All right. Hi, everyone. Good afternoon. We are here at Leerink's Global Healthcare Conference. I am Amanda Acosta- Ruiz, Vice President here in our targeted oncology team, and I'm happy to present Kyntra Bio, formerly FibroGen. Their CEO, Thane Wettig, is here to walk us through their story and their latest developments. I will let him take it away.
Thanks, Amanda, and thanks to the Leerink team for the opportunity to update people on our story. I'm gonna cover our two primary assets over the course of the next 25 or so minutes, and I think we'll have plenty of time to get through the content to provide everybody the update. Forward-looking statement per normal. Now going into our story in terms of our investment highlights. Last year was a really important year for us. We transformed into Kyntra Bio from FibroGen to create what we believe will be outsized impact for both patients as well as shareholders.
We completed the sale of FibroGen China to AstraZeneca, our long-standing partner in China, for approximately $220 million, $85 million in enterprise value and $135 million of cash that AZ took over in our China cash accounts and offshored US dollar for dollar. That allowed us to do two things immediately, pay off our term loan facility with Morgan Stanley Tactical Value of $75 million, plus some additional costs associated with the transaction, and immediately start our phase II trial with our antibody drug conjugate for prostate cancer, which I'll touch on in a moment. Importantly, it extended our cash runway into 2028. Related to the first asset in our portfolio, FG-3246 and FG-3180.
It's kind of a combo, associated with that program, that we believe, has demonstrated some very encouraging data in prostate cancer. FG-3246 is a potential first-in-class, asset targeting CD46, which is a novel epitope on the surface of cancer cells, and in this case, metastatic castration-resistant prostate cancer cells, which has demonstrated clinically meaningful responses in heavily pretreated mCRPC patients, and it's also got a well-characterized, safety profile based upon the history behind the linker and the MMAE payload. Associated with FG-3246 is FG-3180, which is a PET imaging agent. It's also in clinical development. It's a separate clinical development pathway, given the fact that it also has its own IND as a potential novel patient selection biomarker.
We'll talk about the phase II trial that's just started, that's underway in mCRPC in the post one ARPI pre-chemo setting, as well as the expectation of when we are going to start to see data coming out of that trial. The second asset that we're laser-focused on is Roxadustat, which is a phase III-ready development opportunity. FibroGen was most well known for the development and the approval of Roxadustat. It's available in over 40 countries for anemia associated with chronic kidney disease. It's commercialized by AstraZeneca in China and Astellas in Japan, Europe, and a number of other smaller markets. FibroGen , formerly FibroGen, Kyntra Bio now wholly owns the asset in the former AstraZeneca territories, which are primarily North America, South America, and Australia.
We have a phase III-ready U.S. development opportunity in anemia associated with lower risk myelodysplastic syndrome in patients with high red blood cell transfusion burden. Again, we'll talk about the data which has led us to this particular point and the plans for the phase III trial. We did reach an agreement with the FDA through a Type C meeting process in the middle of last year regarding the essential design elements for the phase III trial. We think we've got a pretty well clarified regulatory path forward. We also have received orphan drug designation from the FDA for myelodysplastic syndrome that was granted in December, which gives us a minimum of seven years of regulatory exclusivity if and when approved.
In terms of recent and near-term catalysts, recently, we will share the interim results for the phase II monotherapy trial of FG-3246 and FG-3180 sometime in the second half of this year. We have submitted the phase III protocol to the FDA. We submitted that in December. We're expecting feedback from them imminently, with the potential to start a phase III trial sometime in the second half of 2026. Again, we'll dive further into that as well. First, we'll cover the FG-3246 and the FG-3180 program. Don't have to spend a lot of time talking about the high unmet need in prostate cancer.
I think the most important point here is that there is going to continue to be a significant unmet need given the fact that the disease will continue to be progressive, unfortunately, and most men will want to try many available therapies before they ultimately determine that no other therapy can perhaps help them. There's also a pretty strong movement to put off chemotherapy for as long as possible. We're focused on what we believe is a novel MOA that can treat patients who have progressed on the available treatment options and specifically a non-PSMA approach.
We also think it's important to continue to investigate predictive tools that could help inform patient selection similar to the PSMA PET imaging agents that are now available, which is what is required for somebody to get Pluvicto, which is Novartis' radioligand therapy. First we'll talk about the target, and then we'll talk about the antibody as part of a ADC complex. CD46 is a novel tumor-selective target in solid tumors. This target was identified by Bin Liu at UCSF.
He undertook an agnostic phage display experiment trying to identify novel targets that were overexpressed on cancer cells that were not expressed elsewhere in the body, and he looked at a number of different targets and ultimately landed on CD46, which is highly expressed in tumors, including prostate cancer, colorectal cancer, lung cancer, multiple myeloma. The only other place where it's expressed to any significant degree in the body is in placenta and in prostate epithelium. That's what led him to conclude that this is a target that is worth investigating further. CD46 is a multifunctional protein. It is overexpressed in cancer. It negatively regulates the complement system and helps tumors evade complement-dependent cytotoxicity. It is overexpressed in a number of tumors, including mCRPC.
Its expression is upregulated as prostate cancer progresses from the localized castration-sensitive phase to mCRPC and is further overexpressed following treatment with androgen signaling inhibitors. We believe based upon the data that has been generated to date that 50%-70% of men with mCRPC are estimated to have high expression levels of CD46. We also know that based upon some DNA work that has been done, that CD46 is expressed both more homogeneously and at higher levels compared to PSMA. That's the description of the target. Now, we have developed, or UCSF developed, and we have now access to with our program, a FG-3246 therapeutic and an FG-3180 PET imaging agent.
The therapeutic, if you look at the middle of the slide, is centered on a YS5 antibody that was specifically developed to go after that novel epitope of CD46. It's a fully human, full-length IgG1 monoclonal antibody to the tumor-selective epitope of CD46. As I said, it is less accessible on most normal cells and doesn't interfere with the complement system regulation. The antibody then is part of the ADC complex with the Seattle Genetics or the Seagen linker and MMAE payload. MMAE is a potent anti-microtubule agent. It's a validated chemotherapy. It is available on other currently approved oncology therapies such as Padcev, and so it's been very well characterized. It offers what we believe to be an important androgen receptor agnostic and a non-PSMA approach as well.
Associated with the program, importantly, is also FG-3180, which is the PET imaging agent. It utilizes the same YS5 antibody that the ADC utilizes, and it's delivered with a zirconium-89 tracer, and it has demonstrated specific uptake in CD46-positive tumors. We'll talk a little bit more about this in a moment, given some of the data that was released about a week and a half ago at ASCO GU. We believe it has the potential to inform patient selection, and that we also believe that this PET-based biomarker currently considered is currently considered superior to measuring CD46 positivity via immunohistochemistry in prostate cancer. This is the components of the program, FG-3246 and FG-3180 going after that novel epitope of CD46.
The first data set I'll walk you guys through is from the phase I monotherapy study done by Fortis Therapeutics of FG-3246 in a heavily pretreated patient population. You can see the dose escalation phase of 33 patients. They were dosed from anywhere from 0.1 mg per kg all the way up to 3 mg per kg. It was then determined that 2.7 milligrams per kilogram was the MTD, and that was the dose that was taken into the dose expansion phase where there were two cohorts. The primary one was mCRPC without small cell or neuroendocrine histology.
That was the efficacy analysis was then done on patients who were at 1.2 milligrams per kilogram or above from the dose escalation and the dose expansion phase cohort one. There were a total of 40 patients who were efficacy evaluable. The primary endpoint was, again, of the escalation phase was to identify the MTD dose. Secondary endpoints, the typical PK efficacy parameters, rPFS, PSA50, which we'll walk through next. This was a heavily pretreated patient population, a median of five prior lines of therapy. You can see here, the percent of patients that were on previous androgen deprivation therapy, androgen signaling inhibitors, and there was about 25% of patients who had received docetaxel in the castration-sensitive phase of the disease.
This phase I trial demonstrated importantly an rPFS of 8.7 months, 36% PSA50, 20% ORR, so there were 25 patients who were evaluable for ORR. Five out of 25 did achieve ORR, and the duration of response was also meaningful, 7.5 months. I think it's also important to point out that of those patients who did achieve an ORR, all five of those patients were at the 2.7 milligram per kilogram dose. We do believe that based upon that, as well as some additional exposure response analysis that we have conducted, that we do believe that we have seen a dose-dependent response that is an important component of our ongoing phase II trial.
This is how we see the results from the phase I monotherapy trial at the bottom of 8.7 months comparing to a couple of other programs in a similar stage of development and a similar cohort of patients. Obviously, need to be careful about making cross-trial comparisons, but we think that we've got an asset that, based upon phase I data, compares favorably to other assets that are being talked about in a number of different settings. The adverse event profile was very typical of the MMAE payload-based ADCs. You see a fairly significant rate of grade three or above neutropenia, 36%, about 30% neutrophil count decrease, 27% white cell count decrease. These are very typical of the MMAE payload.
There was a 34% of patients who did experience peripheral neuropathy. Only one of those patients had grade three peripheral neuropathy, but that's also another classic MMAE payload adverse event that we'll continue to pay close attention to, especially as it relates to our phase II trial. Shifting now to the recently disclosed phase Ib/2 IST of FG-3246 in combination with enzalutamide that was conducted by Rahul Aggarwal at UCSF. The inclusion criteria were progressive mCRPC, patients who had progressed on at least one prior androgen receptor signaling inhibitor, no prior taxane in the castration-resistant phase.
The study endpoints were in the first part of the trial, the phase Ib trial, to determine the maximum tolerated dose to take into the phase II expansion phase, and again, many of the same secondary endpoints that we looked at in the phase I monotherapy trial, PSA50, ORR, and rPFS as well. What Dr. Aggarwal presented at ASCO GU about a week and a half ago looked at the results from the entire cohort as well as those patients who had been treated on one prior ARPI, which again is an important part of this trial that we think is informative of our ongoing phase II trial.
Across the entire cohort, there were seven months of rPFS, so 22% PSA50 response, which some people would look at and say, "Boy, that seems a bit underwhelming." The majority of patients had progressed on two or more prior ARPIs. If you look at the subgroup who had progressed on only one prior ARPI, the median rPFS was 10.1 months with a PSA50 response of 40%. We believe that this is very encouraging antitumor activity in patients who had progressed on one prior ARPI. We'll talk about how this compares then with our design for the phase II trial that's ongoing. There were two important outcomes from the IST.
The first was associated with a measure of tumor uptake relative to the response to the ADC. What you see here on the right side of the slide is a PET scan of a patient who was treated with CD46 PET or FG-3180. They then came back six days later, had the PET scan, and then were dosed with the ADC. What you see lit up here in red is very clear evidence of CD46 uptake by tumors, by the lesions in this particular patient.
What was done is there was an analysis that was done looking at the SUVmax over the SUVmean across the blood pool to determine if there was a correlation between the tumor uptake of CD46 and response, and in this case, measured by PSA50. What was determined was that there is a strong correlation or association between tumor uptake of the target of CD46 and PSA50 response. We believe that this is the first evidence demonstrating FG-3180's potential as a PET imaging biomarker for patient selection, and this will be a very important component of the evaluation of the PET imaging agent in the phase II trial.
In addition, the FG-3246 plus enzalutamide combination safety profile was very consistent with what was seen in the FG-3246 phase I monotherapy trial. The one key difference was the rate of neutropenia. There was a substantially reduced rate of neutropenia in Dr. Aggarwal's IST because of his utilization of prophylactic G-CSF to significantly reduce the rate of neutropenia in patients. Again, that is an important design element of our phase II trial with the aim to keep patients on their phase II dose for as long a period as possible without dose interruption or dose reduction, which is what was experienced in the phase I monotherapy trial. In total, this is how we see the phase I monotherapy trial as well as Dr.
Aggarwal's IST, see how they stack up relative to other programs that are in a similar stage of development, again, being careful about cross-trial comparisons. This is why we've been pretty clear that if you take a look at that PSMAfore result for Pluvicto that led to the recent approval of Pluvicto in the post-ARPI pre-chemo setting of 9.3 months of median rPFS, that is in essence the benchmark that we're aiming for in our phase II trial that we think we need to hit and perhaps do a little bit better than that to have a competitive asset to be able to take into the phase III portion of the program. This is the phase II design for the trial that is currently enrolling patients.
Primary endpoint will be the optimal dose that we would take into phase III based upon efficacy, safety, and PK parameters. Secondary endpoint are the classic efficacy endpoints that we've talked about before. Three different dose levels, 1.8, 2.4, and 2.7 milligrams per kilogram to give us a good, wide range to determine again if we see a sweet spot from an efficacy and a safety perspective, two of these doses, 2.4, 2.7 are the higher end of what was used in the phase I monotherapy trial. We plan for an interim analysis with results expected in the second half of this year. There will be a futility analysis that looks at a composite response rate of PSA50 and ORR.
We're going to look for a similar response rate as our phase I monotherapy trial because we believe the most important data will be the more mature rPFS data, which would be a part of the final analysis that we would see in the 2027, late 2027 timeframe. In summary, there are some design elements for our ongoing phase II that we think have the potential to improve upon the 8.7 months of rPFS that was demonstrated in the phase I monotherapy trial. First, as I spoke about the use of the three highest doses, 1.8, 2.4 and 2.7 milligrams per kilogram. The use of prophylaxis G-CSF to help mitigate the MMAE-associated adverse events like neutropenia, which did lead to dose interruption and dose reduction in the phase I trial.
Studying, in essence, a population that is more first- or second-line as opposed to patients who have been treated with a median of five prior lines of therapy in the phase I monotherapy trial. In terms of near-term development highlights, we think we've got in place a development strategy that provides some important optionality in prostate cancer, a robust phase II monotherapy trial that is ongoing in the pre-chemo mCRPC setting designed to select the dose for the optimal benefit-risk profile for the phase III portion of the program. The three factors that we believe could potentially add upon the 8.7 months of rPFS that was demonstrated in the phase I monotherapy trial, and then further exploration and characterization of FG-3180 as a potential patient selection biomarker.
We also think that this has the opportunity to unlock a number of registrational pathways sequentially or in parallel, looking at multiple lines of therapy in prostate cancer, monotherapy and/or combination therapy approaches, and either in an all-comers population or in a population that is more highly expressing of CD46 based upon a correlation of expression in response to our ADC. In summary, we think that this provides a really unique opportunity in mCRPC. We believe that these results are highly encouraging in the two phase one studies. The ADC and the MMAE payload has been very consistently characterized from a safety perspective.
We think we've got a significant opportunity in multiple lines of therapy, a novel mechanism, CD46 target with a novel YS5 antibody, and the importance of the PET biomarker as well as an important part of that program. Now turning to Roxadustat. We are now focused on Roxadustat in anemia associated with lower risk myelodysplastic syndrome. We believe this represents a substantial unmet medical need despite the availability of current therapies. It also represents a substantial commercial opportunity based upon the success, particularly of Luspatercept, by BMS. It is a rare disease. About 75,000 patients are diagnosed with MDS. About two-thirds of those are patients who have anemia with lower risk MDS, and the majority of those are treated with currently available agents.
Despite recent approvals, however, there remains a sizable unmet need in this refractory population for additional treatments that provide both a durable response and perhaps more convenience than the currently available therapies, which are administered in the office either via sub-Q injection or IV infusion. The conviction that we have for roxadustat in anemia associated with lower risk myelodysplastic syndrome comes from our previous phase III trial in lower risk MDS, where we showed a numerical benefit in terms of transfusion independence, but we did not achieve statistical significance. We didn't achieve statistical significance in that previous phase III trial due to the abnormally high placebo response rate that was driven by the inclusion of a sizable population of patients that had a low transfusion burden at baseline. They required one or two units of RBCs upon inclusion into the trial.
This is a patient population, many of whom become transfusion independent spontaneously because of their low transfusion requirements. When we went back and looked at the dataset and specifically looked at those patients who had a higher transfusion burden, these are patients who, based upon the international working group definition, would require four or more units of RBCs in an eight-week period of time. When we went back and looked at that patient population, which is really where these agents are being used in the real world setting today, we saw a meaningful benefit of Roxadustat relative to placebo in terms of eight-week transfusion independence, both within the first 28 weeks of the trial and over the 52 weeks of the trial, and a P value that was nominally statistically significant.
This is what gave us the conviction to approach the FDA through a Type C meeting process in the middle of last year with the intention of seeking their feedback with the aim of starting another phase III trial in this patient population that does have a high transfusion burden. How we see roxadustat ultimately playing in the setting of care for these patients with lower risk myelodysplastic syndrome is we're going to look really hard through the phase III trial at where roxadustat could play. What we've characterized here is the percentage of patients who are del(5q), those who are ring sideroblast positive and those who are ring sideroblast negative. More than half the patients are ring sideroblast negative.
To give you a bit of a background on the current available therapies, Luspatercept, their initial approval was based upon the MEDALIST trial in the second-line setting, head-to-head against placebo, and again, results which were similar to the subgroup results that I shared with you on the previous slide. They studied in that trial only the RS-positive population, and therefore, when you look at the treatment guidelines, they are in essence recommended for second-line therapy in the RS-positive patients. They did not study any RS-negative patients in that particular trial. They then did a head-to-head trial against ESAs in the front-line setting where they did study a portion of patients in the RS-negative category, but most of the patients were RS- positive. They did get a front-line indication, and that's where they've seen a substantial amount of incremental use.
However, they have not shown yet that they have a benefit in this RS-negative population. Our intention is to demonstrate a benefit across the spectrum, both in RS positive and RS negative patients, and potentially over-index or show a differential benefit in the RS- negative patient population, which we believe, given the oral form of Roxadustat relative to an in-office sub-Q injection or IV infusion and a benefit in the RS- negative population could allow us to carve out some front-line share, but very importantly, in addition to that, get very well entrenched in the second-line setting as well. These are some of the design elements that we have gained alignment with the FDA.
Patient population, patients who are requiring four or more RBC units in two consecutive eight-week periods of time, who are refractory to, intolerant to, or are ineligible for prior ESAs. On the safety side, we're gonna manage the potential thrombosis risk through eligibility dose modification and discontinuation criteria. We've worked with the FDA and have gotten alignment on the starting dose, the maximum dose, and the dosing algorithm. In terms of efficacy, we're gonna be looking at both eight-week TI and 16-week TI in terms of measuring the efficacy and the response rates. As I said, we submitted the final protocol in December, and we should hear back from the agency imminently on their feedback to that protocol.
In summary, we believe that in addition to our ADC for prostate cancer, the Roxadustat for lower risk MDS represents a significant opportunity for Kyntra Bio. There remains a sizable unmet need despite recent approvals. There is no oral option. What we hear consistently from clinicians is that this patient population is on average 75 years old. They're highly fatigued. It is difficult for many of these patients to make it into the clinic every three or four weeks for the in-office administration, and so to have the ability to offer an oral alternative for these patients represents a meaningful option for many of them. We think we can also deliver a highly differentiated profile, especially by being indicated and showing efficacy across the RS- positive and RS- negative population with the potential to over-index perhaps in that RS- negative population.
The worldwide MDS market is expected to exceed $4 billion in the next five years, represents a very attractive commercial model, attractive pricing, and therefore, represents a sizable commercial opportunity for Kyntra Bio. That is it. I appreciate everybody's attention today. Happy to take any questions if there are any. We've got a couple of minutes.