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DATE

Thursday, Aug. 13, 2026 at 5:00 p.m. ET

CALL PARTICIPANTS

  • LifeSci Advisors - Gaia Shamis
  • Chief Executive Officer - Thane Wettig
  • Chief Financial Officer - David DeLucia
  • Vice President of Product Development - Carol Gaddum

TAKEAWAYS

  • Total Revenue -- -$1.5 million in the second quarter of 2026 compared to $1.3 million in the second quarter of 2025, primarily due to drug product revenue adjustments.
  • Net Income -- $12.0 million, or $2.96 per basic and diluted share, compared to a net loss of $13.7 million in the same period one year ago.
  • Cash and Investments -- $95.7 million as of June 30, 2026, which management expects will be sufficient to fund operating plans into 2028.
  • Phase I Monotherapy rPFS -- 8.7 months demonstrated in heavily pre-treated patients with metastatic castration-resistant prostate cancer who were biomarker unselected.
  • Phase I Monotherapy PSA50 Response -- 36% for patients treated with FG-3246 in the monotherapy trial.
  • Combination Therapy rPFS -- 10.1 months for patients who progressed on one prior ARPI when FG-3246 was combined with enzalutamide.
  • Combination Therapy PSA50 Response -- 40% achieved in the investigator-initiated study for patients with one prior ARPI.
  • FG-3246 Phase II Enrollment -- 75 patients across three dose levels: 1.8 mg/kg, 2.4 mg/kg, and 2.7 mg/kg.
  • Phase II Interim Analysis -- Scheduled for the fourth quarter of 2026, including data from 36 patients on PSA50 response and safety.
  • Annual mCRPC Diagnoses -- 65,000 men in the U.S. diagnosed annually with drug-treatable castration-resistant metastatic disease.
  • CD46 Expression Frequency -- 50% to 70% of patients estimated to have tumors with high CD46 expression.
  • MMAE Payload Revenue -- $5 billion in worldwide revenue generated in 2025 by five marketed antibody-drug conjugates using this approach.
  • PSMA PET Market Revenue -- Almost $2 billion generated in 2025, highlighting the commercial potential for companion imaging agents like FG-3180.
  • Roxadustat Phase III Milestone -- Planned initiation in the fourth quarter of 2026 for the treatment of anemia in patients with lower-risk myelodysplastic syndromes.
  • MATTERHORN Post Hoc TI Rate -- 36% of patients with high transfusion burden achieved transfusion independence versus 7% in the placebo group.
  • Lower-Risk MDS Anemia Market -- 50,000 patients in the U.S., with current therapies effective for less than 50% of the population.
  • RS- Patient Population -- Represents over 50% of total lower-risk MDS patients, a segment where current leading therapies have not shown differentiated efficacy.
  • Operating Expenses -- $16.1 million in the second quarter of 2026 compared to $13.4 million in the prior year.
  • R&D Expenses -- $6.8 million, up from $5.9 million in the second quarter of 2025.
  • SG&A Expenses -- $9.3 million compared to $7.1 million for the same period last year.
  • Clinical Sites -- 23 live sites at top-tier U.S. institutions currently participating in the ongoing FG-3246 Phase II trial.
  • AstraZeneca Partnership Economics -- 35% entitlement to any economics accruing to the company if roxadustat is developed by a strategic partner.
  • Phase II Pluvicto Exposure -- Approximately 30% of randomized patients in the current FG-3246 trial were previously treated with Lutetium-177.

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RISKS

  • Carol Gaddum warned that "tissue availability is limited given the disease often just being bone disease," creating challenges in addressing scientific questions through biopsies.
  • Thane Wettig noted that if the company partners the roxadustat program, "AstraZeneca would then be entitled to 35% of any economics that would accrue to Kyntra Bio," affecting potential returns.

SUMMARY

Kyntra Bio, Inc. (KYNB +2.38%) reported financial results and clinical developments for the second quarter of 2026, highlighting the advancement of its lead programs in oncology and rare disease. Management emphasized the enrollment progress of the FG-3246 Phase II monotherapy trial in prostate cancer, utilizing optimized dosing and prophylaxis to improve upon previous clinical outcomes. The company confirmed the finalization of Phase III protocols for roxadustat in lower-risk myelodysplastic syndromes, identifying significant commercial opportunities in patient segments underserved by current standards of care. Financial performance included a net income gain driven by a non-cash item related to a subsidiary deconsolidation, while the current cash position is projected to support planned operations into 2028.

  • Wettig noted that the company is evaluating parallel paths for roxadustat, stating management will "ultimately make the call that we believe is in the best interest of shareholders" regarding internal development versus strategic partnering.
  • Gaddum indicated that the Phase III roxadustat trial includes a titration protocol allowing dose adjustments "every six weeks based on what we see from a benefit and risk perspective."
  • Management reported that CD46 expression is more uniform than PSMA with higher median expression in mCRPC tissues, potentially offering a broader therapeutic target for patients who progress on standard therapies.
  • The company is utilizing the FG-3180 PET imaging agent as a companion diagnostic to potentially enable patient selection and enrichment in future Phase III trials.
  • Wettig stated that the use of G-CSF prophylaxis in the current Phase II trial should lead to "fewer dose interruptions or adjustments, extending the duration of therapy" compared to previous studies.

INDUSTRY GLOSSARY

  • mCRPC: Metastatic castration-resistant prostate cancer, a stage of prostate cancer that has spread and no longer responds to testosterone-lowering treatments.
  • ADC: Antibody-drug conjugate, a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer.
  • rPFS: Radiographic progression-free survival, the length of time during and after treatment that a patient lives with the disease but it does not get worse as seen on imaging.
  • ARPI: Androgen receptor pathway inhibitor, a type of hormone therapy used to treat prostate cancer.
  • LR-MDS: Lower-risk myelodysplastic syndromes, a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells.
  • TI: Transfusion independence, the ability of a patient to maintain adequate hemoglobin levels without requiring red blood cell transfusions.
  • RS+ / RS-: Ring sideroblast positive or negative, referring to the presence or absence of specific abnormal red blood cell precursors used to subtype MDS.
  • HIF-PH: Hypoxia-inducible factor prolyl hydroxylase, an enzyme targeted by inhibitors like roxadustat to stimulate red blood cell production.
  • MMAE: Monomethyl auristatin E, a potent anti-mitotic agent used as a payload in several approved antibody-drug conjugates.
  • PET: Positron emission tomography, an imaging test that helps reveal how tissues and organs are functioning.

Full Conference Call Transcript

Operator: Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Gaia Shamis of LifeSci Advisors. Please go ahead.

Gaia Shamis: Thank you, Latonia, and good afternoon, everyone. Thank you for joining today to discuss Kyntra Bio's second quarter 2026 financial and business results. I'm Gaia Shamis from LifeSci Advisors. Joining me on today's call are Thane Wettig, Chief Executive Officer, David DeLucia, Chief Financial Officer, and Carol Gaddum, Vice President of Product Development. Following the prepared remarks, we will open the call to your questions. I would like to remind you that remarks made on today's call include forward-looking statements about Kyntra Bio.

Such statements may include, but are not limited to, collaborations with AstraZeneca and Astellas, financial guidance, the initiation, enrollment, design, conduct, and results of clinical trials, regulatory strategies and potential regulatory results, research and development activities, commercial results and results of operations, risks related to our business, and certain other business matters. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in the statement. A more complete description of these and other material risks can be found in Kyntra Bio's filing with the SEC, including our most recent Form 10-K and Form 10-Q.

Kyntra Bio does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise. The press release reporting the company's financial results and business updates, and a webcast of today's conference call can be found on the investor section of Kyntra Bio website at www.kyntrabio.com. With that, I would like to turn the call over to the CEO, Thane Wettig. Thane?

Thane Wettig: Thank you, Gaia. Good afternoon, everyone, and welcome to our second quarter 2026 earnings call. On today's call, I will provide an update on the important progress we have made across our clinical portfolio. First, with FG-3246, our potential first-in-class antibody drug conjugate targeting CD46 and its companion PET imaging agent in metastatic castration-resistant prostate cancer. Second, with roxadustat, our potential treatment for anemia due to lower risk myelodysplastic syndromes. Then David DeLucia, our CFO, will review the financials, after which we will open the call for your questions. Starting with slide three, I'd like to highlight our mid and late-stage programs and upcoming catalysts.

The phase II monotherapy trial for FG-3246 and its companion diagnostic FG-3180 in the post-ARPI pre-chemo setting in metastatic castration-resistant prostate cancer continues to actively enroll patients, and we are on track for the results from the interim analysis in the fourth quarter of this year. With our roxadustat program, the protocol for the phase III trial has been finalized, and we are advancing towards our goal of initiating the registrational trial in the fourth quarter of 2026. With a simplified capital structure and cash runway into 2028, we remain committed to executing on our strategic vision and look forward to the upcoming catalysts for both clinical programs. Let's start with the FG-3246 and FG-3180 program in mCRPC.

The unmet need for new treatments for the 65,000 men in the U.S. diagnosed every year with drug-treatable castration-resistant metastatic disease is substantial. Targeting CD46, a novel tumor-selected multifunctional epitope that helps tumors evade complement-dependent cytotoxicity could help address this need. Moving to slide five. What sets CD46 apart from non-PSMA tumor antigen targets for metastatic prostate cancer centers on four key points. First, it is highly expressed in prostate cancer and other tumors, yet with limited expression in normal tissue. Second, CD46 is upregulated during tumorigenesis as well as during the progression from localized castration-sensitive prostate cancer to metastatic castration-resistant prostate cancer. Third, an estimate 50%-70% of patients have high CD46-expressing tumors.

Finally, relative to PSMA, CD46 expression is more uniform with lower interpatient variability and with higher median expression in mCRPC tissues, which make it a compelling non-PSMA therapeutic target. Slide six highlights FG-3246, our CD46 targeting potential first-in-class ADC, which combines the YS5 antibody with an MMAE payload. MMAE is the payload for five currently marketed ADCs that generated approximately $5 billion in worldwide revenue in 2025, making it a well-characterized therapeutic approach for treating solid tumors. The YS5 antibody offers an androgen receptor-agnostic and non-PSMA approach, differentiating it from many of the prostate cancer treatments currently in development.

As with the ADC, our companion imaging agent, FG-3180, utilizes the same YS5 targeting antibody and is being developed under its own IND. We believe that having a patient selection biomarker could enable us to potentially enrich the patient population in a phase III trial, while also differentiating FG-3246 in the prostate cancer treatment paradigm. It also represents an important commercial opportunity as a companion diagnostic to FG-3246 similar to the existing PSMA PET agents, which generated revenue of almost $2 billion in 2025. FG-3180 is an important part of our ongoing phase II trial, where we will assess the correlation between CD46 expression as measured by the PET agent and response to FG-3246.

Our aim is a clinically differentiated therapeutic in a competitive yet highly unsatisfied mCRPC market. Importantly, we are the only non-PSMA program in mid to late-stage development that combines a therapeutic with a companion PET imaging agent. The excitement we have in this program comes from the clinical results for FG-3246 across two distinct trials. We believe these results, summarized on slide seven, are competitive when compared to other approved and investigational treatments. In the phase I monotherapy trial highlighted on the left part of the slide, FG-3246 demonstrated a median rPFS of 8.7 months in patients with mCRPC who were heavily pre-treated and were not biomarker selected, with PSA50 response of 36%.

20% of the 25 RECIST evaluable patients achieved an ORR with a meaningful duration of response of 7.5 months. It is important to note that all of these ORRs were demonstrated at the 2.7 mg/kg adjusted body weight dose utilized in the expansion phase of the trial, providing early evidence of a dose-response relationship. In the top line results from the phase I-B/II investigator-initiated study at UCSF summarized on the right side, combination of FG-3246 with enzalutamide demonstrated encouraging anti-tumor activity with seven months of median radiographic progression-free survival in biomarker unselected patients across the entire cohort of 44 patients.

Importantly, in patients who had progressed on only one prior ARPI, the combination of FG-3246 and enzalutamide achieved a meaningful median rPFS of 10.1 months with a PSA50 response of 40%. In addition to the efficacy measures, the IST provided us with important insights into the adverse event profile of the ADC. The use of G-CSF prophylaxis led to a significant decrease in Grade 3 or greater neutropenia compared to the phase I monotherapy trial.

This approach is now designed into our ongoing phase II monotherapy study, where our objective is to keep more patients on their initial dose without the same degree of dose interruption or reduction experienced in the phase I monotherapy trial with the aim to build upon the 8.7 months of rPFS demonstrated in the phase I trial. Moving to slide eight, an additional insight we gained from the IST is that higher tumor uptake of FG-3180 was associated with greater PSA50 response. The PET imaging on the right is from a patient with clear and meaningful expression of CD46 after exposure to FG-3180.

The bottom row of the table on the left shows that patients with a higher average maximum standardized uptake value or SUV of a target lesion when normalized to the SUV of the blood pool demonstrated a trend of greater PSA50 response to FG-3246 versus those with a lower SUV, with a nominal P value that just missed being statistically significant despite the small number of patients. This is the first observed association between CD46 expression and response to FG-3246. We aim to further characterize this association as part of the ongoing phase II monotherapy trial.

Slide nine lays out the design for this phase II monotherapy trial, where we will enroll 75 patients in the post one ARPI pre-chemo setting across three dose levels with the primary objective to select the optimal phase III dose based on efficacy, safety, and PK measures. All patients in the study will be treated with FG-3180 in order to further explore the correlation between CD46 expression and response to the ADC in this biomarker unselected trial. The interim analysis of this open label trial is on track for the fourth quarter of this year and will include PSA50 response, ORR, safety, PK, and exposure response data. Futility will be assessed by a composite response rate of PSA50 and ORR.

Importantly, we expect mature rPFS data to become available throughout 2027 as patients continue their treatment with FG-3246 and the trial progresses toward completion. On slide 10, we would like to emphasize the three design elements we have incorporated with the aim of improving upon the 8.7 months of median rPFS demonstrated in the phase I trial. First, we are testing three of the highest doses from the phase I monotherapy study, 1.8, 2.4, and 2.7 mg/kg. Second, primary prophylaxis with G-CSF is being utilized to mitigate neutropenia, an approach which was successfully implemented in the phase II portion of the IST.

We believe reducing the incidence of Grade 3 or greater neutropenia should lead to fewer dose interruptions or adjustments, extending the duration of therapy and enabling more consistent exposure to the ADC of FG-3246. Third, we are enrolling patients who are earlier in the progression of mCRPC versus the median five prior lines of therapy in the phase I trial. The 10.1 months of median rPFS demonstrated in the IST in patients who progressed on only one prior ARPI underscores the potential of FG-3246 in this patient population.

Together, we believe these design elements have the potential to improve upon the phase I results and achieve a median rPFS of 10 months or greater, which can be viewed as a threshold for commercial competitiveness. Slide 10 shows the sites who are participating in the ongoing phase II trial. We now have 23 sites live at top-tier U.S. institutions, and we continue to be encouraged by our progress to date. We remain on track for the interim analysis of 36 patients in the fourth quarter of this year.

To conclude this update on FG-3246, we are actively enrolling patients in our phase II monotherapy trial in the post one ARPI pre-chemo mCRPC setting with important design elements in place that we believe could enable FG-3246 to surpass the 8.7 months of median rPFS demonstrated in the phase I trial. We look forward to the interim analysis in the fourth quarter of this year. Moving on to the roxadustat lower risk myelodysplastic syndromes program on slide 13. There are approximately 50,000 patients with anemia associated with lower risk MDS in the U.S., with current therapies effective in less than 50% of these patients.

With no oral options currently on the market or in late-stage development, there is a significant opportunity for an effective, durable, convenient oral treatment that works across multiple lines of therapy. Slide 14 highlights why we believe roxadustat can be that treatment. In a post hoc analysis of high transfusion burden patients from our previous phase III MATTERHORN study, using the international working group definition for high transfusion burden of four or more RBC units in two consecutive eight-week periods, we saw that 36% of patients treated with roxadustat achieved transfusion independence for at least eight straight weeks versus only 7% in the placebo group, with a nominal P value of 0.041.

These results are highly similar to the pivotal trial results for the two most recently approved therapies for anemia associated with lower risk MDS. Turning to slide 15, based on these results, our target indication is intended to be for the treatment of anemia in patients with lower risk MDS who are refractory to or ineligible for prior ESA treatment, where we believe roxadustat can raise the standard of care across multiple lines of treatment. We believe we also have a unique opportunity to demonstrate transfusion independence across both RS+ and RS- patients.

As presented in our most recent disclosure at EHA, the European Hematology Association, in a post hoc analysis of the phase III MATTERHORN study, roxadustat demonstrated similar rates of transfusion independence across both RS+ and RS- patients. Primary research that we have conducted with practicing clinicians indicates that roxadustat has the potential to be a useful treatment in both of these patient segments. The RS- opportunity, which represents majority of lower risk MDS patients, is especially relevant given luspatercept, the market leading brand in the treatment of lower risk MDS, has not demonstrated clinically differentiated efficacy in this segment of the lower risk MDS population and is not indicated for use in the second-line setting in RS- patients.

We believe that demonstrating similar efficacy across the entire patient population could position roxadustat favorably in the treatment paradigm of lower risk MDS. Slide 16 provides an overview of the phase III trial. Following our interactions with the FDA, we have now finalized the protocol for the phase III study, which includes a primary endpoint of 8-week transfusion independence over the first 24 weeks of the trial, with key secondary endpoints of 12, 16, and 24-week transfusion independence over 48 weeks. We continue to explore the opportunity to develop roxadustat internally or with a strategic partner, which aligns with our goal of initiating the study in the fourth quarter of 2026.

To summarize the roxadustat opportunity in lower risk MDS on slide 17, with a substantial unmet need, no oral therapeutic options on the market or in late development, significant potential in RS- patients, and an Orphan Drug Designation in hand, we see roxadustat as a compelling commercial opportunity. We have continued to make important progress with the phase III enabling activities. With that, I will now turn the call over to Dave to discuss the company's financials. Dave?

David DeLucia: Thank you, Thane. For the second quarter of 2026, total revenue was -$1.5 million compared to $1.3 million for the same period in 2025. Total operating costs and expenses for the second quarter of 2026 were $16.1 million compared to $13.4 million for the second quarter of 2025. R&D expenses for the second quarter of 2026 were $6.8 million compared to $5.9 million in the second quarter of 2025. SG&A expenses for the second quarter of 2026 were $9.3 million compared to $7.1 million in the second quarter of 2025.

During the second quarter of 2026, we recorded a net income from continuing operations of $12 million, or $2.96 net income per basic and diluted share, compared to a net loss of $13.7 million, or $3.38 net loss per basic and diluted share one year ago. Now shifting towards cash. As of June 30th, we reported $95.7 million in cash equivalents, investments, and accounts receivable. We expect the company to have a cash runway into 2028, enabling us to continue to invest in our U.S. pipeline opportunities. Thank you. I will now turn the call back over to Thane.

Thane Wettig: Thank you, Dave. We entered the second half of 2026 with promising momentum. We will continue our disciplined execution of the FG-3246 and FG-3180 program with results from the interim analysis of the phase II monotherapy trial expected in the fourth quarter of 2026, and continue the phase III enabling activities for roxadustat with the goal of initiating the phase III trial in lower risk MDS in the fourth quarter of 2026. With that, I would now like to turn the call over to the operator for Q&A.

Operator: Certainly. As a reminder, to ask a question, please press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star one again. Please stand by while we compile our Q&A roster. Our first question will come from the line of Alex Ramsey of William Blair. Your line is open.

Alex Ramsey: Hi, this is Alex on for Andy. For the upcoming phase III trial of roxadustat, the dosing regimen begins with 2.5 mg/kg with potential for titrating up to 3.5. We were just wondering how that determination is made, and if it's based on tolerability or efficacy, and how long after starting the treatment the assessment is made. What the titration interval is from both a timing and a dosing perspective.

Thane Wettig: Yeah. Thanks, Alex, for the call. I am going to hand that question over to Carol Gaddum, our VP of Product Development. Carol?

Carol Gaddum: Thank you for the question. Up titration or down titration is based on an assessment of benefit and risk, as you have highlighted, and the assessment is, or a change in dose is possible every six weeks based on what we see from a benefit and risk perspective.

Alex Ramsey: Perfect. Thank you so much. Is it straight from 2.5 to 3.5 mg/kg if they go up in dose, or is there some interval in between? Or some-

Carol Gaddum: There are some intervals in between. There are some intervals in between.

Alex Ramsey: Okay.

Carol Gaddum: Yes.

Alex Ramsey: Okay, perfect. Thank you so much.

Thane Wettig: Yeah. Alex, there will be very specific guidance to the sites on the titration either up or down based upon a number of factors including hemoglobin level and the rate of rise of that hemoglobin level as well.

Alex Ramsey: Perfect. Thank you so much.

Operator: Our next question will be coming from the line of Matthew Keller of H.C. Wainwright. Your line is open.

Matthew Keller: Hey, good afternoon, everyone. Thanks for taking our questions. I guess on the roxadustat program as well. First, I was wondering if you could remind us how contingent are you starting the phase III on a partner? Then a follow-up to that, I was wondering is how has the MATTERHORN data changed your calculus at all on potentially partnering that program?

Thane Wettig: Hey, thanks, Matt, for the question. The start of the phase III, as we've stated previously, we are undergoing both the opportunity to develop internally as well as partner the program. To develop internally, we would have to bring in capital in order to do that. That's a consideration while we also evaluate strategic partners as well. We're running a parallel path with both of these. At the end of the day, we're going to make the decision that we believe is in the best interest of shareholders. There are some dynamics in play related to economics.

If you think about the license that we wholly own in North America and South America, that was a license that was previously held by AstraZeneca during the development of the CKD program. When we negotiated those rights back from AstraZeneca, if we were to develop roxadustat on our own and commercialize on our own, we would owe AstraZeneca a mid-single-digit royalty on net sales. If we were to partner the program with a strategic and somebody else were to develop and commercialize, AstraZeneca would then be entitled to 35% of any economics that would accrue to Kyntra Bio. That's one consideration from an economic perspective. Clearly, there are strategic and operational considerations that we continue to evaluate.

As I said, we're going to ultimately make the call that we believe is in the best interest of shareholders.

Matthew Keller: Yeah, it totally makes sense. Then can you comment at all about how the RS data is maybe playing into that, if at all? If I may, kind of an adjacent question, did the RS data also influence the potential phase III design at all? Sorry, I'm going to pepper you with a couple there.

Thane Wettig: No, it's a great question. The RS dynamic with respect to RS+ and RS-, there's clearly a larger unmet need in the marketplace for RS- patients given the fact that luspatercept has not been able to really show any sort of a benefit relative to ESAs in that particular patient population, and the fact they're not indicated in the second-line setting for RS- patients. The understanding of that dynamic obviously plays into how we think about the opportunity, how we think about the clinical design, how we think about the ultimate forecast should we be successful in the phase III trial.

We're going to make sure that we enroll a requisite number of both RS+ and RS- patients in the phase III trial so that we can have the power to be able to demonstrate that roxadustat works across both of those patient populations. But the RS- opportunity or the MATTERHORN data, we'd be pursuing this regardless of the opportunity for roxadustat to perhaps show a differential benefit in RS- patients relative to RS+ patients. But it clearly does give us, we think, a really nice commercial opportunity across both segments, but especially in the RS- population, which makes up more than 50% of the total patients who have lower-risk myelodysplastic syndrome. Did that answer your question, Matt?

Matthew Keller: It absolutely did. Thank you so much for the color. I really appreciate it.

Thane Wettig: Yeah. David or Carol, anything to add to that?

Carol Gaddum: Thank you. The only thing I would add is, you asked around how MATTERHORN informed the phase III design, it has obviously been a significant driver of the phase III design. Went through a comprehensive analysis of what variables were driving outcomes, roxadustat versus placebo, and isolated transfusion burden as the key variable, and have designed the phase III trial accordingly. To Thane's point, the analysis also shows that roxadustat improves transfusion independence and hemoglobin across RS+ and RS-. That is also reflected in the phase III design.

Matthew Keller: Makes sense. Thank you.

Operator: Our next question will be coming from the line of Michael King of Rodman & Renshaw, LLC. Your line is open.

Michael King: Thanks for taking the question, guys. If I could, I would like to pivot to FG-3246 and FG-3180. Couple of questions on the program. I am just curious how you guys look at it as far as, I know it is one to two prior lines and one prior ARPI, but I am just curious what you anticipate the enrollment might be for individuals who have been treated with Lutetium-177. Whether you can enrich enrollment for that population. The reason I am asking is I am trying to think about whether there is any element of the design of the phase II that could propel you towards some kind of an accelerated approval strategy.

Thane Wettig: Yeah, it's a great question, Mike, and I appreciate the question. I'll go ahead and kick it off, and then Carol, I'll hand it over to you for additional commentary. To your point, we clearly are allowing prior Pluvicto-treated patients into the trial. At the outset of the trial, we kind of had an estimate as it relates to what percent of patients were going to be previous Pluvicto-treated patients.

This far into the trial, while we're not disclosing our enrollment stats yet, what we can say is about 30% of patients who have been enrolled into the trial and randomized were previously treated with Pluvicto, and we've got a pre-specified analysis based upon prior Pluvicto exposure or not so that we've got that built into the SAP so that we will be able to clearly determine is there any sort of a differential impact or effect from FG-3246 based upon prior Pluvicto exposure. Haven't really thought about the ability to go for accelerated approval in that particular patient population if we showed a really nice benefit, but it's an interesting thought.

Ultimately, we're going to be data-driven based upon the outcome of the phase II trial. Carol, go ahead.

Carol Gaddum: No additions from my side.

Michael King: I just wonder, has there been any inflection? Because, I know it's early days, but Novartis just recently received first-line indication. I wonder if that 30% proportion might increase going forward from here.

Thane Wettig: Yeah, it very well could. I think what we've found is that you do not see an immediate or instantaneous adoption, especially in the area of therapy where ARPIs have been really cemented as standard care, both in the castration-sensitive phase as well as if they have not been previously treated with an ARPI in the castration-resistant phase as well. It is something we will continue to keep an eye on. We are closely evaluating the patients who are enrolled to understand, are we seeing an inflection in previously Pluvicto-treated patients? It is clearly an important consideration for us.

Carol Gaddum: Yeah, I would just add to that there is obviously the dynamic around enrollment, and that is obviously also highly driven by the sites in particular and the treatment practice at the individual sites. As we think about the design of a global phase III, we are obviously very closely monitoring market shares in the pre and mCRPC setting and then the metastatic setting to understand eligibility criteria, but also how you set up the control arm and what is the appropriate prior line of therapy. So point well taken around there being a lot of movement in that space.

Michael King: Yeah. Sorry to keep belaboring this point, but one other question I wanted to ask, and that is I know PET imaging is your key guide towards response. I am wondering, is it possible to get both pre and post-treatment biopsy from these individuals? Because I am just curious about the levels of expression of PSMA prior to therapy and post-therapy to see if there is any correlation with the level of expression with PSMA. Are you going to be more active sort of in the post-PSMA setting, less active, or indifferent to PSMA?

Thane Wettig: No, thanks, Mike. Carol, you want to take that one?

Carol Gaddum: Sure. Yeah. It is certainly a very interesting scientific question, and we are doing a lot in terms of tissue collection, PSMA scans, PET scans, and our FG-3180 scans as much as possible to understand how it evolves over time. As you can appreciate, there are limitations as to the burden that you can put on patients.

Michael King: Sure.

Carol Gaddum: This is a bit more on a best effort basis, but it is certainly a key question to address. What I would also just say is, in this disease area, the tissue availability is limited given the disease often just being bone disease and also tissue availability if it is soft tissue disease. So we are coming up against some challenges here in terms of disease, but we are doing all we can to address that scientific question.

Michael King: Well, I know the Prostate Cancer Working Group just updated their guidelines to encourage the use of ctDNA. I do not know, are you going to be looking at ctDNA in these patients?

Carol Gaddum: Correct. Yes, we are.

Thane Wettig: Absolutely. We definitely are. In fact, in the phase I monotherapy trial, there was a really nice ctDNA effect with FG-3246.

Michael King: Okay. All right. I think I've exhausted my questions for now. Thank you.

Thane Wettig: I appreciate it, Mike.

Operator: Our next question will come from the line of Jay Olson of Oppenheimer. Your line is open, Jay.

Jay Olson: Oh, hey. Congrats on all the progress, and thanks for taking our questions. We had a couple questions, starting with FG-3246. Can you just talk about how you're thinking of positioning FG-3246 as a differentiated non-PSMA approach to mCRPCs? Is the greatest opportunity in PSMA-low or PSMA-negative patients, or do you see CD46 targeted therapy as potentially complementary to PSMA-directed approaches? Then just on roxadustat from a longer-term perspective, how are you thinking about eventually moving into the first-line setting? Thank you.

Thane Wettig: Sure thing. Thanks, Jay. Good to hear from you. Carol, you want to take that one, then I'll add on?

Carol Gaddum: Sure. Yeah. I think these are exactly the type of questions we're looking to address with the phase II, and that's why we're allowing prior Lutetium-177 to understand how responses are similar or different in different patient subpopulations. To the prior question, we're also doing the scans to really understand where the patients fall and where there's the greatest unmet need and where we have the most compelling value proposition for FG-3180. I think all strategic options are here on the table, and it ultimately will be data-driven. Then to your point around moving up lines, I think that's what we've traditionally seen, right? Is from the post-chemo setting into the pre-chemo setting into the hormone-sensitive setting.

So those are certainly part of our life cycle considerations moving forward. Thane, back to you.

Thane Wettig: Yeah. Thanks, Carol. Jay, maybe one other comment, and this just comes from discussions with clinicians in this space. This isn't based upon dozens of interviews like we would do as we would contemplate a phase III design. But in speaking with some KOLs, they believe that a PSMA approach will continue to be kind of standard of care in this pre-chemo setting. What they also talk about is with the ARPIs, they're being used more in the castration-sensitive phase, and that clinicians are shying away from this ARPI switch approach just because you only get an incremental 4-6 months of additional rPFS when you switch from one ARPI to another.

So they think that the PSMA approach, like Pluvicto or other PSMA-directed therapies, would be standard of care once a patient has progressed on an ARPI. Once a patient then progresses on a PSMA-directed therapy, they tend to think about a different target, but they also tend to think about a different modality. So if they were on an RLT that targeted PSMA, they then might think about an ADC that targets a different epitope, like CD46. So they wouldn't go from an RLT that targets PSMA to an ADC that targets PSMA. They also may not go from an RLT that targets PSMA to an RLT that targets another epitope. Again, it's more anecdotal than anything.

We'll continue to, as Carol said, explore it. It'll be heavily driven by what we see in our phase II trial. But yeah, it's something that we think about a lot as we contemplate what a phase III design could look like.

Jay Olson: Great. Thanks for taking the questions.

Thane Wettig: You bet.

Operator: I'd now like to turn the call back to Thane for closing remarks.

Thane Wettig: Yeah, we appreciate everybody joining us for today's second quarter earnings call and your continued interest in Kyntra Bio. Enjoy the rest of your day, guys.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.