Kyntra Bio, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

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 7 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 5-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 STEAP1, 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 Seagen payload that has been approved on 5 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 milligrams 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 resist evaluable. The five patients that did have an ORR, all five of them were at the 2.7 milligram 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 7 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 milligram per kilogram or 2.1 milligram 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%.