CorMedix Inc Aktie

Today's conference call is being recorded. [Operator Instructions] At this time, I would like to turn the conference call over to Dan Ferry from LifeSci Advisors. Please go ahead.

Good morning, and welcome to the CorMedix Second Quarter 2026 Earnings and Corporate Update Conference Call. Leading the call today is Joseph Todisco, Chairman and Chief Executive Officer of CorMedix. We're joined by Elizabeth Masson-Hurlburt, EVP and Chief Operating and Commercial Officer, and Susan Blum, EVP and Chief Financial Officer. In addition, Beth Zelnick Kaufman, EVP and Chief Legal and Compliance Officer and Corporate Secretary, and Dr. Matt David, EVP and Chief Business Officer, are on the line and will be available during the Q&A session.

Before we begin, I would like to remind everyone that during the call, management may make what are known as forward-looking statements within the meaning set forth in the Private Securities Litigation Reform Act of 1995. These statements are statements other than statements of historical fact regarding management's expectations, beliefs, goals, and plans, about the company's prospects and future financial position.

Actual results may differ materially from the estimates and projections on which these statements are based due to a variety of important factors, including the risks and uncertainties described in greater detail in CorMedix filings with the SEC, which are available free of charge at the SEC's website or upon request from CorMedix. CorMedix may not actually achieve the goals or plans described in these forward-looking statements. An investor should not place undue reliance on these statements. CorMedix does not intend to update these forward-looking statements, except as required by law.

During this call, the company will discuss certain non-GAAP [indiscernible] on Form 8-K, filed with the SEC. This information is also available on the Investor Relations section of CorMedix's website. At this time, it is now my pleasure to turn the call over to Joseph Todisco, Chairman and Chief Executive Officer of CorMedix. Joe, please go ahead.

Thank you, Dan. Navigate the evolving post-TDAPA landscape, meaningfully advancing our high-value pipeline, highlighted by the positive Phase 3 ReSPECT data for Rezzayo, and now working collaboratively with Mundipharma towards their submission of the sNDA for Rezzayo in the prophylaxis of invasive fungal disease. And lastly, deploying our capital in a disciplined manner to drive long-term value for shareholders while building an increasingly diversified and resilient business.

We announced this morning second quarter consolidated revenue of $101.9 million and adjusted EBITDA of $58.7 million. Susan will provide more granular details of second quarter financial results. Today we also announced that we've signed a multi-year commercial supply agreement for DefenCath with an additional large dialysis organization, or LDO. With this agreement, CorMedix now has commercial supply agreements in place with all 5 of the top dialysis providers in the U.S.

The newly signed LDO has placed an initial order and will initially begin a pilot of DefenCath in the third quarter of this year with a potential opportunity to expand utilization in 2027. We view the signing of this agreement as an important milestone and validation of DefenCath's clinical value proposition with the largest providers in the U.S. dialysis market.

Turning to guidance, we are reaffirming our full-year 2026 revenue guidance with a range of $325 million to $345 million, and raising our full-year adjusted EBITDA guidance to a new range of $125 million to $140 million. We will revisit guidance as the year progresses and as we gain additional visibility into post-TDAPA ordering patterns. While we're only a few weeks into the third quarter, DefenCath order volumes in July have tracked consistent with the post-TDAPA forecast underlying our financial guidance.

In addition to the new LDO agreement, we have signed contract amendments with our major customers covering third and fourth quarter 2026 pricing and in some instances pricing and volume commitments for 2027. These amendments give us improved visibility into pricing and utilization through year-end and are designed to keep patients on therapy through the reimbursement transition. We continue to focus significant internal resources on the DefenCath growth strategy through Medicare Advantage contracting, and I'm pleased with the progress of those discussions. Contracting cycles with these plans can be lengthy, and we have not assumed a contribution for Medicare Advantage in our 2026 guidance. Continually, Medicare Advantage represents a meaningful long-term growth avenue for DefenCath.

DefenCath's clinical value and its potential for meaningful downstream cost savings continue to be supported by a growing body of real-world evidence that our partners are publishing, and we anticipate additional data presentations this fall at the American Society of Nephrology's Kidney Week and at IDWeek.

Turning to our pipeline, we now have top-line results from the ReSPECT study, a Phase 3 clinical study evaluating Rezzayo for the prophylaxis of invasive fungal disease in adult immunosuppressed patients, or IFD. Assuming timely submission and FDA acceptance of the filing, we would anticipate agency action in the first half of the year, including the anticipated addition of 15 to 20 positions across both commercial and medical. These investments are sized to allow us to move quickly at approval while preserving flexibility if regulatory timelines shift and are already reflected in our narrowed full-year cash OPEX guidance of $145 million to $155 million. As a reminder, our cash OPEX guidance excludes non-cash charges such as stock-based compensation.

I would now like to turn the call over to our Chief Operating and Commercial Officer, Elizabeth Masson-Hurlburt, to provide an update on clinical activities. Liz, please go ahead.

Thank you, Joe, and good morning, everyone. As Joe mentioned, we were pleased to announce preliminary top-line results of the ReSPECT study at the end of April, and following a constructive pre-NDA meeting with the FDA, are working diligently with our partner, Mundipharma, in support of their submission of the sNDA for Rezzayo in prophylaxis in the third quarter.

As a reminder, the ReSPECT study met its primary endpoint for FDA of fungal-free survival at day 90, showing non-inferiority versus the standard antifungal regimen, or SAR, meeting the pre-specified non-inferiority margin. In addition, results showed a favorable profile across multiple secondary endpoints, most notably in treatment-emergent adverse events leading to dose reduction, interruption or withdrawal of study drugs, and study discontinuation.

As we stated previously, the objective with the ReSPECT study was to show comparable efficacy to standard of care while also demonstrating a favorable overall safety profile with regard to drug-drug interactions and toxicity. We believe the study has achieved this objective and that the results position Rezzayo, if approved, as a differentiated option for prophylaxis of IFD with a meaningful potential commercial opportunity. It's important to remember that this was a global study conducted by our partner, Mundipharma, who owns global IP rights and will pursue regulatory approvals outside of the United States.

Mundipharma is currently the holder of the U.S. NDA and under the terms of our agreement, transfers ownership of the NDA to CorMedix following approval of an sNDA for the prophylaxis indication, at which point CorMedix would own and control the U.S. assets. Under our agreement, the parties must work together on the publication of data and submissions to FDA. In terms of data publication, we currently expect additional data from the Phase 3 ReSPECT study to be published later this year at 1 or more medical conferences during the fourth quarter.

Turning to DefenCath, we also expect additional real-world evidence to be published in the fourth quarter, with multiple abstracts having been submitted to both ASN and IDWeek. Assuming acceptance, these publications will present the final results from the U.S. Renal Care real-world evidence study, which, at interim analysis, showed a meaningful impact on infection-related hospitalizations and catheter-related bloodstream infections, as well as 2 other external studies. The first will highlight the demonstrated efficacy of DefenCath when used in combination with chlorhexidine antimicrobial caps. The second is expected to highlight the clinical and economic benefits of DefenCath in the outpatient hemodialysis setting related to a meaningful reduction in tPA use by facilities.

All combined, we expect that these data will add to the growing body of evidence supporting the clinical and pharmacoeconomic value of DefenCath. Shifting gears to our Phase 3 TPN study, we recently submitted a protocol amendment to FDA that narrows certain exclusion criteria, which we believe can support increased enrollment in the coming months. And we have additionally activated additional sites. We will continue to update investors on our progress as we move through the year, and we continue to expect study completion in 2028. I would now like to turn the call over to Susan to discuss the company's second quarter financial results and financial position. Susan? Thank you.

Thank you, Liz, and good morning, everyone. We are pleased to announce our second quarter results which reflect strong execution across the business, continued demand for DefenCath, and the contribution from the acquired Melinta portfolio. As a reminder, because the Melinta acquisition closed in August 2025, the second quarter of 2026 is a full quarter of Melinta operations, while the second quarter of 2025 did not. Accordingly, year-over-year comparisons are heavily influenced by the broader product portfolio and cost structure of the combined company. We also filed our Form 10-Q this morning, and I encourage investors to review it for additional details and important disclosures.

Turning to the numbers, second quarter 2026 consolidated revenue was $101.9 million, compared with $39.7 million in the second quarter of 2025. Second quarter revenue included $66.1 million in sales of DefenCath and $35.8 million in revenue associated with the acquired Melinta portfolio. DefenCath sales increased year-over-year largely due to the onboarding of a large dialysis customer in mid-2025. Operating expenses were $34.2 million in the quarter, compared with $18.3 million in the second quarter of 2025, an increase of approximately 87%.

The increase of $15.9 million over the prior year period was driven primarily by the contribution of operating expenses from the Melinta acquisition for the full quarter and reflects the larger combined company. Research and development expenses were $6.7 million in the second quarter of 2026, compared with $2.4 million for the same period in 2025. The increase was due primarily to higher personnel and clinical trial services in support of ongoing clinical programs, including pediatric studies for several [indiscernible] and continued investments in the development of DefenCath for the TPN indications.

Sales and marketing expense increased approximately 95% to $12.4 million in the second quarter of 2026 from $6.4 million in the second quarter of 2025. The increase was due primarily to higher personnel costs associated with a larger product portfolio and related marketing programs. General and administrative expenses increased approximately 59% to $15.1 million in the second quarter of 2026 from $9.5 million in the second quarter of 2025. The increase was driven by higher costs associated with operating as a combined company following [indiscernible], including branded prescription drug fees and higher personnel, information technology, legal, and facilities costs. G&A expenses in the quarter also reflects a reduction to expense of $4.2 million, which represents the amount of expected insurance reimbursement of legal fees incurred by the company to support its ongoing securities litigation.

Of the $4.2 million credit reported in the second quarter, $2.7 million is the amount of credit that the company has incurred related to legal fees that were incurred in prior periods. On the bottom line, CorMedix recorded net income of $26.0 million, or $0.33 and $0.29 per basic and diluted share, respectively, in the second quarter of 2026, compared with net income of $19.8 million, or $0.29 and $0.28 per basic and diluted share, respectively, in the second quarter of 2025. In addition to net revenue and operating expenses, EPS was impacted by income tax expense of $12.7 million, as well as non-operating income and expenses net of approximately $4.2 million associated with the mark-to-market of marketable equity securities and contingent consideration, which reflects the approximate fair value of future milestone and royalties payable to former Melinta shareholders.

On a non-GAAP basis, adjusted EBITDA was $58.7 million for the second quarter of 2026, compared with adjusted EBITDA of $22.4 million in the second quarter of 2025. This adjusted EBITDA metric excludes non-cash items such as depreciation, amortization, and non-GAAP. We ended the second quarter with $256.7 million in cash and cash equivalents for this quarter.

For the first 6 months of 2026, net cash provided by operating activities was $128.6 million, compared with $49.7 million for the first 6 months of 2025. As Joe mentioned, we are confident in our fiscal year 2026 financial guidance, which includes full-year 2026 consolidated revenue of $325 million to $345 million, full-year DefenCath revenue guidance of $175 million to $195 million, and revised full-year adjusted EBITDA guidance of $125 million to $140 million. We continue to believe we are well positioned with a strong balance sheet, meaningful cash generation, and the financial flexibility to support our operating priorities, pipeline development, and shareholder value.

We have a lot of opportunity ahead of us. CorMedix has built meaningful momentum through the first half of 2026 across all 3 pillars of our investment thesis. First, DefenCath continues to perform in line with our internal expectations at the TDAPA expiration, demonstrating durable underlying utilization, which we believe positions the franchise to remain a meaningful value generator following the reimbursement transition. Second, we're advancing a pipeline of high-value late-stage opportunities, including Rezzayo for prophylaxis and DefenCath in TPN, which could meaningfully expand our long-term revenue opportunity.

And third, we have delivered significant profitability in cash generation over the last year. $277.8 million of adjusted EBITDA over the trailing 12 months, and $267 million of combined cash and investments at quarter end allows us to reinvest in growth and pursue business development opportunities. We remain confident in our outlook for this year and our past sustained growth and profitability beyond it. This concludes our prepared remarks, and I'll ask the operator to open up now for questions.

We will now begin the question and answer session.

[Operator Instructions] Our first question comes from Roanna Ruiz with Leerink. Please go ahead.

Hi, guys. This is Anna on for Roanna. Thanks so much for taking our question and congrats on the progress. I just wanted to check in on how the new multi-year agreement with the LDO is expected to impact your 2027 expectations and if you could give any color on how long it takes for a new site to reach this steady state production in line with other operators.

Okay, thanks, Anna. So we just recently signed that agreement and they're rolling out a pilot. We're waiting to see kind of actually what they're looking for and we're hopeful for additional utilization. So once we get better visibility, we'll be in a position probably to talk more about 2027. There's a lot of variables that go into 2027 guidance. I don't expect we'll be in a position to comment on it until either late this year or early next year. So there's just a lot of pushes and pulls. We don't have any cause now to either adjust the top or bottom of that guidance, but as we move through the year and we get better visibility, we can provide updates.

Sure, thanks. And is any of that LDO pilot included in the 2026 guidance?

No, no, right now it's, well obviously it's tracking the revenue, so it's within the revenue that we're seeing from the pilot is within our existing guidance. And for DefenCath, we are right now tracking to the kind of mid-top part of the DefenCath guidance. So let's see where we go through the year. And as I said, we'll update as we go.

Great. Thanks so much. Our next question comes from Leonid Timoshev with RBC Capital Markets. Please go ahead.

Hey, guys. Thanks for taking my question. I want to ask on maybe if you can comment on what you're seeing in terms of volume growth in the existing channels thus far in this quarter, just given that we're in the post-TDAPA period now. And then related to that, just as a follow-up, how are you thinking about how you're going to be able to do that?

So, look, in terms of volume growth, I think what we're seeing in July is really kind of stabilized volumes with the larger players, which is what we expected, and some attrition with the really small players, which is also what we expected, with some adoption and or Medicare Advantage contracting. I think we're cautiously optimistic we're making good progress. That, you know, perhaps we have something in place that takes effect early next year and starts to really impact the DefenCath volumes. Those are really the 2 levers that I see, you know, from the DefenCath standpoint. Now, the final ESRD rule, obviously they put out the proposed rule. It was a little bit different than what we were expecting in terms of the quarterly mechanism. I expect there's going to be a lot of comment on that. Not sure if that's actually what will make it into the final rule, but we'll expect the final rule.

Our next question comes from Jason Butler with Citizens JMP. Please go ahead.

Hi, thanks for taking the questions. First one, can you give any more color on the size or scope of the pilot study being conducted by the new LDO? And then for Rezzayo and profi, can you talk about, you know, since you had the Phase 3 results, the feedback you're getting from potential prescribers, just what the results are? Perception to that data has been as you think about a potential label expansion. Thank you.

Yes, look, right now the size and scope of the pilot, we've shifted initial order. We think it's a couple hundred clinics. We'll see where we can go from there. I don't want to get out over my skis on the pilot yet, Jason. So right now we're really happy to have finally gotten that LDO kind of over the hump and to the point of commercialization. So we're taking that 1 day by day. On the Rezzayo profi, the full data set is not yet out, so we really haven't been able to conduct a robust market research. As we said in the script, we are working with our partner, Mundipharma. We would expect it to be published later in the fourth quarter at 1 or more medical conferences. And once we have that data...

Great, thank you. Our next question comes from Serge Belanger with Needham & Company. Please go ahead. Thank you.

Hi, good morning. Thanks for taking the question. I guess first on the new LDO, first, congratulations. It's just a pilot program. I guess my question is why did the LDO decide to enter an agreement now? Now when the product has been available for 2 years and I know the company had some meaningful efforts to sign them up. Secondly, on Rezzayo, following your FDA meeting, just curious what your expectations are for potential labeling of the product. I believe a Phase 3 trial was conducted in allogeneic HSCT patients. Curious if you'll be able to address the broad patient population that could benefit from Rezzayo. Thanks.

Thanks, Serge. Look, on the new LDO, I really can't speak to the motivations of the company. Obviously, we have built a wealth of real-world evidence around the clinical efficacy and the pharmacoeconomic benefits of DefenCath, and as I said, we're happy that now they are choosing to begin implementation of DefenCath. On Rezzayo, look, it's going to be a label review issue. So until we work through this process, just coming out of the pre-NDA meeting, we don't have yet visibility of what the final label will be.

Our next question comes from Brandon Folkes with H.C. Wainwright. Please go ahead.

Hi, thanks for taking my question and congrats on the progress. Maybe just 1 from me. Can you just talk about the SG&A in the quarter and the updated guidance? Did you take any actions in the quarter, you know, whether it's especially on the sales and marketing infrastructure, right, just on DefenCath or the existing Melinta portfolio, just any color there on the expense discipline on the SG&A line. Thank you.

Thanks, Brandon. I'll let Susan comment. We didn't take any deliberate actions. We're obviously trending a little bit light on the expense side. Some of the staffing, some of that we're bringing on or is coming in later in the year. But, yes.

Also, we did, and we disclosed this in our Form 10-Q, we had a reduction of G&A for $4.2 million in the quarter. It's reflecting artificially low because of that. $2.7 million of that was incurred primarily in Q1 of 2026. So we added the deductible under our insurance policies for the litigation costs. So we were able to claim the reimbursement of those, and that's what we reported in the second quarter. So it essentially eliminated those litigation legal fees that we had incurred in Q1 and in Q2 during the second quarter. So if you think about the run rate for expenses it would be maybe it would be $2.7 million higher because of what we reversed from prior periods.

That makes sense. It does. And then just to confirm, so, you know, there's been no action from the Department of Health on the DefenCath sales and marketing infrastructure ahead of sort of the lower re-embedding period? No, there have been no actions taken in the company. Perfect. Thank you very much and congrats on the progress. Thank you.

This concludes our question and answer session. Thank you for attending today's presentation. You may now disconnect.

Good morning, and welcome to the CorMedix First Quarter 2026 Earnings and Corporate Update Conference Call. Today's conference call is being recorded. At this time, I would like to turn the conference call over to Dan Ferry from LifeSci Advisors. Please go ahead.

Good morning, and welcome to the CorMedix First Quarter 2026 Earnings and Corporate Update Conference Call. Leading the call today is Joe Todisco, Chairman and Chief Executive Officer of CorMedix. And he is joined by Liz Hurlburt, EVP and Chief Operating Officer; and Susan Blum, EVP and Chief Financial Officer. In addition, Beth Zelnick Kaufman, EVP and Chief Legal and Compliance Officer and Corporate Secretary; Mike Seckler, EVP and Chief Commercial Officer; and Dr. Matt David, EVP and Chief Business Officer, are also on the line and will be available during the Q&A session.

Before we begin, I would like to remind everyone that during the call, management may make what are known as forward-looking statements within the meaning set forth in the Private Securities Litigation Reform Act of 1995. These statements are statements other than statements of historical fact regarding management's expectations, beliefs, goals and plans about the company's prospects and future financial position. Actual results may differ materially from the estimates and projections on which these statements are based due to a variety of important factors, including the risks and uncertainties described in greater detail in CorMedix's filings with the SEC, which are available free of charge at the SEC's website or upon request from CorMedix.

CorMedix may not actually achieve the goals or plans described in these forward-looking statements, and investors should not place undue reliance on these statements. CorMedix does not intend to update these forward-looking statements, except as required by law. During this call, the company will discuss certain non-GAAP measures of its performance. GAAP to non-GAAP financial reconciliations and supplemental financial information are provided in CorMedix's earnings release and the current report on Form 8-K filed with the SEC. This information is also available on the Investor Relations section of CorMedix' website. At this time, it is now my pleasure to turn the call over to Joe Todisco, Chairman and Chief Executive Officer of CorMedix. Joe, please go ahead.

Thanks, Dan. Good morning, everyone, and thank you for joining us on this call. CorMedix is entering 2026 with strong momentum across our core priorities, delivering durable DefenCath utilization growth, advancing high-value pipeline opportunities and driving meaningful profitability and cash generation. These elements together form the foundation of our long-term value creation strategy. We announced this morning first quarter net revenue of $127.4 million, significantly above Street consensus and adjusted EBITDA of $70 million. Susan will provide more granular details of first quarter financial results, but I am proud of the team's execution, which led to this fantastic performance.

As a result of our Q1 performance as well as other market intelligence, we are increasing our full year financial guidance for net revenue from the previously announced range of $300 million to $320 million to a revised range of $325 million to $345 million-- the increase in guidance reflects strong first quarter execution and continued confidence in underlying demand trends while incorporating expected variability in DefenCath sales in the second half of 2026 as we transition through reimbursement dynamics.

We're also raising our full year adjusted EBITDA guidance from the previous range of $100 million to $125 million to a new range of $115 million to $135 million. DefenCath variability in the back half of 2026 is the result of the expiration of our initial TDAPA reimbursement and the transition to the post-TDAPA add-on phase of reimbursement by CMS. Based on current CMS calculation methodology, the company expects a significant increase in the post-TDAPA add-on amount in 2027 compared to the second half of 2026, which is expected to produce a higher net selling price per unit in 2027 compared to our current estimates for Q3 and Q4 of this year.

Our primary objective for Q3 and Q4 is to maintain or grow existing patient utilization heading into 2027. Based upon our first quarter performance and feedback from existing customers, we are raising our full year DefenCath guidance from the previously announced $150 million to $170 million range to a new range of $175 million to $195 million. This guidance is based on existing customer run rates and does not include potential upside from new customers or any new volumes that result from potential successful contracting with Medicare Advantage, both of which we are actively working hard to pursue.

Despite pending TDAPA expiration, we continue to see DefenCath evolving into a standard of care therapy within its target population, supported by strong clinical value and increasing adoption. It's worth noting that our 3 current largest customers for DefenCath have either recently published or presented information demonstrating the positive clinical impact that DefenCath has had on their patients' infection and/or CRBSI-related hospitalization rates or made similar public comments related to the positive impact DefenCath has had in their clinics.

In addition to strong Q1 financial performance, we were also excited to recently announce the preliminary top line clinical results from the ReSPECT study, a Phase III clinical study evaluating REZZAYO for the prophylaxis of invasive fungal disease in adult immunosuppressed patients undergoing allogeneic bone and marrow transplant. As Liz will explain in more detail, we believe the top line results position REZZAYO to become an attractive option for clinicians for prophylaxis of IFD, and we will now begin to work together with our global partner to prepare for FDA submission of the sNDA in the second half of this year and plan for a potential commercial launch in 2027.

With respect to commercial readiness and as we begin to prepare our commercial infrastructure for a potential launch of REZZAYO for prophylaxis, we expect to incur incremental spend in the back half of this year, including the anticipated addition of between 15 to 20 incremental headcount across both commercial and medical. This increase in resources and operating spend is reflected in our full year cash OpEx guidance of $145 million to $160 million. As a reminder, our cash OpEx guidance excludes noncash charges such as stock-based compensation. I'd now like to turn the call over to our Chief Operating Officer, Liz Hurlburt, to provide an update on clinical activities. Liz, please go ahead.

Thank you, Joe, and good morning, everyone. As Joe mentioned, we were delighted to announce preliminary top line results of the ReSPECT study at the end of April. The ReSPECT study met its primary endpoint for FDA of fungal-free survival at day 90, showing non-inferiority versus the standard antifungal regimen with 60.7% fungal-free survival at day 90 for REZZAYO compared to 59% for the standard antifungal regimen or SAR. Importantly, we believe top line results demonstrate that REZZAYO has comparable efficacy to SAR against invasive fungal infections from all 3 measured pathogens, Candida, Aspergillus and Nosocomial.

In addition, results showed a favorable profile in multiple secondary endpoints, most notably treatment-emergent adverse events leading to dose reduction, interruption or withdrawal of study drug and study discontinuation. As we stated previously, the objective with the ReSPECT study was to show comparable efficacy to the standard of care while also demonstrating a better overall safety profile with regards to drug-drug interactions and toxicity.

We believe this study has achieved that objective and that the results position REZZAYO as a differentiated prophylactic therapy with a meaningful commercial opportunity. It's important to remember that this was a global study conducted by our partner, Mundipharma, who owns global IP rights and will pursue regulatory approvals outside of the United States. Mundipharma is currently the holder of the U.S. NDA filing and under the terms of our agreement, transfers ownership of the NDA to CorMedix following approval of an sNDA for the prophylaxis indication.

As such, the parties must work together on the publication of data and any submissions to FDA. Currently, the parties expect to hold a pre-NDA meeting with FDA in the coming weeks and to submit the sNDA in the second half of 2026. Shifting gears to our Phase III TPN study. Despite efforts to increase study enrollment, total enrollment remains at about 1/3 of the total number of patients needed for an interim analysis of 90 patients.

The adaptive design of the NUTRI-GAURD study allows for a minimum of 90 and maximum of 200 participants based on the incidence rate of CLABSI. An interim assessment will be made by the independent data monitoring committee after 15 participants have experienced a CLABSI event. In addition, cumulative infections have shown to be lower than our pre-study estimates, which also impacts our statistical projections for study timing. Based on these 2 factors, study completion timing is now trending into 2028. We are actively taking steps to accelerate this time line. Most importantly, we intend to open additional clinical sites as well as submit a protocol amendment to FDA, which, if approved, should support expanded inclusion criteria and broader enrollment.

We will continue to update on progress as we move throughout the year. I'd now like to turn the call over to Susan to discuss the company's first quarter financial results and financial position. Susan?

Thanks, Liz, and good morning, everyone. We are pleased with our first quarter results, which reflect strong execution across the business and the benefit of the contribution from the acquired Melinta portfolio. As a reminder, because the Melinta acquisition closed in August 2025, the first quarter of 2026 includes a full quarter of Melinta operations, while the first quarter of 2025 does not.

Accordingly, year-over-year comparisons are heavily weighted by the broader product portfolio and relative cost structure of the combined company. We also filed our Form 10-Q this morning, and I encourage you to review it for additional detail and important disclosures.

Turning to the numbers. First quarter 2026 net revenue was $127.4 million compared with $39.1 million in the first quarter of 2025. First quarter revenue included $97.5 million from DefenCath and $29.9 million from the Melinta portfolio. The year-over-year increase was driven primarily by higher sustained DefenCath demand, including the impact of sales to our largest dialysis customer that we onboarded mid last year and the addition of Melinta revenue. First quarter DefenCath sales benefited from a nonrecurring $9 million favorable change in estimate related to certain sales allowances, primarily Medicaid rebates and product returns as noted in our earnings release.

However, even excluding this change in estimate, our net revenue was above consensus for the first quarter of 2026. Operating expenses were $41.5 million in the quarter, including $7.2 million in R&D, $12.5 million in selling and marketing, and $21.7 million in G&A. The increases versus the prior year period reflect the larger combined company, including higher personnel-related costs, more robust commercial and IT infrastructure and a greater level of development activity across the broader portfolio, including a focus on pediatric programs and a biodefense indication for Baxdela, many of which are partnered with BARDA.

We are also subject to higher branded prescription fees attributable to the addition of Melinta's commercial products as well as to year-over-year product sales growth. Year-over-year increases in OpEx were also driven moderately by moderately higher legal fees and our continued investment in the development of DefenCath for the TPN indication. On the bottom line, we recorded net income of $38.6 million or $0.48 per basic share and $0.43 per diluted share compared with net income of $20.6 million or $0.32 per basic share and $0.30 per diluted share in the first quarter of 2025.

In addition to net revenue and operating expenses, EPS was impacted by nonoperating expenses of approximately $25 million associated with the routine quarterly mark-to-market of marketable equity securities and contingent consideration, which reflects the approximate fair value of the future milestone and royalties payable to former Melinta shareholders as well as income tax expense under U.S. GAAP.

On a non-GAAP basis, adjusted EBITDA was $70 million for the quarter compared with $23.6 million in the first quarter of 2025. This EBITDA metric excludes onetime acquisition-related and reorganization costs, stock-based compensation and the nonrecurring revenue adjustment this quarter, and it provides additional insight into the strength of our core operating performance. A reconciliation to the most comparable GAAP measure is included in this morning's earnings release. We ended the quarter with $178.1 million in cash and cash equivalents, excluding restricted cash.

During the quarter, we generated cash from operating activities of $42.4 million, which was impacted by large incentive rebate payments made to customers during the first quarter. You'll note a related and significant decline in accrued expenses of approximately $50 million from December 31, 2025, to March 31, 2026, on our balance sheet.

Cash flow from operating activities was partially offset by $11.1 million used in cash to repurchase shares under our stock buyback program, driving a $33.3 million increase in cash during the first quarter. We continue to believe we are well positioned with a strong balance sheet to support our operating priorities and growth initiatives. And now I will turn the call back to Joe for closing remarks. Joe?

Thanks, Susan. I'm very excited about where the company is today and where we have the potential to go. CorMedix has entered 2026 with strong momentum across all 3 pillars of our investment thesis. First, DefenCath continues to exceed expectations despite pending TDAPA expiration, demonstrating strong underlying utilization demand, which we believe positions itself well to become a durable cash-generating franchise post TDAPA.

Second, we are advancing a pipeline of high-value late-stage opportunities, including REZZAYO for prophylaxis and DefenCath in TPN, which could meaningfully expand our long-term revenue opportunity. And third, we've delivered significant profitability and cash generation over the last year, allowing us to reinvest in growth as well as shareholder value creation through stock repurchases while maintaining financial flexibility. We remain confident in the outlook for this year and our path to future growth and sustained profitability. We'd now like to open it up for questions.

[Operator Instructions] The first question comes from Jason Butler with Citizens.

Congrats on the quarter. Wondering if you could comment on the trend in revenue that we should expect to see for DefenCath for the second quarter. Obviously, adjusting for the onetime $9 million benefit, should we expect a consistent net price? Are you expecting demand growth? And then to any extent you can comment, what are your updated thoughts on the guidance you gave for DefenCath in 2027?

Thanks, Jason. Appreciate the questions. So I think a couple of things to think about when you think about DefenCath through 2026 to start. First, we did have the $9 million good guy, right, in the first quarter. That's kind of a one-timer. For the second quarter, and I know we mentioned on the last call, it's really for us, a kind of a 2-month quarter. Because as we move into June and given the price dynamic that's going to take effect on July 1, we're going to take a decent shelf stock adjustment in the month of June.

Right now, we're accruing for that at about 4 weeks of stock as our largest customer typically holds about 4 weeks. Some customers hold a little less, so maybe we end up having some favorability there. But we're assuming it's going to be a 2-month quarter and expect it to be in the range of about $60 million, right, give or take, a couple of million. And then for the back part of the year, I think you can kind of just break out the rest of the guidance, spread it across Q3 and Q4 for the back part of the year.

For 2027, as we mentioned in the script, we expect to see appreciation in the net selling price as we move into 2027 compared to that third and fourth quarter. Right now, I think I'm comfortable saying we're affirming the guidance we put out previously for 2027. It's a little bit premature, right? We'd like to see how we move through the year into the third and fourth quarter and would love to be in a position later this year, early next year to take that guidance upwards. I think I'd want to reiterate that, as we mentioned, neither guidance really includes upside from anything we may do with Medicare Advantage or onboarding, potential new customers.

Really helpful. Thanks Joe. And then can I just a quick follow-up. The TPN trial, can you give us any more color on the changes in the exclusion/inclusion criteria and how that both changes your view on enrollment, but also the patient profile that you'll end up with in the study?

Look, and I'll let Liz comment in a moment. I don't think the patient profile changes during the study. And I really don't want to put out specifics of what criteria we've asked. We've simply asked FDA to amend.

Yes. So I think, Jason, right, these are really medically complex patients. I think we did a solid job in estimating the number of infections we anticipated them to have. But when you look at the overall pool of TPN patients, there's really subgroups and subpopulations within that. And the actual group of eligible patients is smaller. And there are a lot of logistical challenges that we've seen with them because they are so medically complex.

We are asking FDA to take a look at inclusion criteria to see if we can be a little bit more generous with it without compromising the data. But I think until we get feedback on that amendment, -- we're going to have to stay quiet on the specifics of it, but we're hopeful, obviously, that enrollment would reaccelerate once -- if that amendment goes through so that we can include more TPN patients that maybe do have some additional comorbidities going on as well.

Yes. And I think it's also worth noting, right, when you have a projection like this on study timing, it's a moment in time, right? And to the extent we are able to increase enrollment, those time lines can shift pretty quickly.

The next question comes from Roanna Ruiz with Leerink Partners.

A couple for me. First on DefenCath, I noticed you talked about increasing customer run rates. I was curious if you could elaborate a bit more on that? And are there any strategies that you want to use going forward to keep bolstering it?

Sure. Thanks, Rona. Yes, I think when I said increasing run rates, we saw a little bit of an uptick from Q4 to Q1 in terms of utilization, and that was nice to see. That was not something that was in our initial guidance or budget. So we're happy to see that, I guess, patient numbers continue to grow. What we're doing going forward is a lot of the initiatives we talked about, specifically with outreach to Medicare Advantage and opening up that patient pool.

Right now, based on data we see, we think we've -- most of our patients, the overwhelming majority are Medicare fee-for-service, probably more than 90% of our patients are in Medicare fee-for-service. So that's a big opportunity over the long term would be in Medicare Advantage.

Got it. And I have a follow-up on the TPN study. With the amending of the protocol, does that impact the statistical plan at all? And could it actually impact the future label? And are there any steps you're taking to ensure tight trial execution going forward as you expand?

Sure. So I'll take on the trial execution. So I pride us that we run these studies in-house. We've got a really robust team that is on top of all of the details of execution on this. A couple of things, right? We are adding additional sites in the U.S. We have 5 additional sites in Turkey being activated over the next 45 days.

So we expect to see some enrollment there. In terms of the statistical plan, yes, there would be changes to the statistical plan if the amendment is approved. I do not anticipate potential label changes, but I would say it's really premature to comment on what the label is because data guides the label. That being said, the intent of the study and what the projected label that we are working towards would be for risk reduction of CLABSI in adult patients with TPN. So I think that would remain the same. And depending on the additional populations that could be included in it, that could potentially expand, but we need to wait for feedback from FDA.

The next question comes from Leo Timashev with RBC Capital Markets.

Now that you have the top line REZZAYO data in hand, I was just wondering if you could comment on some of the assumptions that you had made before around payer negotiations, expectations for pricing? And if there's any early feedback you've gotten from KOLs as you sort of discussed the data and what your expectations are for utilization?

Thanks, Leo. Just a couple of things. So the full data has not yet been published, right? So we've put out a press release in combination with our partner, Mundipharma, that announces some of the top line results. In the upcoming months, we're going to be working with Mundipharma, to get a more full data package made public.

At that time, we'll be able to have conversations with KOLs around the specific data. So we're not really in a position today to have those conversations yet and then really start talking or doing a lot of the things that we're going to be doing around market research for pricing and penetration assumptions. So I'd say later this year, we can probably give a little bit more color on that.

The next question comes from Les Sulewski with Truist Securities.

This is Jean on for Les. First one is what specific customer repair actions have followed the recent positive real-world data for DefenCath? And then separately, where do you think -- based on the data you have right now, where do you think REZZAYO could have the most launch friction if you think about hospital protocols, pricing or generics?

Yes. I think I'm going to start with the REZZAYO question, and I'm going to kind of defer to what I had said to Leo is that it's -- we need to have substive conversations once the full data is made public with key opinion leaders and take feedback. We'll be in a position to do that in the next couple of quarters and by the end of the year, be in a better position to kind of give directional guidance of how we think or the direction of the TAM and potential peak sales maybe by the end of the year. And on your first question, I just want to make sure I understand what you had asked. You asked if the real-world evidence has had any customer or feedback impact. Is that what you had asked?

Yes, just positive developments on the customer or payer front after the publications.

Well, look, I mean, it's been positively received all around, right? And not just on the real-world evidence that U.S. Renal Care has published, but our other customers as well. IRC has put out some public information around the significant impact that DefenCath has had in their clinics. Fresenius has made public statements, right, on their recent earnings call about the value of DefenCath in their clinics.

So we're happy about what we are seeing play out in real time from a clinical standpoint in terms of the utility of the product. We're using all of that information in discussions. When you talk about payers, it's really Medicare Advantage, right? We're using all of that information in our ongoing discussions with the EMA plans.

The next question comes from Brandon Folkes with H.C. Wainwright.

Congrats on a really good quarter. Maybe just one for me. Given the success of REZZAYO and prophylactic, do you still place a high priority in bringing in additional assets over the next 12 to 18 months? It seems like Talphera will read out potentially late '26 or '27. Has the bar changed in terms of bringing in additional assets given that the internal opportunities are a lot more derisked given the positive REZZAYO data from here?

No. I mean, I wouldn't say it changed. I'd say it's actually the other way, right? I think it's actually even more important to find things that are complementary to where we potentially see REZZAYO sales deployment, right, in those hematology/oncology clinics, bone marrow transplant centers. So looking for products that could potentially be complementary in that space is definitely a priority.

The next question comes from Serge Belanger with Needham & Company.

A couple of REZZAYO questions from us. The first one, I know we have a pre-NDA meeting planned ahead of potential sNDA filing in the second half of this year. Just curious at this point, if you expect that you'll require more than the trial generated in the ReSPECT trial to file the sNDA? And do you expect coming out of the pre-NDA meeting, you'll have some clarity on what the potential label of the label expansion could look like?

Look, I'll let Liz give her feedback. I think from a label standpoint, we won't have that feedback, right, until later on in the process. And I think in terms of your first question, that's really what the pre-NDA meeting is for, Serge, is to kind of get confirmation from FDA that the data that we have from -- in terms of the ReSPECT study and then other supportive data is sufficient, right, to support the submission of the NDA. Anything to add?

Yes. No, I would agree. Just again, Monday is the marketing authorization holder here. They are leading regulatory activities at this point in concert with us. But I would say, once we have initial meetings with FDA and get that feedback, the team will certainly strategize on next steps, but it would be premature to comment on the label, certainly before the full data set is available.

The next question comes from Jason Kolbert with D. B.

A couple of questions. I'm struggling a little bit on the DefenCath guidance and the numbers. If I take the $97 million and I subtract the onetime payment and I kind of annualize that out for the rest of the quarters, I come very close to the full year guidance without the Melinta product. So I'm trying to understand how much of the quarter number is inventory versus how much is real use? And what's the normalized run rate for DefenCath in these patients?

So Jason, and I think I really kind of addressed this with Jason Butler's first question from Citizens. I guess, first, you have to understand the nature of TDAPA, right? And our TDAPA is going to expire on June 30, which is going to move us into a bundled payment system for Q3 and 4. As we've said on previous calls, we're going to take some price erosion in Q3 and 4 with the goal of maintaining patient volumes. When you talk about inventory, the inventory turnover is pretty quick, right? So at most, as I said, our largest customer, we believe, holds about 4 weeks of stock on hand. Others are in the 2- to 3-week range. The reason you can't just straight line, right, the 88 across is because, as I said, the second quarter, we're going to have that shelf stock adjustment in June, right? So we expect utilization to remain pretty strong, and we'll take some price erosion in June, right, in advance of moving into the back part of the year, right? So that's kind of how you should think about the guidance. And then in 2027, right, as we said, we expect to kind of step back up in price across the same utilization, which will produce a higher revenue amount in '27. So that's how you should be thinking about DefenCath trajectory.

Okay. I mean I'll continue to look at the numbers, but it still seems like a pretty big drop-off is going to be required in order to stay in your guidance, not go above it. Can you talk about the tax rate, too? I was surprised. The tax rate seemed pretty high. Were there not a lot of offsets applied to it? And what's the normalized tax rate going forward?

So our tax rate is essentially the statutory tax rate, the federal rate plus a blended rate for state taxes. And the GAAP rate is just that. It's about 28%. If you look at the tax expense compared to operating income. So if you exclude the noncash mark-to-market of our marketable equity securities and the mark-to-market of our contingent consideration, it's about 28%. That is a GAAP rate. We do have significant tax attributes, most prominently NOLs that will reduce the taxable income that we pay -- the taxes that we pay. But the GAAP rate is -- you can think about it as a statutory rate. We don't have a lot of transactions that result in permanent differences.

Congrats on the numbers.

This concludes our question-and-answer session. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Good morning, and welcome to the CorMedix Fourth Quarter and Full Year 2025 Earnings and Corporate Update Conference Call. Today's conference call is being recorded. [Operator Instructions] At this time, I would like to turn the conference call over to Dan Ferry from LifeSci Advisors. Please go ahead.

Good morning, and welcome to the CorMedix Fourth Quarter and Full Year 2025 Earnings and Corporate Update Conference Call. Leading the call today is Joe Todisco, Chairman and Chief Executive Officer of CorMedix. And he is joined by Liz Hurlburt, EVP and Chief Operating Officer; and Susan Blum, EVP and Chief Financial Officer. In addition, Beth Zelnick Kaufman, EVP and Chief Legal and Compliance Officer; Mike Seckler, EVP and Chief Commercial Officer; and Dr. Matt David, EVP and Chief Business Officer, are also on the line and will be available during the Q&A session.

Before we begin, I would like to remind everyone that during the call, management may make what are known as forward-looking statements within the meaning set forth in the Private Securities Litigation Reform Act of 1995. These statements are statements other than statements of historical facts regarding management's expectations, beliefs, goals and plans about the company's prospects and future financial position.

Actual results may differ materially from the estimates and projections on which these statements are based due to a variety of important factors, including the risks and uncertainties described in greater detail in CorMedix's filings with the SEC, which are available free of charge at the SEC's website or upon request from CorMedix. CorMedix may not actually achieve the goals or plans described in these forward-looking statements. Investors should not place undue reliance on these statements. CorMedix does not intend to update these forward-looking statements, except as required by law.

During this call, the company will discuss certain non-GAAP measures of its performance. GAAP to non-GAAP financial reconciliations and supplemental financial information are provided in CorMedix' earnings release and the current report on Form 8-K filed with the SEC. This information is also available on the Investor Relations section of CorMedix' website. At this time, it is now my pleasure to turn the call over to Joe Todisco, Chairman and Chief Executive Officer of CorMedix. Joe, please go ahead.

Thank you, Dan. Good morning, everyone, and thank you for joining us on this call. 2025 was truly a transformational year for CorMedix. While DefenCath achieved peak sales of just under $260 million, we are excited to have both announced and closed the acquisition of Melinta Therapeutics in the third quarter of the year. In addition, the team worked expeditiously to facilitate integration and achieve our target synergy of $35 million during the fourth quarter of 2025. This is a monumental achievement and truly a testament to the operational execution capabilities of the CorMedix leadership team.

As we turn our attention to the year ahead, there is much focus on our post-TDAPA add-on period strategy for maintaining patient utilization rates for DefenCath in outpatient hemodialysis. As a reminder, on July 1 of this year, the TDAPA reimbursement for DefenCath will transition from a buy-and-bill format to a bundled add-on mechanism. We've had multiple conversations with our top customers and are in the process of finalizing supply pricing for Q3 and Q4 of 2026 as well as for 2027. At this time, we are affirming our 2026 DefenCath guidance of $150 million to $170 million and 2027 DefenCath guidance of $100 million to $125 million.

With respect to 2026, we expect much of the revenue concentration to be front-loaded in the first half of the year as price erosion related to the post-TDAPA add-on occurs in the third and fourth quarter. Assuming CMS utilizes the same methodology to calculate the 2027 bundle addition, we do expect a meaningful increase in traditional Medicare provider reimbursement in 2027, which we expect to translate into a higher net selling price in 2027 compared to Q3 and Q4 of 2026. To that extent, we took the extra step of issuing 2027 DefenCath guidance, which is based on existing patient utilization rates as well as our current estimates for the range of net selling prices and does not include potential upside from new customers or managed care contracting.

In addition to DefenCath guidance, the company is also affirming its full year 2026 financial guidance of revenue of $300 million to $320 million and adjusted EBITDA of $100 million to $125 million.

That said, we are actively in discussions with multiple Medicare Advantage providers as well as new potential customers for DefenCath in both the inpatient and outpatient settings of care, focused on execution of sales and marketing efforts for REZZAYO, MINOCIN, and VABOMERE, and we'll evaluate appropriate updates to financial guidance as we progress throughout 2026. This past month, we completed our first Analyst R&D Day in which we focus on educating our analysts and investor community on the market opportunity for our antifungal product, REZZAYO, in its current approved indication in the treatment of invasive fungal infections as well as our key pipeline assets of REZZAYO in development for prophylaxis of invasive fungal infections and DefenCath in development for prevention of CLABSI in adult patients receiving total parenteral nutrition.

Liz will provide an update on the status of these development programs shortly. During the Analyst Day event, stakeholders were given the opportunity to engage with multiple panels of physician thought leaders around key aspects for each of these 3 growth opportunities for CorMedix. The webcast of the event and associated materials remains available on our website, and I encourage all investors to review those materials. The feedback from thought leaders was excellent and underscores our view for the large potential market opportunity for REZZAYO, which we estimate at approximately $2.5 billion across both potential indications and for DefenCath and TPN, which we estimate between $500 million and $750 million.

2026 is expected to be a transitional year for CorMedix with a heightened investor focus on new catalysts and value drivers, most notably our Phase III ReSPECT data for REZZAYO in prophylaxis, which is on track for the second quarter of this year. With the acquisition of Melinta, not only did we acquire what we believe will be an exceptional growth asset in REZZAYO, but also added highly durable institutionally administered products like MINOCIN and VABOMERE, which we expect to provide a stable base of revenue while the company builds toward future growth. I believe CorMedix has done an exceptional job of maximizing the value of the initial TDAPA period afforded to DefenCath in outpatient hemodialysis and parlay that success into building a pipeline that positions the company for long-term sustainable growth.

I'd now like to turn the call over to our Chief Operating Officer, Liz Hurlburt, to provide an update on clinical activities. Liz, please go ahead.

Thank you, Joe, and good morning. The combined clinical development and operations teams, along with field medical affairs have been working diligently on numerous clinical activities. As we shared last fall, enrollment for the global Phase III ReSPECT study evaluating REZZAYO for the prophylaxis of fungal infections in adult allogeneic bone marrow transplant patients completed in September. This pivotal trial is being conducted by our global partner, Mundipharma, who has confirmed that all sites have completed study participation, and they are on track for an anticipated database lock later this month. We expect to announce top line data from the ReSPECT study in the second quarter of 2026.

Top line results will include the primary efficacy outcome of fungal-free survival at day 90, discontinuation of study drug due to toxicity or intolerance all-cause mortality and attributable mortality with invasive fungal disease as determined by the data review committee and the cumulative incidence of invasive fungal disease at day 90 by the data review committee and by Azole CHOICE. Additionally, safety data, including overall adverse events, treatment-emergent adverse events and serious adverse events is expected to be included in top line results. The team continues to work closely with investigators and clinical experts in the field to deepen our understanding of the evolving clinical practices and the needs of these patients as we prepare to support a potential commercialization in 2027.

As Joe mentioned earlier, our panel of thought leaders provided excellent insights into the market opportunity for our long-acting echinocandin in the prophylaxis of invasive fungal infections, and we are looking forward to our Phase III data readout.

Turning to DefenCath. I'm pleased to share that the Phase III Nutri-Guard clinical study, which is evaluating the impact on central line associated bloodstream infections, or CLABSI, for adult patients receiving total parenteral nutrition via a central venous catheter is approximately 30% enrolled toward our minimum patient target of 90 patients, and we are working to increase enrollment rates as we progress throughout 2026 with new sites in Turkey. At this time, we are still anticipating study completion in early 2027. The adaptive design of the Nutri-Guard study allows for a minimum of 90 and maximum of 200 participants based on the incidence rate of CLABSI. An interim assessment will be made by the independent data monitoring committee after 15 participants have experienced a CLABSI event.

I would now like to turn the call over to Susan to discuss the company's fourth quarter and full year financial results and financial position. Susan?

Thanks, Liz, and good morning, everyone. We are pleased to share our fourth quarter and full year 2025 financial results, which reflect our ongoing commercial and operational execution. A few things to note on the financial results before I jump in. Following the close of the Melinta acquisition on August 29, 2025, the fourth quarter of 2025 represents the first full reporting period incorporating Melinta's operations into our consolidated results. Also, the company has filed its annual report on Form 10-K for the year ended December 31, 2025, and I encourage you to review this filing for a more comprehensive discussion of our financial performance and operating results.

As Joe mentioned, we had a strong quarter on the revenue front. For the fourth quarter, net revenue of $128.6 million reflected continued growth across our commercial portfolio, driven primarily by DefenCath, which contributed $91.2 million and supplemented by a full quarter contribution from the Melinta portfolio, which totaled $37.4 million compared to net revenue of $31.2 million in the fourth quarter of 2024, which included only results from DefenCath, this represents a meaningful year-over-year increase and highlights the company's ability to execute on product launches and business development initiatives. Total revenue on a pro forma basis for 2025, which is full year revenue for both the CorMedix and Melinta businesses was $401.3 million, which is in line with our previously established guidance. Of the total, DefenCath generated $258.8 million in net sales for the year.

Turning to OpEx. Fourth quarter operating expenses of $48.2 million increased from $17.1 million in the comparable prior year period, reflecting the expected -- the expanded cost structure of the combined organization, merger-related costs associated with the Melinta acquisition, including severance expenses and additional investment in expanded indications for DefenCath, most notably our Phase III clinical program focused on the prevention of CLABSI in TPN patients. Our operating expenses for the fourth quarter were consistent with our expectations and aligned with our strategic focus on building a platform for long-term sustainable growth, which was supported by the execution and integration of the Melinta acquisition. Our employee base has grown significantly in connection with the merger and scaling of the business.

Last year, at this time, we had a workforce of approximately 100 people. And today, we have just under 200 employees. The expanded infrastructure serves to support growth and is expected to provide significant operating leverage in the periods to come. Now that we have successfully streamlined the 2 organizations, we can focus on executing our business growth strategy and preparation for the anticipated new launch opportunities of DefenCath and TPN and REZZAYO for prophylaxis. On the bottom line, CorMedix recognized net income of $14 million in the fourth quarter of 2025. Net income was impacted by tax expense of $42.4 million, the majority of which was noncash, resulting from the utilization of deferred tax assets that were established in the third quarter of 2025. On a pretax basis for the fourth quarter, income was $56.4 million, an increase of $43 million from the fourth quarter of 2024.

Turning to non-GAAP results. Adjusted EBITDA for the fourth quarter was $77.2 million, which was within our previously established guidance and reflects modest growth quarter-over-quarter. This metric excludes onetime acquisition-related and reorganization costs, stock-based compensation and the tax benefit and expenses recognized during the year, and it provides additional insight into the strength of our core operating performance. A reconciliation to GAAP results is included in the press release issued with our earnings announcement. From a liquidity perspective, we ended the quarter with cash and cash equivalents and short-term investments of $148.5 million, driven by strong operating cash flow of almost $100 million during the quarter and ongoing working capital optimization. Where we stand today, given our financial flexibility and commercial momentum, we believe we are well positioned for both organic growth from existing pipeline and promoted assets and potential inorganic growth from new business development opportunities. I'm excited to be a part of the journey as we move forward.

And now I will turn the call back to Joe for closing remarks. Joe?

Thanks, Susan. As I mentioned, 2025 was a transformational year and 2026 will be a transitional year that we believe sets up CorMedix for long-term sustainable growth in 2027 and beyond. We recently announced a share repurchase program and have been active in repurchasing shares throughout the first quarter. We intend to continue to be active throughout the year, subject to normal blackout periods, applicable volume restrictions and other business needs as we believe our balance sheet has sufficient flexibility to pursue this repurchase while leaving sufficient dry powder for new business development opportunities. The company sits here today with a diversified product portfolio, multiple late-stage pipeline opportunities, financial flexibility and a capital structure to support future growth. We remain confident in the outlook for this year and our path to future growth and sustained profitability.

I'd like to now open up the call for Q&A.

[Operator Instructions] The first question today comes from Roanna Ruiz with Leerink.

A couple of questions for me. I was thinking in terms of your conversations with dialysis customers and talking about supply and contract pricing for DefenCath, could you give a little bit more color on how those are going? Are you trying to build in certain features to drive DefenCath volume in 2026 and beyond? Or how are you thinking about these different levers?

Thanks, Roanna. So I'd say conversations, I believe, are going fairly well. The near-term focus is on preserving patient utilization through the back part of '26 and creating a structure for an increase in selling price in '27. And that's what we've been working toward negotiating with customers, and that's what we're hopeful we'll be finalizing shortly. We are also setting these up with flexibility to allow for changes in the event we are successful with Medicare Advantage contracting as we progress through this year and into next year. So overall, I'm happy with the progress that we've made and hopeful in the near term, we'll have some things finalized for the back part of the year.

Sounds good. And then I had a different question about REZZAYO. It sounds like you're going to share a lot of interesting information with the top line for the Phase III. Could you help frame what in that information you think is most clinically meaningful for physicians? How do you plan to leverage some of this data and potential future discussions with payers, et cetera, if all goes well and the top line is positive?

Thanks. Before I let Liz comment, I'll just give you a little bit of my thoughts. And the way I look at the REZZAYO top line data, I think there's obviously various degrees of success, right? There's meeting the top line endpoint and then there's going to be different aspects of the pathogen data with -- in the top line data as well as, right, secondary endpoint around the discontinuation of the standard of care. And I think, obviously, what we're able to show will guide toward right, the commercial utility and how we're going to think about marketing and promoting the product. But Liz, do you want to comment any further?

Sure. Roanna, I think when it comes to how we're going to use the data, a lot of this is going to be dependent on the pathogens that we see in top line. Obviously, the more, the better. I think if we are successful in the way that ReSPECT reads out, there is a lot of opportunity for us to be able to talk to the payers about an option that does not have the drug-drug interactions that the Azoles and some of the other therapeutics are presenting right now. And we're hopeful that, that will lead to understanding around less hospitalizations, getting patients out quickly and to more safely be on their anticancer regimen. So it will be certainly data dependent, but I'm confident that once it comes out, we'll be able to take a look at that data and strategically place it with payers and the clinical community.

And the next question comes from Les Sulewski with Truist Securities.

This is Jean on for Les. First, any developments on the bipartisan proposed TDAPA extension bills and if the timing here has changed based on recent global events? And then also, any updates on a potential partnership with the other LDO and how post-TDAPA dynamics change the odds here?

Look, the legislation is always speculative. What I can say is that we've spent a lot of time. We're working closely with the other company that's actively in TDAPA, Akebia. We've been pounding the payment on the Hill as well as with career staff at CMS, political point staff at CMS. We've been -- we've got a large number of cosponsors of the bill. Now timing is tricky, right, because this likely needs to be attached to another piece of legislation. There's a war in the Middle East. So we really can't speculate on whether this can happen before June 30 or December 31.

I think if it happens after June 30, I think there is a pathway for potential retroactivity of some aspects of the bill to impact positively on DefenCath. So that's something we'd actively be working on as well behind the scenes. But it's really hard to kind of pinpoint a timing with everything that's going on in Washington right now. With respect to the other LDO, I can't comment on ongoing discussions with customers.

And your next question comes from Serge Belanger with Needham & Company.

This is John on for Serge today. One on DefenCath and then another one on the Melinta product portfolio. So first, just curious if you have any updates on the inpatient opportunity with DefenCath. Have the size of the current contributions has been growing? And just curious what growth profile you see from this segment in '26 and '27. And then on the Melinta portfolio, you mentioned MINOCIN and VABOMERE being potential -- significant contributors along with REZZAYO. Curious if there's anything promotionally sensitive that you could kind of reinforce into these products to see some growth in the future?

All right. Thanks, John. And I'm not sure I fully understood your DefenCath question, but what I'll kind of touch on is our guidance and how we constructed our guidance for '26 and '27. So the way we looked at 2026, obviously, with the way CMS did the calculation for the bundle adjustment, the $2.37 that goes into the bundle for the third and fourth quarter, it doesn't fully reimburse providers, right, for -- based on current utilization rates. They use an older period of time to do that calculation that was based on our first year of launch. But we have provisions in our agreements with customers that allow for that type of situation where there are certain floor pricing under these contracts. What we're working on now is hopefully getting a little bit better than that floor pricing. But our guidance was somewhat based on the floor, right? And we're working through that process now.

Now for 2027, what we wanted to do was give investors comfort that there's at least a base business level of DefenCath for which we expect to see price appreciation and hopefully stable volumes based on what we're doing now in the outpatient hemodialysis sector to kind of steady the market with customers. Now we elected not to include in that 2027 guidance potential upside from what we're trying to do with Medicare Advantage contracting with a potential new customers, both in outpatient hemodialysis and on the inpatient side. Because when it comes to a guidance, it's very difficult, right, to guide towards something that is still under the way in terms of execution, right?

So as we progress throughout the year and should we get a Medicare Advantage contract across the goal line, and we have the ability to look and make a forecast around volumes, we would update our guidance accordingly as we progress through the year. On the Melinta portfolio question, look, I think MINOCIN and VABOMERE are 2 really good durable products that have entrenched utilizations in the hospital inpatient segment for treatments of niche infections, right? I think MINOCIN is closing in and around $50 million in sales. VABOMERE is just under $30 million. So we do have a little bit of promotional efforts on there. We don't think that they are hugely promotionally sensitive the way a launch product would be, but we think there's a couple of percentage points of growth there that we expect to get this year.

And your next question comes from Brandon Folkes with H.C. Wainwright.

Congrats on the quarter. Maybe just 2 for me. Firstly, on DefenCath. Can you just talk about the customer mix currently and whether you anticipate any change of that in your 2026 and 2027 guidance? How should we think about the opportunity in the other midsized operators for DefenCath?

So right now, I'd say we're fairly heavily concentrated volume-wise with one of the LDOs and then 2 of the 3 midsized players are driving probably 90-something percent of our volume amongst the 3 of them. We have -- there's a third midsized provider that's utilizing, but not at the scale of others. And then we have a number of small accounts that even if they're utilizing it fairly broadly, they don't represent as large of a market impact because they may only have 20 clinics or 15 clinics. So that's certainly kind of the mix today.

Now in terms of changes we would anticipate in '26 and '27, right, would depend in a large extent to our ability to onboard either the other LDO or to get the third midsized player to meaningfully increase volume. So the only things that would really kind of, I'd say, change the mix in any meaningful fashion. What we're doing on the inpatient side in terms of promoting DefenCath, while that's a good dollar market opportunity, we believe the volumes there would be much lower, right, from a volume distribution standpoint. So I hope that answers the question.

That does. And if I just may ask one more. I know you mentioned you filed the 10-K, sorry, I haven't been through it. But can you just talk about the operating cash flow in the quarter? It looks very strong. So just anything to consider there? And then also maybe how we should think about it in 2026?

Yes. Look, I think roughly, we'd like to say that EBITDA is -- could be a proxy for cash flow for the year. I think there's some items that could impact in terms of our need to maybe stockpile some inventory this year as we're working through a few tech transfers. We also have some rebates that -- large accrued rebates that you'll see on the balance sheet that will get paid out in the early part of this year. So those are kind of really the big items that impact cash flow. Susan, anything you want to add to that?

No, you covered it, Joe.

This concludes our question-and-answer session and today's conference call. Thank you for attending today's presentation. You may now disconnect.

Hello, and welcome. My name is Matt David, Executive Vice President and Chief Business Officer of CorMedix. Thank you for joining us today. Both here in person and virtually. We appreciate the time and interest of our analysts and investor community, and we are pleased to have you with us for today's Analyst Day.

Today's session is intended to provide a deeper look into our company our strategy, our portfolio and the long-term opportunities we see ahead. Over the course of the afternoon, you will hear directly from members of our leadership team, who will share updates on our commercial execution, pipeline progress and key operational priorities. We are also pleased to be joined by external experts who will provide additional perspective on the evolving market landscape and unmet needs within our therapeutic focus areas.

As a public company, transparency and disciplined execution are central to how we operate. Our objective today is to give you a clear view of where we are, how we think about value creation and how we are positioning the business for sustainable growth. We also look forward to engaging in a thoughtful dialogue during the Q&A sessions later this afternoon.

Before we begin, I would like to remind everyone that today's presentations will include forward-looking statements, which are subject to risks and uncertainties. Please refer to our SEC filings for a discussion of the factors that could cause actual results to differ materially. We do not undertake any obligation to update forward-looking statements beyond what is required by law.

On behalf of our Board of Directors and our leadership team, I want to extend our sincere thanks for your continued engagement and support.

Now it is my pleasure to turn things over to our Chairman and CEO, Joe Todisco, who will kick off this exciting event.

Everybody hear me okay? Okay. Well, thank you. And I am Joe Todisco, I'm the Chairman and CEO of CorMedix, and welcome to our 2026 Analyst and Investor Day. We do have a pretty ambitious agenda. We're going to try to move as quickly as possible through some of the background sections to leave a lot of time for the thought leader panels as well as Q&A at the end.

Happy to be joined here today by my talented leadership team. In addition to myself, Liz Hurlburt, our Chief Operating Officer, will be presenting. I'd like to welcome 2 new additions to the CorMedix leadership team. Susan Blum joined us late last year as Chief Financial Officer; and Mike Sechler joined us a few weeks ago as Chief Commercial Officer. You've met Dr. Matt David, our Chief Business Officer and also happy to welcome Beth Segno Kauffman, our Chief Legal and Compliance Officer as well today.

So 2025 was a record year for CorMedix. And during the heart of our TDAPA reimbursement for defend [indiscernible] in hemodialysis, we achieved just under $260 million in net sales and drove really strong cash flow throughout the year. We parlayed that success into the acquisition of Melinta Therapeutics, which in addition to providing about $140 million of revenue on a pro forma basis, really transformed us into a diversified specialty pharmaceutical company with a portfolio of commercial stage drugs and a pipeline that is now positioned to create long-term sustainable value.

So 2026 is now a transitional year for CorMedix. We focus on promoting our existing commercial stage assets, but we are also preparing for upcoming potential future launches from the pipeline. Just a quick look at our overall commercial portfolio post acquisition of Melinta. As you can see, almost all of the products are injectable drugs used in institutional setting of care which is really core to our business development strategy and where we are looking now to find synergy.

Institutional settings would be areas such as hospitals, clinics, infusion centers, places where products are administered to a patient by a health care professional. Most of our current products are anti-infectives. But from an expansion standpoint, we are more focused on the setting of care than in a particular therapeutic area.

So for the purpose of today, our goal is to provide significant depth education into 3 areas. The first is the opportunity for REZZAYO in its current treatment indication, but also for our pipeline, which I do believe is an overlooked future value driver. For REZZAYO specifically, there's an ongoing Phase III study in prophylaxis of invasive fungal disease in patients that are immune compromised. But there are also 2 ongoing Phase II studies in treatment, one for Pneumocystis, the other for [indiscernible]. For REZZAYO, I think it's important to understand that these studies are being run by our global development partner, Mundipharma, who is the current sponsor of those studies and currently is the NDA holder for REZZAYO in the U.S.

We're also excited to provide more information in detail around our Phase III study for DefenCath in prevention of collapsing patients undergoing total parental nutrition. So just a quick look at our overall financial picture, which I do believe is stronger than perhaps the investment community currently appreciates. So we are sitting here today with approximately 0 net debt, about $150 million in cash, $150 million debt. We've guided 2026 EBITDA in the $100 million to $125 million range.

And today, we sit here with a market cap that's approximately 5x that EBITDA guidance. As I mentioned, '26 is a transition year because of the change in our defensive reimbursement that will occur in July. But we do expect a meaningful rebound in defend cat in hemodialysis in 2027 compared to the back part of as more dollars are expected to be added into the dialysis bundle by CMS in '27.

For that reason, we took the unusual step to provide longer-term financial guidance, specifically for DefenCath into 2027. Now I think if you look at this chart on the left, it visualizes a couple of things really well. First, the general durability of the momentum-based business, which is highly important to provide financial stability and I think really underscores kind of the rationale when we talk about the stability of the base business and the Melinta transaction. But what I also think you can kind of see is the atypical revenue curve that the TDAPA reimbursement structure, right, causes during a product launch, where you have this bolus of revenue coming during a 24-month period.

Now over the last couple of weeks, I think we've spent quite a lot of time working to educate investors on how we plan to manage our post TDAPA customer contracts, why we believe we can maintain patient momentum from the back part of '26 into 2027 as well as our thoughts on the pending to TDAPA legislation that is before Congress. For the purposes of today, we're really here to focus on providing education for our other growth drivers. So to the extent there are TDAPA questions, I think I'd kindly ask that either you hold them for the very end of Q&A or perhaps even we can address one-on-one post meeting. Because we have 3 excellent panels of thought leaders here today, each to talk about these 3 different market opportunities REZZAYO for treatment, REZZAYO or the prophylaxis segment and DefenCath TPN, as you say, each of which has a sizable total addressable population.

And with that, I'm happy to welcome Liz Hurlburt to come up and give a brief background on the market opportunity and overview for REZZAYO for its treatment indication.

Thanks, Joe. So it's my pleasure today to discuss our first lead asset, REZZAYO, or rezafungin. It's a next-generation echinocandin antifungal, which is FDA approved to treat candidemia and the more severe invasive candidiasis, or IC. Rezafungin has broad spectrum activity against [indiscernible], Aspergillus and Pneumocystis.

REZZAYO is dosed weekly with a long-acting PK and front-loaded plasma drug concentration that provides treatment for 7 days versus daily dosing with the first-generation echinocandins. In STRIVE and restore the 2 NDA-enabling studies a favorable safety profile is consistently demonstrated. Unlike AZOLS, rezafungin has demonstrated no hepatotoxicity or clinically relevant drug-drug interactions.p

Candidemia is simply the presence of Candida in the blood. Invasive candidiasis or IC is a deep-seated infection that may or may not be in the blood, but occurs when Candida impacts otherwise sterile organs like the heart, brain, abdomen or bones. The Centers for Disease Control recommend intravenous echinocandin therapy as the first line treatment for IC for at least 14 days after negative blood cultures and REZZAYO has unique properties that other [indiscernible] don't.

In addition to once weekly dosing, utilizing REZZAYO eliminates the need for a patient to get a [ pICline ]. It could potentially allow for earlier discharge and demonstrates activity against azole-resistant Candida species. While REZZAYO launched in 2023, CorMedix sees significant opportunity now and in the future with the current indication for growth.

Over the past 2 years, Melinta has made solid progress in hospital systems with formulary adoption and driving clinical interest, which is now translating into broader adoption and utilization. We see substantial growth drivers in the outpatient infusion center space, where more favorable reimbursement exists and the logistical challenges are minimized. In the past years, the emergence of Corus creates numerous challenges in treatment due to increasing azole resistance and the organisms ability to travel quickly in a health care setting.

When we think about additional patient populations, those such as patients with intra-abdominal candidiasis a severe and often fatal type of infection without candidemia or those with the need for long-term therapy due to deep-seated infections, are perfect potentially for rezafungin. These opportunities combine the total addressable market of $250 million to $350 million.

To share deeper insights on the treatment of candidemia and invasive candidiasis, it is my pleasure to introduce our first panel. Dr. Neil Clancy, Professor of Medicine at the University of Pittsburgh. Dr. Clancy has been funded by the National Institutes of Health for over 25 years for research on pathogenesis, antifungal resistance and the clinical aspects of invasive fungal infections. Dr. Michael Mansour serves as an associate professor of medicine in transplant and infectious diseases at Harvard Medical School and is the head of his own laboratory at Massachusetts General Hospital, where they focused on developing novel cellular diagnostics and therapies for invasive fungal infections and Dr. Travis King, earned his doctor a pharmacy degree from the University of Mississippi School of Pharmacy. He completed his PGY1 pharmacy practice residency at Methodist University Hospital in Memphis, Tennessee, and went on to complete a PGY2 infectious disease residency at the University of Mississippi Center in Jackson, Mississippi.

Dr. King specializes in transplant infectious diseases and antimicrobial stewardship as well as clinical microbiology.

Welcome.

Thank you.

So thank you again for being here with us. When we talk about rezafungin and it's placed in the market and how you're utilizing it in clinical practice, it would help our audience, I think, to talk about what factors most influence your choice of antifungal therapies. Pathogens, host factors, drug toxicity, resistance, institutional protocols. Let's start with you, Dr. Clancy.

Well, probably all of the above -- but I think the key is understanding your local epidemiology. So what types of infections do you see at your center among your various patient populations? And then with that, understanding the microbiology, what species are you seeing and what the general resistance patterns are. And from there, you can devise rational diagnostic and treatment strategies and then place different agents based on their unique properties appropriately into sort of the treatment algorithms that you put together.

Great. Dr. Mandsor?

Let me add to Dr. Clancy's great comments and say one concern that I have is the really rapidly growing patient population that's composed of those undergoing solid organ transplants and stem cell transplants as well as the growing oncology population. And I focus on those patients that I care for because they happen to have a large burden of other drugs required for all those diseases and processes.

So the drug-drug interactions for me become front and foremost when I'm considering how to treat their candidemia or invasive candidiasis. The azols happen to carry a lot of drug-drug interactions that can be quite detrimental and hinder treatment. And so the kind of candins and having rezafungin as a as a week long agent becomes really attractive. So those are the factors I'm considering when I'm designing an antifungal regimen.

Okay. Great. Thank you. So Dr. King you're often in the position of overseeing surveillance of these infections and opining on the best course of treatment for patients. What outcomes matter most to you when you are assessing the success in candidemia management? Are you looking at survival, infection clearance, quality of life for the patient? What are you most focused on?

Sure. That's -- I think to take a job there over Clansy answer all of them. Certainly, [indiscernible] first and foremost, for your patient. I spent a lot of time on the transplant side. So certainly, graph success is huge. You had someone go to the length of donating an organ, whether living or deceased, you would like that graft to survive. And so thinking about those long-term outcomes for our patients is obviously very important. Other things that we always think about for our patients is also maximizing the quality of life. And so certainly thinking about once weekly options such as rezafungin may fit better with their work life balance, with certain things that are going on from a social side of things. So that's -- those are the kind of the big ones. But again, all of them are very important and they're on right.

Excellent. So we know there are a number of operational barriers within institutions that you see. What are those that most impact timely antifungal care, right? Are we looking at diagnostic access, stewardship oversight, care transitions, what are most impactful when you're managing a patient with IC or candidemia.

I'll say, I think the major challenge facing the field that if you compare candidiasis to say a disease like aspergillosis, what's really lacking, I think, our diagnostics and early interventions. So we're still largely dependent upon cultures, cultivating an organism that we're taking either from the blood or appetitive site of infection and growing it in the lab.

The sensitivity of that for canadisis is only about 50%. So in this half the cases to begin with, and then it takes typically 2 to 3 days for the organism to grow. During which time, we're either not treating the patient or we're treating the patient empirically. The advances in survival with aspergillosis have been combining a diagnostic test, galactomanin systematically employed in high-risk patients and then treating early based on that result. And we don't do that in Canadiasis. We largely wait for cultures. We're reactive. We're treating too late and mortality rates since the time I was in training, despite the introduction of new drugs, really have not changed. So I think diagnostic and treatment algorithms based on early diagnosis and treatment, sometimes empirically is what the field really needs.

Great. So Dr. Manser, you have a lab where they're focusing on cellular diagnostics and therapies for IFIs. Would you like to expand on that?

Our lab focus is really on trying to promote immune health and having that immune system recognize and clear those invasive fungal infections. That goes hand-in-hand with the appropriate timely diagnosis as Dr. Clancy just said, and really trying to use the best antifungal drugs in conjunction with the best immune health immune response.

Often these patients who are undergoing transplant really just won't have a deficient immune response because they're on antirejection medications or chemotherapy agents for their disease. So it's a fine balance to really assemble together that appropriate response. And I think overall, for me, getting the patient out of the hospital as just one big driver, removing them from all the exposures to nosocomial infections and drug-resistant bacteria, et cetera, really begin to touch on a critical variable of lifestyle, getting them home to be in a better, healthier environment, having them move around and having physical activity returns.

So having them tied down with requiring IV therapies and other things that could be moved to the home become a better, more attractive scenario. So long-acting agents, and we have some in the gram-positive bacteria area. And now with rezafungin in the Candida area, really gives additional opportunities administratively to get them out of the hospital and get back home.

I'll follow up on something Dr. Manser just said. He's talking about the long-acting aspect of rezafungin which is a very favorable pharmacokinetic profile. But the other thing it does and it ties into the inadequacy of diagnostics is it gets a very early peak concentration, which is the reason that you can give them once a week. And if you look at the major driver of response in animal models and other models, it's getting that early peak of drug at the site of infection. And the theoretical advantage that rezafungin may have is by doing this, if your diagnostics are suboptimal and you're diagnosing late, getting that early peak may give you a greater chance of clearing infection. And I think that's part of the reason the clinical trial, there was a signal that you had earlier clearance of blood cultures becoming sterile with rezafungin compared to the comparator or cinacandins.

So I think something that might be helpful for people to understand is the management of these DDIs. So we throw out terms like hepatotoxicity, neurotoxicity and those concerns. But what does that look like from a clinician standpoint, what does that look like for the patient and what they're dealing with. Dr. King maybe you want to...

It's obviously, the pharmacists and the drug interactions are very give hard and more importantly avoiding them. And unfortunately, the population that we see more commonly in to the Dr. Manser was pointing that is rapidly growing is that immunocompromised population who doesn't really have options. We can't really negotiate our shoe size when we think about having the prophylaxis against certain fungal infections, be it candida molds, aspergillis, what have you. And so we run into issues of trying to negotiate different dosing regimens, which kind of makes the treatment regimens oftentimes very confusing for the patients because again, patients first in everything that we do. And so having options that are clean, certainly the kind of [indiscernible] as a class are that, but then also having ones that we can, again, avoid simple line catheters for patients that are already immunocompromised and even those that aren't, but getting plastic out of a vein is really the best case scenario. So it does give us a lot of laterality, both on the drug direct negotiation range and also just the ease of treatment management and avoiding unnecessary things like central lines, pieces of plastic that can lead to secondary infections.

That's helpful. Dr. Manser.

Maybe we're all saying a very harmonized, we're trying to paint a really clear picture. I mean there's like real cases that I remember. Patients who could not receive specific chemotherapy agents. Oncology has taken on a different sphere, a different era where you now have such a wealth of agents and biologics. And there's really a lot of amazing medications in oncology where like a drug-drug interactions may mean you don't get that option. When -- specifically when using an azole. So many patients that I've cared for were unable to continue or we have to make a decision on switching antifungal agents because that DDI was very severe.

In the [indiscernible] organ transplant world using azols often requires adjusting agents like tacrolimus or other antirejection medications. We've had many times where liver numbers go up, and so now we wonder is that the azole? Is that rejection? And these lead to very serious decisions where we have to collect the biopsy to make sure that graft is not being rejected because we would have to intensify treatment regimen.

So these decisions have very real consequences. Someone's going to biopsy you. Someone's going to really increase your steroids or other antirejection medications, leading at risk for more infection. So they're not benign blips in liver numbers. They lead to very serious consequences.

Yes, I think the thing you have to bear in mind with DDI's toxicity side effects in these patient populations is how sick they are to begin with. I mean, these are profoundly immunosuppressed patients that transplant [indiscernible] malignancy patients, but also other critically ill patients in the intensive care. The patients undergone complicated abdominal surgeries, liver and gall bladder surgeries.

So under the best of circumstances, tolerating your other drugs is very challenging, getting reliable drug exposure in these patients is very challenging. So then when you have an agent you're adding on, that's interacting with these and further confounding it, it becomes incredibly difficult. So these are your sickest of your hospitalized patients who are at risk for developing these diseases and in whom you're using these antifungal drugs and the fastest-growing population.

Atleast in my hospital, that is the fastest-growing population. Are these immune-compromised individuals.

Yes. And again, to go back to understanding your local lymphology, at the University of Pittsburgh, we have very big liver transplant program, but we also have probably the largest liver surgery program in the country. So you wouldn't think of these necessarily as classically immunosuppressed patients are not taking chemotherapy agents, but they're functionally immunosuppressed. Can do the lives in your gut. That's where the infection comes from. So anything you do to disturb the gut potentially causes leakage of Candida and either bloodstream infection or otherwise sterile site infections such as within the abdominal cavity.

So my patient population overlaps but has unique aspects of it compared to Dr. Manser and I have to understand that if I'm going to use a drug properly at my center and the considerations might be different than at his center.

And one thing that I will add, too, just thinking of my population in New Orleans. Outside of the immunocompromised population outside of the transplant, the BMT, certainly, we have a large volume of perimeter volume patients. And the fastest way to get my cardiology clinical pharma stuff in arms is to throw an azole on someone who is being treated for Afib with a non-orphan regimen.

So it becomes very difficult to manage and that we don't necessarily have the gray anti-coag parameters to follow when I have to introduce an azole to that very complex regimen. That's just one small example. If you think about patients that come in with arhythmias, we have issues with QT prolongation obviously, that is something we don't have to worry about here, which is fantastic. So I think that the opportunity to avoid drug interactions in these patients is huge, and it expands certainly in those that are near and dear to our heart with immunocompromised but also far reaching outside of just that group.

So we've talked a lot about, and thank you for bringing up the severely immunosuppressed patient population. What are the other patient groups that we're not thinking about that could potentially benefit from treatment with the long-term echinocandin like [indiscernible]

So speaking to people, colleagues of mine throughout the country. I think largely nonblood-borne noncandidemia candida infections are often overlooked.

The invasive [indiscernible].

[indiscernible] and what you spoke about, I say in your introduction. It's a lot harder to diagnose these, drawing blood, it's invasive, but it's accessible. If you've got a deep tissue infection, you've got to go into the site of infection in order to draw fluid out and potentially culture and organism.

So I think we miss a lot of these because we're not diagnosing them to begin with. The yield on culture is not great from these sites because the bugs are not uniformly distributed. So even if you go away, you've got a 50-50 chance that you're going to miss it. And people are not conditioned because the clinical trials are largely done in patients with candidemia because they're easier to identify. And oftentimes, within the abdominal cavity or other sites of infection, you also have bacteria mixed in there.

So people will focus on the bacteria and pay less attention to the candidate. So at the University of Pittsburgh, we actually see more non bloodstream infections per year than we see candidemia. That's not true at every center. But I would guess that nationwide, probably the population we're most missing are diseases like intra-abdominal candidiasis osteomyelitis some of the other end-organ infections that often will not have a positive blood culture.

That makes a lot of sense. CDC says we're seeing 40,000 to 60,000 invasive candidiasis instances a year. I think people know how to really put in context what candidemia is, but I think it's a little harder sometimes to say, what does an IC patient look like? So...

And they're a lot tougher to treat because oftentimes, you've got to go in and do an intervention to remove the focus of infection. So if I'm treating the intra-abdominal abscess, the antifungal drug, I'll typically give for several weeks until the [ abscess ] is gone. But hand in glove with that, you've generally got to go in and drain the abscess, which requires an intervention. If you've got a leak of your hepatic or global bladder drainage system, they have had a biliary system, you'll get biofluid that goes into the abdomen. You've got to repair that leak in order to prevent the infection from recurring over and over again, which is very, very difficult to do.

So as a general rule, these non bloodstream infections require longer courses of treatment, oftentimes on the order of several weeks -- they require a surgical or intervention component, oftentimes as part of it, and they're just more difficult to manage over time. And I think they're underrecognized and underdiagnosed to begin with. I think to add another variable to that and not thinking with a focus only on immune compromised patients is the Candida species itself, right?

So I think that's the other elephant in the room, which is [indiscernible], as a group, are one of the most common fungal infections we experience, but really Candida's composed of many different types of species, Candida albicans, Canara, [indiscernible], you mentioned those and the [indiscernible] Joe mentioned those in the introduction. But some of those species are rapid risers and making lots of headlines as being drug-resistant candor is being sometimes multidrug-resistant.

So there where you need to treat for a long period of time, you may have lost the azols completely. And now you may be stuck with a patient who's attempting to recover and rehab and improve but they require long-term echinocandin treatment. And you get kind of stuck and put into a corner where you need to either use a PICC line or some sort of central catheter. And as we were mentioning, not the most ideal scenario because now you've got risk for secondary bacterial infections.

So again, that's a great area that we worry about and where we can use long-term pharmacokinetics like rezafungin to maybe avoid those catheters and get through a very prolonged treatment depending on what drug resistant species we're trying to deal with.

I'm sorry, I was going to say the other one that I always think about and certainly identifying the patients that are drug-resistant the deep-sea infections. We have a large population of oil and gas workers and agriculture workers in Southeast Louisiana. And if I had to ask them if they would like to go to the refinery with a pink line in, so a central line answers, right? And that's actually the best case for the patient because there's a high risk of severe complications. And so we try to at least identify those patients.

Sometimes they fit, sometimes they prefer to sit it on the pig. That's up to them. But it is kind of an untapped market thinking about that patient's work life balance and what they're actually doing to minimize secondary complications. The other that I'd like to kind of position a once-weekly medication such as rezafungin in is our transplant population or depending on how your clinic functions, a lot of our patients travel from very long distances come in and so we'll set up around Robin clinics for them. So they're rapid fire with their cardiologists, endocrinologists, transplant surgeon infectious disease if they need us. And so we can streamline that care all in 1 day to minimize the burden on their actual just day-to-day life, that also, again, just kind of helps coordination of care and streamlining servers on the same page.

So certainly, the infectious complications, infections issues are worried, but I think there's the social side of things that plays a very large factor for us.

So speaking of the social side, I know we talked about this a little bit earlier. There are social determinants of health that certainly weigh into patients that may benefit from a long-term echinocandin a bit more. And we've talked a little bit about the geographic disparities as it comes to like Dr. Clancy as said, knowing your local epidemiology but from a social determinants health standpoint. Can you expand a little bit on that?

Sure. So just from my personal experience, what we end up running into more times than not is a patient's ability to physically show up to our infusion suite. Or do they have the support structure at home to be able to help facilitate deal in [indiscernible] on daily, whatever your medication may be. But -- because again, you think about all the secondary complications that are not benign when we introduce a foreign object into a patient.

So certainly, transportation coverage is always an issue -- but we haven't thought that too much, which has been good. And again, thinking about just where our patients are coming from and again, where they're living, what their actual support structure is, tends to be the biggest one. again, thinking about patient comorbidities, things to avoid. I think we hit on the drug-drug actions very well. So yes, I always like to bring up the social side of [indiscernible] because having a 1-week option like rezafungin very, very nicely dovetails into making life a lot easier for someone than having a daily infusion again, but also making sure that we can actually get them to our infusion suites.

So...

Yes. I mean I think if you look at our health care system, Dr. Kennedy University Kripa, because it's typical of a lot of modern large health care systems now and that we've got the urban core, where the primary university-based hospital is. And then we service a vast underserved largely rural hinterland, in our case, Western Pennsylvania, West Virginia, where there's extremely poor access to care. And the other issue that we face increasingly in Western PA is the fentanyl and injection drug scourge. And this is a population where for both bacterial and fungal infections, which we increasingly see in that population having a once weekly treatment option where you don't have to have a permanent indwelling access device is very, very important and allows care in these patients.

Previously, these were people that we would have to keep in a facility for 6 to 8 weeks to complete a course of treatment for endocarditis, for example. So having the ability to come in once a week, get treatment, not have a permanent and dwelling line has made a real difference in that population.

I echo the same. We've definitely seen wonderful advances where you can get someone to appropriate care by not being tethered to a central line, especially if -- they have barriers to access to care, other issues that they're dealing with, such as substance abuse. They really have more options if they can leave the main hospital and really begin to engage with care without those anchors.

And the once weekly agents have really made an impact there.

I did want to follow up on 1 thing Dr. Manser mentioned about resistance. Just to point out, the 3 top priority resistant candida that have been highlighted at CDC and WHO are all potentially azole-resistant. And that includes Candida Aris, 95% fluconazole resistant, azol-resistant cantaperopsalosis, which we've seen now over the past 5, 10 years, previously did not exist and then [indiscernible] with 15% to 30% as resistance. So azole-resistance is going to be an increasing challenge, already a big challenge, but it's just going to get bigger.

Great. Well, I'd like to thank you all so much for your continued commitment to patients and educating us today.

With that, I'd like to welcome Dr. Pete Sullivan, Senior Vice President of Market Access and Board certified oncology pharmacist.

Thank you, [indiscernible] Thank you. As we look beyond the current market with REZZAYO, we are most enthusiastic about the opportunity of prophylaxis in patients undergoing immunosuppressive therapies. These patients are profoundly immunocompromised and highly susceptible to opportunistic infections, patients battling hematologic malignancies like leukemia and lymphoma and those undergoing highly immunosuppressive therapies are the 2 key patient populations at risk and require long-term prophylaxis, including antifungal therapy. The treatments for these malignancies, while potent against cancer leave the patients with limited natural immunity ahead here.

One critical patient population requiring long-term prophylaxis is those patients undergoing stem cell transplant. Similar to the treatment of fungal infections, there are a number of different agents used to prevent infections based on patients' risk. Today, azoles are the standard of care for allogeneic stem cell transplants with alternative agents such as the first-generation short-acting kind of candens.

In addition, hematological malignancies like AML and ALL are also most likely to receive prophylaxis due to the treatment and disease burden these patients have. Based on recent market research that we conducted with stem cell transplant physicians and ID physicians, there is a wide variety of antifungal agents use in prophylaxis. This prophylaxis is dictated by risk factors and protocols. Although the majority of the top 10 transplant centers in the United States, prefer posaconazole, we see a large opportunity for rezafungin REZZAYO in this patient population based on the variety of products and agents used for prophylaxis. In the same market research, we found a strong signal for the willingness of prescribers to prescriber REZZAYO in patients receiving stem cell transplants and undergoing treatment for hematologic [indiscernible] as prophylaxis and well within our target goal to penetrate the TAM.

Looking beyond our current indication, we believe the convergence of the unmet clinical need, growing economic pressures within the health care system and evolving standards of care, it's creating a meaningful and durable opportunity for REZZAYO expansion. We determine the opportunity as expanding into a broad patient population at risk for invasive opportunities infections, including those caused by Candida, Aspergillus and PJP. We estimate the total addressable market is over $2 billion. And we'd be happy to speak more about the granularity of how that addressable market is comprised and certainly, the Phase III trial data and the FDA label will impact that addressable market and market potential.

In terms of why we are so excited about the potential for REZZAYO in prophylaxis as an indication despite the current available options, as was previously discussed in the previous panel, patients that experience -- patients currently experience unacceptably high rates of hepatotoxicity and drug-drug interactions, potentially compromising their treatment and exposing them to serious adverse events that we'll talk about here momentarily.

Supporting the prophylactic indication is our ongoing Phase III study run by our global partner, Mundipharma, Respect is a global Phase III randomized double-blind trial evaluating the efficacy and safety of once-weekly rezafungin or REZZAYO, compared to the standard antimicrobial regimen for the prevention of invasive fungal disease in adult patients undergoing allogeneic blood and marrow transplant.

Enrollment was completed in late 2025, and the top line results are expected later in Q2 of this year. In addition to the primary efficacy endpoint, respect evaluates the discontinuation of rezafungin compared to the standard anti-infective regimen, secondary to toxicity and intolerance as we heard by the panel. We've also heard from the clinical community that this still remains a serious concern. It is now my pleasure to introduce our panel today to talk about infection prophylaxis in high-risk BMT in hematologic patients.

Dr. Jay [indiscernible] is an assistant professor of leukemia, an affiliate faculty member in clinical cancer genetics at MD Anderson Cancer Center, Houston. He focuses on the management of patients with acute and chronic leukemias along with drug development and translational research in high-risk myeloid leukemias. Dr. Melinda Cook is a Board-certified oncology pharmacist. She practices in both the inpatient and outpatient setting as a bone marrow transplant clinical pharmacy specialist at Memorial Sun Center and Cancer Center. And Dr. Doris Ponce is a hematologist oncologist specialized in bone marrow transplantation. She is an Associate Professor of Medicine and Memorial Son Kettering Cancer Center, where she is the Director of the graft versus host disease research and translational program and the co-chair of the Center for hematologic Malignancies Research Council.

Thank you very much for being here.

All right. So the previous panel talked about treatment, and we're going to shift to talk about prophylaxis and how that impacts your patients. So Dr. [indiscernible], how do you -- how do you approach infection risk across the transplant continuum from induction to early transplant to prolong neutropenia and GPH. How does that shape your prophylaxis strategy across the patients?

Okay. So we need to take into account that we have a very unique patient population. So these patients with hematostrpelic disease or advanced nonligand hematology condition, typically will undergo through song treatment before transplant most of them and they already will comment to us with some level of immunity compromised. So they already got exposed to some chemotherapy agents, they might have some experience with infections in the past when they come to us.

So then when they come to transplant, they go to this spirit of conditioning treatment where we basically remove their immunity with this very aggressive therapy to allay out the new stem cells to grow and thrive in the new environment. So with that, we advise for patients at that period is very sensitive for infection. And then on top of that, they will lose their accounts and they will have neutrophils or other cells from the immune system, sophisticated upfront cells, the core battle any infection.

So they are in a quite sensitive period of time through their transplant. Now after account recovery that can take 2 to 3 weeks from the time they get their stem cells. They're still quite immunocompromised because even though they recover their neutrophils just like the upfront of the soldiers in the battle, the more sophisticated immune system hasn't recovered yet, which is why or prophylaxis for like, for example, antifungal and others last longer than just the neutropenia recovery because that sophisticated immune system has to kick back in.

So these patients are quite sensitive for any source of infection. And that's why all of that universally will receive prophylaxis.

Okay. So those patients are on long-term prophylaxis, whether it be fungal or PJP or anything else. What are the biggest limitations? And maybe this is a question for the full panel. What are the biggest limitations to the current antifungal prophylaxis options when it comes to safety, tolerability, maybe long-term use? And do you see any development of resistance in those current therapies?

Maybe Dr. Cook...

Yes, so I think as the other panel kind of talked about drug interactions, of course, is a major issue. And it's especially a problem in the transplant population with them being on immunosuppressants as was mentioned. So any time we're having to start 1 of the azole antifungals, we're having to take into account their immunosuppression dose adjusting it.

We probably are going to have to bring the patient back in to monitor them and their levels more frequently. And so that's definitely a challenge. And then just drug interactions with all medications in general, it takes looking at the patient's medication list very closely to ensure that there is no adjustments or like that is even safe to give the azole for that patient.

So that is a major challenge, and we may have to make adjustments to the antifungal we use based off of those drug interactions. We do run into issues where the -- it's rising at the level of the immunosuppression, it's so high that they'd be at risk for toxicities from that immunosuppression.

So we may have to switch to an antifungal that has fewer drug interaction concerns. And then in terms of side effects, that's probably another major issue to talk about hepatotoxic hepatotoxicity we've talked about is probably the biggest issue. We -- it's especially important in the BMT population, just because the transplant itself has its own liver complications associated with it. And so if a patient is showing signs of hepatotoxicity, it can be hard to distinguish if it's drug toxicity from the azole or if it's a true complication from the transplant. And so the azole tends to be kind of the first one that needs to go just to rule it out as a cause for this potential hepatotoxicity and so that's a big challenge. And then trying to find switching them to an antifungal. That's going to be a bit more tolerable as an issue.

Dr. [indiscernible], how does that impact your leukemia patients receiving high-dose chemotherapy as well?

Right. So I'm going to give a little bit of background. In the last 30 years, the survival of leukemia has doubled. Let's call them acute myeloid leukemia, acute lymphoblastic leukemia. And we cannot put our backs by saying it has only been because of leukemia medication.

So a lot of it has been because we were able to deliver better leukemia therapy, while we are able to cover patients with better antifungals, antibacterials during the peak neutropenic periods. And the efficacy of any antifungal drug at the end is determined by the compliance to that medication. When we are trying to develop new acute myeloid leukemia therapies or acute lymphoblastic leukemia therapies, the aim is now more combination trials in the last year itself, FDA has approved 3 new drugs in acute myeloid leukemia for relapsed/refractory. And if you go deeper into the way the journey of these drug approvals, all of them started with Phase I drugs that did not allow us antifungals.

Because of drug-drug interaction potential for liver toxicity, being the primary veins to drug development when you're trying to combine them with good antifungal drugs. As a result of which, developing drugs with limited drug-drug interactions so that you can take the leukemia field forward with the respect to drug development is supremely important, that's point A. Point B, a lot of these patients when I'm as a leukemia physician, trying to put them on an agent, which is supposedly going to work very well for the leukemia. I'm worried to add on an asuntifungal low and behold, the liver and sensor to go up and then have to come down on the leukemia directed therapy, which in no way leads to better outcomes.

So then we are talking about hepatotoxicity. And the third part of it is the compliance to treatment, which I started with. When you are not giving patients as all antifungals, you are worried whether price a week caspofungin or available drugs would be able to provide them adequate candida or even more prophylaxis compared to a drug like rezafungin where there is strong pharmacokinetic evidence of the drug having persistent efficacy with the peak and that was shown in both the [ restore ] as well as the STRIVE trial with 5-day early fungal clearance, which is extremely important in these patients with profound and deep neutropenia with not only one axis of the immune system being affected, but multiple access and low neutrophil counts, mucocell injury from the chemotherapy as well as other arms of the innate immune system being affected secondary to the therapy.

So reduced rub brag interaction is important, reduced toxicity to other organ systems are important and improving compliance. And I think that's where rezafungin hits all the boxes.

I want to add something to the challenge that we got in transplant. If a patient is very high risk for mall infection and they go -- as they start their transplant conditioning, we compromise of not giving any coverage for mall infection because the drug-drug interaction is so severe that we will not be able to achieve a therapeutic dose of the anti-rejection treatment of the immune suppressant and therefore, they spend a good period of time about 2 weeks or longer with our proper coverage with the trade war that, okay, I will at least get a therapeutic level of immunosuppression, but at the cost of adding the risk for [indiscernible]

I'm going to add a point to that if you have time. Inotuzumab it's a drug which we used very commonly in acute lymphoblastic leukemia. We led the development of this drug. It's now bread-and-butter and acute lymphoblastic like management approved both in pediatric and adults. And this drug is known to cause hepatotoxicity. So I'm going to cite some important data from clinical trials. When the initial trial of this drug was approved, 27% of patients end up having significant inhibitor toxicity, especially if the renter transplant.

So these patients end up not getting azole antifungals, and we develop this protocol, but a lot of these patients end up developing other fungal infections. And we are not able to cover them adequately, as Doris mentioned, as a trade-off giving them good leukemia therapy, preventing them hepatotoxicity so that they go to transplant. But on the other hand, compromising on the antifungal drugs because we haven't got any good, which patients can get adequately in the outpatient settings with good coverage. So getting long-acting drugs, which does not affect the liver with low drug-drug and correction is a strong need at this point.

Okay. So making that choice, right, making that balance of achieving therapeutic doses but also protecting the patient from high-risk infection. How often are you making that choice? And does REZZAYO into that category, assuming the data supports it.

Well, as mentioned, we do have a compromise where at least for us is actually is not negotiable where we need to make that trade off. Even with a strong history of mall infection, like patients as previous -- since they received treatment in the past, they're already immunocompromisin they can come to us with history as forges infection. And our trade-off is that we will expose them through the transplant process of beginning with our coverage, which is quite concerning. And now that we are adopting a new prophylaxis regimen for represents disease that is cyclophosphamide, that actually makes adding the main drug draconian drop which is immunosuppressant medication actually later.

So now we are -- the problem is getting worse because we're pushing the clock when to be able to add more coverage to later. And I think now that this is widely adopted, we see this problem even more.

And I will say that we do run into like the scenarios I kind of talked about where patients are developed being signs of potential hepatotoxicity and we have to hold the azoles. It could be significant enough that we don't want to use any azole, and we might have to compromise coverage again and like go to like micafungin and not have that aspergillus coverage that we would want.

Yes. Thank you. We talked to...

Some minor thing, too. it might also need to say in the hospital longer for treatment, that's another issue. And when they go in the outpatient setting, sometimes we only option we have because of hepatotoxicity, for example, is giving a drug 3x a week like micafungin, which is not -- we don't reach the adequate PK throughout that week treatment. And obviously, we -- again, we compromise that coverage.

So great point leads to my next question. From a feasibility standpoint, that long-term prophylaxis is hard to manage, right? So whether it be different treatment cycles or patient tolerability or patient compliance, what are the main challenges in maintaining adequate long-term prophylaxis in BMT patients or even long-term leukemia patients.

I'll start. So the main challenge with maintaining long-term prophylaxis is toxicity. There is an additive toxicity there was a class effect to azole toxicity hepatic particularly. But especially in high-risk leukemia where the depth of remissions are not good, and we are looking forward to new drugs -- most of the Phase I trials, which we envisage high-risk leukemia patients who have relapsed frontline therapy, we should be able to be treating them on clinical trials as per NCCN guidelines. We're not able to do that on azole antifungals, given significant amount of toxicity risks. As well as drug-drug interactions because any clinical trial would want to do PK analysis of their own drug and we don't know how azole antifungals are affecting A. B, Venetoclax, which is a drug now most ubiquitously used in leukemia and it needs a ramp-up for both acute myeloid leukemia, chronic lymphocytic leukemia is strongly influenced by azole antifungals, there was so much of drug interaction. So during the ramp-up phase, especially if you're doing it outpatient, you are basing your judgment of the best antifungal prophylaxis to be 3 times a week, as Doris was mentioning, which is not ideal and providing them some form of antifungal drug for a long duration with adequate levels, while you're ramping up the dose of venetoclax as per the label provides you good coverage without compromise.

So -- the challenges remain in being able to optimize leukemia therapy, while continuing good coverage for antifungal drugs.

So we mentioned the challenges. We mentioned the new therapies evolving, whether it be post transplant Si or the new therapies in leukemia. Looking ahead for antifungal prophylaxis evolving in a couple of years what would meaningfully improve patient care in both the transplant setting and the leukemia setting.

I think like a steady treatment with compliance will be really important -- if you take a look at any of our transplant patients, you will see that they have -- they need to take like 20 medications a day, is quite a heavy list, and I have patients complaining with 12 medications like, "Oh, actually, it's not a lot. So the -- it's almost like you need to make a mathematical algorithm of the drug-drug interaction to really allow to be safe in their journey of treatment during the transplant period.

So it's really difficult, like if they take I don't know, great fruit or something that they bought in [indiscernible] . You can already -- you can start seeing some shift in the interactions and that can really modify immunosuppression levels or other drugs. So for us, achieving a cell therapeutic immunosuppression level can be detrimental in the patient like have on control offers a host disease and some time -- it's just you have to tell what happened? Like you had a steady level what happened, what do you do? And then you start seeing that all these interactions, even outside of our medications can employee.

So that can really affect the safety of the transplant journey. And some patients might be a little bit careless when they get out of the hospital things are better, I'm feeling better and then maybe they not be so consistent with their treatment regimen, even the timing of your drug matters. So that -- those are small issues that they add on into a bigger problem.

I want to take a page from the previous panel and from the societal view, right? So as a pharmacist, you're managing the patient's medications both while they're being treated in the hospital, discharge planning and then the outpatient follow-ups, which are pretty recurrent. -- how challenging is the pill burden, right, in a transplant or leukemia setting of how many pills are taking, how often they're having to take it and just removing some of those challenges change the -- maybe the outcome or the lifestyle of the patient.

Yes. It's definitely a big issue for patients. I go in and talk to every patient before they leave the hospital after transplant. And just like bringing in that giant bag of medications is like immediately very shocking for the patient and they get -- many of them are very scared to take all of these pills and just being able to handle it, we have to give them a pillbox to make sure that they can actually manage taking all these medications at the right time. The can be on medications up to 4 times a day. We try to limit that the best we can. But yes, any reduction in their pill burden always helps. And right now with like the azole antifungals, it's one of the medications that it's on for a little bit longer.

So there's not as much hope to give the patient like, oh, you're going to be on this for a couple of more months. So yes, it's definitely a challenge. And the longer they're out of the hospital, yes, the less -- they feel like they need to take some of these oral medications. So yes.

Yes. I had patients where I see a huge swing in their immunosuppression level. And then I found out that they forgot to take our antifungal. So always taking those con didn't take a escape today, but tomorrow took it then I have a side effect that caught the pill in half and like those patients tend to have super and subtherapeutic levels throughout the week on and off, which really compromise or transplant. So -- and really having a treatment that you could -- you force the patient to be compliant on a medication and doesn't cause a drug darker accident. It will be really relevant for us as a tool to offer to our patients, too.

Yes. So it's a great point, and I think it's easy to not fully grasp that challenge there, right? And so we're thinking about drug-drug interactions and transplant patients. They're on immunosuppressive therapy, right? You say you kind of talked, they're going to be on maybe a micafungin in the beginning and then you want to transfer them to an azole. How much does that actually impact maybe their [indiscernible] levels, right? So if someone is on tacro for immune suppression and you start posaconsole, right? So as the pharmacists on the team, how much is that dose actually changing?

So yes, if it's like a Posco [indiscernible] , usually, we're reducing the dose by half or voriconazole half less with some of the other azoles, but yes, it's a pretty big dose reduction. And it's something we just have to watch really closely to because especially in that early transplant period, we want to make sure they have therapeutic levels, and we don't want it to go too low, and you can't always predict exactly how a patient is going to metabolize medication.

So yes, the -- it's definitely an issue. And yes, we have to just watch them really closely.

Thank you for that. Any last questions or thoughts on antifungal prophylaxis in leukemia or transplant.

No, I just want to say that there are other instances beside the early [indiscernible] period like patients who have like [indiscernible] disease, which is a transplant complication where you need to actually add more new suppressions for medication Main drug is like corticosteroids, and those patients actually require to resume antifunal treatment. And many of them have hepatic involvement and it's quite difficult to manage. So those are small scenarios where not that small, that you call encounter later on after the initial transplant period that they are backlog.

Two things. One, I think a good anti-mold prophylaxis is supremely important at this point. I'm very eager to look at the data of the RESTORE trial whenever it's read out. It's a very well-designed trial with posaconazole on the competitor arm and with a very small inferiority margin. So it would really open a box of opportunities for these patients to get drugs that have less interactions and less toxicity. The second is to understand that these drug interactions that we try to put it in 1 box that, okay, drug game might increase the dose of venetoclax 4x, drug B could increase it by 2x. It is done in a very small group of populations, which are not ethnically diverse and the drug metabolization is very different in individuals, even based on the profile of the immune suppression that they are on the type of leukemia therapy they have received.

There is one as a antifungal will not name it. Initially, it was supposed to increase the dose of venetoclax 3x. Now we know it increases it by 8x. So as a result of which, we are learning more and more. And even though we probably are getting better at modifying the dose of leukemia drugs with respect to infectious drugs. It can never be as refined as treating with a drug that does not cause drug-drug interaction. So that is extremely important. And now -- in the present generation of leukemia therapy, I'm talking essentially pretransplant or post-transplant unfortunate relapses. The aim is no more to try a single rug because it doesn't work.

So we try to do combination anti-leukemia drugs, which certainly gets better control of the leukemia, but the immunosuppression is also more profound, deeper, longer and more arms of the immune system compromised. And the mix of it, when we try to add drugs, which have strong drug-drug interaction, toxicity potential, it prevents better leukemia drug development. And as a result of which, we need those kind of drugs, which would be able to give us a longer duration of good profile axes.

SP-42 I want to do a final comment on it. I don't know if I mentioned that, but at least on the BMD side, we're seeing more and more Superbox resistance and breakthrough tripophlaxis. So I think in this timely manner is too to have another tool because we are seeing these cases, and we have not too many tools to treat the patients that have a breakthrough.

I just want to add something we haven't really talked about yet is just like the financial and insurance barriers to using the oral as -- it's a major issue on that actually is the main decider in what antifungal I use for patients that we're going to use for patients for prophylaxis. If a patient does have toxicity or we're running into drug interactions issues. We might want to switch to another antifungal, but the antifungal with less drug interaction concerns or side effect concerns is also the one that's harder to get approved by insurance and also has higher co-pays. But really, all the azoles can have co-pay issues for patients, depending on their insurance and their deductibles can run in -- once January every year, we have patients coming and telling us they -- all of a sudden, their posaconazole co-pay went up by this much, and they can't afford their co-pay. And have to figure out as fast as we can, some way to get them that drug affordably.

So that's a major challenge.

Yes. Just to put one last point on practical situation. There are these patients who have breakthrough frontal infections, both azolprophylaxis or otherwise -- and they are on triple antifungal therapy. We try to get them out of the hospital because we don't want to keep them in the hospital for weeks. They get out of the hospital now they're coming every other day, driving 4 hours. And often, the companies better off in the hospital. So on 1 hand, quality of life and resource utilization versus providing them better therapy, we have to start really now thinking from the patient's perspective and developing drugs, which really helps in improving quality of life, just improving survival in leukemia therapy, while they were spending the better part of their life in the hospital and in the clinic it's not good improvement in leukemia therapy.

I think that's -- it's easy to sometimes overlook, but that's why we're here, right? To improve the quality of life of our patients that whether we're developing drugs for them or treating them in clinic or managing to try to get them on the hospital. So -- thank you very much. I thought this was a very insightful panel and appreciate you being here with us today. Thank you.

And with that, I want to welcome Dr. Jared Crandon, Executive Director of Clinical Portfolio Management.

All right. So as Joe had mentioned, we are transitioning indications with the fin cap into the total parenteral nutrition space. And while there are a variety of patient populations that utilize central venous catheters, you can see the total parenteral nutrition space actually uses them almost universally. And I think as Dr. King put it earlier, these are effectively pieces of plastic that we're sticking into the veins of our patients. And so TPN specifically is delivery of nutrition via the vein. So these patients are unable to tolerate nutrition [indiscernible], so we're putting directly into the vein. So all of that's going through that device that's either inserted peripherally. So we talked a little bit about PIC lines earlier, so those would be in the periphery or actual central venous catheters, which will go right in the neck or the chest directly into the heart.

Having TP in and of itself creates a variety of complications. Most notably, the metabolic abnormalities noted here in the middle. But having that piece of plastic in the vein certainly puts patients at risk for things such as thrombolytic complications, so blood clots, specifically in that catheter as well as central line associated bloodstream infections is what we're going to talk about today. These infections can be caused by both intra or inside the lumen of the catheter sources as well as extra outside the lumen of the catheter. They can be caused by a variety of gram-positive gram-negative bacteria. As well as fungal pathogens. I mean we talked a lot about fungal pathogens, so you understand some of the concerns there.

These infections are associated with significant morbidity as well as mortality. On the upper end of that mortality range, you can see things in the neighborhood of 15% or even 30%, particularly with those fungal organisms. In a given year, we estimate that roughly around 26% of patients, TPN patients will develop one of these [indiscernible]. So current prevention strategies are really focused on the extra luminal sources of these infections. So things like washing your hands, making sure that you're changing dressings commonly we even -- there's even use of these chlorhexidine or drug-containing dressings. Certainly, every time the site is accessed, they're scrubbing the hub to make sure you try to kill these many pathogens as you can. And so those are really focused on the sort of extra luminal cases. Guidelines do suggest the use of preventative lock solutions. And so if I can kind of just take you through, so a patient gets TPN. So you have this nutrition going through their vein. At the end of that time, they'll take a saline syringe, they'll just flush it out so sort of clear all that nutrition out. And then the patient will put something in that tube effectively to kind of keep it valuable.

So most commonly, heparin is what's used and heparin is used to prevent blood clot. And so that will go inside of the vein and then inside of the catheter and then the patient will go about their day until they get TP in the next day. And so those don't have any antimicrobial components to them, but guidelines do recommend that you could use these antimicrobial containing lock solutions. However, there currently is no FDA-approved catheter lock solution that's antimicrobial in the TPM population.

So our product [indiscernible] is a combination of heparin, which I mentioned, is there to reduce clotting as well as Taroladine, which is a non-antibiotic antimicrobial has a broad spectrum of activity against both gram-positive, gram-negative as well as fungal pathogens. So it pretty much covers the waterfront as far as the organisms that cause these types of infections. [indiscernible] currently has no known resistance, here's pretty high concentrations of the drug within the catheter. And even in a bacterial study trying to develop resistance in the laboratory, we're unable to actually do so after 20 passages of these types of studies.

Given this unmet need, we think that this TPN market represents a significant opportunity for [indiscernible] there are approximately 40,000 patients in the U.S. each year that will have TPN, whether it be at home or in the hospital. And those equate to about 4.7 million infusions each year, we size that market to be addressable at $500 million to $750 million. So we've conducted a little bit of market research recently to kind of look at the -- sort of the defend cap market and TPN versus some of the other indications, and it's certainly different -- most notably, TPN patients, about half of them actually have commercial coverage. And we are -- we anticipate that the fin cat in this population will be covered as a separately billable Part B drug. Also through our discussions with these payers, we found that not only are they likely but also willing to cover anticipate coverage for TPN patients in the [indiscernible]. I think there's recognition of certainly this unmet need, which I sort of outlined before, but also the potential returns on the back end for prevention of these infections as well as hospitalizations and certainly mortality. To support our indication in the TPN population, we're currently enrolling in a Phase III program called NutraGard. This is a study looking at the efficacy of DefenCath versus the standard of care, which is heparin at the reduction of [indiscernible] in a 12-month period in TPN patients.

So our target population is 90 subjects, and we are currently about 1/4 of the way through enrollment. So with that, I would like to call up our last panel for today. First, we have Dr. Michael Owen Machine, who is a physician nutrition specialist, and Assistant Professor of Medicine at the Institute of Human Nutrition at Columbia University, serves as a Director of Medical Nutrition at Columbia University Irvine Medical Center, where he oversees inpatient and home parenteral nutrition for adults with a wide range of complex medical conditions.

Next, Dr. Alise Brett is a clinical endocrinologist and diabetes specialist and solo independent practice in Manhattan. She was trained in nutrition support during her endocrinology fellowship at Mount Sinai Hospital. Following her training, she has become a certified nutrition support clinician, for more than 20 years, she regularly consulted on patients at the Mount side hospital for the management of parenteral and inter nutrition and also manage patients receiving home parenteral nutrition.

And lastly, Dr. Jason [indiscernible] is a Clinical Professor of Pharmacy at the University of Michigan College of Pharmacy. He's an infectious disease clinical pharmacist at Michigan medicine, recognize Esper and epidemiology and the management of infections due to antimicrobial resistant organisms and antimicrobial stewardship with over 150 peer-reviewed publications on these topics and has been an invited speaker at numerous national and international conferences.

So thank you all for joining.

All right. So to start off, I thought perhaps Dr. Brett, you could kind of take us through and we talked a little bit about perhaps some of the vulnerabilities of this TPN population, the fact that they have these severe gastrointestinal disorders. Maybe take us through a little bit about what development of the labs might look like in this already sort of vulnerable population.

Got it. So thinking about the home TPN population. So all these patients are told, as soon as you get a fever, as soon as you get chills, you call us. And they call us and they come to the hospital. And so this is a major impact on their quality of life and often the quality of life of their caregivers, and they come to the hospital, they get blood cultures, they get put on antibiotics and often they're looking at atleast a 7-day hospital admission and exposure to antibiotics, they're at risk for drug reactions. They are at risk for C. diff infections, just being in the hospital. They're at risk for other nosocomial infections. And then depending on the type of infection, the pathogen itself and whether or not there is a port access, whether or not there's a there's a tunnel infection, they may need their access removed so they may have to undergo surgery to have their access removed and another surgery to have a new device placed and depending on how many times this has happened, they may be looking at decreased loss of vascular access. So these infections are really a big deal for these patients.

Yes. So it sounds like even -- so when you're sending a patient home on TPN, you're probably already having a conversation with them about, hey, you're at some level of risk because you do have this catheter -- is that more.

They're all told, but this is the major risk of being on predilution. The metabolic complications we can handle. We can take care of that. But they're all told when they go home, they have nurses come to their homes, they're all taught aseptic technique, how to handle these, but we can't prevent all these infections. And they're all told that this is even when we start them in the hospital, they're all told that infection is the biggest risk of being on the parenteral nutrition.

Could you just highlight then maybe a few of the key characteristics. So what is it about being on TPN specifically that comes with an increased risk for these cloud Cs?

So I mean -- so specifically, the metabolic risks that increase the risk -- the main thing that I think of is hyperglycemia, specific to my field that increases the risk. So hypoglycemia does several things. hypoglycemia, it serves as a substrate for the bacteria itself, -- it's a carbon source for the bacteria, so it increases the bacterias virulent growth and adherence. It also decreases the acute hypoglycemia decreases the host immunity. So it decreases the host ability to trap and kill the bacteria. And it also increases the production of cytokines, so like TNF-alpha and IL-6 and therefore, hyperglycemia worsens the host response to a bloodstream infection and decreases that risk. So we're worried we're always worried about hypoglycemia. And it's not just people with diabetes that get hypoglycemia. It's also metabolically stressed patients in the hospital that are at risk for hypoglycemia and people on certain medications, in particular, like steroids, -- so that's 1 of the biggest things that we worry about, and we need to -- we have strategies have how to get on top of that and control it and start with insulin in the formula when we need to and start with low dextrose and then raise up the next dose and the insulin as needed. That's the main thing that.

From a metabolic perspective. Yes, excellent. And then some of the -- you had mentioned some of the ideas around even just the fact that you're delivering this nutrition specifically. Can you speak a little bit to that context or anybody.

Yes. So the other thing that comes to mind is the delivery of lipids in the GPN formula. So just giving lipids increases the risk for infection and in particular, with our older lipid formulas, the intralipid, which is primarily soybean-based formula, which is mostly Omega 6 that is proinflammatory and has been shown to increase the risk of infection. And that's actually compared to the newer lipid formulas which are mostly omega-3, which contain fish oil and MCT oil and olive oil and our soybean sparing was in a little bit of -- always need a little bit of soybean oil because that contains essential fatty acids but -- but using any amount of lipids in the TPN does increase infection risk, and we have to -- and we have to think about when to start the lipids and make sure that we're not overfeeding lipids. And some of the society guidelines actually recommend holding lipids or limiting the amount of lipids at least for the first 7 to 10 days of providing TPN, particularly in critically ill patients or [indiscernible] patients.

Darrin, I would just add on to that. I think it's a really key point. You're giving food, right? So you're giving food in the microorganisms like the food. And 1 thing I think that's notable about TPN associated cloud needs in particular, that we certainly are concerned with our normal bugs of interest like you worry about staff res and resistance that comes with that. But you do see a little bit more gram-negatives. Even fungal and we've talked a lot about candidemia already today. So you see kind of a broader array of microorganisms that can cause collabs in these patients because, again, you are putting food and it's not just us that likes the food.

That's right. Yes, please go on the topic of lipids. There are some in vitro studies actually looking at what we call 2-in-1 TPN of just extrosin amino acids that you can't really culture a lot of bacteria or fungi. But when you add the lipids, you can culture Canada in the lab. So we do see that increased risk. And at least our data at Colombia, we see increased in roci and candida infections for patients on TPN -- and I think just to add to some of the risk factors, we have to consider other host factors. So a lot of the patients there's a reason that they're on TPM. They can't eat. They have GI dysfunction, so they may have bioleac that we heard about other things that are putting them at higher risk for perhaps look for some might be a transient bacteremia, but when you have this central line, then you develop claps.

I think Dr. [indiscernible]. So when you -- so you have a patient, you're going to send them home. You say, "Hey, you're on TPN now we're going to have you do this at home.

What sort of preventative strategies do you send them home with currently to help sort of prevent these things that we've been talking about.

The things that you mentioned, so you covered it, but hand hygiene, sterile technique when changing dressings, cleaning the hub and using chlorhexidine dressings. Those are kind of the main things the bundle that's come out from CDC to prevent cases both in the hospital and the home setting. But we've really -- when I there's a lot of fear and shame associated with this. And a lot of these patients -- doctors will say to them, "Why don't you just eat? Why don't you just see don't you know how dangerous this TPN is and there's a lack of understanding that I can't eat, I can't eat. Patients are desperate for some way to reduce this infectious risk because it is so disruptive to your life to be admitted to the hospital repeatedly. And then the medical complications of the risk of endocarditis and other metastatic infections.

Yes. I think that's an excellent point. And so I think we did touch on the -- there are some guidelines that sort of suggest that maybe you could use an antimicrobial in your practice, have you seen much antimicrobial catheter lock something actually in the lumen of the catheter. We have not found anything that's just practical to use that's commercially available covered by insurance. And there's ethanol locks or one possibility. Some pharmacies will compound an epical outlook a lot of insurance won't pay for it, and then there's the risk of actually damaging the catheter over time through exposure to ethanol.

So while ideally, we would love to have some sort of antibiotic lock or way to prevent line infections, it just is not currently available. It's not something that we use. Sometimes we'll do gentamicin lock as like a catheter salvage after you've had a line infection, but routinely preventatively, we're not doing that now.

All right. So basically, we've got these populations at risk, they're at home. They ultimately then develop this infection. And I think as you said, Dr. Betten, they present to the hospital. And so -- they come to you, they're in the hospital. And so when you're thinking about that classic patient, you touched a little bit on resistance a little bit. Maybe just talk through what are you thinking about in the context of the course of treatment and any associated outcomes with these particular patients?

Yes. I think Dr. Brett did a nice job of kind of setting the stage for this. It's what brings them to the hospital, right? And they were worried about it to begin with, so they present sick, right? And that can be a wide variety of presentations, right? It can be redness, it can be pain spelling fever but you also have a chunk of those patients that are going to have septus, maybe even septic shock. And what's interesting, Jared, is that [indiscernible] is very well published and research in the hospital setting. But this type of patient, you often don't find a lot of good evidence to kind of how does that journey look and there's a really nice publication that came out -- just a couple of years ago out of Hopkins and University of Maryland Medical Center that really looked at that journey that you're talking about. And Again, it's significant. You talk about 20% of patients going to the ICU, average length of stay, 8 days, over 1/4 of patients needing to be in the hospital for 2 weeks.

Mortality is 10% in these patients. So 1 out of 10 patients are dying well, they're in the hospital. And if you push that out to 30 days, you're now talking 1 in 6 patients. So huge burden of illness -- and that doesn't even get to some of the infectious complications that we heard a little bit about before, right? Patients have line infections, they can get metastatic complications. So you can get infective endocarditis, so heart infection can get bone and joint infections, you get septic thrombophlebitis, where you're essentially stirring off blood clots, so from the bacteremia or the fungemia. And so -- it's a huge burden of illness. There's a wide array of what it might look like. But as you can kind of tell, it impacts a lot of patients in significant ways.

So when you think about this patient population, you're thinking about empiric, okay, so I think this patient might have a cabs or they've got a line, they're here. What -- do you think about resistance passengers? Like, what do you think about when you -- as you're starting empiric therapy, we talked a little bit about therapy today, but.

Yes. Resistance is a huge issue in this population, much like it is in most of our populations. But -- and I think we touched on this a little bit before. But when you talk about line infection, the first thing you think about is Grand Plaza board is on staff and in particular, MRSA, right?

[indiscernible] safaris is associated with devastating outcomes in patients loves the metastasize. It's a sticky budget likes to go places. And even though we've had antibiotics that treat this for like 4 decades at this point, we still don't really know the best way and the outcomes are poor. Sometimes we get multiple antibiotics. We're trying to find that right cocktail. And so I think from a resistance standpoint, you're immediately thinking going to -- I'm going to start to 1 gram-positive therapy to cover from RSA. But as we talked about a little bit before, I really like what you said about the transient bacteremia and that can colonize the catheter. See a lot of gram negatives in this population as well. And so what I think you had a lovely list up there of [indiscernible].coli Club Sella and you have 15% to 20% of those isolates are resistant to our standard cephalosporin therapy that we would give patients. And so that leads to a couple of different complications. First off, it means that 1 out of every 5 times when we empirically treat those patients, we're going to miss, which put those patients at risk for worse outcomes. But then our drug of choice, which we have a really good 1 for those patients, which is the carbapenems you give a couple of weeks of carbopenems do you have a lot -- you're perpetuating the cycle of resistance in that scenario. So I think of that as well. And I think it was touched on a lot in the rezafungin discussions. But again, you see fungemia in these patients as well. And when you think about resistance, I thought Dr. Clancy did a nice job of summing it up. But certainly, you can see [indiscernible] in these patients. You can see [indiscernible]. You can see all of these and so really across the spectrum of these different bacteria or fungi that can cause this infection, they're worried about resistance that might compromise empiric therapy makes it more likely the way you start up front won't be active, and that's going to put your patient behind the 8 ball for worse outcomes.

Yes. So I think -- and we've been focused, I mean, obviously, these infections are severe. Resistance is a big issue. I mean, we're talking a lot about these patients being at home coming to hospital. But there's also another side of this coin, which is that these patients oftentimes have other things that bring them the hospital, not infection.

So Dr. [indiscernible], I know you have recently had a publication, maybe you could briefly share with us kind of what you found specifically around that topic of inpatient risk.

Yes. So we did an observational retrospective study of a cohort of patients with central lines either on TPN or not on TPN in our medical center and then also compared it longitudinally to a couple of other time points over the past decade. And we did find an increased risk of central line infection in patients on TPN, which was not unexpected. There has been improvement in that risk over time, especially with implementation of some of the CDC guidelines. But that risk remains. I will say I think there is a perception, especially among physicians and other providers. The risk is much larger than maybe in reality of this. We usually quote patients 1 in 100 days.

So 1 in 100 days on TPN, we could expect on caps. Patients will tell me Dr. Sons said, if you start this, I'm going to have mushrooms in my blood tomorrow and I. I'm like, well, no, it's not quite like that. But I think for me to explain to patients to patients and other providers, okay, we're doing the line maintenance. We're doing all the guideline-based clappevention, and now we have something else. We have an extra tool to prevent caps in this population, that would be like a dream.

Yes. Thank you. So basically, we've got this population now that potentially is in your hospital, thinking out for some other reason. And then they develop because they are at risk as we just described, so they may develop an infection. So can you just talk through some of the implications of that to you and your hospital and some of the things you think about there?

For sure. And before you even get to the implications for me or the hospital, I think let's talk about the implications for the patient, right? And so first and foremost, there's an attributable mortality for a hospital onset clouds of 12% to 15%. Again, you're talking 1 in 6, 18 patients. That's a huge mortality rate. So that's the first thing. And if you survive, you buy yourself another 10 to 14 days in the hospital. And as previous panel is nicely touched on before.

Every day, you're in the hospital, you're risk for $8 billion other things occurring in that scenario. So I think first and foremost, there's that piece. Now from the hospital standpoint, there's a couple of pieces as well. hospital onset Club C is the most expensive HAI. So if you look at surgical site infections, you look at Coty, you look at VAP even Class is the most expensive of all those. It's about $40,000 to $50,000 per case is usually what's quoted if you look at the literature on this.

So there's a big cost, which is going to push you over DRG and have reimbursement issues that you're going to have to deal with. But even in addition to that, it's publicly reportable and so [indiscernible] rate, you can go search it for any institution right now. And so the last thing our institution wants is more and more of these in that scenario. And so there's a prestige per that patients can go look at this and it might impact people coming to your institution for care. And even in addition to that, there's potential CMS penalties with reimbursement that come with that as well, too. And so there's a -- again, patient first, but both the patient and the hospital side, there are significant implications of that hospital-acquired infection.

Certainly detrimental on all aspects. And so in the last little bit of time we hear, Dr. [indiscernible], you're part of our NutriGard Phase III program, your principal investigator at your site. Maybe just tell us a little bit what was your interest in the study and kind of where you are as far as enrollment and patient population.

Yes, I think -- I've said that to have another tool to prevent Clopsy in this very vulnerable population, having that line if you can't eat a drink, sometimes since being an infant. That's your lifeline. And to lose that, it's devastating. We heard about each time there's a [indiscernible], trying to get a new line and the risk of not having vascular access. So to me, I think it's very important to my practice and for my patients to I really hope that this study works. And when I mention it to patients, there's a lot of interest. We haven't had people say, "Oh no, I don't -- they want this to, they want to get involved.

That's great. And so I guess -- and lastly, Dr. Brett, you had mentioned, obviously, you're sending patients out the door and you're telling them, hey, you're at risk for these infections. So what having an opportunity to talk about a drug like DefinKat? What might that mean for that conversation?

I think that would give me a lot of confidence and be very reassuring to patients. I think that's...

Yes. Thank you. So any other last comments or points or anybody.

I just wanted to add and that that choice of line and choice of sight and the ability to use a new mine with an untouched lumen and a single lumen catheter when available can also help make the difference as far as risk of line related infection. So we don't always get our choice of catheter, and we don't always get to use a fresh line, but that can make a big difference and just things about like mine site like, for example, if you've got a patient who's got a tracheostomy and they've got a whole bunch of secretions, you don't necessarily want neck line, you might be better off with the pikline. And then sometimes patient already has a Hickman and they've got a multiminute device and the risk with a multilumen device is much higher than with a single lumen so again, we don't always get our choice, but some of those factors play a role. And the risk of line-related infection.

Well, great. Well, I thank you all for joining and helping us understand a little bit more about [indiscernible] and the detrimental effects it has to these TPN patients.

And so with that, I will turn it back over to our CEO, Joe Todisco.

Thanks, Jared. Before we get into Q&A, I just -- I really want to thank the thought leaders who came here today and the team that put this together. A lot of work went into today, and I really appreciate the efforts of everyone. But I also just want to touch on a couple of things before we go to questions. In less than 18 months, we've gone from a single product company with no commercial history, pigeon hold into the renal sector, to a multiproduct cash flow-generating, diversified specialty pharmaceutical company with multiple pipeline opportunities. in my view, we didn't just change ZIP codes we move countries, right? So I'd also like to highlight that we announced the Melinta acquisition in August -- closed it in August, and in less than 4 months, achieved over $35 million in operating synergies. And I really think that highlights the capabilities of this team to execute on our objectives.

But going forward, we've got a great trajectory ahead of us. You heard a lot today from the -- about the value of our pipeline. We have 2 meaningful assets with REZZAYO and prophylaxis as well as defect in the TPM space. And we have the ability to do creative business development deals. We didn't present on it today, but it is worth highlighting the strategic investment we made in [indiscernible] gives us a tollhold in a highly complementary acute care asset with a near-term data readout hopefully later this year. And on the long term, we're an attractive durable platform with launch experience across multiple therapeutic areas and settings of care. And we have the ability to onboard additional new assets.

So I'm excited about our capabilities and what we've built going forward. And I think lastly, just from a value creation for shareholder standpoint, I do want to highlight the recently announced share repurchase program where the Board authorized the repurchase up to $75 million of our common stock. I think this does underscore and kind of bellies our view that public markets are not currently appropriately valuing CorMedix and the value that we have here. We have started the repurchase process and expect to be active in repurchases throughout the year.

So for Q&A, I'd like Liz, Pete and Jared to come join me, and we can start to take some questions from the audience.

Sorry, Go ahead. right here. You need a mic. Sorry.

It's Leo from RBC Capital Markets. I just wanted to go back to the discussion around payers for a second. I think -- what we heard was physicians don't always have the choice of what drug they want to use. So can you talk a little bit more about how access is going to work if payers want only higher-risk patients, how easy it is to stratify patients who might need use prophylaxis by risk. And similarly for TPN, is there a way to stratify which patients might be highest risk or receiving TPN just to maybe make the role for payers easier.

Yes. I mean I'll let Liz comment on it in a minute. But I think for REZZAYO, certainly, I think you also want to draw a distinction between the azoles, which we expect -- which are Medicare Part D and REZZAYO prophylaxis, which we would expect, if approved, would be Part B, right? So you have a little bit different dynamic with economics. And certainly, we have the ability for both products, right, to engage in payer discussions and contracting, that's certainly a part of our launch strategy.

Yes. I would say for TPN in particular, we have done extensive market research with the payers themselves. -- unlike maybe some other therapeutic indications, I think there is broad agreement that all TPN patients are considered high risk because of the long-term indwelling device that they have. we saw very positive reception to covering and reimbursing defend cath for TPN patients at a number of different price points. I think from a payer perspective, when you're looking at total cost of care and understanding what it costs for these patients to become repeatedly hospitalized they're willing to make that strategic investment upfront.

So I don't think from a -- we'll see when the data reads out and certainly when we get to contracting, but from what we've seen so far directionally, we're seeing very positive feedback from payers as it comes to TPN. I don't anticipate that it's going to be that different from a Roseoprofe standpoint, right? There's a significant investment made into these patients for the transplant journey. And so to think about not protecting the patient from something like a fungal infection after investing weeks, months, sometimes years of treatment and inpatient stay that could total millions of dollars to not protect them. I anticipate we will see something similar with the payers. We haven't started to engage and pay our research around periphylaxis. But anecdotally, what we're hearing certainly from the clinical community is there is a need, right, for a long-term antifungal regimen that does not have the DDIs that they're seeing now. And given those challenges that are being presented with the rehospitalizations and the constant titration of men's, I would anticipate that we would have some fairly positive feedback as well.

I just want to add to that. I think specifically for DefenCath, right, the real world in the in hemodialysis showed a 70% reduction in hospitalization.

Absolutely.

Right? And if we can read through that, obviously, it's not guaranteed. But into TPN, it's obviously a meaningful savings for the payer.

So it's Neil Clancy again. And this is really Pete, for your group. One thing that always struck me about from the earliest days of rezafungin is actually the potential for pneumocystis prophylaxis, which really didn't come up and if you want to talk about drugs that are difficult to use, the azoles are difficult to use, trametsulfur historic anti-neumocistis agent is among the most difficult drugs for patients to tolerate, particularly in these patients. So for the panel, do you see the pneumocystis activity playing and potentially now you could avoid both as walls and trimethromsulfhin in prophylaxis, which is a game changer, really.

I'll take just 20 seconds to answer that, but Yes, especially in CLL, which is the most common leukemia in this part of the world, when we are using our triplet combination and using CD20 monoclonal antibodies. They were at very high risk of pneumocystis prophylaxis. And you mentioned primeteprim, selfemetuxaola bacterium, extremely toxic drug, renal dysfunction and all of that. And in those patients who need prophylaxis for a long period. Again, a long-acting echinocandin would fit in very profoundly, not just to prevent immosistes, but also to protect them from Candida and malls during the period of neutropenia.

Jason? .

I guess this is another question for the panel, too. Could you maybe talk about -- when you think about the adoption of REZZAYO's clinical practice in prophy which of the patient segments that you would prioritize first? And then how do you think about the duration of prophylaxis versus today? Could it -- would it be the same? Could it be longer because the drug is easier to use? And then just 1 follow-up. How should we think about REZZAYO in this dynamic of increasing resistance to azoles?

I believe that question was for the panel. We need a microphone over here.

Everything that you said is correct. But 1 thing, again, I want to add to the entire dynamic of prophylaxis as CAR-T, which we didn't discuss today. A lot of patients will now be bridged after chemotherapy with CAR-T and not go to transplant. And these are patients who are profoundly immunosuppressed, not just low neutrophil counts but also need PGP prophylaxis, like Lance mentioned. And we do not have a good drug that would cover all of them.

So good profile axis against PJP Candida, which is already kind of established with Rezafungin, looking forward to the more profile access activity, which could come in the next few months or so and with less toxicity. So I think -- as of now, with the MOL data are not active, even with Candida and PGP, there is a good case for rezafungin. And once the Phase III restore gets read out, we don't know maybe more profile access could also being optimistic about it.

Thank you. Did you cover everything, Jay?

I would just say on the antifungal end. What I like about this is that you're going to get activity against azole resistance and that front loading with the peak gives you a real margin and a greater likelihood of PK target attainment for efficacy of the drug. Moreover, because you get this massive peak and you have this upfront loading, there's potential to even treat some makinicamdin resistant infections that have what we call FKS mutations, a target mutation that the other canacandidates can't get, but because you're getting so far above your PK target early on, -- and there's animal in vitro data to support that as well. So you may be able to even use it against some echinocandin-resistant candidate.

Thank you. We're going to do [indiscernible].

A couple of questions on REZZAYO. The first one, Joe, we're going to see results from the RESPECT study next quarter. Just wondering what you we consider a success from those results? And then secondly, does this respect study open up the entire I think there's 130,000 patients or the $2 billion TAM that you talked about -- or does Mondi need to conduct additional studies to open that up? And then lastly, just regarding capital allocation and regarding the share buyback program, how should we think about BD going forward? Does that mean more of a bolt-on or SP-63 Something as big as Melinta again.

Okay. I'm going to try to remember all those questions. I may have okay. So look, with the second question, obviously, we cut the TAM and moved away from 130,000 patients to more of a dollarized base system that really kind of takes into account the duration of therapy that is needed for the various underlying conditions. In terms of what will be available to REZZAYO, if approved, it's really going to depend upon the Phase III data results as well as the final label from the FDA, Right? So there may be potential to pursue investigator-initiated studies, maybe opportunity to pursue additional Phase III studies that's something we'll have to review once that Phase III data comes out. Now in terms of, obviously, what are we looking to see? Yes, we want to hit the primary endpoint, I want to hit the secondary endpoints. I think in terms of what will be available with top line, I don't anticipate that pathogen data will be available immediately. It will likely take a few weeks or months, right, for that data to be calculated and ultimately published. But right, we want to meet the endpoints of the study. Right?

In terms of capital allocation, certainly, we wouldn't have announced the share repurchase program if we weren't comfortable in our cash flow forecast and our ability to do both of those things to pursue additional kind of tuck-in BD as well as the ability to repurchase shares. In terms of the types of opportunities that we're focused on, last year, we were pretty clear we were out looking to do something transformational, right? That's what we're looking to do. Melinta was #1 on our target list. We went out and we got that deal done. Where we sit today, I don't necessarily think we need to do anything transformational. I think our focus from a business development standpoint is really on finding assets that are synergistic that can be kind of tucked into 1 of our existing field deployments or where we may need to be with REZZAYO and prophylaxis right? Doesn't mean I'll never close the door on something larger than that, but that's not where we're spending a lot of our time today.

So I have a couple of questions. One, there is part of the discussion talking about top 10 transplant centers, having certain preferences for agents like posaconazole. I was curious what would it take or what types of metrics or data would you need to show these centers or other centers of excellence to prefer REZZAYO over time? And then the second question, I think, might be for more of the panelists just thinking about who would be the best candidates to start REZZAYO on and out of the gate? Like who would you want to give REZZAYO initially if you had it available?

And just to clarify your second question, you're speaking prophylactically.

Prophylactically, Yes.

Great. I guess for the first question, -- so I think from our interviews with key opinion leaders and some of those here today, the data in the microbes that come out in the study, right? So if it does cover mold and aspergilspecifically, Candida and PJP, I think it has a very good chance of competing across the spectrum of activity. And so where that starts and when it starts, I think it all starts the data, right? And effectively, if we can compete with those 3 categories of microbes, I think REZZAYO has a very strong chance of competing starting therapy at those centers and across the country. Where and what type of patients Dr. Cook or Dr. Panza.

No. So we got -- that's one. We will consider a patient like high risk for in the get-go. So for example, patient with history of mall infection coming into transplant, where that trade-off is quite concerning that they will have a gap of normal coverage. Those will be the ones that I will particularly be interested Also, there are certain regimens for conditioning that put the patient on higher risk like that wants to cause more epithelial damage, like high-dose radiation. Those will be other and even like meta base, regimens that are more GI disrupted. Those will be the 1 that I would probably consider. And also in that scenario, we'll give me a peace of mind that I will not have this fluctuating immunosuppressant levels for those patients to.

I'll have 2 settings, nontransplant, of course. One is certainly CAR T, and this is something that I feel like the urge to explain. We are doing so many more CAR-Ts nowadays as definitive therapy to reduce the duration of treatment, especially in ALL. Hopefully, in AML in the future, and these patients are at high risk of PJP candidates well as malls and all these patients need prophylaxis. As of now, they get PGP profile axis with pentamidine, which is not a good drug. Nobody likes back prime or at vac. So there is a huge need for a long-acting PGP profile axis. And for all patients who are going on clinical trials, even in frontline settings, we face a lot of challenge putting them on azole antifungals because of DDI, which was discussed at great length.

So there is a huge scope of patients, CAR-T, frontline, relapsed/refractory are going on Phase I trials as well as post transplant.

And I'll just add in the saga transplant patient population. Liver and even above the diagram lung transplant, where Candida can be a very large problem. Following a complex surgery, we often put these patients on prophylactic regimens of azoles and that can be really a major burden. So again, in that patient population, I'd say, right out of the gate would be they're low-hanging fruit.

And prophylaxis and solid order transplant is highly heterogeneous and center dependent. There's 1 transplant problems, for example, a lot of people on 4 to 6 months of post-transplant azoles. So that's a lot of consumption of Azoles.

Maybe just following on from that question. We've heard a lot of places where Baseoprophylaxics can be used. Can you just help us contextualize how long do you think it takes to establish a consensus sort of guideline or protocol within these different centers in terms of where you are going to use it longer term?

So I'll start off that REZZAYO in treatment guidelines today in NCC and for treatment, right? And so effectively, when the data is available, we'll be looking to go after those nationally recognized and understood guidelines based on the data, right? And I think I won't speak for the panel, but from prior personal experience, those guidelines nationally really drive adoption at the large nationally recognized clinical practice sites, right, a number of these panelists are after.

So I think understanding where that data is. We have the benefit of that data being read out several months before the FDA decision and the FDA label, but we will be working with the market access team doing preinformation exchange at the appropriate time to drive that information while the FDA is evaluating the application.

Maybe just want to follow up on TPN. As we think about maximizing the DefenCath TPN opportunity, anything which you have to consider or balance from the potential contracting of DefenCath under the current indication?

Yes. I think -- I mean, I think what your question is more related to is reimbursement and pricing across channels, right? So what I'd say is that we have a right now, call it, a regulatory and development strategy to pursue a separate J-code, right, in TPM, Presumably, if we are successful in doing that, that's 1 pathway and a little bit easier to differentiate. If we are not successful in obtaining a separate J-code, we have a different strategy around, call it, channel pricing, it gets a little bit tougher, right? We could be -- and we'll have to be mindful of ASP management and how we're going to go about contracting across the therapeutic areas.

A couple of questions. First on REZZAYO and just to build up on the previous question. If you have this dynamic, I love to hear, what proportion of the prophylactic addressable 130 patient pool, whether it's AML or nachos actually prophylax today versus eligible clinically eligible but not treated. And then you stated prophylactic has a lower barrier due to less formulary dependence and you expect -- would you expect materially faster uptake curve versus the treatment indication I have a follow-up on TPN.

All right. As I said before, in terms of the 130,000 patients, that was an older kind of market research, we've kind of recut how we're looking at the total addressable market, and we can provide a little more detail less in some one-on-ones as we move forward around how we think about the subset of patients with multiple underlying conditions that are currently getting prophylaxis for Candida, Aspergillus and PJP. And then there's another subset of patients that are getting PJP only therapy after, right after they complete the Candida and Aspergillus.

So we'll come back to you on a percentage. In terms of our analysis on the TAM, all of those patients are currently getting prophy. So that -- so we recut it a little bit differently, have only included patients that would currently be getting some type of prophylaxis. But what was the second question.

Faster uptake versus treatment like...

Look, I don't think we're ready to guide yet on the ramp to peak for Prof. Obviously, it's going to depend to a large extent on the pathogen data on the strength of the Phase III results. And once we have our top line results, maybe we can comment on it a little bit more.

That's helpful. And maybe on TPN front. Is the 200-patient NUTRI-LAC study sufficiently powered to capture the 1 to 4 infection episodes per 1,000 catheter days. And then what clinical endpoints do you think will drive the PTN adoption or P&T adoption and payer coverage? And then just lastly, you mentioned the 50% commercial coverage on that subgroup. What's the other half of the payer landscape look like? And what kind of dynamics around formulary versus inpatient versus at home.

I'll address the third question first, and then you can get to it. So we have the breakdown on that chart. If you look at the slides, it will say about 50% is commercial -- there's another percentage that's Medicare, Medicaid right and government. So we do have that breakdown. That's from our most recent market research.

Do you want to talk a little bit about the power of the study and then we can go into clinical endpoints?

Sure. Yes. So the way the study was designed is actually -- it's an adaptive design. So it initially sort of teed up to have 90 patients that would be in the trial. And then after those 90 patients, and once we saw 14 infections, then it would actually go to a data safety monitoring board that want to evaluate effectively those 2 treatment arms, they would then be able to do a number of things. So 1 of which would be we didn't see the infection rate that we thought. And so that's how that allowed for us to increase up to the $200 million they could also say that there seems to be a discrepancy between the 2 treatment arms, and they may then have a conversation through FDA to say, and maybe might consider ethically stopping the study early. So I think we sort of...

No, I don't know where that came from. To get excited.

So nevertheless, the study effectively was powered at 90%, with the option to increase if the infection rate was not quite as high as we have seen in the literature because there is a pretty large range in literature around infection rates.

Yes. And I think the last part of your question was what clinical endpoints did the community need to see. And I think right? We've talked about before. It's in the guidelines to have an antimicrobial catheter lock solution. To date, there isn't 1 that's FDA approved. So I think if we are able to demonstrate a meaningful reduction in infections as well as hospitalizations are related to infections I don't anticipate that we would have a high burden on top of the data that's coming out of Nutriguard, right? I think just as we've heard to our panelists and from the market, there is nothing right now. Our drive to go into TPN was it was our #1 place that we were getting requests because patients were getting referred to hospice because they had no other options. So I think that both inpatient and outpatient, right, the avoidance of colabsy is such a driver for a number of reasons that I don't anticipate that we'll have a lot of clinical hurdles to jump through, provided the data reads out as we hope.

Got about 3 or 4 minutes left. Any last questions?

Did I ask, are there any TDAPA questions in the last.

All right. Well, thank you, everybody, for attending. Really appreciate it. Thank you.

Thank you very much.

Hi, all, and welcome to the session. My name is Arvind, and I'm an associate at JPMorgan. I'm excited today to introduce CorMedix. With us today, we have Joe Todisco, Chairman and CEO. And just a reminder on format, we'll have a 20-minute presentation followed by 20 minutes of Q&A. So please hold all your questions until the end. Thank you.

Thank you, Arvind. I know it's late in the day, so I appreciate such a packed room for this time of day, and I know it's been long, so I'll try and keep it succinct. I am Joe Todisco, I'm the Chairman and CEO of CorMedix, and welcome to CorMedix 2026 JPMorgan presentation. A quick look at our forward-looking statements, which you can find in more detail in our SEC filings.

I'll start by talking a little bit about who is CorMedix Therapeutics. So CorMedix Therapeutics is a diversified specialty pharmaceutical company with a portfolio of commercial and pipeline drugs predominantly focused on institutional settings of care, and that would be products that are utilized in hospitals, infusion centers, mostly injectable drugs. We have an attractive financial profile. We have about $150 million cash on hand, close to 0 net debt. Our revenue guidance for 2026 is over $300 million in revenue and $100 million to $125 million of EBITDA. But most importantly, from a cash position, we expect to add to cash throughout the year.

We are a scalable platform, right? We've got a solid commercial team with experience across multiple therapeutic areas on which we can onboard additional assets. And then most importantly, we have 2 meaningful growth drivers in our pipeline. The first is REZZAYO, which is actively in Phase III clinical studies with a readout in the second quarter for prophylaxis of fungal infections in patients that are immune compromised. The second is an expanded indication for DefenCath in TPN. Both of those have large total addressable markets with REZZAYO at over $2 billion and DefenCath and TPN at up to $750 million.

As I mentioned, we have a deep and experienced leadership team. Much of the leadership team has been with us over the last few years since we began, as we officially became a commercial company a few years back, but I do want to highlight 2 new additions to the team. The first is Mike Seckler, who joined us as Chief Commercial Officer this past week. Mike brings to the organization a wealth of experience, most recently as CEO of Evome Medical Technologies, but also as a Senior Commercial Executive at Ferring International and Chief Operating Officer at FerGene. I'd also like to highlight Susan Blum, who recently joined us as CFO, came to the organization as part of the Melinta transaction, and we're super excited to have her as part of the team.

So a quick look at our key financial statistics. 2025 was a record year for CorMedix. Two significant positives with the heart of our TDAPA reimbursement for our lead product, DefenCath, took place during 2025, which allowed us to drive almost $260 million of revenue for DefenCath. In addition, we completed the transaction of acquiring Melinta, which added another $140 million on a pro forma basis. So for the full year, revenue exceeded the $400 million mark.

We just issued our 2026 guidance of $300 million to $320 million. 2026 is going to be a transitional year for the company as the first half of the year is the end of our 2-year ASP-based TDAPA reimbursement period and July begins our post-TDAPA add-on period. So we're going to have a little bit of a revenue transition that takes place during the year. We also thought it was important to give investors visibility into the revenue runway for DefenCath. So we took the unusual step to issue 2027 revenue guidance.

We do expect, and we'll talk about it a little more as we move through the deck under TDAPA and the way CMS does the price add-on calculations for our net selling price in 2027 to increase from where we are going to be at the end of Q3 and Q4 of 2026. But I do want to highlight the balance sheet, $150 million in cash, $150 million in debt, close to 0 net debt. The combined portfolio spans 8 products, most of which, as I said, are used in the institutional setting. Those call points are hospitals, infusion clinics, some home infusion, predominantly injectable drugs, predominantly anti-infectives currently. I want to talk about a couple of the products in a little bit more detail.

So DefenCath, historically, our lead drug, DefenCath was approved in 2023 -- late '23. It's what's called a catheter lock solution. It's not injected into the patient. It dwells in the catheter in between times the catheter is accessed. The standard of care for catheter locking is heparin. Our product is a combination of heparin and our proprietary new chemical entity, taurolidine. Taurolidine is a unique molecule. It's not an antibiotic, it's an amino acid, but it shows broad spectrum activity against gram-positive and gram-negative bacteria, as well as fungus, but it's not demonstrated any antimicrobial resistance to date. Now I said the product was approved in 2023, but launched in the middle of 2024. The initial indication for which DefenCath is approved is in the reduction in risk associated with catheter-related bloodstream infections or CRBSIs, in patients that are undergoing hemodialysis through a CVC.

Now the hemodialysis space is highly concentrated. Though it's a large market, about 40 million vials of DefenCath, 90% of that takes place in outpatient hemodialysis centers. And in the U.S., 5 dialysis operators make up about 90% of that market. We do have 4 of those top 5, about 60% of the market actively implementing DefenCath in patients. But what's unique to this space is really the reimbursement. So under its current label, DefenCath falls under what CMS classifies as the end-stage renal disease prospective payment system or the ESRD PPS, which is a bundled payment system.

Now to incentivize innovation, they've created something called the TDAPA, transitional drug add-on payment adjustment. This is essentially 5 years of reimbursement, of which the first 2 years is on a buy-and-bill basis, very similar to any other Medicare B drug. But then it transitions into a post TDAPA add-on. Now as we go through this transition in 2026, our first 2 years of TDAPA are coming to an end at the end of June and we will transition into a post TDAPA bundle adjustment.

Now for the last 2 quarters of 2026, the way in which CMS has done the calculation for the add-on, they have taken an older period of time that doesn't exactly match up with our current utilization. So it is going to, under our customer agreements, produce a lower net selling price for those 2 quarters, but we do expect that to rebound in 2027, which is why we've taken the additional step to give that 2027 revenue guidance. That guidance, however, doesn't include upside from our strategy of pursuing Medicare Advantage contracting. And that is a meaningful part of our post TDAPA patient utilization growth strategy.

Now I think it is worth spending some time just talking about catheter-related bloodstream infections and the impact on the health care system and the impact on patients. These infections, they're the most significant consequence associated with getting hemodialysis through a CVC and they're actually one of the most significant consequences of having a CVC for any indication.

These infections, they happen fast. About half of all infections happen in the first 90 days a patient has a catheter. They happen often, right? About 1/3 of patients will get a CRBSI that have a catheter, and they come with at an alarming rate, right? Despite the prevalence of other risk mitigation techniques for infections, the mortality rate from these infections is still 25% on average in the U.S. But there's also a corresponding impact on the health care system from a cost standpoint, right? Patients that have a CRBSI have doubled the amount of hospitalizations a year, 4x longer hospital stays and twice the hospitalization cost as patients that don't.

Now DefenCath as a preventative is in a position to offset a large amount of that cost for the health care system if broadly deployed. Now our Phase III clinical study, LOCK-IT-100 demonstrated a 71% reduction in risk associated with CRBSI. But I think what is really more relevant and more interesting and more current is the impact we've had in the real world, right?

So U.S. Renal Care, which is the third largest dialysis operator in the country, was our initial anchor customer for DefenCath. They were the first to implement DefenCath broadly in patients in July of 2024. And we collaborated with U.S. Renal Care on tracking outcomes in thousands of patients. We tracked infection rates, hospitalization rates in a large group of patients compared to their baseline retrospectively. And what we saw was really compelling, right?

Not only were we able to replicate our Phase III clinical results from a CRBSI infection rate, we were able to have a corresponding reduction in hospitalizations, a 70% reduction in hospitalizations. Medicare alone spends over $3 billion a year on costs associated with CRBSIs and treatment and related hospitalizations, and we are in a position to offset a meaningful amount of that cost if broadly deployed as the standard of care.

I'd also like to spend some time talking a little bit about REZZAYO and some of the Melinta products, specifically. The acquisition we did last year, a big part of the catalyst was what we saw as the ability to add a very stable-ish base business with a portfolio of assets, but also a meaningful growth driver in REZZAYO. And we really look at REZZAYO as one of our most -- or our most valuable future growth asset.

Now it's currently approved with a fairly modest total addressable market in its existing label, right? So it's a long-acting once-weekly echinocandin IV that is approved for the treatment of invasive fungal infections specific to Candida, right? So this is a 4-week course of therapy. It is a patient population of about 55,000 a year. It's a TAM of about $250 million a year. But we're really excited about REZZAYO, and we'll talk about in a couple of slides, is the future indication for which we are currently in Phase III. The study is fully enrolled and expected to read out in the second quarter, which is for the prophylaxis of invasive fungal infections in patients that are immune compromised.

I look at some of the other kind of meaningful contributors from the Melinta portfolio. MINOCIN has shown a pretty good growth trajectory over the last few years, growing from $39 million to almost $50 million in 2025. We do expect it to break the $50 million mark in 2026. VABOMERE also has grown from $20 million to $26 million, and it's closing in on $30 million in annualized net sales. Both of these products are anti-infectives utilized in a hospital inpatient setting and both patent-protected MINOCIN through 2032, VABOMERE through 2039.

So let's talk about a little bit about where we were and kind of where we are and where we're going, right? So 18 months ago, CorMedix was a pre-commercial single product company on the verge of launching DefenCath, right? I think that we've done a really excellent job of maximizing the value of our 24-month TDAPA period. We've parlayed that cash flow into the acquisition of Melinta, right, as I said, which has given us a fairly sizable base business as well as an attractive growth asset with REZZAYO.

We have very rapidly integrated Melinta, right? We've achieved $35 million in synergies in 4 months and have fully integrated on a run rate basis forward. And now we're focused on future growth. As I said, the REZZAYO Phase III study is going to read out in the second quarter. We have an attractive opportunity in the Phase III study for TPN, for DefenCath for TPN. Hopeful for that study to read out early in 2027.

We also, as I said, a very flexible balance sheet, strong cash position, the ability to do smart strategic tuck-in BD. I think the Talphera transaction is a great example of the type of product that we pursue that is highly complementary to our existing field team and gives us another shot on goal with a modest risk. But ultimately, where we are and where we see ourselves is a scalable platform, experienced team in multiple therapeutic areas and the ability to onboard additional assets as we move forward.

Sorry, it's been a long day. But I do want to take some time and walk through some of our clinical studies. And as I mentioned, REZZAYO is currently in Phase III for prophylaxis with that second quarter readout. We also have 2 ongoing Phase II studies, one in pneumocystis, and these are treatment studies, the other in aspergillus. Now the pneumocystis study is fully enrolled, and we expect that data to be available by the end of this year. And the aspergillus study should be fully enrolled by the end of this year with data in 2027. While those are both Phase II studies, they do have the ability to be supportive of an expanded label for treatment with FDA, and we'll certainly look to pursue that based on the strength of that data. For DefenCath, we have the ongoing Phase III for TPN, which is targeted toward completion in early 2027. We also have an ongoing hemodialysis study that's part of our post-marketing commitment to FDA.

I want to take some time talking about the study design for the Phase III Prophy study for REZZAYO as well as the total addressable market and why we're excited about this opportunity and why we consider this to be our most -- one of our most valuable assets.

The study is a global study. It's being run in conjunction with our development partner, Mundipharma. For the REZZAYO product, CorMedix holds U.S. rights, but Mundipharma has all ex-U.S. marketing rights. It is designed as a non-inferiority study compared to the standard of care with the primary endpoint being fungal-free survival at day 90.

Now the standard of care is a combination regimen of either fluconazole or posaconazole in combination with Bactrim and is a 13-week course of therapy currently being run in allogeneic bone and marrow transplants that are immune compromised. I think why we're most excited is certainly we want to hit our primary endpoint, but it is in the secondary endpoint, right? When we look at the standard of care, our market research indicates a significantly high discontinuation rate of the standard of care due to issues of toxicity or drug-drug interactions with other drugs in the regimen that these patients are taking.

Both fluconazole and posaconazole are known to be hepatoxic. Bactrim is known to be myelosuppressive, and we think we do have an opportunity with a secondary endpoint here in a non-inferiority study to really differentiate ourselves and carve out a meaningful niche for REZZAYO as a prophylactic antifungal therapy in these immune-compromised patients. And when we look at the total patient population, different from what we saw with DefenCath, where nothing was really being done from a prophylactic standpoint when we entered the market. Here, you do have a somewhat of a formed market, right? We have 130,000 patients in the U.S. with various underlying conditions that are actively getting prophylactic antifungal therapy. We see this as a total addressable market of over $2 billion. And as I said, given a favorable clinical outcome, we do think we have an opportunity to drive meaningful value here with this product.

TPN study is also well underway. This is a smaller study compared to what we ran for LOCK-IT-100 for DefenCath with a little bit more straightforward endpoint in terms of incidence of CLABSI. CLABSI or central line associated bloodstream infections are very similar to CRBSIs. And we are running head-to-head against heparin, which is the standard of care for catheter lock in.

Now I think what's interesting in terms of what's very similar to the hemodialysis market when you look at TPN, which is basically patients getting IV nutrition therapy, is you have very high infection rates, right, where we -- you have infection rates of upwards of 25% in this patient population, and you have significant mortality from those infections in this patient population as well as very little being done prophylactically to prevent these infections.

So you have a critical unmet medical need in this patient population, but what's different from hemodialysis is the reimbursement landscape. This is not a bundled payment system, right? This is -- most of these patients are reimbursed or under Medicare Part B or commercial, similar outpatient services. So we do see this as a meaningful value proposition, total addressable market up to $750 million, about 5 million infusions a year with more traditional reimbursement.

So as we said, we have a very -- we're in a very strong cash position, about $150 million. We do expect to have sustained profitability through 2026 and beyond. We expect to bolster that cash significantly over the course of this year. And we have the ability to pursue, as I'd say, smart strategic tuck-in business development, similar to what we've done.

I do want to highlight the Talphera transaction. For Talphera, we took a minority strategic investment, just under 20% in conjunction with a right of first negotiation to acquire the company upon favorable Phase III data readout for their product, Niyad. Niyad is an anticoagulant that is used predominantly in a hospital inpatient setting as part of the CRRT process. This product would fit incredibly well from a sales force deployment standpoint with our existing field team, and we're excited for that data readout, hopefully toward the midpoint or the third quarter of this year.

We also have a number of upcoming catalysts and milestones toward the first half and toward the back part of this year and into '27. Most notably is the Phase III data readout on REZZAYO, as I said, coming in the second quarter. We're also going to be doing an Analyst Day in February, on February 10. And I think one of the things that's important is that we do a better job on educating investors and analysts on the other catalysts beyond DefenCath and hemodialysis. And our Analyst Day on February 10, we'll have KOLs. We'll be talking a lot more about the disease state for both REZZAYO prophylaxis as well as DefenCath TPN and really setting the stage for the growth trajectory for the company over the next couple of years.

We do have other catalysts as we move toward the back part of the year. We -- as I said, the Niyad study for Talphera. We expect to provide some updates on the TPN study with clinical data, hopefully available in the first half of 2027, early part of 2027 and hopefully, submission of the REZZAYO sNDA for prophylaxis as well as updates from CMS on the 2027 add-on reimbursement for DefenCath for fee-for-service patients.

Where we are, I think, in closing, look, we are a robust, diversified specialty pharmaceutical company. We have a strong financial profile, strong base business, cash flow generating through 2026. And we haven't put out guidance yet for 2027, but we see ourselves as a growth story, right? We think this is an attractive platform, one that is likely underrecognized and underappreciated and a deep and experienced leadership team with experience in launching drugs across multiple therapeutic settings. So we're excited about 2026 and where we're going to take this business in '27 and '28 and happy to take questions from the audience.

Thanks, Joe. CorMedix currently trades at a fairly low multiple of EBITDA and revenue relative to peers. Do you think this is reflective of the actual business fundamentals? Or is there something investors in Wall Street might be missing?

It's a really good first question, Arvind. Thank you. Look, I think from our view, I think it's pretty clear that something is missing, right, that we need to do a better job at messaging, right? We don't necessarily trade a discount. We're at a pretty big discount to where our peers are right now. Our peers are probably in the 12x EBITDA range, 4x revs. We're at about 5x and probably less than 2x. So I think that tells me that we need to do a better job in educating on the kind of the sum of the parts of our business.

I think clearly, with this valuation, a lot of emphasis is on the DefenCath hemodialysis revenue stream. But unfortunately, I think it's solely on that. And I don't think any real value right now is being ascribed to REZZAYO for prophylaxis DefenCath for TPN or candidly, the base business for Melinta, which we've acquired. I think if any one of those pieces traded independently as its own business, there'd be a meaningful valuation. So we've got work to do, right, on our end from an educational standpoint.

So assuming that it is undervalued, what can the company do to drive increased shareholder value?

Look, I think a couple of things, right? So -- and the first is what I just mentioned is better education, right? We're starting here today, a lot of one-on-ones and into the Analyst Day on February 10 and really kind of laying out the groundwork for what are the key value drivers here and why should investors be excited about CorMedix, right, beyond DefenCath in hemodialysis.

Look, beyond that, I think everything is on the table, right? I think as we move throughout the year, if we see that we're still not getting appropriate valuation from public markets, share repurchase is on the table. Let's see where we go, but I certainly echo the sentiment and agree that we're currently undervalued.

You guided cash OpEx of $145 million to $160 million. Is that net of synergies from the Melinta deal? And how should we think about go-forward OpEx beyond 2026 as well as future EBITDA trends?

Okay. I'll take the first part of that first. So -- the OpEx guidance of $145 million to $160 million, yes, that is net of synergies. So on a combined basis, CorMedix and Melinta historically would have been at about $180 million, $185 million of cash OpEx. So $145 million to $160 million is net of synergies. And I guess the delta between the $145 million to $160 million is really kind of gated based on the prophylaxis study data, right? So there's a decent amount of prelaunch activities we would want to do in the second half of the year. Presumably, if that data is positive, and that's what puts us up at the upper end of that range.

Now you asked about -- it was a read-through to EBITDA, I think, in '26 and beyond. Look, so obviously, we can't -- we're not going to guide 2027 EBITDA. And I think if you kind of look at where we're trading today, the read-through obviously must be that EBITDA is either uncertain or declining and certainly not the way we see things, right? So 2026, EBITDA $100 million to $125 million. And we're looking at this as a growth story, right? We've got big catalysts, some coming in early '27, some coming later, some coming in '28, looking for this to be a growth story over the next couple of years.

Great. You guided 2026 DefenCath sales between $150 million and $170 million, but posted more than $90 million for Q4 2025. Can you give some color around what assumptions drive the 2026 guidance and the sales trend for the first half of the year for the TDAPA expiration? Also, what drives your confidence in your 2027 DefenCath revenue to be able to provide guidance and what assumptions does it make?

Those are 2 good questions. Yes. So the read-through from Q4 to Q1 shouldn't assume that utilization is dropping. So during the 24-month TDAPA period, our customer agreements are essentially under an ASP pricing model, where we essentially sell at ASP minus some percentage, and then there's rebates involved. And as those rebates get paid, ASP declines over time. And with most buy-and-bill drugs, that ASP erosion happens over the course of a decade. With the TDAPA drug, that ASP erosion happens over a couple of quarters, right?

So we have a situation where as we're coming to the last 2 quarters of our 24-month TDAPA period, we're going to see some ASP step downs in Q1 and Q2. We are expecting utilization growth between Q4 and Q1. And then what we've kind of assumed is let's assume to be conservative that we maintain that utilization as opposed to building growth into our base assumptions.

We also have a dynamic where the first half of our year is really about 5 months' worth of volume or value. Once we get to June, we do have an obligation to do a shelf stock adjustment for customers based on July pricing. So we've conservatively built in about 4 weeks, assuming they have 4 weeks of inventory on hand when we get to July, there might be some favorability there with smaller customers. But again, we want to be conservative when we issue our guidance.

Now the back part of the year is really where, as I said, we have this anomaly that's kind of been caused by the way CMS did their post TDAPA add-on calculation, they've created this 2 quarter, what we've been referring to as a stub period, where they've kind of under captured the utilization from a dollar value standpoint, but really are going to kind of try to make it up in 2027 with a higher reimbursement and a post-TDAPA add-on.

So when you say kind of what gives us the confidence in our guidance around '27, a lot of it's math, right? So we have a good sense for what we've shipped and what utilization is going to go into that post-TDAPA calculation. We've given a range of 3x to 5x, right, publicly. I think we're hopeful it will be toward the top end of that range based on our calculations. And ultimately, we've taken a lot of steps -- and part of the lower pricing in the third and fourth quarter is to do right by customers and keep that utilization, right, as we move into '27.

So we do have a decent level of comfort to be able to issue that guidance this far out. And we'll update as we go throughout the year. But I think it's also worth mentioning there are a couple of upsides that we've excluded from guidance. First, as I said before, we've not taken any benefit from potential Medicare Advantage contracting, right? That's a big part of our strategy, right? We have our real-world evidence data that shows a meaningful impact on hospitalizations. The Medicare Advantage plans are the ones that are on the hook for those costs, a huge amount of cost in the system. So I do think we have a compelling value proposition for Medicare Advantage, and we're going to update right, as we go through the year.

The other big upside is really there's legislation pending that could really upend TDAPA for the better. There's bipartisan bills currently in the House and the Senate that there's a possibility could be attached to legislation over the next couple of months. We have an eye on that. But again, legislation is always speculative, right? It wouldn't be right to take that in our base forecast, but that's a meaningful upside catalyst just specific to DefenCath in hemodialysis.

You talked about doing complementary BD in your presentation and highlighted the Talphera deal as a modest shot on goal. Would the company consider larger M&A type deals similar to what you did with Melinta last year?

Yes. Well, look, we're in a little bit different of a position than where we were last year, right? So last year, I think we were pretty clear that the strategy was a transformational M&A deal, right? So we raised money at risk. We went out. We got our #1 target, which was Melinta. This was #1 on our list in terms of fit and strategic value. And then we've integrated it fairly quickly. So from a transformational M&A standpoint, I think certainly, we're always open-minded. It's -- but we're not at the position where we were last year. Let's see where we progress, right, from a share appreciation standpoint. We need to execute on the things I talked about in terms of messaging and creating value for shareholders, right? So...

Great. We'll open up questions to the audience. Please raise your hand if you have any.

[Indiscernible]

Sure. So DefenCath, DefenCath is -- first has data exclusivity in 2 forms, has an NCE 5 years of exclusivity as well as stacked GAIN exclusivity. So that gives 10 years of exclusivity under which FDA cannot approve a generic ANDA against DefenCath. The earliest an ANDA can be filed is on the GAIN Act exclusivity minus 1 date. So that would be in November of 2032. It would be the earliest somebody could file.

In addition, we do have what I'll call a composition patent that goes to 2042 that has, in my view, some decently broad claims that will be difficult for a generic to design around. I think it'd be more likely they'd have to pursue an invalidity case and that patent went through reexam. So we do feel good about the IP that is around DefenCath.

Now from a REZZAYO standpoint, it also has NCE and GAIN exclusivity to 2033. So again, the earliest somebody could file is 2032. But it also -- but REZZAYO has composition of matter coverage until 2032, a pending patent term extension that could bring it to 2036 and has other patents that go to 2038.

Any other questions? No other questions, that concludes the presentation. Thanks, Joe.

All right. Thank you, everybody. Appreciate the time.

Good day, and welcome to the CorMedix Third Quarter 2025 Earnings and Corporate Update Conference Call. [Operator Instructions] Please note this event is being recorded.

I would now like to turn the conference over to Daniel Ferry of LifeSci Advisors. Please go ahead.

Thank you, operator. Good morning, and welcome to the CorMedix Third Quarter 2025 Earnings and Corporate Update Conference Call. Leading the call today is Joe Todisco, Chief Executive Officer of CorMedix; and he is joined by Liz Hurlburt, EVP and Chief Operating Officer; and Susan Blum, EVP and Chief Financial Officer.

In addition, Beth Zelnick Kaufman, EVP and Chief Legal and Compliance Officer; and Dr. Matt David, EVP and Chief Business Officer, are on the line and will be available during the Q&A session.

Before we begin, I would like to remind everyone that during the call, management may make what are known as forward-looking statements within the meaning set forth in the Private Securities Litigation Reform Act of 1995. These statements are statements other than statements of historical fact regarding management's expectations, beliefs, goals and plans about the company's prospects and future financial position.

Actual results may differ materially from the estimates and projections on which these statements are based due to a variety of important factors, including the risks and uncertainties described in greater detail in CorMedix filings with the SEC, which are available free of charge at the SEC's website or upon request from CorMedix.

CorMedix may not actually achieve the goals or plans described in these forward-looking statements, and investors should not place undue reliance on these statements. CorMedix does not intend to update these forward-looking statements except as required by law. During this call, the company will discuss certain non-GAAP measures of its performance. GAAP to non-GAAP financial reconciliations and supplemental financial information are provided in CorMedix earnings release and the current report on Form 8-K filed with the SEC. This information is available on the Investor Relations section of CorMedix website.

At this time, it's now my pleasure to turn the call over to Joe Todisco, Chief Executive Officer of CorMedix. Joe, please go ahead.

Thank you, Dan. Good morning, everyone, and thank you for joining us on this call. This has been an exciting quarter in the evolution of CorMedix as we announced and closed the acquisition of Melinta Therapeutics in a combination of cash and stock transaction. This deal is transformational for CorMedix creating a diversified specialty pharmaceutical company with a broad portfolio of commercial and late-stage pipeline products. Integration of the legacy CorMedix and Melinta operations has progressed faster than originally expected. As we announced in October, we expect to capture approximately $30 million of the projected $35 million to $45 million of total synergies on a run rate basis before the end of 2025.

I'm excited to announce today that as part of our integration, CorMedix, Inc. will be rebranding as CorMedix Therapeutics, and all employees will unify under this company name. We're also adopting a new logo to signify the go-forward organizational commitment to develop and commercialize novel therapies for the prevention and treatment of life-threatening conditions.

This past quarter marks the most successful quarter from a financial perspective in company history, registering record levels for revenue of $104.3 million, net income of $108.6 million and adjusted EBITDA of $71.8 million. Our revenue performance was largely driven by faster-than-expected adoption by our DefenCath LDO customer, utilization growth from our existing customer base as well as partial quarter contribution from the Melinta portfolio assets.

Based on the recent momentum, today, we are raising our pro forma combined full year revenue guidance from a minimum of $375 million to a range of $390 million to $410 million. In addition, we are increasing our previous guidance for pro forma fully synergized adjusted EBITDA for 2025 from a range of $165 million to $185 million to a new range of $220 million to $240 million.

On the business development front, we also successfully closed our strategic minority investment in Talphera Inc. This small strategic investment gives us a foothold in a late-stage critical care product that is highly complementary to CorMedix's acute care portfolio. As part of the transaction, CorMedix has granted a right-of-first negotiation to acquire Talphera following the announcement of Phase III results, which we anticipate to be available in the first half of 2026.

We will continue to evaluate Talphera in the coming months as their clinical trial progresses toward completion. With respect to DefenCath, we are very pleased overall with the utilization of DefenCath in the outpatient hemodialysis segment during our initial phase of TDAPA and we have now begun planning with customers for the post TDAPA add-on periods, which we expect will begin in July of 2026. In line with our strategy to increase patient utilization of DefenCath during our post-TDAPA add-on periods. We'll be working over the coming months to finalize supply pricing with customers under existing contracts based upon the final post-TDAPA add-on framework as well as engaging in conversations with Medicare Advantage payers following the publication of our real-world evidence data later this year.

Lastly, as CorMedix evolves, I think it's important for investors to begin focusing on important near- and medium-term catalysts and value drivers for the company beyond the hemodialysis sector. First and most importantly, the second quarter of 2026 is expected to bring top line data for the use of Rezzayo as prophylaxis of invasive fungal infections. We believe the total addressable market for immune compromised patients that are currently undergoing antifungal prophylaxis is more than $2 billion.

The Phase III RESPECT study is running head-to-head against the current standard of care, which is a combination of posaconazole, an antifungal, and Bactrim an antibiotic that also has antifungal activity. Posaconazole demonstrates severe drug-to-drug interactions with many medications the target patient population is currently taking, including immunosuppressive drugs like tacrolimas and cyclosporin as well as numerous therapeutics used in treating hematological malignancies such as leukemia, multiple myeloma or non-Hodgkin's lymphoma, all patient populations that may undergo bone and marrow transplantation as part of their therapy.

For these patients, Rezzayo used as prophylaxis against these invasive fungal infections could represent a new standard of care that may allow patients to experience less drug-to-drug interactions, less frequent dosing and more flexibility in their setting of care for treatment. Our second near-term catalyst outside of hemodialysis is the expected expansion of DefenCath into the prevention of [indiscernible] for adult patients receiving total parenteral nutrition or TPN.

Our most recent market research continues to highlight the critical unmet medical need and pervasively high blood stream infection rates in this patient population. Prophylactic intervention is urgently needed for these vulnerable patients. We have previously guided to a total addressable market in this indication of up to $750 million and anticipate Phase III completion as early as the end of 2026 or beginning of 2027.

I believe that CorMedix has done an exceptional job of maximizing the value of the initial TDAPA period afforded to DefenCath as a long-term strategy in hemodialysis for post-TDAPA periods and has redeployed cash flow into a pipeline that can position the company for long-term sustainable growth. I am excited about the future.

I would now like to turn the call over to our Chief Operating Officer, Liz Hurlburt, to provide an update on clinical activities, operations and integration. Liz, please go ahead.

Thank you, Joe, and good morning. The combined clinical development and operation teams, along with field medical affairs have been working diligently on numerous clinical activities. As we shared in late September, enrollment for the global Phase III RESPECT study evaluating Rezzayo for the prophylaxis of fungal infections in allogeneic bone marrow transplant patients has completed. This pivotal trial is being conducted by our global partner, Mundipharma, and the team has begun to progress the program in anticipation of study closeout.

The team continues to work closely with investigators and clinical experts in the field to deepen our understanding of the evolving clinical practices and needs of these patients. We expect to announce top line results from the RESPECT study in the second quarter of 2026.

Turning to DefenCath. I'm pleased to share that the Phase III NutrIGARd clinical study, which evaluates the reduction in central line associated bloodstream infections or CLABSI for adult patients receiving total parental nutrition via a central venous catheter has garnered international interest. In the coming months, we will expand clinical study sites into Turkey to broaden the diversity of patients and potentially expedite enrollment time lines. At this time, we are still anticipating study completion by the end of 2026 or early 2027.

Lastly, our real-world evidence study in collaboration with U.S. Renal Care has entered the second year of data collection. The team is currently conducting an analysis of the first year of data, and we anticipate sharing those interim results by the end of this year. This study is designed to demonstrate the real-world effects of the broad use of DefenCath in a real-world setting and examines not only the reduction in catheter-related bloodstream infections or CRBSI, but also reduction in costly infection-related hospitalizations. Secondary data points of missed treatment sessions, antibiotic utilization and TPA utilization are also being reviewed.

Now turning to integration progress. I am heartened by the significant efforts of the teams to both integrate and optimize operations as a unified organization. We have made meaningful strides in merging the teams identifying synergies and creatively preserving key elements of both legacy organizations. In addition to our new corporate branding as CorMedix Therapeutics, we have refined our mission, vision and values as a new organization and are excited to see our integrated teams work together to create a new culture and execute together on key objectives.

Currently, all functional areas have fully integrated from a personnel standpoint, which includes clinical, medical affairs, technical operations, supply chain, finance, legal, quality, human resources and commercial. Systems integration is still underway and expected to complete in 2026, in line with our original estimates. The legacy contracted hospital sales team for DefenCath will conclude its service by the end of this year, and DefenCath promotion in the hospital setting will transition in January to the post-integration internal field organization.

Beginning in early Q1 2026, our unified sales organization covering acute care clinics and hospitals will seamlessly support all promoted portfolio products, including both DefenCath and Rezzayo and will offer enhanced capabilities and customer support. The collective expertise of our team positions us to deliver comprehensive solutions to many challenges in the acute care space and ultimately with the goal of driving better patient outcomes.

We are incredibly proud of the team and their hard work in moving this integration forward while continuing to focus on sales and patient access. I would now like to turn the call over to Susan to discuss the company's third quarter financial results and financial position. Susan?

Thanks, Liz, and good morning, everyone. We are pleased to report our third quarter financial results, reflecting continued commercial momentum and a path towards sustained profitability. Our results demonstrate solid growth across the business, including strong performance from DefenCath and growth in the legacy Melinta product portfolio.

We closed the Melinta acquisition on August 29, 2025, and therefore, 1 month of its operations are included in our consolidated financial results for the third quarter. The company has filed its quarterly report on Form 10-Q for the quarter ended September 30, 2025. I encourage you to read the information contained in the report for a more complete discussion of our financial results.

As Joe mentioned, for the third quarter, net revenue was $104.3 million, including the DefenCath sales of $88.8 million representing a total net revenue increase of $77.5 million year-over-year. The remainder of revenue totaling approximately $15.5 million reflects the contribution from Melinta for the month of September, $12.8 million of which was driven by Melinta portfolio sales.

Operating expenses for the third quarter were $42.6 million compared to $14.1 million for CorMedix on a stand-alone basis in the same quarter last year. The increase of $28.5 million over the prior period includes nonrecurring costs of $12.7 million associated with the transaction and integration as well as severance costs associated with the Melinta acquisition.

Other increases in costs were driven by stock-based compensation, OpEx contribution from Melinta's business and increased investment in R&D associated with expanded indications for DefenCath, including the Phase III clinical study for prevention of CLABS and TPN patients. While costs have increased in these areas this past quarter, they are aligned with our previously communicated expectations and support our strategic priority, which is to position the company for long-term sustainable growth.

In addition, as Joe mentioned, we are working to quickly capture synergies associated with the Melinta acquisition with approximately $30 million of synergies on a run rate basis expected to be captured from actions taken prior to the end of the year. We expect to realize these synergies in the P&L beginning in the fourth quarter of 2025.

Overall, for the third quarter of 2025, we achieved net income of $108.6 million or $1.26 per diluted share marking meaningful progress compared to the third quarter of 2024. During which period, we recognized a loss of $2.8 million and a net loss per diluted share of $0.05. A large driver of net income for the quarter was a substantial tax benefit of $59.7 million, due primarily to the realization of deferred tax assets equating to 100% of the CorMedix historical net operating losses or NOLs.

The recognition of this sizable tax benefit underscores our confidence in sustained future profitability, which will drive the utilization of our NOL carryforwards against taxable income, which equates to cash tax savings and tangible value for the company and for shareholders.

Turning to non-GAAP measures. Adjusted EBITDA for the third quarter of 2025 was $71.8 million up from a loss of $2 million in the third quarter of 2024, reflecting the momentum of our operations over the past year. This non-GAAP measure provides additional insight into our core operating performance and profitability trends, highlights the underlying strength of our operations and excludes onetime acquisition-related costs, stock-based compensation and the tax benefit we realized this quarter.

Please refer to our press release that we issued this morning for a reconciliation of this non-GAAP measure to GAAP net income. On the cash front, we raised gross proceeds of $150 million in a convertible debt offering and those proceeds together with cash on hand and $40 million in common stock issued to the seller were used to fund the acquisition of Melinta in August 2025.

This financing strategy supported the transaction while maintaining what we believe to be a healthy liquidity position and flexibility for future growth investments. As a result, our cash flow during the third quarter reflects the timing of these financing and acquisition activities, and we ended the quarter with cash, cash equivalents and short-term investments of $55.7 million.

Looking ahead, we expect significant cash generation in the fourth quarter, driven by strong operational performance. We anticipate ending the year with approximately $100 million of cash and cash equivalents, supported by ongoing positive operating cash flow and working capital optimization. To drive this balance, we are guiding to fourth quarter net revenue in the range of $115 million to $135 million, reflecting continued momentum from DefenCath and a full quarter contribution from Melinta.

And now I will turn the call back to Joe for closing remarks. Joe?

Thank you, Susan. The third quarter of 2025 marked a period of meaningful progress and disciplined execution. We advanced our strategic objectives, strengthened our financial foundation and delivered solid results while completing a transformative acquisition. The company now has a diversified product portfolio, multiple late-stage pipeline opportunities, financial flexibility and a diversified capital structure to support future growth.

We remain confident in the outlook for the remainder of this year and the path to sustained growth and profitability. I'd now like the operator open up for questions.

[Operator Instructions] Our first question comes from Les Sulewski with Truist.

Congrats on the progress. First, on DefenCath, do you have a sense of inventory stocking versus utilization in 3Q and we understand you're not providing guidance for next year at this time. But how should we think about potential seasonality throughout the year? Or how ordering rates could impact quarterly revenue cadence? And then outside of additional cohort expansion is 4Q implied guidance, I guess, a good representation of a normalized utilization patterns. And then I have a follow-up.

Thanks, Les. I try make sure I get all these right. So in terms of third quarter stocking, I think our smaller customers from what we've seen are holding on average about 2 to 3 weeks on hand. The LDO is somewhere between 3 to 4 weeks, and I think that's what we saw normalized. I'd say there was probably a couple of million dollars shipped at the cutover if you're trying to kind of back into third quarter versus fourth quarter DefenCath revenue and kind of where we're trending. So there was a couple of million dollars on that right on that cutoff that probably that ended up getting captured in Q3 that a day later is going to be in Q4. But for the most part, I wouldn't say there's a significant amount of stocking in Q3, just normal stocking that they hold on hand.

The second question, I believe, was about quarter-to-quarter guidance and seasonality. The business, certainly, we'll separate the DefenCath business from the Melinta business, doesn't have a historic seasonality in terms of times of the year where patients receive hemodialysis more than others. As we've been progressing over the last 2 years and we've added new customers, we've had new cohorts, we've continued to see, right, an increase in utilization and growth in overall revenue. Obviously, I think there's a lot of eyes focused on next year. I don't know at what point we're going to be ready to provide financial guidance for 2026.

I think everyone is aware, just by the nature of TDAPA and the change that comes in July, there should be a little bit of front-endedness, right to the overall revenue, not necessarily utilization for the overall year, and we're still trying to figure out what the full year is going to look like.

Now in the Melinta portfolio, again, they're not -- though a large number of them are any infectives, they're not cough/cold type products. So you wouldn't see that type of winter seasonality. I think the -- there's always a small amount of December stocking into January of all products. I don't know that it's going to be overly material to the business case, but we don't -- wouldn't expect to see significant seasonality there as well.

In terms of cohort expansion, I do believe that there's still opportunities with all of the customers that I think that was on that question is specific to DefenCath that there's still an opportunity to grow with our existing customer base. And that's something that we are continuing to focus on over the coming months and even in the post-TDAPA period. It's a big part of our post-TDAPA strategy is the engagement with Medicare Advantage. We currently believe the overwhelming majority of the patients in which DefenCath is being used in the outpatient setting are Medicare fee-for-service patients. Medicare Advantage is now the largest cohort of patients and a big part of the opportunity for our future expansion post-TDAPA. And you had a follow-up.

I do. So it is on key data actually. So is the real world evidence that mutually inclusive with agreements on final pricing around the post TDAPA period. Can you provide maybe some sort of a sense of your inkling into the price negotiation period into -- heading into July on the TDAPA side?

Well, look, you have to separate, the real-world evidence in our view, is going to be most applicable and useful with Medicare Advantage, right? Medicare Advantage is not bound by the post-TDAPA add-on. They have the flexibility to contract separately, right? That's the strategy we want to employ. We have very little market share right now of Medicare Advantage patients, and we think it's a compelling value proposition for the MA plan. Ultimately, they are the payer of those downstream costs, those hospitalizations that drive so much cost in the health care system.

So we want to, obviously, with data, make the argument that investing in prevention, right, is going to save them a significant amount of value. On the traditional Medicare side, there's not much of an opportunity for negotiation less. It's really based on when the ESRD final rule publishes, what they ultimately determine is going to be the fee-for-service adjustment, and we'll work around that once it's published.

And the next question comes from Jason Butler with Citizens.

Congrats on the quarter. Two for me, Joe. First one, you mentioned that the ordering from the LDO has been faster than you'd expected. How has the use been in terms of the number of patients and the type of patients that the LDO has been using the product in? And then secondly, when we think about the real-world data coming at the end of the year, can you just give us some color about what to expect in terms of the number of patients, the endpoints and how we assess the benefit here relative, for example, to the Phase III results, if that is at all relevant?

All right. Thanks, Jason. So Yes. So the LDO, it wasn't just a matter of ordering, right, faster, right? The data we're getting from inventory on hand demonstrates that the utilization is also faster than what we expected in the ramp. And I know that we had guided previously that the expectation was to target an initial rollout of 6,000 patients. We don't have today an exact number of where we are. We believe we are significantly higher than 6,000 patients. And we're -- so we're pleased with the rollout, but we don't have the ability to give a patient number at this time.

In terms of kind of the stratification, I don't know if you were asking about high risk or type of insurance. We don't have great visibility into that data. I think our expectation is that it's mostly fee-for-service patients at this time and that there's an opportunity with Medicare Advantage. On the real-world evidence question, I'm going to ask Liz to address.

Sure. Jason, so we are expecting the year 1 results to come out later this year. It's approximately 2,000 patients. So we're double what we had in our Phase III LOCKET study. And we expect that we're going to read out data on the reduction in actual CRBSI, reduction in hospitalizations due to CRBSI. There are some secondary endpoints we're looking at as well, missed treatment sessions, utilization of TPA and antibiotic utilization. And those are all being compared to the historic infection rates. So we should have that out sometime in the next 6 to 7 weeks.

And the next question comes from Roanna Ruiz with Leerink Partners.

So a couple from me. First one is, given some of the trends you're seeing in DefenCath utilization so far, how should we think about the second half '26 revenues and pricing dynamics post TDAPA? And what are some of the pushes and pulls that could drive DefenCath revenues either higher or lower after this TDAPA period?

Thanks, Rana. As I think I said to Les, we're not in a position to give a lot of clarity right now on that back part of '26. Obviously, we do know there's going to be price compression, right, because it's going to shift from the ASP method into the post TDAPA add-on absent the passing of legislation that is currently pending before the Senate. But the pushes and pulls would be related to how CMS does the calculation for utilization. The method that they had proposed in the proposed rule, which we commented on would have created or will create a dynamic where the adjustment for Q3 and 4 of '26 is lower than the adjustment for '27.

And if that's the framework, I think we're prepared to work around that. We're just waiting for a final determination in the final rule, which was expected a couple of weeks ago. I know the government shutdown has delayed quite a few things. We're expecting it to come any day now. And once we have that, we'll be able to finalize things with customers and just continue moving forward.

Got it. That's helpful. And another quick follow-up for me. I was curious, with your discussions with customers into the post-TDAPA period, what are some of the goals of these discussions? And what data are you bringing forward right now to help those discussions as well?

Well, look, I think the real-world evidence data is going to be critical, right? And that should be -- it's interim midpoint data available by the end of the year. And I think the ability to demonstrate the impact on the health care system is an important one. We've gotten anecdotal feedback from multiple customers that they've seen a noticeable difference, right, in their infection rates. I know that's not data, right? But it's -- if they are feeling it and visually seeing it, certainly, that's a positive and something that we will want to build on.

And the next question comes from Brandon Folkes with H.C. Wainwright.

On all the progress. Two from me, maybe just firstly, any color on how you're viewing the DefenCath inpatient opportunity? How is that progressing? And how do you expect that to progress in '26, just given the scale and relationships that Melinta brings in that setting? And then maybe secondly, just changing gears to Niyad. How are you thinking about that investment well in Talphera, but sort of Niyad as a product? It seems like a product you can sort of simply drop into your commercial infrastructure and drive pretty strong EBITDA accretion on day 1. Is that how you think about the product? Or do you think there's material investment required behind that opportunity should you execute on your option?

Thank you, Brandon. So look, on the inpatient side, I think we're continuing to -- over the course of this year, we've seen good progress. I'd say it's a drop in the bucket compared to the magnitude of what we've seen outpatient, but it has been good steady growth over the course of the year. As Liz mentioned in the script, starting next year, as we are migrating from the legacy contracted field team that was inpatient for CorMedix into the new combined field team post-Melinta integration, we'll be training that team in December on DefenCath. And in January, they'll begin promoting in the inpatient segment.

So I do expect to continue to see lift there as a good opportunity for growth. As we talked a lot about over the last 2 years, while the inpatient volume might be lower, right? The pricing there is a little bit better and the revenue per patient higher, right? So it's a good profit opportunity, right, for DefenCath in the inpatient setting. On Niyad, obviously, we did the strategic investment because we like the product. We like the fit with us from a commercial infrastructure standpoint. We're going to continue to watch the clinical results and evaluate the opportunity.

I don't know that I'm prepared to comment that no investment, right, would be required, Brandon, if we were to acquire the business. Obviously, there's an investment if we were to acquire Talphera. I imagine there's some amount of marketing expense related. But I think from a sales deployment standpoint, our current expectation is it fits very well with our existing call points.

And the next question comes from Serge Belanger with Needham & Company.

A couple for us, Joe. The first one, can you just give us an update on the pricing of death and cat over the third quarter? And then on TDAPA, it sounds like the ESRD rule is going to determine the calculation for post period starting in July. Are you going to be able to provide guidance once the ESRD rule is published? And then secondly, are you aware of any legislation bills in Congress that could modify the TDAPA reimbursement?

All right. Thanks, Serge. In terms of specific pricing on DefenCath, obviously, we don't give that. We have guided historically that quarter-over-quarter, there is a slight erosion based on the structure of the agreements. We track -- typically, our ASP is a discount off -- our selling price is a discount off government ASP, which has kind of tracked down quarter-over-quarter, but volume has obviously grown significantly to more than offset the changes in price.

So I think the TDAPA rule and the methodology will inform -- we set agreements in place with all of our customers, right? And there were formulas laid out for how pricing needs to be determined. I think one of the things we're waiting to see is that dynamic whether or not CMS uses a methodology where the Q3 and Q4 of '26 will be lower than 27. And if that's the case, we may try to negotiate a blended price over a period of time. But that's really the only nuance that we're looking at. I don't -- again, I don't know that I would want to give any customer-specific pricing, but we should be able to talk a little bit more directionally in the early part of next year about what we're going to see for the back part of the year.

And then lastly, in terms of the legislation, there is a bill that was proposed by Senator Booker, Marshall Blackburn, bipartisan bill that would make significant changes to TDAPA in terms of incentivizing innovation. I think most importantly, it would expand the ASP-based pricing period from 2 years to 3 years. It would make the post-DAPA add-on permanent, but also have that add-on track drug utilization in terms of follow drug utilization. Right now, the methodology CMS uses, they bundleize based on market share of total dialysis, irrespective of whether drug is dispensed.

The proposed methodology in the legislation would allocate that market share based on percentage of drug claims submitted over time. And I think that's certainly a better measure and hopeful that, that legislation can make its way into law in the early part of next year. I know the government shutdown has stalled quite a few things. But hopefully, the new Congress in early '26 can advance that forward.

I'll now pass it to Dan Ferry for written questions from the audience.

Thank you, operator. Joe, we had quite a few here, but it looks like a lot of them were covered during the live Q&A. I do have one additional one, though that you might help us out with here. What do you think is misunderstood regarding the Melinta transaction? And why are investors not crediting the value of Melinta?

I mean, thanks, Dan. I just chuckled a little bit because as I was going through all of the analyst questions, it struck me we didn't get a single question on Roseeo on the potential impact on how we're viewing Melinta, right? And I think there's obviously a lot of historic focus on DefenCath and for good reason, right? It's the largest revenue driver in the business currently. But when I look at what -- why we did the acquisition of Melinta, what it brings to the table, I certainly do think there's a lot of things that are not currently being appreciated. one of which is the stabilizing factor of the base business that was acquired from a risk mitigation standpoint, right?

We got quite a few questions around what's going to happen in the back part of the year next year with DefenCath. And the Momenta base business gives us a good stable base of revenue from which we're able to take operating synergies and really entrench the business. Second, I think Rezzayo prophylaxis as a pipeline opportunity is certainly not being valued appropriately. This has the potential to be a larger peak sales product than even DefenCath, right?

You've got a total addressable market over $2 billion. You've got a market segment that is already getting prophylactic antifungal therapy, right? These patients that are immune compromised. So it's not as if we have to change patterns. Similar to the launch of DefenCath, where nothing was being done prophylactically, we really had to change mindsets. This is a different situation where prophylactic action is already being taken and the standard of care has some deficiencies with it, right? The severe drug-drug interactions, I don't think should be discounted.

The ability to shift to weekly dosing to perhaps increase convenience for the patients as well as a large amount of the dosing or administration would be in an outpatient hematology/oncology clinic setting, which is buy-and-bill reimbursement, right? So I think there's a lot of favorabilities and opportunity around Rezzayo prophylaxis as a future growth driver of the business as well as TPN, right? I think we're excited about the opportunity for TPN. We've just done some updated internal market research, right, that has confirmed how high the infection rates are in that patient population, how much the doctors are looking for an intervention. So I think we're excited about the future growth prospects for the business outside of hemodialysis. And I think that's -- those are important catalysts that I think investors need to start focusing on.

Excellent. Okay. Thank you, Joe. Operator, you may now close the call.

This concludes our question-and-answer session. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.