraging phase I efficacy results, which shows clinical activity. The safety profile is well-characterized. We did see in the phase I monotherapy trial an adverse event profile that is entirely consistent with those observed with other MMAE-based ADC therapies.
And we also believe that in addition to being able to explore this, not only in multiple lines of mCRPC, we also have seen CD46 expressed in colorectal cancer, in multiple myeloma, as well as in lung and breast tumors, and so opportunities to expand outside of mCRPC. Finally, I'd like to touch on roxadustat, provide a brief update here. We continue to see strong performance from volume growth in China. We announced in 2023 that roxadustat achieved net revenue of $284 million in China, and we've guided to $300 million-$340 million in net revenue for 2024.
and so it's a really important part of our story, and something that probably doesn't get as much attention perhaps as it should, because not only is it generating significant top-line revenue, but it's also a positive cash generator for FibroGen on a quarterly basis. In addition, we believe that there is also an opportunity for a further development of roxadustat in anemia associated with myelodysplastic syndrome. While there is other therapies available, most notably luspatercept, which this year will likely do $1.3 billion-$1.4 billion in revenue, and I think the peak analyst estimate is in excess of $3 billion. There still is a sizable number of patients who don't benefit either from ESA therapy or luspatercept therapy.
I'm sure everyone is familiar with the imetelstat story and the positive AdC om, and then the near-term decision that the FDA will make. We do believe, however, there's continues to be a significant and will continue to be a significant opportunity in this patient population, especially for a treatment that has a unique mechanism of action that can be delivered orally three times a week. What gives us the confidence on the further development of roxadustat in this patient population is data that was presented at ASH in December.
We released, along with AstraZeneca and Astellas, top-line data on the Matterhorn trial in May of last year, where we showed a numerical advantage but not a statistically significant advantage of roxadustat relative to placebo in transfusion independence in patients with low-risk MDS. When we looked at the placebo response, it was pretty clear that the high placebo response was driven by a sizable patient population that was enrolled into the trial that had a low transfusion burden at baseline.
So when there was a post-hoc subset analysis done on looking at those patients that had a high transfusion burden at baseline and looked at the response of roxadustat relative to placebo, which you see here on the left, there was a clear benefit of roxadustat relative to placebo in terms of transfusion independence for at least 56 days, not only within the 28 weeks of the trial, but also by the end of therapy. So this gives us confidence that if we were able to enroll in another Phase III trial patients that had a high transfusion burden at baseline and replicated these results, that it would, it could lead to a NDA being filed in the U.S., and a potential approval in this important patient population, which, again, represents a meaningful commercial opportunity.
We have started outreach with companies that have a presence in the hematology and oncology space, who would believe that this would be an important bolt-on opportunity as a part of their franchise, a very focused development, a path forward, a very efficient commercial model to commercialize this, within the hemo community, and again, something that we're actively exploring for a potential out-license for continued development for roxadustat. So with that, you know, I hope that this provides an update on the FibroGen story. A very important quarter for us in the next, you know, really 2024.
Two readouts in pancreatic cancer upcoming yet this quarter with pamrevlumab, a phase II start for our CD46-targeted antibody-drug conjugate, along with continued PET biomarker development, associated with that particular program, a filing of an IND for an anti-galectin-9 antibody, continued, robust growth of our roxadustat business that's positive cash-generating for FibroGen, and then a strong balance sheet, whereas at the end of 2023, we had $248 million of cash, and a sufficient runway to take us into 2026. So Joey, why don't I, turn it back over to you?
Great, Thane. Thank you so much for the presentation. We'll move to the Q&A session. We see we've got a few questions from the audience. First one, for me, I suppose when you go to meet with FDA around the 346 development path forward, what do you think are gonna be the potential pushbacks or the main sticking points that you'd expect to have a healthy discussion on?
Yeah, well, I think first and foremost, you know, we're really excited about the clinical activity that we've shown. We've shown clinical activity not only with respect to PSA50, we've also shown important survival benefit as it relates to the RPFS number. And so we think that that's the most important thing that we're gonna have to ensure that the FDA understands. There'll be an important conversation around this dose optimization approach that we want to do next, and we're not gonna disclose today, you know, what those potential, you know, couple of doses might be. And then, you know, I'm sure that there'll be a conversation around, you know, the patient population that we'd like to go after. So I don't know if there'd be sticking points or pushback.
I think, you know, we anticipate it will be a very, you know, collaborative conversation, but an important one for us that will then inform the go-forward approach.
And then, lastly for me, the financing strategy. What are the potentially non-dilutive options that you have available? What's the thinking there, and maybe what are the options available to you?
Yeah, it's a really important question, and so, you know, what we've announced is that we have a cash runway into 2026. That assumes that, you know, if we have a negative readout for both of the pancreatic cancer programs, that we would likely tie a bow around that program, and then proceed forward with a laser focus on the CD46-targeted ADC, and obviously then thinking about the earlier stage IO programs as well, which don't, you know, need a lot of cash in the near term, just based upon where they are in terms of their stage. If we're able to show a positive outcome for one or both of the pancreatic cancer trials, we think that creates an important capital raise opportunity as well.
You know, you, you've seen how much activity there is in the space as it relates to follow-on offerings, as it relates to PIPEs. You know, we, we have had some, some inbound inquiries as it relates to FibroGen, especially, you know, given all the excitement around the ADC and, you know, some of the, the recent transactions which have occurred. But yeah, we, we think that there's a couple of approaches. One is positive pancreatic cancer readout, potential for financing options there. We also, you know, would believe that there would be partnering opportunities associated with pamrevlumab for pancreatic cancer.
Our approach would be to go it alone in the U.S. and partner it outside the United States, and again, that would be an opportunity for clear, non-dilutive capital to come into the organization as well.
Got it. Great! Well, thank you, everyone, for joining us on the webcast. Thank you, Thane Wettig, for the presentation and the discussion. Everyone, have a good day and a good rest of the conference.
Thanks, Joey. Appreciate it.