Okay, well, good afternoon, everyone, and welcome to our next session. I'll be your moderator, Sarah Nick, and I'd like to introduce our next presenter, Thane Wettig, CEO of FibroGen, a biopharmaceutical company focused on developing therapeutics to treat cancer and its related conditions. The floor is yours.
Great. Thank you, Sarah, and thanks to the H.C. Wainwright team for allowing us the opportunity to update the audience on the FibroGen story, which has evolved quite significantly over the past 12 months or so. Forward-looking statements are here. We'll dive right into an overview of the investment opportunity before we then dive into a couple of the key programs. The first area of focus for FibroGen at this point in time is on FG-3246, which is a first-in-class CD46-targeted ADC for metastatic castration-resistant prostate cancer. We recently have released data from two phase I studies in mCRPC, one monotherapy trial, and we'll go into the results a bit more in detail in a moment.
but a monotherapy dose optimization study, where data was released in the Q1 of this year, and then top-line results from the phase II portion of FG-3246 plus enzalutamide is expected in the H1 of 2025, and that will be a complement to the data that was released at ASCO earlier this year in combination with enzalutamide. but we'll touch on both of those trials later on in the discussion. In addition to FG-3246, we are also highly focused on a growing roxadustat revenue and cash flow picture. roxadustat is approved in more than 40 countries, commercialized by AstraZeneca in China in collaboration with FibroGen, and then commercialized by Astellas in Japan and Europe and many other countries.
In the Q2 earnings call conducted about a month ago, we updated our full-year net product revenue guidance for net sales in China, as well as the revenue that we report under U.S. GAAP, as follows: $320-$350 million for the year in net revenue in China, and $135-$150 million in revenue to FibroGen. So the $320-$350 is total molecule between AZ and FibroGen, and FibroGen recognizes will recognize $135-$150 million. roxadustat did $92.3 million in net sales in the Q2 of this year.
We're also expecting an approval decision for the chemotherapy-induced anemia indication sometime in the next couple of months. While not as large of an opportunity as the anemia associated with CKD, which is already approved, it is a meaningful opportunity from an incremental net revenue perspective and would also enable a $10 million milestone payment from AZ to FibroGen if, in fact, we are able to get an approval in China. The third area of focus is some partnership opportunities that we have started across our pipeline. In March of this year, we regained rights to roxadustat in the AZ territories. This excludes China and South Korea, creating a potential partnership opportunity in indications such as anemia in patients with lower risk myelodysplastic syndrome, and we'll touch on that opportunity as part of this presentation as well.
And then we have two IO assets that are early in development. We have a FG-3165, which is a galectin-9-targeted antibody for solid tumors. The IND was cleared in April of this year, and it's phase I ready. And then we have a CCR8-targeted antibody for solid tumors that's about 12 months away from IND filing status. We're excited about both of these, but given the recent reduction in force that we have undertaken after the pembrolizumab pancreatic cancer phase III readouts, we don't have the substrate or the internal capability at this point in time to prosecute those programs as quickly as they deserve to be prosecuted. There's one other galectin-9 that's in the clinic. It's a PureTech company called Gallop Oncology, and then there are multiple CCR8 targets that are in the clinic.
We've characterized the other CCR8 assets, and we've done some very good work on our CCR8 in terms of affinity, maturity, and potency, and selectivity, and when we match those up against the antibodies that are in the clinic, specifically, we think that the BMS and the Gilead antibodies look the best. We think this one competes very favorably from an SAR perspective, and, like I said, we've started outreach from a partnership perspective on both of those opportunities. And then we also announced during our Q2 earnings call, $147 million in cash, with funds expected to get us into 2026, so I'll touch on the FG-3246 program now.
Don't need to tell the audience, I don't think, a lot about prostate cancer, how significant the unmet need is in this space, and the fact that these men who undergo treatment for prostate cancer end up on multiple lines of therapy, especially in the castrate-resistant phase, with a five-year survival for mCRPC of approximately 30%. The novelty of our program is in the target. And so with 3246, it has the standard linker and MMAE payload, this, the Seattle Genetics MMAE payload. The novelty for us is in the targeting antibody, YS5, that's focused on CD46. CD46 is a ten-transmembrane protein that negatively regulates the complement system. It's upregulated in tumorigenesis. It binds to both C3b and C4b, and it helps the tumors evade the complement-dependent cytotoxicity.
And we know it's overexpressed in prostate cancer and in colorectal cancer and other solid tumors. In conjunction with this, the ADC, we also have a PET46 biomarker, which utilizes the same targeting antibody, the YS5 antibody, as FG-3246, as the ADC does with a zirconium carrier. And we do know also that this biomarker has demonstrated specific uptake in CD46 positive tumors, and you can see some graphics there on the right, in both the mouse model as well as in the human model. And that human example was from the combination trial with enzalutamide that is ongoing at this point in time. And so, again, we're excited about the ADC, the CD46 target, and also recognize the importance of the PET biomarker, which is PET 46.
Now, we believe that a biomarker that is combined with the ADC would allow us, if in fact, we're able to demonstrate the correlation between expression of the target and response to the ADC, would allow us to have a greater likelihood of showing a clinically differentiated profile in prostate cancer. Based upon data that we have generated and that has been generated at UCSF as well, it's estimated that about 50%-70% of mCRPC patients will express CD46 to a higher degree. And we also know that PSMA PET biomarkers have demonstrated a positive impact on patient outcomes. And in fact, the PSMA PET biomarker that is marketed by Lantheus, that biomarker, that diagnostic by itself generated over $1 billion in revenue in 2023.
There's not only an opportunity for the ADC, we also think that there's an important commercial opportunity for the PET biomarker as well. The PET-based biomarker that we're currently considering, we believe is superior to a CD46 IHC in prostate cancer due to higher accuracy, as well as the applicability to patients who are not only bone-only disease. Those patients with bone-only disease are not amenable for IHC testing. About 50% of patients with advanced mCRPC have bone-only disease, where IHC would not be applicable to that patient population. What we plan on doing in the phase II trial, that we will start at the beginning of next year, is to treat everybody with the PET46, to then do a post-hoc correlation of expression of the target to response to the drug.
If the hypothesis proves itself out, and there is a correlation between expression and response, that would allow us to then go into the phase III portion of the program, and with an enriched patient selection opportunity to again be able to demonstrate an even greater RPFS and OS result for the ADC. This is data from the monotherapy trial, which again was released earlier this year. This is in a biomarker unselected and heavily pretreated patient population, median of five previous lines of therapy. This looked at the dose escalation cohort levels that were at 1.2 mg per kg, as well as the cohort one, the expansion cohort in the adenocarcinoma patient population.
We showed or demonstrated a median RPFS of 8.7 months, PSA50 decline at 36% ORR in those patients that were evaluable of 20%, and a median duration of response of 7.5 months. The safety profile was consistent with adverse events seen with other MMAE-based ADC therapies as follows: the classic MMAE adverse events, peripheral neuropathy. You can see 34% of patients in total, only 2% of patients Grade 3 or higher. Neutropenia, all grades, 45.5%, Grade 3 or higher, about 36%. Some infusion-related reactions, although very few that were Grade 3 or higher, and importantly, we have not seen any ocular toxicities. And then all of the AEs in this monotherapy trial were managed by the institutional standard of care.
And it was the 2.7 mGy per kg adjusted body weight was declared as the maximum tolerated dose in this particular study. Here's just more detail on the adverse event profile, and again, what you see is the classic MMAE adverse events: fatigue, the neutropenia, neutrophil count decreased, the neuropathies, and things of that nature. So you can see it split all grades and then those, which were Grade 3 or higher. The combination trial, which is ongoing, it's an investigator-sponsored trial, run by UCSF. Rahul Aggarwal is the principal investigator.
In the escalation component of the trial, again, which was presented at ASCO in June, the primary endpoint in this portion of the trial was the maximum tolerated dose, so that we could then transition into the phase II portion of the trial. That maximum tolerated dose in this combination trial with enzalutamide has been identified as 2.1 mGy per kg adjusted body weight, with G-CSF prophylaxis, and again, that's in combination with enzalutamide. The preliminary antitumor activity in the first 18 or so patients that were treated was RPFS of 10.2 months, again, which we think is very compelling, in addition to the 8.7 months in the monotherapy trial. PSA declines in about 70% of evaluable patients.
Continued accrual is occurring in the phase II portion, and all of these patients in the phase II portion of this combination trial with enzalutamide are being treated with mandatory YS5 PET during screening to again determine the potential utility in patient selection. So there'll be a correlation analysis done on this or on this expansion cohort as the data matures, and we would expect top-line results from the phase II portion of this trial in the H1 of next year. Finally, this is a schematic that we put together, and it's tough to do direct comparisons of programs when they aren't going head-to-head against one another. And so the caveat here is, this is very much an indirect comparison. But when we look at the RPFS results-...
from trials such as TRITON-3 and PSMAfore, and SPLASH and PROFOUND, we compare that to what we've seen in terms of the RPFS results from our monotherapy in combination phase I or phase I/II trial. We think we again, we know the target is active, that CD46 is active, and we think that these RPFS results are very important, and in our view, very compelling. Again, we'll see maturity of that combination data with enzalutamide sometime in the first part of 2025. In terms of the phase II design for the monotherapy trial, which again, we expect to start in the H1 of next year, we're looking at three different dose levels. Arm A, dose level of 1.8 mGy per kg, Arm B, 2.4, Arm C, 2.7, 25 patients in each cohort.
All arms will use primary prophylaxis with G-CSF to again mitigate the neutropenia that was seen in the phase I monotherapy trial. We will establish a safety review committee with a planned review when 10 patients in each arm have completed the first cycle, as well as when 25 patients in each arm have completed cycle one as well. Interim analysis, we will look at a futility of RPFS at six months. We will also be able to do an exposure response analysis at that point in time. Again, expression of the target in response to the drug, and that will be done when 15 patients have been enrolled and have received six months' worth of therapy.
The final analysis will be at 12 months for all 25 patients in each cohort, and then with a recommended phase III dose, provided it hits the efficacy benchmarks, that we believe it needs to hit in order to progress. And there will be a decision at that point in time on PET46 as well, and if there is the correlation that we believe there will be, it will allow us to, again, enrich the phase III patient population. So these are just the upcoming catalysts, filing of the IND, and the reason that we're filing the IND is the phase I monotherapy trial and the combination therapy were done under the Fortis IND, which is who we licensed the program from in May of 2023. And then we'll also submit an IND for PET46.
It requires a separate IND, and again, initiation of the phase II dose optimization monotherapy trial in the first part of next year, and top-line results from the combination therapy with enzalutamide trial in the H1 of 2025 . In summary, again, novel mechanism of action, potential first-in-class opportunity with the uniqueness on the CD46 target, with the companion PET biomarker imaging agent for potential patient screening. We covered the efficacy results, consistent safety profile observed with other MMAE-based ADC therapies, and a potential for not only development in mCRPC, but in colorectal and other solid tumors that have expressed CD46. Turning to roxadustat, just a few updates on roxadustat. This shows the revenue curve in China, Q2 of 2022, 2023, and 2024.
So you see continued very, very rapid growth in China, 21% year-over-year revenue growth, and that was based upon about 33% increase in volume. And so the brand continues to perform exceedingly well in China and is a meaningful contributor of net revenue and of cash for our company. This just gives you a perspective on how the brand is performing. roxadustat is the top line there. This is in value share, not volume share, but you can see it's the, by far, the top brand in the anemia CKD category in the China market. And in addition to, obviously, in China, Astellas has rights in Europe, in Japan, and in many other markets.
FibroGen, however, now does have rights in the U.S. and other markets that are not licensed to Astellas, excluding China and South Korea, which affords us the opportunity to partner roxadustat with a primary focus on the U.S. in conditions such as anemia associated with myelodysplastic syndrome. In May of last year, we released top-line results from the phase II/3 MDS trial, where roxadustat demonstrated a numerical advantage relative to placebo in terms of transfusion independence, but we did not achieve statistical significance. The reason we did not achieve statistical significance is there was a high placebo response in the patients who entered the trial with a lower transfusion burden at baseline.
And so when there was a subgroup, a post hoc subgroup analysis performed on those patients who had a higher transfusion burden at baseline, this data was presented at ASH by Moshe Mittelman in December of last year. Again, the caveat here is it's post hoc subgroup analysis with a nominal p-value. But when you look at the roxadustat performance relative to placebo in those patients who did have a higher transfusion burden at baseline, as defined by two or more RBC units over a four-week period of time prior to enrolling in the trial, we see results that are very consistent with the results from luspatercept and from imetelstat.
36% roxadustat transfusion independence result, it's 11.5 for placebo, which are very, very similar to the results for an imetelstat and luspatercept. Luspatercept, which is Reblozyl from BMS, $640 million in revenue in the first six months of this year. So it will in the US alone, it will exceed $1.3 billion this year in the US. The imetelstat, Leerink just initiated coverage of Geron, and they are, Leerink is projecting first full year-