Earnings Call Transcript - NUVB Q4 2025

Operator, Operator

Hello, and welcome to Nuvation Bio's Fourth Quarter and Full Year 2025 Financial Results and Corporate Update Call. Today's call is being recorded, and a replay will be available. Now I'd like to turn the call over to JR DeVita, Executive Director of Corporate Development and Investor Relations at Nuvation Bio. Please go ahead.

JR DeVita, Executive Director of Corporate Development and Investor Relations

Thank you, and good afternoon, everyone. Welcome to the Nuvation Bio Fourth Quarter and Full Year 2025 Earnings Conference Call. Earlier today, we released financial results for the quarter and year ending December 31, 2025, and provided a business update. The press release is available on the Investors section of our website at nuvationbio.com and a recording of this conference call will also be available on our website following its completion. I'd like to remind you that today's call includes forward-looking statements, including statements about the therapeutic and commercial potential of IBTROZI and safusidenib, the components of our anticipated product revenue, expected milestone payments and our cash runway. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K, which we filed with the U.S. Securities and Exchange Commission today. Joining me on today's call are our Founder, President and Chief Executive Officer; Dr. David Hung; our Chief Commercial Officer, Colleen Sjogren, and our Chief Financial Officer, Philippe Sauvage. David will provide an overview of our key achievements in 2025 and other business updates, Colleen will provide details on the commercial launch of IBTROZI and Philippe will discuss our financial, partnering and operating updates. David will then conclude with closing remarks. Now I'll turn the call over to Dr. David Hung. David?

David Hung, CEO

Thanks, JR. Good afternoon, everyone. Thank you for joining us. 2025 was a pivotal year for Nuvation Bio, and I'm pleased to discuss our full year and fourth quarter results with you today. Our most significant achievement occurred on June 11 with the full U.S. FDA approval of our first therapy IBTROZI, indicated to treat people living with advanced ROS1-positive non-small cell lung cancer, or NSCLC. Since then, we've been working tirelessly to bring IBTROZI to patients with this aggressive disease. And based on the number of patients who have started our therapy, and the confidence we have in this differentiated profile, we believe that IBTROZI is becoming the new standard of care for ROS1-positive NSCLC. By the end of 2025, 432 new patients started IBTROZI, including 216 in the fourth quarter. For IQVIA data, patients are being prescribed IBTROZI at a rate that is approximately six times faster than the two prior ROS1 TKI launches over their first two full quarters following approval. Our fourth quarter patient starts also reflect an increase over the 204 new patient starts in the third quarter during a time of year that may be impacted by seasonal factors. We continue to see a steady cadence of new patient starts in the first two months of 2026 from those who have filled a TKI, those currently on a TKI, who have switched to IBTROZI, and those naive to therapy. This broad patient mix further highlights the strength of our launch and collective belief in our medicine. Feedback from key opinion leaders, daily interactions with healthcare providers, and results from our market research have consistently been overwhelmingly positive. Since launch, we've learned that IBTROZI's efficacy profile resonates strongly with physicians and equally important, its safety profile, especially limited CNS toxicity, may allow earlier line patients to remain on therapy for years. An essential factor in a space where long-term duration therapy is paramount. As I mentioned, and consistent with this, we continue to see switches to IBTROZI from all three of the other therapies approved for ROS1 positive lung cancer. The reasons for these switches include disease progression, tolerability challenges, brain penetrants, and physician confidence in the strength of IBTROZI's clinical data, particularly in the durability of response. I'm thrilled with how our team has executed despite the fact that rare disease launches always provide a variety of challenges. Their efforts have resulted in significant impact, and most importantly, on patients, but also on how providers choose to treat this disease. Colleen and Philippe will provide more detail on launch dynamics and net product revenue later in the call. Looking ahead, we are focusing on increasing our prescriber base and identifying more newly diagnosed first-line patients to be treated with IBTROZI. We believe that treating these patients will significantly increase the collective time our active patient population stays on therapy while we continue to simultaneously treat patients in the later line setting, who are in urgent need of our medicines. We also plan to present additional long-term IBTROZI data at multiple medical conferences in 2026. As a reminder, on our prior earnings call, we reported that as of August 2025, IBTROZI's median duration of response has now reached 50 months in a pooled analysis of TKI-naive patients in the TRUST-I and TRUST-II pivotal studies, populations in which IBTROZI has previously shown an 89% confirmed overall response rate or ORR. We believe these long-term IBTROZI data represent the greatest patient benefit seen to date in ROS1-positive NSCLC. And unlike ongoing studies of other ROS1 TKIs, our pivotal study did not exclude patients with other concomitant oncogenic mutations making the results with IBTROZI, we believe, representative and applicable to real-world patients. We look forward to providing more clinical analyses from the August 2025 data cutoff in the first half of this year. Our scientific updates in 2026 may also further characterize IBTROZI's unique balance of activity against two important targets: ROS1 and TRKb. IBTROZI is 11 to 20-fold more selective for ROS1 than TRKb and remains strikingly potent against ROS1 with picomolar-level inhibitory activity. But importantly, IBTROZI also has measured inhibitory activity against TRKb. What is starting to emerge with improved scientific understanding is that the degree to which a lung cancer therapy inhibits TRKb, in addition to its primary oncogenic driver, may play a significant role in not only controlling the growth of the primary tumor but may also inhibit the ability of that primary tumor to metastasize and grow in distant sites, particularly in the brain. Remember that ROS1-positive lung cancer has a particularly high propensity to spread to the brain, as 36% of newly diagnosed patients present with brain metastases. In an additional 50% of cases, the first site of disease progression will be in the brain. We believe the ability to control and even prevent brain metastases in ROS1-positive lung cancer may be one of the most important determinants of long-term survival and will be reflected in a therapy's durability of benefit. TRKb is an oncogene, meaning that it drives cancer growth and metastasis and the natural ligand for the TRKb receptor is BDNF or brain-derived neurotrophic factor, as the name implies, this factor is expressed at high levels in the brain and can fuel the growth of cancer cells via the TRKb pathway if that pathway is not inhibited sufficiently. However, too much inhibition has been shown to lead to neurological side effects. IBTROZI is far more potent against ROS1 than TRKb, about 20-fold, which may explain why it has such a high response rate and durability in ROS1-driven lung cancer. And yet, while IBTROZI does have adequate activity against TRKb, this inhibition is measured enough that its dizziness rate is similar to that of crizotinib, a drug that doesn't cross the blood-brain barrier. In a recent commentary published in the Journal of Thoracic Oncology, renowned thoracic oncologists, Dr. Ross Camidge, Dr. William Phillips, Dr. Rafael Nemanov, and Dr. Diana Sitelli, hypothesized that this selectivity could make IBTROZI the best-tolerated next-generation ROS1 inhibitor. And we believe IBTROZI's intentional, but well-tolerated TRKb inhibition may contribute meaningfully to intracranial disease control and ultimately survival without introducing the significant CNS toxicity that has limited other agents, to the point Dr. Camidge and team emphasized in their analysis. Separately, published data have linked uninhibited TRKb signaling to larger tumor burden, higher stage disease, increased risk of CNS metastases, and poor outcomes across multiple solid tumors, including lung cancer. In our view, IBTROZI strikes a particularly effective balance, deep durable inhibition of ROS1, paired with measured TRKb activity that potentially supports CNS disease control while preserving tolerability. Interestingly, the only other approved TKI to demonstrate longer durability in TKI-naive patients than IBTROZI is lorlatinib in ALK-positive NSCLC, which showed a median progression-free survival, or PFS, of over 5 years in the CROWN study. Lorlatinib has even greater TRKb inhibition than IBTROZI, which we believe is likely related to lorlatinib's high rate of CNS events like mood disorders. However, given the high propensity for CNS involvement in ALK-positive disease, Dr. Camidge speculates that it is lorlatinib's significant TRKb inhibition that may account for its high intracranial response rate in 5-year duration of response. We do not view the shared prolonged durability of lorlatinib and IBTROZI as coincidental. Taken together, we believe that IBTROZI's ability to strongly suppress ROS1 while modulating TRKb in a tolerable way could help explain the durability, intracranial activity, and safety profile we continue to observe as real-world use increases. We also continue to envision and develop IBTROZI for a broader ROS1 positive lung cancer population. Based on our label, IBTROZI has been prescribed to a significant number of patients in the advanced setting across lines of therapy. The next step for us is to move to earlier stages of lung cancer. As previously shared, we have dosed the first patient in TRUST-IV, a randomized, placebo-controlled Phase III study evaluating taletrectinib as an adjuvant therapy for patients with resected ROS1-positive early-stage non-small cell lung cancer. Adjuvant therapy is fundamentally different from treatment in advanced disease and is an area we targeted for study only after garnering support from multiple lung cancer KOLs. These patients have undergone surgery, often feel healthy, and are understandably unwilling to remain on our therapy that is difficult to tolerate or interferes with daily life. As a result, only a drug with a manageable and highly tolerable safety profile can realistically be developed in this study. We believe it is particularly meaningful that IBTROZI is the only ROS1 inhibitor currently being studied in the adjuvant setting, and we view this as a further testament to its safety and tolerability profile. Across our clinical database of 337 patients with advanced ROS1-positive non-small cell lung cancer, only one patient discontinued treatment due to any of the six most common adverse events, including diarrhea, nausea, vomiting, dizziness, or liver enzyme elevations. While this does not summarize all adverse events detailed in our prescribing information, this level of tolerability for our most prevalent adverse events is critical when considering use immediately following surgery and why we believe IBTROZI may provide benefit in the adjuvant setting. Lastly, we not only aim to bring IBTROZI to patients across the ROS1 positive disease spectrum, but also to the patients and providers around the world. Last year, we received approval for IBTROZI in China and our partners at Innovent Biologics and in Japan with our partners at Nippon Kayaku. In January, we were thrilled to announce a strategic partnership with Eisai to develop IBTROZI in Europe and other ex-U.S. territories outside China and Japan. We are working diligently with Eisai to submit IBTROZI for approval in Europe in the first half of this year. In short, we believe our continued launch performance, the latest updates reconfirming IBTROZI's efficacy and tolerability profile, and additional development, regulatory and commercial achievements, all show why we believe IBTROZI is becoming the standard of care for ROS1-positive lung cancer. We also made exciting progress developing our second program, safusidenib. Safusidenib is an inhibitor of mutant IDH1 being developed for IDH1 mutant glioma, a devastating type of brain cancer. Importantly, not only are there very few treatment options available for this disease, but these younger patients are typically diagnosed between the ages of 38 and 45. Clearly, there is an opportunity to make an impact for these patients and their families. IDH1-mutant glioma is described using two types of terminology: grade and tumor classification. A grade of a glioma indicates the level of risk while the classification describes certain biological features of the tumor. Malignant IDH1 mutant tumors can be defined using grades 2, 3, and 4, and these tumors can be classified as either oligodendroglioma or astrocytoma. Both descriptors together indicate the level of risk, aggressiveness of the disease, and estimated time patients may live with their disease. To simplify this, we describe both grade 2 oligodendroglioma and astrocytoma as low-grade IDH1-mutant glioma, while high-grade IDH1-mutant gliomas consist of grade 3 oligodendroglioma, grade 3 astrocytoma, and grade 4 astrocytoma. Each year, there are approximately 2,400 new cases of IDH1-mutant glioma in the U.S., split almost evenly between the low-grade and high-grade population. The key difference is that based on published median overall survival data, patients with low-grade IDH1-mutant glioma live approximately 12 to 20 years, while high-grade patients live on average approximately 2 to 12 years. The only targeted treatment option available for patients with IDH1-mutant glioma is vorasidenib, which was approved by the U.S. FDA in August 2024, where only patients with grade 2 oligodendroglioma and grade 2 astrocytoma are the low-grade population. In this pivotal INDIGO study, which included 168 grade 2 patients with non-enhancing or low-risk disease in the active study arm, vorasidenib demonstrated a median PFS of 27.7 months, a 41% progression rate at 24 months, and an ORR of 11%. In a separate Phase I study of 30 patients, vorasidenib showed a confirmed ORR of 0% in a high-grade enhancing population, which is not included in its approved label. In November, results from our Phase II study of safusidenib for low-grade IDH1-mutant glioma were published in neuro-oncology. This patient population was treated with safusidenib following surgery and prior to radiation or chemotherapy - the same types of prior treatments patients received in the INDIGO study. In this study of 27 patients, safusidenib demonstrated a median PFS that has not been reached, a 12% progression rate at 24 months, and a confirmed ORR of 44%. As a reminder, in a Phase I study of 35 patients, safusidenib also showed a 17% confirmed ORR including two complete responses that lasted multiple years in a high-grade enhancing population. As we've discussed previously, vorasidenib is already approaching a $1 billion U.S. net revenue run rate, less than two years after its approval. This rapid commercial uptake underscores both the unmet need and the willingness of physicians to adopt targeted therapies in this setting. While we acknowledge the inherent complexity and limitations of cross-trial comparisons due to differences in study design, patient populations, endpoints, and sample size, recently published data in neuro-oncology and data from our Phase I study highlight the encouraging clinical profile of safusidenib and its potential to address significant unmet need in this patient population. In parallel, we continue to learn more about safusidenib's safety profile. While the drug is generally well tolerated, we observed a distinct set of dermatological related adverse events, including alopecia, arthralgia, and skin hyperpigmentation. We believe the presence of these events may be due to a different pharmacological profile of safusidenib, and we continue to investigate if safusidenib may inhibit targets other than IDH1. Importantly, the drug-related discontinuation rate in the Phase II study, which was conducted at the pivotal 250-milligram twice-a-day dose, remains low at approximately 8%. The patients who had discontinued therapy were able to recover with interruption and appropriate management. Based on data generated to date, we announced in February that we started enrolling our pivotal Phase III study called SIGMA. This global randomized study is evaluating the efficacy and safety of safusidenib versus placebo for the maintenance treatment of high-risk and high-grade IDH1 mutant glioma following standard of care. Specifically, the study population includes 300 patients with grade 2 or grade 3 astrocytoma who show certain high-risk features, along with all patients with grade 4 astrocytoma. As an important reminder, these patients have no FDA-approved targeted therapy options. Considering the high unmet need and the exciting profile of safusidenib, we are optimistic about the speed of recruitment in this trial. Due to the sizable population being enrolled to support approval and the use of PFS as the primary endpoint, we expect this study will read out in 2029. Importantly, we recently announced the initiation of a second non-pivotal cohort evaluating safusidenib in patients with grade 3 oligodendroglioma, a patient population that is considered to be within the lower risk end of the high-grade glioma spectrum. This grade 3 oligodendroglioma study will enroll approximately 40 patients with measurable disease, including patients with residual disease following surgery for those with recurrent disease, and will evaluate ORR as the primary endpoint. Given that we have 31 sites activated in the U.S. already, we estimate that we will be able to provide a full study readout in 2027. Importantly, if we see significant objective response in this study, we will meet with the FDA to discuss the results and potential options for further development, aiming towards an accelerated approval pathway. Patients with grade 3 oligodendroglioma frequently seek alternatives due to the cumulative toxicities associated with prolonged radiation and chemotherapy given the relatively young age at diagnosis and median life expectancy of 12 to 14 years. Yet, there are currently no approved targeted therapies for this group either. While there are approximately 400 new grade 3 oligodendroglioma cases diagnosed annually in the U.S., we believe this represents a much larger prevalent population of several thousand patients, who are underserved today and could meaningfully benefit from an effective, well-tolerated targeted therapy. We view safusidenib as an ideal complement to IBTROZI as we now have an approved therapy and a late-stage program that both address a clear unmet need for patients. We look forward to generating updates from our evaluation of safusidenib as quickly as possible. Lastly, our drug-drug conjugate or DDC platform represents a novel modality in targeted cancer therapy designed to conjugate two small molecules, a targeting agent and a warhead. While we discontinued development of our first DDC NUV-1511 in the fourth quarter, we were able to gather valuable insights into DDC development and are already applying these learnings to new preclinical candidates in our pipeline. We hope to have updates on the next phase of our DDC program by year-end. We remain confident in our capabilities to successfully execute our program goals, build lasting value, and most importantly, serve patients. With that, I'll turn it over to Colleen to provide more color on the launch of IBTROZI.

Colleen Sjogren, Chief Commercial Officer

Thank you, David, and good afternoon, everyone. I'm excited to report that the launch of IBTROZI continues to build what we believe is market-defining momentum in a rare disease indication. From our approval in June through the end of 2025, we treated 432 new patients with IBTROZI, which represents a rate that is six times faster than the two most recent TKI launches in ROS1-positive lung cancer. As David mentioned, we continue to see patient starts from three distinct populations. Patients who have failed prior ROS1 TKI, switches from those currently treated with ROS1 TKI, and newly diagnosed patients who are TKI naive. This momentum underscores that a significant medical need in ROS1-positive non-small cell lung cancer still exists. And it is clear to us that the efforts of our incredible team, our tailored strategy, and IBTROZI's compelling efficacy and safety profile are well positioned to address this need. By the end of the year, we had engaged all top-tier target accounts, and our field-facing interactions reinforce that physicians are quickly gaining comfort prescribing IBTROZI for their patients. Prescriptions have been written in 100% of our 47 sales territories by multiple repeat prescribers. Per IQVIA data, we are showing significant growth in market share of new patients treated with a ROS1 TKI. On the market access front, payer engagement continues to be constructive and effective. At this point in our launch, we have achieved broad coverage to label for patients across the country. Finally, our patient support program, Innovation Connect, continues to help eligible patients receive support and access to IBTROZI while reimbursement is secured. Now I'd like to walk you through some key dynamics of our launch to further characterize where we are today and what lies ahead. As we've noted, IBTROZI is being prescribed across both TKI-naive and TKI-pretreated patient populations. With our extremely high response rate in TKI-naive patients, we do expect an overwhelming majority of this population to be treated with IBTROZI for an extended period, which we are now starting to see. It is typical at the beginning of any oncology launch that the majority of patients who start therapy are in need of a third or even fourth medicine and the response and duration of treatment will unfortunately be lower. While we expect IBTROZI to benefit these patients for a relatively shorter duration, meaning most will not remain on therapy for multiple quarters, we view this as an encouraging signal that providers are motivated to offer their patients a differentiated therapeutic option. While we have limited visibility into the characteristics of all IBTROZI patients, we do have some insight into the segment of patients that come through our Innovation Connect support program and specialty pharmacies. Within this group in 2025, we know that about 75% of discontinuations came from later-line populations. We're encouraged that IBTROZI is providing another meaningful option for patients across lines of therapy, and the patterns we've observed through this experience have given us three important insights. First, discontinuation is strongly correlated with the line of therapy. IBTROZI has been well tolerated by first-line or TKI-naive patients who have shown extremely high response rates in clinical trials. We also know that median DOR and PFS are much longer in this population than in the TKI-pretreated population. Therefore, we expect to see far lower discontinuations as we move IBTROZI upstream in the treatment paradigm. Second, the fact that a significant share of our new patient starts at the beginning of launch were in the third-line plus setting helps explain the gap between an unprecedented number of patients starting IBTROZI and our net product revenue growth from the third to fourth quarter. As I mentioned, this late-line population unfortunately tends to discontinue therapy relatively quickly, and as a result, the majority of these patients are not treated for multiple quarters, which directly impacts near-term revenue trends. By the end of 2026, we expect to see a more direct correlation between growth in new patient starts and growth in our revenue, as a larger portion of active patients treated with IBTROZI shift to those who are newly diagnosed. Lastly, first-line IBTROZI patients are the main driver for our long-term growth. The reason we are so optimistic about our launch is that we continue to see a meaningful, steady increase in first-line patients starting on IBTROZI in recent months. Our data, including the number of previously treated patients in the market, suggest that we are expanding the ROS1 TKI landscape rather than simply competing for a fixed pool of patients. We anticipate this will directly impact the number of active patients on IBTROZI over multiple quarters going forward. We plan to elaborate further on this trend as we collect more data in 2026. Switching to another key area of our launch dynamics, we continue to see use from providers in both academic and community settings nationwide. As of the end of 2025, approximately 70% of our new patient starts had come from the academic centers or IDNs and 30% from community centers, compared to a 75%-25% split at the end of the third quarter. It is typical in a rare oncology launch that immediate uptake occurs in the academic setting. That said, this gradual shift towards the community is expected to increase over time, and in turn will support prescription growth and momentum. This is important because the majority of ROS1 patients will be found and treated in community centers. Looking ahead, we are focused on deepening adoption and continuing to raise awareness of the importance of patient identification. Today, DNA-based testing should identify roughly 3,000 advanced ROS1-positive non-small cell lung cancer patients annually in the U.S. And as the field shifts towards also utilizing RNA-based testing, which publications suggest may help to detect approximately 30% more ROS1 patients, the annual addressable population could potentially expand to roughly 4,000 advanced patients in the U.S. alone. Because of IBTROZI's unprecedented durability, especially in the TKI-naive setting, this small incidence population turns into a substantial prevalence population, generating an opportunity to treat a meaningful number of patients over a period of several years. Finally, I want to commend the efforts of our commercial team. We believe their hard work has positioned IBTROZI as the emerging market leader in this disease. There is still educational work that needs to be done, but I am beyond thrilled we have been able to deliver this therapy to so many patients in need.

Philippe Sauvage, CFO

Thanks, Colleen, and good afternoon, everyone. For detailed fourth quarter 2025 financials, please refer to our earnings press release, which is available on our website. Now let's go over some important highlights of the quarter. I'm pleased to inform you that in the fourth quarter, we generated $41.9 million in total revenue, including receipt of the milestone payments, which brings our total revenue for 2025 to $62.9 million. These figures include $15.7 million and $24.7 million in IBTROZI net U.S. product revenue in the fourth quarter and full year 2025, respectively. As Colleen mentioned, we know a significant share of our product revenue was driven by patients treated with IBTROZI as a third-line plus option. Unfortunately, these patients do not remain on therapy for very long. We do expect that over time, the bulk of our sales will be from first-line patients, staying on drug for many years. This trend of more TKI patients benefiting from IBTROZI is what makes us extremely optimistic about our long-term growth. As this occurs, we'll be able to see the true impact of our 50-month median DOR on revenue growth. Still, this dynamic will play out gradually over time, and we will continue to update you on emerging trends. Our channel movements are stabilizing as we expected we would. Today, we believe our specialty pharmacy and distribution partners hold approximately 2 to 4 weeks of inventory on hand. This is standard and shows that our product revenue has been driven by true patient demand for IBTROZI. In addition, our free trial program continues to provide patients with IBTROZI before they are fully reimbursed, and this prescription generates full commercial revenue in the patient's second month on therapy at the latest. Our approach to access has been extremely successful and has resulted in broad coverage for patients across the country. As I mentioned on our last call, our level of gross to net will naturally increase as we enter more contracts that allow us to cover more lives. As a result, our gross to net now sits around 25%, and we would expect this to slightly increase before stabilizing long term. This is based on our balance of business with commercial, Medicare, Medicaid, and 340B plans and the limited amount of free medicine provided to date. The remaining revenue for 2025 came from our collaboration and license agreements, including milestone payments, royalties, product supply, and research and development services. In addition to ongoing royalty revenue from our partner in China, Innovent Biologics, we began receiving royalty revenue from our partner in Japan, Nippon Kayaku, following regulatory approval and reimbursement in November, an event for which we received a milestone payment of $25 million. We also continued our mission to bring IBTROZI to as many patients as possible outside of the United States. In January, we announced our strategic partnership with Eisai, covering Europe and select territories outside of China and Japan. As a reminder, commercial rights in China and Japan were previously out-licensed, and when those deal values are combined with the Eisai deal, this represents a total deal value of nearly $520 million for most territories outside of the U.S., but still excluding Latin America. Under our agreement with Eisai, we received an upfront payment of approximately $60 million and are eligible for a payment of about $30 million upon European approval. We will also earn up to $140 million in milestone payments upon the achievement of certain sales levels, in addition to double-digit tiered royalties up to the high teens on net sales in Eisai's territories. This partnership meaningfully strengthens our cash position, allows us to reinvest in our own programs, and allows us to precisely focus on our commercialization efforts in the United States. Looking ahead, we expect to file IBTROZI for approval in Europe with Eisai in the first half of this year. On the expense side, R&D expenses were $34.3 million for the quarter and $115.1 million for 2025. We continue to invest in IBTROZI and importantly, are focused on bringing safusidenib to patients as quickly as possible. SG&A expenses were $40.3 million for the quarter and $151.6 million for 2025, primarily driven by support for commercialization. As discussed in prior quarters, we do not expect material increases in commercial headcount going forward. Turning to the balance sheet, we ended 2025 with $529.2 million in cash, cash equivalents, and marketable securities. This cash position has increased by approximately $60 million following the upfront payment we received from Eisai. As a reminder, an additional $50 million remains available to us under our term loan agreement with Sagard Healthcare Partners until June 30, 2026. Our robust capital position gives us flexibility to invest in our launch and pipeline while also enabling the evaluation of additional business development opportunities that can create shareholder value, similar to our acquisition of AnHeart. Based on our current operating plan, revenue trajectory, and disciplined expense management, we do not anticipate the need for additional external financing to reach profitability. We remain a well-managed and agile organization that is positioned to execute our 2026 objectives. I'll now hand it back to David.

David Hung, CEO

Thanks, Philippe. When I take a step back and reflect on our 2025, what gives me particular confidence is the foundation we've built for what comes next: an increasingly durable commercial franchise, a pipeline with meaningful long-term potential, and a capital position that allows us to execute with discipline and flexibility. I'm incredibly proud of the team and grateful for the support of our investigators, partners, shareholders, and most importantly, patients as we continue this journey into 2026. With that, I'll ask the operator to open the line for questions.

Operator, Operator

The first question comes from the line of Farzin Haque with Jefferies.

Farzin Haque, Analyst

Congrats on the progress. So you're not providing any revenue guidance yet for 2026. But what are you seeing in 1Q in terms of first-line and second-line plus mix that gives you confidence in meeting the consensus mark of $150 million for the year?

David Hung, CEO

Thank you for the question, Farzin. This is David speaking. We believe there is a substantial number of patients available. The strong performance in the first two quarters indicates that we are successfully reaching many of these patients. If you examine the number of new patient starts, the trend looks promising. Most of our new patient starts have been in later treatment lines, which is expected, but we are also observing growth in first-line starts. However, we have previously mentioned that we lack visibility on many of these patients because we only have access to their information if they register with the Nuvation Connect Portal. Currently, we are primarily seeing usage in later lines of therapy, which are characterized by shorter response durations, resulting in higher discontinuation rates. Most of the discontinuations we have encountered are among these late-line patients. Nevertheless, we are optimistic that we will see an increase in second-line and first-line usage over time. We believe the patients are present, and we expect first-line usage to develop with significantly longer durability, contributing to the revenue potential we have discussed before.

Farzin Haque, Analyst

Perfect. And then for safusidenib, can you provide an update on the current enrollment trajectory for the Phase III? And do you anticipate any interim analysis before the projected 2029 completion?

David Hung, CEO

We haven't commented on our enrollment. Those patients are definitely there. As you know, there's absolutely nothing for high-grade disease or vorasidenib approved only in a subset of low-grade disease. So we think that trial will enroll well. But it is a PFS study, so it's going to take a while to get the number of events we need to see the results. So that's why we've guided to a 2029 readout for that. But I would say that the patients are there. We feel very confident in the capabilities of our clinical operations and clinical development team. So we think that trial will enroll on target. We do not have any plans right now for interim analysis.

Operator, Operator

The next question comes from the line of Leonid Timashev with RBC.

Leonid Timashev, Analyst

I just want to ask a little bit more about the IBTROZI trajectory. I guess, in the fourth quarter, there was potentially some seasonality; maybe changes in diagnosis have also been a historically weaker quarter for some lung cancer drugs. I guess how should we think about the seasonal bounce back we should see in the first part of 2026? Is any of those maybe weather-related seasonality going to pull through into the first quarter? And any kind of payer dynamics that we should be thinking about in the first quarter as well?

David Hung, CEO

The data we discussed indicated that the seasonality was based solely on ROS1 TKI use over the past four years. Although there was slightly less usage in the fourth quarter, it's difficult to determine if this trend will predict future outcomes. We are confident that patients are present, as indicated by our interactions with the centers we work with. We believe that while there is always room for improvement in genetic testing, new patient diagnoses will occur. There is a pool of over 1,000 patients who have experience with TKIs, and these patients will be the easiest to identify since they have used a ROS1 agent before. We've captured a significant number of those patients already. However, I'm uncertain whether the seasonality will lead to a rebound; it is possible, but I'm unable to say for sure. Recently, we experienced a significant blizzard, which was a notable weather event, but I'm not sure if that will have any lasting impact.

Operator, Operator

The next question comes from the line of Michael Yee with UBS.

Unknown Analyst, Analyst

This is Matt on for Mike. I wanted to ask on your expectations just kind of further trajectory cadence of patient uptake for the year, especially with maybe a competitor entering the market in the second-line setting later in the year. How do you expect to see kind of the market shake out? I know you guys talked about TRKb as an important factor for you guys? Just kind of speak to the longer-term competitive landscape here would be great.

David Hung, CEO

We have seen over 200 new patient starts per quarter in the first two quarters, and we believe this trend will continue. Most of these patients are in later-line therapy, and we have identified around 1,000 TKI-experienced patients that we believe are available. By year-end, we expect to have captured a significant majority of these patients. Our focus is on growth in the first-line setting, as we have a 50-month duration of response, which is exceptional, along with a strong tolerability profile. We anticipate dominating this space. While we have already addressed much of the later-line use, our primary goal is to expand into the first-line segment, which is where we see the greatest opportunity. The durability of our drug is one of its most compelling features, with efficacy largely determined by how long a treatment remains effective. TRKb is a crucial factor in maintaining durability. The lorlatinib data shows that there is no TKI with a longer median progression-free survival than lorlatinib, which is over five years. Lorlatinib also has significant TRKb activity and a high CNS control rate, which is essential for treating ROS1 lung cancer, known for its high incidence of CNS involvement. Our intracranial response rate in the second-line setting is at 66%, unmatched by competitors. This positions our drug as both effective and tolerable. We are focusing on the first line, where we see ongoing unmet needs after addressing the later lines of therapy. We are optimistic and confident about our current trajectory and future prospects.

Operator, Operator

The next question comes from the line of Mary Coleman with Clear Street.

Unknown Analyst, Analyst

Congratulations on the progress. For taletrectinib or IBTROZI, just in general, how much adoption of TKIs have you observed following the NCCN guideline changes, especially in the community setting or community practices? What factors or initiatives could further drive first-line use of IBTROZI there? And I have a couple after that regarding safusidenib.

David Hung, CEO

Sure. So we did note that if you look at the other TKIs prior to our approval, we actually saw an increase in scripts in the other TKIs after the NCCN guidelines came out. So I think those guidelines were helpful and they did increase TKI use. Now since the introduction of IBTROZI to the market after our approval, we've seen clear growth from the little glimpse that we see. We have been seeing increasing first-line use, but it's — again, our glimpse into that window is still limited at this point. I don't — I can't really speak in detail about it; we'll need to wait until we have maybe a quarter or two more under our belt. But we feel that things are going in the right direction. We think the NCCN guidelines are going to be a real benefit. Just the amount of IO/chemo use before those new guidelines was significant. Even after the guidelines, we still think that's a challenge, but I think now that IO is actually contraindicated, I think that's only going to help drive the appropriate therapy. There is no other therapy that can match our metrics on efficacy or even tolerability, so I think we are well positioned to capture this. The greatest tailwind we have is just the strength of our label.

Unknown Analyst, Analyst

All right. That's helpful. And for the Phase III astrocytoma trial, what efficacy outcomes would be considered both clinically meaningful and commercially attractive? And what is the estimated market opportunity or value that it can provide? And for the other cohort, what was the rationale for adding the oligodendroglioma patients as a separate cohort? And how might this become a value-generating program?

David Hung, CEO

Yes. That's a great question. So when I think about glioma, I divide it into a pie about 50-50 low-grade on one side and about 50% high-grade on the other side. But within those subsets, you can divide them again. So each side, both the lower and high grade have low-risk and high-risk features. Currently, vorasidenib is only approved in one of those pieces of that pie. It's only approved in low grade, low risk. That means what remains for an opportunity is high risk, low grade, low risk; high grade and high risk high grade. The Phase III study that we're doing targets three of those parts — three pieces of that pie. Instead of the vorasidenib one piece, our Phase III trial targets three of those pieces. So we think that's a very significant unmet need for patients. It's clearly a much larger commercial opportunity. To get that drug approved in those three pieces of that pie, we have to do an overall — we have to do a progression-free survival study, which is why we need to enroll a certain number of patients. We have to follow them for a certain amount of time; that's why the readout is 2029. Now that said, we also think that it's important for us to get this drug out to patients as quickly as possible. There is yet another piece of that pie that isn't currently being adequately addressed, which is — if you look at all grade 3 oligodendroglioma patients, these patients are a little bit different because, unlike the Phase III study patients I talked about, those patients have completed surgery and radiotherapy and somewhere between six and 12 cycles of temozolomide. So as a result, they don't tend to have measurable disease. When you don't have measurable disease, you have to use PFS; you can't use response rate. Clearly, response rates are a much faster readout than PFS. The grade 3 oligodendroglioma study is important because those patients have measurable disease. These are patients who have not had a resection; haven't had a recent one, and have significant measurable disease. They just can't take because these patients often live 15 years plus; they can’t tolerate chemotherapy or radiation every day. We think it’s a huge unmet need. But because now these patients have measurable disease, we can use overall response rate; unlike the SIGMA Phase III study, which is a PFS readout — this will be an ORR readout by RANO 2.0 criteria. If we see a significant response rate in that study and we're guided to read it out by 2027, clearly, that's a much earlier readout. We know there are examples of glioma drugs being approved on a very small data set with response rate. The first glioma drug was approved on less than 80 patients. We think if we see robust response rates, that would justify a discussion with the FDA to figure out how to get this drug approved to get it to patients a lot sooner than a readout in 2029 for the Phase III study. It’s an important unmet need for patients who can’t take chemo and radiation for 15 years; that’s just not tenable. Overall response rate is critical here, especially since vorasidenib has a 0% response rate in this high-grade group. We think seeing the activity of this drug in an area where nothing else works will compel physicians and patients to think, hey, this is a drug that has activity where nothing else does.

Operator, Operator

The next question comes from the line of Mayank Mamtani with B. Riley Securities.

Mayank Mamtani, Analyst

Congrats on the progress. I appreciate the level of detail on the IBTROZI launch. Just maybe on the metrics should we expect for you to provide the new patient start numbers in the coming quarters, like you have and expect to see this 200-patient quarterly run rate to sort of continue in the coming quarters, including perhaps when there's a competitor entrant later in the year? And also, what's the real-world discontinuation you're seeing in the earlier line? I know you gave the 75% discontinuation rate in later line. But I was just curious if you had something in frontline, I understand the sample size will be small there. Then I have a follow-up.

David Hung, CEO

So we have said since our very first quarter that we reported sales that we would continue to look at new patient starts. I think that's an important metric. It's particularly important in the first year where depending on the mix of patients and the duration of response or the rate of discontinuation, your revenues will not necessarily track with your new patient starts, especially as an example of your third-line patient; you just continue in a month or two. You're not going to have the kind of revenues that you would expect in the first line setting. We think it's important, and we said this since June 11, when we got approved, that we would focus on new patient starts at least for the first year because that’s the best metric; do physicians want to prescribe it? Over time, what you'll see is that we’ve said there are about 1,000 or so TKI-experienced patients. If you continue to see 200 patients per quarter and we know that at some point, we’re going to have captured the majority of those, any growth at all in that 200 number has to be in first-line patients. While that revenue may not appear immediately, it takes you a year to start stacking. When you start to see growth in first line, you will see over time revenue stacking, and you will see a significant increase in revenue. It's just not going to happen immediately because those third-line patients are going to come off; some of them discontinue within a month. We think those first-line patients will be on for five months. For the next couple of quarters, we still think new patient starts are important. By the third quarter of this year, we will continue that trend. If we continue to get 200-plus patients per quarter and the majority of those are TKI experienced, we will have captured the majority of the TKI-experienced market. So any growth in that number must be in the first line, and we think revenues will catch up with that in a few more quarters.

Mayank Mamtani, Analyst

On the discontinuation on the earlier line.

David Hung, CEO

Oh, yes, sorry. So 75% of our discontinuations came from late-line patients. So very late.

Philippe Sauvage, CFO

For the patients that we know, as David said, it's a subset of patients, the ones that are going through the hub or patients going through the hub and discontinuing; 75% of them were late line, which gives a lot of confidence to us about the fact that yes, the main patients will discontinue are clearly late line patients. If you go back to our clinical trial, the rate of discontinuation was very low, as you know, 6.5%. This is really what we're going to see. We're going to see some of those late-line patients, unfortunately, as is expected in oncology, not responding very well to a third or fourth line of therapy. That's true in oncology, and what we've seen in our subset going through the hub is that those are the most discontinuation we see by far.

Mayank Mamtani, Analyst

Understood. And then on the non-pivotal cohort SIGMA study that David, you just touched on, is there a threshold on ORR that you may have quantified or have in mind that would warrant that accelerated approval discussion? Sorry if I missed that.

David Hung, CEO

I think that we've seen an OR anywhere north of 20%. This is a population, as you said, the biggest glioma drug in the world, vorasidenib, has a 0% response rate in that population. So it couldn't be lower, maybe, but certainly at 20% or higher. I think that would be extremely interesting.

Operator, Operator

The next question comes from the line of Greg Renza with Truist.

Gregory Renza, Analyst

Congrats on the progress. David, just maybe on your current resource position. As you've commented on the current financial structure and also the path with the IBTROZI launch, maybe providing that path to potential profitability. Just wondering if you could provide a finer point on maybe what that horizon looks like. Related to this, as you've spoken about business development, you've mentioned the complementarity that IBTROZI and safusidenib provide for the pipeline. How are you thinking about adding to that mix especially in light of that focus or that mention of profitability?

David Hung, CEO

You might recall that last year, before we announced the Sagard Healthcare deal, we had said that at that point, we had enough cash to reach profitability. Well, since we made that statement, we raised $150 million with Sagard, along with another $50 million in debt. Since then, we've done a deal with Eisai, where we got another $60 million, and we'll have another $30 million upon European approval submission or approval next year. We stand by that statement. We have certainly far more cash than we need to get to profitability. If we do a significant business development deal that would require some cash. We are aware of the importance of getting to profitability without having to need additional financing. These are still difficult markets. We've been relatively conservative on that front. We will carefully weigh the upside of a deal. Any deal we do would have to be what we consider a good deal, as we consider AnHeart; we think that was a great deal for us. Any further business would have to be a great deal for us, so we have to weigh the benefits and downsides of using our cash and cutting into our runway to profitability. Still, we feel very confident that we will get to profitability easily with what we have on hand. We do believe that given what we have, further business development is important. It has always been an important part of our company growth historically. We will continue to look for compelling opportunities that capture some of the synergies that we already have within our company.

Gregory Renza, Analyst

That's great. I appreciate that color. And maybe just one last one. If you could just comment on the DDC platform. I think I heard you mention maybe some updates into the year. Just remind us of your conviction on the platform as you invest in that area of the business?

David Hung, CEO

We are absolutely convinced that, that platform is real and has real potential. That was a first-in-class compound. It’s actually the first in history compound. We learned a lot with 1511. It wasn’t that we didn’t see any responses at all. We did see responses with 1511; they just weren't consistent enough for us to invest $100 million in a Phase III study. We look at all our drug candidates as would this be worth spending $100 million on or should we make it better? We always have to balance that in early-stage programs. The answer for 1511 was probably not. We learned enough to figure out how to make it better and are hard at work doing that. We feel very confident that our DDC program will yield molecules that will go to the clinic and that we probably will take forward in development. We’ll update you all hopefully by year-end this year.

Operator, Operator

The next question comes from the line of Yaron Werber with TD Securities.

Steven Ionov, Analyst

Thank you very much, team, for the question. This is Steven on for Yaron. On the IBTROZI launch, in terms of trying to get more penetration in the first-line setting where it seems like crizotinib might still be entrenched, what else can you do in terms of increasing the potential for first line? Have you engaged regulators to try to perhaps get a preference in the first-line setting in the NCCN guidelines? And if so, how is that going? Secondly, any update or perhaps any news on the BET inhibitor NUV-868? And then thirdly, on the approval in Europe, I seem to remember that there was a head-to-head trial versus XALKORI that was thought to be necessary for approval. It seems like that's no longer the case. Can you maybe update on the thinking there?

David Hung, CEO

Sure. Crizotinib is still used significantly because it is pretty well tolerated. But as you know, crizotinib does not cross the blood-brain barrier. And when there were no options other than crizotinib, that would have been appropriate. Today, I would consider it about practice to use crizotinib in the first-line setting for patients who don’t have CNS issues. One-third of them present with brain metastasis. Even if they don't, 50% will develop them. I can't tell which one of two will do that. To give a drug that doesn't have any CNS coverage, in my opinion as an oncologist, is malpractice. That is inappropriate for patients. I can't comment on how long crizotinib will be entrenched; KOLs and patients appreciate the importance of CNS coverage. I think that’s part of our job and Colleen’s team — that’s one of our main messages. I think we have to continue to do that. I can’t really tell you crizotinib will go away, but I do think over time, it is the absolutely wrong drug to use for this disease. In terms of engaging regulators to get preference in the first line setting, we believe that our drug is differentiated. We are looking at strategies to have that captured within the NCCN guidance. On that, I would say stay tuned. We are well aware of the difference in performance metrics of our drug against other drugs. Colleen?

Colleen Sjogren, Chief Commercial Officer

Steven, I just want to elaborate a little bit more. David spoke about the patients who are being pretreated and the progression toxicity that you've just referenced. We are looking to expand the market and take it very personally. These patients are going through their journey in the appropriate way. One way is to ensure patients are tested before treatment decisions are made. When we look at educational opportunities, we have several of them in this idea that patients are not only getting tissue but liquid biopsies. I spoke earlier about DNA testing being very important to understand the actionable mutations before treatment decisions are made. In addition to us getting patients that are switched off other TKIs, we are definitely growing the market and helping to educate more on the importance of understanding the entire picture before treatment decisions are made.

David Hung, CEO

On the European side, we don't believe that any additional clinical trials will be needed. We’ll give you more details once the MA is submitted. On 868, there’s been some interesting interest in that compound. We’re looking at all our options.

Silvan Tuerkcan, Analyst

I just wanted to ask if the gross to net for the pricing has stabilized at this point? Can you share where that's coming out? And if you have any idea where that will end up?

David Hung, CEO

Yes. Thanks for your question, Silvan. I mentioned during my presentation that we were a little bit above 25% for Q4 and that we were still expecting this to grow a little beyond that. To say exactly when it's going to stabilize is always a very tricky question because it all depends on negotiations with payers. Yes, we think that we're in a very good place in terms of access, which is what we wanted. We wanted to make sure that all patients that needed that access reported. Doing all that will take us probably a little bit further up, but not too high. I can’t give you much more detail than that. But yes, we are still going to increase that a little bit in the coming quarters.

Operator, Operator

There are no further questions waiting at this time. That will conclude today's call. I would now like to pass the conference back over to the management team for closing.

David Hung, CEO

Thanks so much. We want to thank you for all your support. Launches can be anxious. I think everyone has been looking at our numbers. We've received some feedback that some people might have been disappointed with the gap they perceived between the new patient starts and the revenue number. This is to be expected. As you know, in launches, especially in oncology, late-line patients get started first; they're the ones that are out of options, and the pool is already identified. It’s hard to find new patients. When you get those late-line patients, they're going to discontinue faster. I would say just be patient. It's all going to happen. We're very confident in this launch. We like the way things are going, and we think that we will get the first-line patients as long as those NPS numbers continue anywhere remotely in that ballpark. We know that we are running out of TKI-experienced patients. The growth will be in first line. Thank you for your continued support, and we look forward to updating you further on our next call.

Operator, Operator

That concludes today's call. Thank you for your participation, and enjoy the rest of your day.