Thanks for joining our Virtual Healthcare Conference. I'm Matt Biegler. I'm an analyst here covering up oncology here at Oppenheimer. Pleased to introduce our next presenting company, which is Kyntra Bio, and Thane Wettig, CEO. Thane, if you wanna roll through the slides?
Yeah. Thanks, Matt, and good afternoon, everybody. I appreciate the opportunity from the Oppenheimer team. I'm Thane Wettig, the Chief Executive Officer of Kyntra Bio. We rebranded from FibroGen to Kyntra Bio just ahead of the J.P. Morgan conference last month. We really did this to reflect the transformation that we have been undergoing for the past couple of years. FibroGen was founded on the basis of fibrosis and collagen. We're now focused on oncology and rare disease. We felt it was important to reflect that in the rebranding of the company to Kyntra Bio, to really take advantage of what we feel is a strong momentum and kinetic energy that we have right now with our go-forward approach.
This presentation is available on the IR portion of our website as well, for those of you that would like to refer to it after our discussion today. I'm also gonna be joined by David DeLucia, our Chief Financial Officer, for the Q&A portion of the presentation as well. Forward-looking statements. From an investment highlight perspective, I talked about the transformation into Kyntra Bio, which we believe allows us to create an outsized impact for both patients as well as the various stakeholders. In the latter part of last year, we completed the sale of FibroGen China to AstraZeneca, a total consideration of $220 million.
That allowed us to successfully pay off our term loan facility with Morgan Stanley Tactical Value, simplifying our capital structure, and in essence, wiping off all of the senior secured debt from our balance sheet, and extended our cash runway into 2028. It also enabled us to immediately start our phase II trial in metastatic castration-resistant prostate cancer with our assets, FG-3246 and FG-3180, which I will detail more fully in a moment. 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, prostate cancer. We've seen what we believe to be meaningful clinical responses in the previous clinical studies. It also has a companion PET imaging agent, FG-3180, that is also in clinical development as a potential patient selection biomarker.
As I stated, we have started the phase II monotherapy trial of FG-3246 and FG-3180 in the post-ARPI pre-chemo setting in mCRPC. We are enrolling with interim results expected in the latter part of this year. We also have a very interesting opportunity with roxadustat, which is the asset that formerly FibroGen is most well known for. It's a product that is approved in more than 40 countries, commercialized by AstraZeneca in China and Astellas in more than 40 markets for anemia associated with chronic kidney disease. We wholly own 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 who have a high red blood cell transfusion burden.
We have reached agreement with the FDA on the important phase III clinical design elements, and we believe that we've got a regulatory path forward to start the phase III trial in the second half of this year. We also have received orphan drug designation from the FDA, which was granted also in December. In terms of our upcoming catalysts, we'll talk about some data that's being presented today at ASCO GU on an IST of our ADC in combination with enzalutamide.
We would expect interim results from the phase II monotherapy trial of the ADC in the second half of this year. We have submitted the phase III protocol to the FDA and are waiting feedback from them, again, with the potential to start the phase III trial for roxadustat in lower-risk myelodysplastic syndrome in the second half of this year. Turning to our FG-3246 and FG-3180 program in mCRPC, the thing I'd like to highlight on this particular slide is how large the unmet need is in mCRPC. You hear a lot about, well, it's a highly competitive space. There's a lot of clinical activity. There is clear that patients need therapies that can extend survival, especially if you're ineligible for or who have progressed on androgen receptor pathway inhibitors and/or chemotherapy and really novel MOAs that can treat patients who progress on other available treatment options.
And in our case, you know, it's really important to have a non-PSMA approach, as well as the ability to combine the therapeutic with a diagnostic as well to help potentially inform patient selection. There's no doubt that there is going to continue to be some significant unmet need in the metastatic castration-resistant prostate cancer space. We've got a novel target in CD46. It's an epitope on the surface of cancer cells. It was a target that was identified by Bin Liu and colleagues at UCSF. They did an agnostic phage display trying to identify epitopes, which were highly expressed on cancer cells but weren't expressed elsewhere.
They identified CD46 as being highly expressed in a number of different tumors, prostate, colorectal, multiple myeloma, lung, to name a few, that was not also expressed in other tissues. The only other place you find CD46 expression is in placenta and in prostate epithelium. This is what then led the group at UCSF to engineer an antibody, YS5, specifically going after CD46. CD46 is overexpressed in mCRPC. There's a lot of attention focused on PSMA, but there are some other novel epitopes such as STEAP1, Trop-2, B7-H3, and CD46, which are becoming much more prevalent in terms of science associated with prostate cancer.
The expression of CD46 is upregulated as prostate cancer progresses from the castration-sensitive phase to the metastatic castration-resistant phase, and it's further overexpressed as patients are treated with these androgen receptor inhibitors. We estimate that about 50%-70% of mCRPC patients have high expression of CD46, and we also know, based upon genetic expression profiling, that CD46 is expressed more homogeneously and at higher levels compared to PSMA. We're very excited about the target, and we're very excited about the therapeutic that we have to go after this particular target. There are two components of our program. The first is the FG-3246 therapeutic, which is our targeting antibody, plus an MMAE payload.
This MMAE payload, as many of you, I'm sure, are aware, has been validated as a payload in a number of other cancer therapies that have been approved, none in prostate, but in other cancer therapies. We think it offers an androgen receptor agnostic and a non-PSMA approach. Again, the important part of this is the YS5 antibody, which is a fully human IgG1 antibody to the tumor-selective epitope of CD46, that, like I said, less accessible on most normal cells, which importantly also doesn't interfere with the complement system regulation. The other important component of the program, FG-3180, is the PET imaging agent. It uses the same YS5 targeting antibody delivered with a zirconium-89 tracer that, again, we think can potentially help inform patient selection in the further clinical development program.
In the phase I monotherapy study that was previously done by Fortis Therapeutics, which is the company from whom we licensed the FG-3246 program from, there was the dose escalation and the dose expansion phase, a total of 56 patients treated. The dose escalation phase looked at patients from 1.1 mg/ kg all the way up to 3 mg per kg. Baseline characteristics, not unlike a trial where patients have been treated with a median of 5 prior lines of therapy. You see, obviously, the androgen deprivation, you see a lot of androgen receptor inhibitor use as well, and a number of patients who have been on previous taxane therapy also.
In this phase I monotherapy trial, we did demonstrate an RPFS of 8.7 months. Again, this is in a patient population that had been treated with a prior line, 5 prior lines of therapy. Some people look at the PSA decline of 36%, the PSA 50 number of 36%, and thinks that that's a bit on the low side. We're gonna continue to focus on the RPFS number, again, because of the non-PSMA approach that we have here and the 8.7 months that was demonstrated in the efficacy in a valuable population from the phase I monotherapy trial. When we compare the our results in our phase I monotherapy trial to other programs in a similar phase...
You know, be careful not to draw too many conclusions here just because of the nature of cross-trial comparisons. If you think about the Janux program, where they showed really impressive PSA 50 and PSA 90 results, they haven't necessarily followed that with as impressive of an RPFS result, and that's why we're gonna continue to focus on RPFS as the most meaningful measure of our program going forward. The safety profile that we saw in our phase I monotherapy trial was consistent with other MMAE-based ADCs. You see, you know, a pretty high rate of neutropenia, neutrophil count decreases that were grade 3 and above. I'll talk about how we plan on mitigating that in a moment. Really, a very little additional grade 3 or above adverse events.
There was about a third of patients who did exhibit peripheral neuropathy. Most of those were grade 1 or grade 2. As you all know, sometimes grade 1 and 2 peripheral neuropathy can be problematic for a number of patients, so that's another adverse event that we're gonna continue to keep an eye on. This is data that is being presented by Rahul Aggarwal from UCSF today. It was an IST at UCSF and at 1B escalation phase and in a phase II expansion phase. 44 patients in total treated. The primary endpoint for the phase I portion was determining the MTD and the recommended phase II dose.
The primary endpoint from the phase II portion was a number of efficacy measures, as well as adverse event measures, in addition. This is data that was released in abstract form on Monday. Dr. Aggarwal, as we speak, is presenting the poster at ASCO GU. The total population, we had an RPFS of seven months and a PSA 50 response of 22%, which one may look at and say, that's a bit underwhelming. What we're most focused on, and I'll talk about why in a moment, are those patients who had progressed on only one prior ARPI, where the RPFS in that population, which was about 40% of this population, the RPFS of 10.1 months and a PSA 50 response of 40%.
We look at this, and when we think about the design of our ongoing phase II monotherapy trial, gives us a continued encouragement for the relevance of CD46 and our YS5 antibody as part of the ADC complex. We think this does demonstrate encouraging anti-tumor activity in patients who have progressed on only one prior ARPI. In terms of the adverse event profile, we see a pretty similar adverse event profile that we saw with the phase I monotherapy trial. A few of these, you saw a higher rate of fatigue, a higher rate of peripheral neuropathy, and a higher rate of anorexia that we think is due to the combination of enzalutamide with FG-3246.
I would like to point out that we think that the approach of utilizing GCSF as part of a mandatory prophylaxis of neutropenia worked really well in Dr. Aggarwal's IST. You'll see that that's an important design element of our phase II monotherapy trial, to really knock that grade 3 or above neutropenia rate down, that will then, we believe, allow patients to stay on their dose early in cycles of therapy and not have dose interruption or dose reduction, which was seen in our phase I monotherapy trial. One other really important part of the of the IST, again, that is being presented today, was for the first time we have seen an association between the tumor uptake of CD46 as measured by PET imaging and response to the ADC.
What you see there on the right is you see a PET scan, and in the red are the tumors where you see uptake of CD46 and as measured by our PET46 imaging agent. You see a nice profile of CD46 positive lesions. What we have here in the table on the left is a look at PSA50 response by the measure of the tumor volume that expresses CD46. Really pay attention to this row on the bottom. You have SUVmax AB and SUV in the blood pool.
Really, SUVmax measures this absolute peak uptake in a lesion, while the max in the mean blood pool normalizes that peak against the blood's background radioactivity and provides a more consistent and comparative metric for staging and how a therapy responds. They, in essence, quantify this by looking pixel by pixel within the PET image, to then come up with a degree or a measure of the expression of the target, and in our case, CD46, and then normalize it for background as well. You can see that if you are a higher expressor of CD46 versus a lower expressor, you are more likely to get a positive PSA 50 response. There was a strong trend, a p-value, that just missed statistical significance.
Obviously, it's a nominal p-value based upon a post-hoc analysis. Again, for the first time, we think that we now see evidence of a correlation between expression of the target, as measured by our PET imaging agent, in response to the ADC. That will be further evaluated in the ongoing phase II monotherapy trial. We look at our phase II monotherapy trial, we are treating 75 patients, 25 in each one of three dose cohorts: 1.8 mg/ kg, 2.4 mg/kg, and 2.7 mg/kg. Again, to remind everyone, 2.7 mg/ kg was the dose in the expansion phase of the phase I monotherapy trial. Unfortunately, a number of these patients had to be dose interrupted or downward titrated because of neutropenia.
We are going to use primary prophylaxis with GCSF to knock that neutropenia rate down, just as Dr. Aggarwal demonstrated in his IST. All patients will also undergo, be treated with FG-3180, the CD46 PET imaging agent. They'll get the PET imaging agent. Five or six days later, they'll come back for their baseline scan, and then get their first dose of the ADC. We will then do an interim analysis that we expect in the latter part of this year, that's planned for 12 weeks after 12 patients in each one of the arms are enrolled. We're gonna be looking at a composite response rate from a futility perspective, the PSA 50 and ORR.
We're gonna be looking for a similar result as we saw in the phase I monotherapy trial, because we really wanna get to the final analysis where we see fully mature RPFS data. That's gonna be the measure for us. We think that there are some important design elements that could enable us to build upon the 8.7 months of RPFS that we saw in the phase I monotherapy trial, using three of the higher doses, given the dose response relationship that we've established as part of the phase I monotherapy trial. All five of the ORRs that were experienced in the phase I trial were at the 2.7 mg per kg dose.
Utilization of primary prophylaxis of GCSF to mitigate against the MMAE adverse events like neutropenia, and then studying patients not with a previous five prior lines of therapy, but post 1 ARPI prior to chemotherapy. As we think about the goal that we're aiming at for this phase II trial, we really think we need to hit about 10 months of RPFS. Our best comparator, we believe, is the most recent PLUVICTO indication in this post 1 ARPI pre-chemo setting, where they demonstrated 9.3 months of RPFS to gain that indication. That's what we're, in essence, we're gonna be looking at as our hurdle rate for the phase II, and importantly, being able to further characterize the expression level of FG-3246 with response to the ADC. Now, turning to roxadustat.
The indication that we are now solely focused on for development of this fully owned asset in now what is the Kyntra Bio territories, which is North America, South America, and Australia, is anemia associated with lower-risk myelodysplastic syndrome. This represents a significant commercial opportunity. The leading product in the category is luspatercept or REBLOZYL from BMS. 2025 revenue of $2.3 billion, 80% of that revenue in the U.S., the majority of that revenue in lower-risk myelodysplastic syndrome. We believe that there is a substantial commercial opportunity given the fact that the majority of patients don't achieve transfusion independence when being treated with the currently available therapies. There's also an opportunity for a more durable response as well.
This, our approach is really predicated on data from a previous phase III trial of roxadustat in lower-risk MDS, where we showed a numerical advantage of transfusion independence, but missed statistical significance because of an unusually high placebo response rate that was driven by the enrollment of a number of patients who had a low transfusion burden at baseline. These are patients who, many of whom, would require one or two units over an eight-week period of time and would spontaneously become transfusion independent.
When we did the subset analysis and looked at those patients who have a high transfusion burden at baseline, as determined by the International Working Group definition of four or more RBC units in two consecutive eight-week periods of time, we saw a meaningful difference of transfusion independence with roxadustat over versus placebo in eight straight weeks over both 28 weeks and 52 weeks, and a result which was nominally statistically significant. This is what gave us the conviction to approach the FDA in 2025 through a type C meeting process, where we had a very good outcome with the agency.
Where we ultimately would see, pending a positive phase III trial and approval, where we see roxadustat being able to play in the current treatment setting is luspatercept currently is approved as a first-line agent based upon their head-to-head trial against ESAs, in both RS positive and RS negative. Although they did not study RS negative patients in their head-to-head trial against the ESAs. They're also indicated for second-line therapy only in RS positive patients. We think that roxadustat, based upon, again, a positive phase III trial, would have an opportunity to play both in second line as well as in third line therapy.
We think if we're able to demonstrate perhaps an effect that is similar across RS positive or RS negative patients, or maybe even an outsized effect in RS negative patients, we think we would even have an opportunity to move further up line. In terms of the trial design that we got alignment on with the FDA, we were aligned on the patient population, these high transfusion burden patients, refractory to, intolerant to, or ineligible for prior ESAs. We will ensure that we appropriately manage the potential thrombotic risk through eligibility, dose modification, and discontinuation criteria, looking at eight-week and 16-week RBC- TI response rates.
What we believe is a really strong and important part of our potential value proposition is the oral route of administration that the patient can take three times a week at home, as opposed to having to go into the clinic for IV infusion or sub-Q injection of an ESA or luspatercept, of a MEDALIST. We did submit the final protocol to the agency in December of 2025, and we are waiting to hear back from them. In addition to that, we did receive, as I stated earlier, orphan drug designation, which gives us sesven years of regulatory exclusivity in the U.S.
In summary, we think we've got a couple of really exciting opportunities with our ADC and phase II trial, with the companion PET imaging agent in metastatic castration-resistant prostate cancer, and then a phase III-ready opportunity with roxadustat in MDS. Relative to the MDS opportunity in roxadustat, we are undergoing the RFP process for the selection of a CRO. We've secured all of the clinical supply for the phase III trial, and we now are undertaking a parallel process where we are having conversations with strategics for potential business development opportunities, as well as the opportunity to run the trial on our own by raising various forms of capital.
We'll be able to determine what we think that path forward is that would lead to a phase II start in the second half of this year. We'll have further clarity on what that looks like in the next 90- 120 days. Matt, back to you. Appreciate again the opportunity.
Yeah, great. Thanks. It's a lot to get through in 20 minutes. Nice job. Perfect timing with the ASCO GU IST data out there today. Definitely wanna talk about that. It's kind of interesting. I'm sure the data is nuanced, but when I look at it from a high level, it almost looks like your monotherapy data looked better. Do you have any views on that? Is it a different patient population? Do you think there's a combination adverse events here that are leading patients to get either under dose or going on dose holidays, or maybe enza's just not a great partner? Like, what are your thoughts there?
Yeah, I wish Dr. Aggarwal were here and not presenting the poster as we speak, because he could speak to it much more explicitly than we can. Again, given the IST nature of the trial, we were hands-off up until just most recently, when the abstract was accepted and the poster content was put together. I think there are a couple of important points, Matt, is, these patients who are part of the combination with enzalutamide, you know, 60% of them were on two or three prior ARPI. That means that they were on two prior ARPIs, and then they were put on enzalutamide, so the third ARPI, or they were on three prior ARPIs, and they were put on enzalutamide to make it the fourth ARPI.
We just have to be cognizant of, you know, these patients having been heavily pre-treated with this ARPI category and really not looking to get any additional benefit of the combination therapy. That's really kind of, you know, what you think you may see from the ADC itself, but these were patients that were treated with a number of prior lines of therapy. You also have to look at the discontinuation rate of about 36%, which was much higher than we saw in the monotherapy trial.
Mm.
I think Dr. Aggarwal would probably say that's likely due to the fact that it was both enzalutamide and the ADC in combination. Like I tried to point out, there were a number of these adverse events where you saw 10 and 20 or higher percentage point increases in the adverse event than we saw in the phase I monotherapy trial with the ADC by itself. Then I think you used a dose of 2.1 mg/ kg in the combo trial, as opposed to the 2.7 mg/ kg, which was utilized in the phase I monotherapy trial. So I think there were a few reasons why.
Again, that's why we tend to wanna focus on those patients who had one prior ARPI, progressed on only one prior ARPI, and looking at that 10.1, so 10.1 months of RPFS in that patient population. Again, which we think, and Dr. Aggarwal also believes, is an encouraging sign as we continue to enroll the phase II trial.
Do you think that enzalutamide is a good choice for a partner? It seems like a lot of developers in prostate these days are combining with some form of taxane. Obviously, you know, it's kind of a chemo-on-chemo thing, whereas some of the other developers are looking at a T-cell engager plus taxane to kinda get synergies there. Yeah, what are your thoughts on maybe the ideal combination?
Yeah, I'm not sure yet. I don't think it's an ARPI after a number of ARPIs have already been utilized.
Mm-hmm.
You know, you clearly see the ARPIs moving forward into the castration-sensitive phase. You're also seeing less of this ARPI switch utilization.
Mm.
Where they'd go from, let's say, an enzalutamide to abiraterone or vice versa.
Mm.
You're, but at the same time, clinicians are wanting to put off chemotherapy as long as possible. We think there's a really important sweet spot here, post-ARPI, prior to chemotherapy, which is exactly what PLUVICTO proved when they did their PSMA fore trial, and they went head-to-head against an ARPI switch approach, right? I think that the, you know, when we ultimately see our phase II data, if we see data that we like, that we think can be competitive, and we take into the phase III portion of the trial, you know, we'll have to make the decision at that time. Is it a, you know, monotherapy approach against, for instance, you know, physicians', next choice? Might it be a head-to-head against PLUVICTO as a non-PSMA approach.
Mm-hmm.
We've got a lot to learn between now and then. You know, the phase II program will be highly informative of that. I will say that, you know, we're gonna continue to put a lot of effort and emphasis in the companion PET imaging approach.
Yep .
Right, the CD46 imaging agent. If we see, again, a correlation between tumor uptake of CD46 in response to the ADC in the phase II, and let's say that we come up with an RPFS that, you know, we look at and say, "Well, we're not really certain that that would be competitive," but we see an outsized RPFS in those patients that have higher expression of the target, then we would still consider that to be a win. That would allow us to go into the phase III portion of the program, self-select, select these patients who are higher expressers of CD46 and enroll them, and then get what we believe would be a, an RPFS result that would be competitive.
Yeah, that makes sense. On the plus side from today, it does look like that nice correlation with the PET imaging agent to select patients. What are your kind of internal thoughts on the percent of patients that would qualify as CD46 positive based on the PET diagnostic?
Yeah, yeah. We think that, you know, that there are based on what we know today, maybe 50%-70% of patients will be high expressers. We think that, you know, majority of patients, probably 80%+, express CD46. UCSF has done some work where they looked at both concordance and discordance of PSMA expression and CD46 expression, and they do see a high rate of concordance. They've also seen examples of patients who don't express PSMA, that do express CD46, and vice versa, those that don't express CD46 but that do express PSMA. We are gonna be able to see a number of patients, especially since we're allowing previously PLUVICTO treated patients into our phase II monotherapy trial, so they will have had previous PSMA scans.
We're gonna be able to, I think, do some characterization as it relates to not only, what percent of patients express CD46, what is the variability of that expression from no to low to moderate to high, and then how does that compare to these same patients in terms of their expression of PSMA. You know, we're gonna be a lot smarter about this in the coming months. You know, the good thing is, because of the open label nature of the trial and the fact that these patients will get the PET scan at the outset of the trial, we're gonna be able to, you know, start the characterization of CD46 expression early on.
Yeah. Maybe just one last question on the mechanism of action here, the MMA payload. I remember when I covered Ambrx getting a lot of flak for the fact there wasn't a topo-based payload, and it seems like all ADCs are heading in that direction with the high DAR, topo-based payload, cleavable linker, et cetera, and Ambrx always flew against that. It's interesting you're also using MMA payload. Maybe, maybe the rationale here is that in prostate, you know, the topo ones just don't make as much mechanistic sense, like irinotecan-type chemotherapies don't work as well, whereas in prostate, obviously, cabazitaxel are taxane-based. Do you have any thoughts on that?
No, I think, you know, this predates, right, the licensing of the program. I think that that's, that was the rationale that UCSF used at the time, and that Fortis bought into when they licensed the program out of UCSF. I'm not sure I really, well, you know, can comment any deeper on that as it relates to why MMAE was chosen as opposed to another payload. You know, we know with MMAE, it's been pretty well characterized, right? We know that it's been approved as a payload on a number of other PADCEV , a number of other chemotherapy agents. I think that it's been very well characterized and profiled, and we know what we're gonna get.
One of the important things that we're gonna be looking for, because in the phase I monotherapy trial, we didn't see any ocular events, which again, is has been demonstrated with some other ADCs. That might be an opportunity for us to demonstrate an advantage as well over other shots on goal.
Makes sense. Always good to talk to you guys. Yeah, well, congrats on the progress. Catch up soon.
No, thanks, man. Again, appreciate the opportunity, and thanks to the Oppenheimer team.
Absolutely.
Appreciate it.
All right.
See you guys. Thanks.