Good afternoon, everyone. Welcome to our next session at the H.C. Wainwright 28th Annual Global Investment Conference. My name is Matt Keller, and it is now my pleasure to introduce our next presenting company, Kyntra Bio, and speaking for the company is Thane Wettig, CEO. Thane, please go ahead.
Thank you, Matt. Appreciate you including us in the 28th year. That's pretty impressive. It used to be where I was the youngest person in a room like this, and that's not the case anymore. It's a pleasure to be here today talking about Kyntra Bio. For those of you who are not familiar with Kyntra Bio, it was formerly FibroGen, and we rebranded from FibroGen to Kyntra Bio in January of this year to really reflect the transformation that we have undertaken over the past couple of years from a company that was initially focused on fibrosis and human collagen to one that's now focused on oncology and rare disease. These are the forward-looking statements that I'm obligated to provide.
What I'm going to do is just provide a general overview of Kyntra Bio and then dive somewhat deep into both of our clinical stage programs, which we're really excited about. We are advancing mid and late-stage assets in both prostate cancer as well as rare disease. Most recently, we completed the finalizer, completed the transformation of our balance sheet, and reduced the maximum aggregate payments under our previous royalty obligation to NovaQuest from roughly $125 million to $65 million, which represents a $60 million in savings in exchange for an accelerated payment of roughly $42.5 million. That has now adjusted our cash runway into the fourth quarter of 2027. Now we're wholly focused on our two clinical stage programs.
The first is FG-3246 and FG-3180, which is the program that we have that's actively enrolling in a phase II trial in metastatic castration-resistant prostate cancer. We'll talk a little bit more about the science and the mechanism, as well as some of the initial data that has been generated, both in a phase I monotherapy trial as well as in a phase I-B/II IST from UCSF. Again, we are currently enrolling in the phase II portion of the program. We expect interim results in the fourth quarter of this year, so we're not too far away from that. We're also very excited about roxadustat. Roxadustat is the product that the company is most well-known for. Approved for anemia associated with chronic kidney disease in both dialysis and non-dialysis patients in roughly 45 markets.
Astellas is the commercialization partner for us in Japan and Europe and a number of other smaller markets. We had a very successful profit share quasi joint venture with AstraZeneca in China before we sold our rights to AZ, that we closed on roughly 12 months ago. We are now advancing roxadustat, which is a wholly owned asset for Kyntra Bio, and we are advancing it toward the start of a phase III trial in lower risk myelodysplastic syndromes, and I will detail that as well. We have gotten really strong alignment with the FDA on the essential design elements of the phase III trial, and we received orphan drug designation in December of last year, and so we will have at least seven years of regulatory exclusivity if and when we are approved in the United States.
In terms of recent and near-term catalysts, I spoke about the interim results that we expect in the fourth quarter of this year with our ADC targeting metastatic castration-resistant prostate cancer. Then again, the goal of initiating the phase III trial for roxadustat in lower risk MDS also in the fourth quarter of this year. First touching on our FG-3246 and FG-3180 program. I do not have to spend a lot of time on highlighting the substantial unmet need for men with prostate cancer. 13% of men will be diagnosed with prostate cancer at some point during their lives. There are approximately 65,000 drug-treatable patients every year in the U.S. with metastatic castration-resistant prostate cancer, and unfortunately, a five-year survival of about 30%.
There is a need for therapies that can extend survival in patients who are either ineligible for or who have progressed on either ARPI and/or chemotherapy. We think that we have got an asset that has shown some important clinical results in both monotherapy as well as in combination with enzalutamide. CD46 is a novel tumor-selective epitope on the surface of a number of tumors, both solid as well as liquid tumors. Typically, you hear a lot of discussion around PSMA. The other targets that are being spoken about most actively today include STEAP-1, Trop-2, B7H3, and CD46. CD46 is a multifunctional protein. It is, as I said, overexpressed on the surface of cancer cells. It negatively regulates the complement system, and therefore it helps tumors evade the complement-dependent cytotoxicity.
It is highly expressed in mCRPC and other solid tumors, and the expression actually is upregulated as the prostate cancer progresses from the localized castration sensitive phase to metastatic castration resistant. It is estimated that about 50%-70% of patients are high expressers of CD46. We do know based upon some clinical experiments that have been done, that CD46 is expressed more homogeneously and at higher levels relative to PSMA. Talking about then the asset itself, on the left-hand side is FG-3246, which is the therapeutic. It has got the targeting antibody plus an MMAE payload. The MMAE payload is the Seattle Genetics payload that has been approved on five cancer therapeutics that in 2025 generated about $5 billion in revenue, and so the payload is very well characterized from both an effectiveness as well as a tolerability and a safety perspective. In the middle, it talks about the YS5 antibody.
It's a fully human, full-length IgG1 monoclonal antibody to the tumor-selective epitope of CD46. It's less accessible on most normal cells, and it doesn't interfere with the complement system regulation. The science comes out of UCSF. There was a series of experiments looking for targets or antigens on the surface of cancer cells that were highly expressed on the surface of cancer cells that were not highly expressed anywhere else. The only other place in the body that you find CD46 expressed at a high level is in placenta and prostate epithelium. That's why the scientists at UCSF then went to work on identifying an antibody specific to that novel epitope of CD46, and that's where the YS5 antibody comes from. Also developed at UCSF is a companion PET imaging agent that targets the same CD46 epitope utilized in the same YS5 antibody.
However, it's delivered with a zirconium-89 tracer. It's an important part of our ongoing phase II trial, which I'll speak about in a moment. First turning to the phase I monotherapy study of FG-3246 in patients with mCRPC. It was the classic dose escalation and dose expansion trial, 33 patients in the escalation phase, 23 in the expansion phase, 18 of which did not have the neuroendocrine histology. There were a total of 51 patients that were included in the efficacy analysis. In terms of their baseline characteristics, what you see on the right-hand side of the slide here is that there were patients who were treated with a median of five prior lines of therapy, androgen deprivation, essentially in everybody, as well as most patients receiving two or more androgen signaling inhibitors. Their taxane therapy was allowed in the castration-sensitive phase as well.
In terms of the results, 8.7 months of median rPFS. These were patients both in the escalation as well as the expansion phase. The expansion dose was 2.7 mg per kilogram. In addition to the 8.7 months of median rPFS, there was a 36% PSA50 response, 20% ORR, and the duration of response for the ORR was seven and a half months. It's important to note that all five of these 25 patients, there were 25 patients who were evaluable for ORR that were RECIST evaluable. The five patients that did have an ORR, all five of them were at the 2.7 mg per kilogram dose. That, in addition to some other pharmacokinetic data that was generated, we felt that it did demonstrate an important dose-response relationship. We saw the traditional or the classic MMAE-based adverse events.
Primarily, if you're looking at those that had Grade 3 or above that are bolded here, you'll see the classic neutropenia adverse event that is associated with this particular payload. That's important to pay attention to this as we think about then some additional data that has been generated as well as the design of our ongoing phase II trial. There was a Grade 1 and 2 peripheral neuropathy. Only one patient had Grade 3 peripheral neuropathy. This can be a problematic adverse event, especially as patients are on therapy for a prolonged period of time. So it's another adverse event that we are paying close attention to throughout the ongoing phase II trial. In addition to the phase I monotherapy trial, there was also a pretty large phase I-B/II IST at UCSF. Again, the typical design dose escalation followed by dose expansion.
This was in combination with enzalutamide on patients who had progressed on one or more prior ARPIs. The majority of patients progressed on two or more ARPIs. In the total population, 44 patients, median rPFS of seven months with a 22% PSA50 response. Importantly, in those patients who had progressed on only one ARPI, which is the design of our ongoing phase II trial, there was encouraging anti-tumor activity, 10.1 months of median rPFS, and a PSA50 response of 40%. Dr. Rahul Aggarwal, the principal investigator of this particular IST, he was also the PI of the phase I monotherapy trial and is the PI of our ongoing phase II trial, presented this data at ASCO GU earlier this year, and he termed this as encouraging anti-tumor activity, particularly in those patients who had progressed on one prior ARPI.
Thinking about that adverse event profile that I shared on the phase I monotherapy trial, Dr. Aggarwal and his colleagues went about trying to figure out how they could knock that Grade 3 and above neutropenia rate down. The reason that was important is because a number of those patients who had Grade 3 or greater neutropenia had to be either dose adjusted or dose stopped or downward titrated from that 2.4 mg per kilogram or 2.1 mg per kilogram in his IST, as well as in the phase I monotherapy trial. He utilized prophylactic G-CSF on all of the patients in his IST. If you look at the third column from the right, that rate of neutropenia in the orange of Grade 3 or greater, which in the phase I monotherapy trial was roughly 30%-35%.
You can see he knocked that down to about 5%. That's an important strategy that we have employed in our ongoing phase II monotherapy trial as well. As we think about how the data that's been generated to date compares to other programs at a similar stage of development, as well as in late-stage trials. Down at the bottom, you can see the 8.7 months of median rPFS in the phase I monotherapy trial in that heavily pre-treated patient population. Then the 10.1 months of rPFS in the patients who had progressed on one prior ARPI in the combination trial with enzalutamide. As we think about those results and we think about the ongoing phase II trial, we're really paying a lot of attention to the PSMAfore results that Pluvicto generated that led to the second indication for Pluvicto. The initial indication was post-chemotherapy.
This indication is post progression on one prior ARPI and prior to chemotherapy, 9.3 months of rPFS. This, in essence, has set the standard or the hurdle that we're going after in our phase II trial. We believe that we need to achieve a median rPFS of at least 10 months for us to then be confident that we've got a profile that we can take into the phase III portion of the trial. Speaking of the ongoing phase II trial, it is a monotherapy trial. It's a dose optimization in, again, this post-one ARPI pre-chemo setting. We're looking at three different dose cohorts, 1.8 mg, 2.4 mg, and 2.7 mg per kilogram. We do expect an interim analysis in the fourth quarter of this year that's planned for up to 12 weeks after 10 - 12 patients have reached this composite endpoint of PSA50 and ORR.
In order to continue the phase II trial, we are looking at a composite endpoint result that is similar to what we saw in the phase I monotherapy trial because we are most interested in getting into 2027 and being able to generate more mature rPFS data. The final analysis planned for 12 months after 25 patients are enrolled in each cohort. We are going to look at the benefit risk assessment, the recommended phase III dose. We are also going to be talking about the companion PET imaging agent that we have, FG-3180. Going back to Dr. Aggarwal's IST, in addition to being able to institute the prophylaxis with G-CSF to knock that neutropenia rate down, Dr. Aggarwal was also able to demonstrate for the first time an association between higher tumor uptake of the PET 46 agent with PSA50 response.
This was measured by the SUVmax AB over the SUV and the mean blood pool. On the right-hand side, you see what is a pretty typical scan of a patient who has really lit up well with CD46. That is what you see in the yellow and the red. If you are able to quantitatively measure that and then look at the patients who responded via a PSA50 response versus those that did not respond to the ADC, you see those that responded were more likely to have a higher expression of CD46. Again, that is an important part of our ongoing phase II trial as we are going to do in addition to the 25 patients that Dr. Aggarwal was able to measure this against in his IST.
We have got 75 patients in our ongoing phase II monotherapy trial where we are going to be able to look at CD46 expression as measured by the PET imaging agent. They come into the trial, they get the PET imaging agent, five or six days later, they come back, and they get their PET scan, and they are immediately started on cycle one with the ADC. We are going to be able to, over time, throughout the conduct of the phase II trial, continue to do assessments of CD46 expression and also assessments of the correlation between expression levels and response to the ADC. The premise is, as we think about 10 months being this benchmark of rPFS that we would like to see in the phase II trial, that can either be in an all-comers population, or it could be in those patients who are higher expressors of CD46.
If there is a correlation from this phase II trial of expression and response, that would allow us to then enrich the phase III portion of the program with those patients who are higher expressors of CD46. There are three important design elements in our ongoing phase II trial that we think can improve upon the 8.7 months of rPFS that was demonstrated in the phase I monotherapy trial. First is using three of the highest doses of the monotherapy trial. Second, as I spoke about, using prophylactic G-CSF to knock down that neutropenia, which led to dose interruption and downward titration. Then moving patients up line instead of a median of five prior lines of therapy, looking at first or second-line mCRPC. We are actively enrolling patients.
We've got 23 sites activated in the U.S., with one in startup mode, and they're the who's who, if you will, of oncology clinical trials. Again, in terms of near-term development highlights, we think we've got a strategy that provides significant optionality in prostate cancer with a robust monotherapy trial in phase II that's ongoing, which could unlock multiple pathways from a registrational perspective, either sequentially or in parallel. Again, the upcoming catalyst for us is the interim analysis in the fourth quarter of this year. Turning to roxadustat again, as I mentioned, roxadustat approved in more than 40 markets for anemia associated with chronic kidney disease. Unfortunately, we received a complete response letter in anemia of CKD back in 2021 when AZ was a license holder.
We were able to get the license back, and we are now pursuing an opportunity for roxadustat in anemia associated with lower risk MDS. If you're not familiar with lower risk MDS, it's an orphan disease. About 75,000 patients live with MDS in the U.S. The vast majority of them suffer from really debilitating anemia, which impacts the quality of life. The current agents that are available, luspatercept and roxadustat ESAs, are effective in less than 50% of the patients, and the effects are not durable, and there are limited treatment options beyond first-line therapy. In addition, the standards of care are difficult to both calibrate as well as to administer. All these patients require in-office infusion or injections every three or four weeks. Roxadustat is an oral agent that can be taken at home three times a week.
There's continuing to be a significant unmet need for these patients. We did a subset analysis of roxadustat in a previous phase III trial in lower risk MDS, where we showed a numerical advantage but missed statistical significance in the primary endpoint of transfusion independence. It was really driven by an ultra-high placebo response, caused by the enrollment of patients who had a high transfusion burden or a low transfusion burden at baseline. When we went back and cut the data of those patients who had a high transfusion burden at baseline, as measured by four or more RBC units within an eight-week period of time, we saw a meaningful response for roxadustat relative to placebo.
Eight straight weeks of transfusion independence, both within the first 28 weeks of the trial as well as over the 52 weeks of the trial, 36% versus 7%, and 45% versus 13%. These results were nominally statistically significant. That's what gave us the conviction to approach the FDA in the middle part of last year through a type C meeting process, to seek their alignment with the potential to start another phase III trial in lower risk MDS in these high transfusion burden patients. That's exactly where we're headed. How we think roxadustat can play relative to the currently available opportunities is ESAs and luspatercept are not indicated. ESAs are not indicated, luspatercept is indicated as frontline therapy, but ESAs are used there, in both RS-positive as well as RS-negative patients.
Luspatercept is about a $2.5 billion a year drug in the BMS portfolio. The majority of that is in the U.S., the majority of that is in lower risk MDS, and they have not shown a benefit in the RS-negative patient population. We think that there's a great opportunity for an agent like roxadustat to be able to generate compelling data through another phase III program across both RS-positive and RS-negative patients in the second line and beyond setting. We think we can index especially well in the RS-negative setting, given some additional subset analysis that we did from that previous MATTERHORN data, which showed that relative to placebo, we had a very nice response in this RS-negative population.
That'll be an important design element for the phase III trial that again, we intend to activate the first site toward the end of this year. We've aligned with the FDA on the patient population. These high transfusion burden patients requiring four or more units over an eight-week period of time who are refractory to intolerant or ineligible for ESA therapy. On the safety side, we've gotten alignment on how we're going to manage thrombotic risk, both through inclusion, exclusion criteria, as well as if in fact an event occurs during the conduct of the trial. We're going to be looking at eight straight weeks of transfusion independence with key secondary endpoints at 12, 16, and 24 weeks.
Again, a dose regimen that is entirely consistent with the previous phase III MATTERHORN trial of 2.5 mg per kg to start, maximum dose of 3.5 mg per kilogram with a titration algorithm that ensures that we don't raise hemoglobin too high, too fast. The phase III protocol is finalized, again, with the goal of initiating the trial in the fourth quarter of this year. I can't highlight enough the substantial unmet need that exists in this particular condition, and that we believe we've got the opportunity for a highly differentiated profile with roxadustat, both in terms of its safety profile as well as its route of administration. The market opportunity is substantial.
We think that the worldwide MDS market is expected to exceed more than $4 billion within the next five years, and it doesn't take a large share of that in order to carve out a pretty meaningful revenue line. That is it. Thank you guys very much, and be happy to take any questions that you have.
We have a moment to take maybe one question if there are any in the audience. Otherwise, we will wrap it there. Thank you again, Thane and Kyntra Bio for the-