Nuvation Bio (NUVB) Q4 2025 Earnings Transcript

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DATE

Monday, March 2, 2026 at 4:30 p.m. ET

CALL PARTICIPANTS

• Founder, President, and Chief Executive Officer — Dr. David Hung
• Chief Commercial Officer — Colleen Sjogren
• Chief Financial Officer — Philippe Sauvage
• Senior Vice President, Investor Relations — J.R. DeVita

TAKEAWAYS

• Total Revenue -- $41.9 million for the fourth quarter and $62.9 million for the year, including both product and partnership revenue.
• U.S. Net Product Revenue -- $15.7 million in the fourth quarter and $24.7 million for the full year, with performance influenced by high initial use in late-line settings where duration on therapy is limited.
• Iptrozi Launch Uptake -- 432 new U.S. patients started therapy since launch, with 216 initiated in the fourth quarter; new patient start rate is approximately six times that of the prior two ROS1 TKI launches in their initial two quarters.
• First-Line Patient Penetration -- Repeat prescribing and steady increases in first-line use are reported, but the majority of current patient starts remain among later-line patients, impacting projected duration on therapy and near-term revenue stacking.
• Median Duration of Response (DOR) -- "As of August 2025, Introzy’s median duration of response has now reached 50 months in a pooled analysis of TKI-naive patients in the TRUST-1 and TRUST-2 pivotal studies."
• Clinical Discontinuations (Adverse Events) -- Across 337 patients with advanced ROS1-positive NSCLC, only one patient discontinued Iptrozi due to any of the six most common adverse events reported in trials.
• Net Revenue Mix and Operational Dynamics -- Late-line patients accounted for about 75% of discontinuations, with expectations for greater revenue correlation as the first-line share rises by late 2026.
• Inventory and Access -- Specialty pharmacy and distributor inventory is reported at approximately two to four weeks on hand, and national payer coverage for Iptrozi is described as broad.
• Gross-to-Net Ratio -- CFO Philippe Sauvage said, "our gross-to-net now sits around 25%, and we would expect this to slightly increase before stabilizing long term."
• Collaborations and Milestone Revenue -- Ex-U.S. partnerships totaled nearly $520 million in deal value, with a $60 million upfront payment from Eisai booked and a $25 million milestone from Nippon Kayaku received following regulatory approval in Japan.
• Operating Expenses -- R&D expenses were $34.3 million in the quarter and $115.1 million for the year; SG&A expenses were $40.3 million for the quarter and $151.6 million for the year, mainly supporting commercialization.
• Year-End Cash Position -- Cash, cash equivalents, and marketable securities totaled $529.2 million, bolstered by partnership payments.
• Phase 3 Sacrocitinib Program -- The SIGMA trial, enrolling globally for high-grade IDH1-mutant glioma, aims for a 2029 readout with no interim analyses currently planned.
• Grade 3 Oligodendroglioma Cohort -- Enrollment initiated for a 40-patient phase 2 cohort on sacrocitinib, targeting an ORR primary endpoint with results anticipated by 2027.
• Drug-Drug Conjugate (DDC) Platform -- NUV 1511 program discontinued in Q4 after "valuable insight" generation, with refocused preclinical DDC candidates expected to yield updates by year end.

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RISKS

• "the majority of our NPS, our new patient starts, to date have been later lines, as you would expect. But we are seeing increases in first-line use. But we have also made the point previously that we do not have visibility into the majority of these patients." suggests uncertainty regarding the exact mix of patient lines and corresponding revenue durability.
• "While we expect EMTROJI 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." implies near-term net revenue may lag new patient starts due to high discontinuation rates in late-line cohorts.
• "gross-to-net now sits around 25%, and we would expect this to slightly increase before stabilizing long term," indicating potential short-term margin pressure as more access contracts are secured.
• The SIGMA study’s primary endpoint is progression-free survival with final readout expected in 2029; patients enrolled "have no FDA-approved targeted therapy options," underscoring clinical risk if efficacy is not demonstrated.

SUMMARY

Management confirmed full U.S. FDA approval and a rapid commercial launch for Iptrozi, with prescription velocity well above recent analogs. The company's cash position improved substantially due to ex-U.S. partnership milestone receipts, especially from Eisai and Nippon Kayaku. First-line market penetration remains limited, but a shift toward greater first-line use is expected to drive both longer duration on therapy and future revenue stacking. Large-scale pivotal programs for sacrocitinib are underway, with management highlighting both unmet clinical need and a multi-year timeline for readouts. The discontinued NUV 1511 provided learnings being applied to preclinical DDC assets, which are expected to see further development updates within the year.

• Enrollment is ongoing in global pivotal and non-pivotal studies of sacrocitinib, targeting IDH1-mutant glioma patient segments not addressed by current approvals.
• Milestone payments and royalties from international partners form a growing portion of non-U.S. revenue, strengthening future financial flexibility.
• Management cited targeted initiatives to improve first-line adoption by leveraging patient identification, genetic testing, and payer coverage expansion for Iptrozi.
• Gross-to-net adjustments are expected to increase modestly as payer negotiations progress, with management emphasizing focus on sustained revenue recognition and expense discipline.

INDUSTRY GLOSSARY

• TRKB: Tropomyosin receptor kinase B, an oncogenic protein implicated in tumor growth and metastasis, modulation of which may impact CNS disease control and drug tolerability in cancer therapy.
• Gross-to-Net: The percentage difference between gross revenue and net recognized revenue, reflecting allowances, discounts, rebates, and payer contractual provisions.
• DDC (Drug-Drug Conjugate): A therapeutic modality combining a targeting small molecule with a cytotoxic or functional warhead for enhanced specificity in cancer treatment.
• IDN: Integrated Delivery Network, large healthcare networks including both hospitals and physicians, often referenced regarding patient access and drug uptake in institutional settings.
• TKI: Tyrosine kinase inhibitor, a class of targeted therapy commonly used in oncology; referenced here as prior-treatment category for patient stratification.
• NCCN: National Comprehensive Cancer Network, which issues treatment guidelines frequently cited to influence practice and payor coverage decisions.

Full Conference Call Transcript

J.R. DeVita: Thank you, and good afternoon, everyone. Welcome to the Nuvation Bio Inc. fourth quarter and full year 2025 earnings conference call. Earlier today, we released financial results for the quarter and year ending 12/31/2025, and provided a business update. The press release is available on the investor section of our website at investors.nuvationbio.com, and a recording of this conference call will also be available on our website following its completion. I would like to remind you that today's call includes forward-looking statements, including statements about the therapeutic and commercial potential of the iprtrozia and acitinib, 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-Ks, 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 Iptrozi and Philippe will discuss our financial, partnering, and operating updates.

David will then conclude with closing remarks. I will now turn the call over to Dr. David Hung. David?

David Hung: Thanks, J.R. Good afternoon, everyone. Thank you for joining us. 2025 was a pivotal year for Nuvation Bio Inc. And I am 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, atrozy, indicated to treat people living with advanced ROS1-positive non-small cell lung cancer, or NSCLC. Since then, we have been working tirelessly to bring atrozy 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 Prozyn is becoming the new standard of care for ROS1-positive NSCLC.

By the end of 2025, 432 new patients started Iptrozi, including 216 in the fourth quarter. Per IQVIA data, patients are being prescribed iptrozia 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 from 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 failed a TKI, those currently on a TKI who have switched to Ipzrozee, 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 health care providers, and results from our market research have consistently been overwhelmingly positive. Since launch, we have learned that Introzy’s efficacy profile resonates strongly with physicians. And equally important, its safety profile, especially its limited CNS toxicity, may allow early-line patients to remain on therapy for years. This is essential in a space where long-term duration of therapy is paramount. As I mentioned and consistent with this feedback, we continue to see switches to Uptrozi from all three of the other therapies approved for ROS1-positive lung cancer.

The reasons for these switches include disease progression, tolerability challenges, brain penetrance, and physician confidence in the strength of atrozy’s clinical data, particularly in the durability of response. I am 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 on, most importantly, 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 atrozy. 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 medicine. We also plan to present additional long-term IMBRUXI data at multiple medical conferences in 2026.

As a reminder, on our prior earnings call, we reported that as of August 2025, Introzy’s median duration of response has now reached 50 months in a pooled analysis of TKI-naive patients in the TRUST-1 and TRUST-2 pivotal studies, a population in which Trozy has previously shown an 89% confirmed overall response rate, or ORR. We believe these long-term ENTROZA 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 opigenic mutations, making the results with atrozy, 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 Introzy’s unique balance of activity against two important targets, ROS1 and TRKB. If Truzi is 11- to 20-fold more selective for ROS1 over TRKB, and remains strikingly potent against ROS1 with picomolar-level inhibitory activity. But importantly, Ibn Trosi also has measured inhibitory activity against TREC B. 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 optogenic 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, with brain metastases, as 36% of newly diagnosed patients present and 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 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. 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 path if that pathway is not inhibited sufficiently. However, too much inhibition has been shown to lead to neurological side effects. Iptrosy 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 eptrozy does have adequate activity against TRKB, this inhibition is measured enough that its dizziness rate is similar to that of crizotinib, a drug that does not 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 Satelli hypothesized that this selectivity could make atrozy the best tolerated next-generation ROS1 inhibitor. And we believe that Trozi’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, a 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, iptrozi strikes a particularly effective balance: deep, durable inhibition of ROS1 paired with measured CREP 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 atrozy is lorlatinib in ALK-positive NSCLC, which showed a median progression-free survival, or PFS, of over five years in the CROWN study. Zolatans has even greater TRKB inhibition than iptosi, 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 and five-year duration of response. We do not view the shared prolonged durability of lorlatinib and amtrozia as coincidental.

Taken together, we believe ibtrozia’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 ipchozy for a broader ROS1-positive lung cancer population. Based on our label, Iptrozi has been prescribed to a significant number of patients in the advanced setting across lines of therapy, and 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-4, a randomized, placebo-controlled phase 3 study evaluating telotrectinib 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 who have undergone surgery often feel healthy and are understandably unwilling to remain on a 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 setting. We believe it is particularly meaningful that eptrozi 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 iptrozi may provide benefit in the adjuvant setting.

Lastly, we not only aim to bring iptrozi to patients across the ROS1-positive disease spectrum, but also to patients and providers around the world. Last year, we received approval for iptrozia in China with 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 iptrozy in Europe and other ex-U.S. territories outside China and Japan. We are working diligently with Eisai to submit iprozi for approval in Europe in the first half of this year.

In short, we believe our continued launch performance, the latest updates reconfirming Ipetrozy’s efficacy and tolerability profile, and additional development, regulatory, and commercial achievements all show why we believe that Prozyn is becoming the standard of care for ROS1-positive lung cancer.

We also made exciting progress developing our second program, sacrocitinib. Sacrocitinib is an inhibitor of mutant IDH1 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. The 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 an oligodendroglioma or an astrocytoma. Both descriptors together indicate the level of risk, aggressiveness of 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., 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 vorasitinib, which was approved by the U.S. FDA in August 2024 for only patients with grade 2 oligodendroglioma and grade 2 astrocytoma, for the low-grade population.

In its pivotal INDiGO study, which included 168 grade 2 patients with non-enhancing or low-risk disease in the active study arm, vorasitinib demonstrated a median PFS of 27.7 months, a 41% progression rate at 24 months, and an ORR of 11%. In a separate phase 1 study of 30 patients, orocitinib 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 2 study of sapacitinib for low-grade IDH mutant glioma were published in Neuro-Oncology. This patient population was treated with sacusitinib 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, saclucidim demonstrated a median PFS not reached, a 12% progression rate at 24 months, and a confirmed ORR of 44%. As a reminder, in a phase 1 study of 35 patients, saclucidiv also showed a 17% confirmed ORR, including two complete responses that lasted multiple years in a high-grade enhancing population. As we have discussed previously, vorasitamab 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 of study designs, patient populations, endpoints, and sample size, recently published data in Neuro-Oncology from our phase 1 study highlight the encouraging clinical profile of saplusinib and its potential to address significant unmet need in this patient population.

In parallel, we continue to learn more about savvocitinib’s safety profile. While the drug is generally well tolerated, we observe 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 sapucitanib, and we continue to investigate if sapucitanib may inhibit targets other than IDH1. Importantly, the drug-related discontinuation rate in the phase 2 study conducted at the pivotal 250 mg twice-a-day dose remains low at approximately 8%. The patients who 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 3 study called SIGMA. This global randomized study is evaluating the efficacy and safety of sacrosanctin aversal placebo as 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, and 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 sacrocitinib, 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 saprocitinib 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 or 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 to the cumulative toxicities associated with prolonged radiation and chemotherapy, given their relatively young age at diagnosis and median life expectancy of 12 to 14 years. 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 sacrocitinib as an ideal complement to Iptrozine 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 for our evaluation of sapacitinib 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 ADC, NUV 1511, in the fourth quarter, we were able to gather valuable insight 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 will turn it over to Colleen to provide more color on the launch of Iptrozi.

Thank you, David, and good afternoon, everyone.

Colleen Sjogren: I am excited to report that the launch of Trozy 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 iprzy, 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 patients currently treated with ROS1 TKIs, 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 Eptrozy’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 Natuzzi for their patients. Prescriptions have been written in 100% of our 47 sales territories by multiple repeat prescribers and, 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, Nuvation Connect, continues to help eligible patients receive support and access to Iptrozi while reimbursement is secured.

Now I would like to walk you through some of the key dynamics of our launch to further characterize where we are today and what lies ahead. As we have noted, Imtrozia 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 iptrozine for an extended period, which we are now starting to see. Still, it is typical at the beginning of any oncology launch that the majority of patients who start therapy are in need of a third, even fourth medicine and their response and duration of treatment will unfortunately be lower.

While we expect EMTROJI 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 iptrozi patients, we do have some insight into the segment of patients that come through our Nuvation Connect support program and specialty pharmacies. Within this group in 2025, we know that about 75% of discontinuations came from later-line populations. We are encouraged that IMPROSAY is providing another meaningful option for patients across lines of therapy, and the patterns we have observed through this experience have given us three important insights. First, discontinuation is strongly correlated with the line of therapy. If Truzi 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 iptrozi 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 at Trozi and our net product revenue growth from the third to fourth quarter. As I mentioned, this late-line population 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 iprzy shift to those who are newly diagnosed. Lastly, first-line iptrozi patients are the main driver to our long-term growth. And the reason we are so optimistic about our launch is because we continue to see a meaningful, steady increase in first-line patients starting on Neptrozi in recent months. Our data, including the number of previously treated patients in the market, suggests 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 Iptrozi over multiple quarters going forward, and we plan to elaborate further on this trend as we gather more data in 2026.

Switching to another key area of our launch dynamic, 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 fusions, the annual addressable population could potentially expand to roughly 4,000 advanced patients in the U.S. alone. Because of atrozy’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 Iptrozi 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. With that, I will now turn it over to Philippe.

Philippe Sauvage: Thanks, Colleen. Good afternoon, everyone. For detailed fourth quarter 2025 financials, please refer to our earnings press release, which is available on our website. Now I will go over some important highlights from the quarter. I am pleased to inform you that in the fourth quarter, we generated $41.9 million in total revenue, including receipt of a milestone payment, bringing our total revenue for 2025 to $62.9 million. These figures include $15.7 million and $24.7 million in 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 Yuktrozy as a third-line plus option, but 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 eCrosi is what makes us extremely optimistic about our long-term growth. As this occurs, we will 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 they would, and today, we believe our specialty pharmacy and distribution partners hold approximately two to four weeks of inventory on hand. This is standard and shows that our product revenue has been driven by true patient demand for our therapy. In addition, our free trial program continues to provide patients with iprosis before they are fully reimbursed, and these prescriptions generate 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 fee-for-service plans, and the limited amount of free medicine provided today. The remaining revenue for 2025 came from our collaboration 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 the milestone payment of $25 million.

We also continued our mission to bring Introzy to as many patients as possible outside of the United States. In January, we announced a 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 a proxy 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 New Jersey; importantly, we are focused on bringing tafasitidine 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 in our term loan agreement with Sagard Healthcare Partners until 06/30/2026. A robust capital position gives us the 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 Enhance. 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 will now hand it back to David.

David Hung: Thanks, Philippe. As I take a step back and reflect on 2025, what gives me particular confidence is the foundation we have 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 am incredibly proud of the team and grateful for the support of our investigators, partners, shareholders, and, most importantly, patients, as we continue this journey to 2026. With that, I will ask the operator to open the line for questions.

Operator: At this time, we will begin the question-and-answer session. To ask a question, please press star-one on your telephone keypad. The first question comes from the line of Farzin Haque with Jefferies. You may proceed.

Farzin Haque: Congrats on the progress and thank you for taking my questions. You are 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 $150,000,000 for the year.

David Hung: Farzin, thanks for the question. This is David. So as we said, we feel that the patients are out there. We think that the robustness of the first two quarters shows that we are able to capture a significant number of these patients just if you look at the number of new patient starts. I think the trajectory has been pretty good. As we did say, the majority of our NPS, our new patient starts, to date have been later lines, as you would expect. But we are seeing increases in first-line use.

But we have also made the point previously that we do not have visibility into the majority of these patients because unless they come to the Nuvation Connect portal, we do not actually necessarily know what we need to know about them to know what line of therapy they are. But from what we have seen, we do see a majority of our use currently in later lines of therapy. Hopefully, those are not the ultimate prize. Those patients, especially in the third-line setting, have relatively short durations of response, and so that would lead to a much higher discontinuation rate. In fact, the vast majority of the discontinuations that we have seen are due to these late-line patients.

But we are confident that over time, we are going to see growth moving toward the second-line and then to the first-line setting. And so we think that the patients are there, and we think that ultimately we will start to see first-line use much longer and then the revenue stack that we previously talked about.

Farzin Haque: Perfect. And then for stephucid, can you provide an update on the current enrollment project for the phase 3? And do you anticipate any interim analysis before the projected 2029 completion?

David Hung: You know, we have not commented on our enrollment. Those patients are definitely there. As you know, there is absolutely nothing for high-grade disease. Vorasitinib is 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 is going to take a while to get the number of events we need to see it, to see the results. So that is why we have guided to a 2029 readout for that. But, you know, 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 will not be any later than 2029 in reading that result out. And also, we do not have any plans right now for interim analysis, so I just forgot to mention that.

Operator: The next question comes from the line of Leonid Timashev with RBC. You may proceed.

Leonid Timashev: Hey, guys. Thanks for taking my question. I just want to ask a little bit more about the Atrozy trajectory. I guess in the fourth quarter, there is potentially some seasonality, maybe changes in diagnosis. Both have been a historically weaker quarter for lung cancer drugs, I guess? How should we think about the seasonal bounce back we should see in 2026? Is any of those, you know, maybe weather-related seasonality is 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: You know, the dataset that we discussed, the seasonality was still based on just ROS1 TKI use in the last four years. So while there was a somewhat lower use in the fourth quarter, I would say it is hard to know if that would necessarily predict what is going to happen going forward. We feel confident the patients are there. We know that from just our interactions with all the centers that we are at, these patients are there. We think that while there are always ways to improve the amount of genetic and genomic testing, we think that new patient diagnosis will happen.

We know there is a prevalence pool of over a thousand patients who are TKI experienced. Clearly, those are the ones that are going to be the easiest ones to identify because they have already been on a ROS1 agent. And clearly, we have already captured a significant number of those. But I do not really know if the seasonality will necessarily result in a bounce back. It could, but I cannot tell. And also, as you know, we just had a significant blizzard recently. So, you know, that was a pretty significant weather event, but I do not, again, know if that will change anything.

Operator: The next question comes from the line of Michael Yee with UBS. You may proceed.

Michael Yee: Hey. Thanks, guys. This is Matt on for Mike. I wanted to ask on your expectations, just kind of for the 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. Thank you.

David Hung: Sure. Well, you know, you have already seen from the first February that we are over 200 new patient starts per quarter so far, and we think that is going to continue. And I have already said that the majority of those are later-line therapy. So if you talk about second or third line, we have already captured a significant amount of the, you know, about a thousand TKI-experienced patients that we believe are out there. So by the end of the year, we think that we will have probably captured a significant majority of all of those patients.

And as I said, what we are looking for is growth in the first-line setting, and given our 50-month duration of response, which is unmatched, and our tolerability profile, we would expect to claim the majority of that. So that is what we are really looking for. We are not really looking any more at later-line use because that is, you know, we have been there, and we have captured much of that. But we are looking towards first-line growth, and that is what everyone should be focusing on. I think one of the most compelling features of our drug is its durability.

As you know, patients and doctors decide on therapy based on efficacy, and by far the most important metric for efficacy is how long that drug will work. We think that TRKB is an important factor in durability. If you look at the lorlatinib data, there is no TKI with longer median PFS than lorlatinib in the CROWN study, which is over five years. And lorlatinib has significant TRKB activity. And if you look at CNS control rate, it is really high.

And as you know, for a cancer like ROS1 lung cancer, which is so CNS tropic where it starts in the brain more than a third of the time and goes to the brain another 50% of the time, it is really important to have as robust control of CNS as you can, and we think that TRKB will play a significant role there. And as I have already discussed previously, we look at our intracovenant response rate in our second-line setting of 66%. That has not been matched. There is nothing close to that. So we think that the profile of this drug is extremely compelling, the tolerability, the efficacy.

We are looking to move to first line, and we think that is where the unmet need will persist after we have, you know, taken care of the later lines of therapy, which we are capturing. So we feel bullish. You know, we feel we are just where we need to be, and things are heading in the right direction.

Operator: The next question comes from the line of Barry Coleman with Clear Street. You may proceed.

Barry Coleman: Yes. Good evening. Thanks for taking my questions, and congratulations on the progress. For telotrectinib, Ibaroprozy, just in general, how much adoption of TKIs in the first-line setting have you observed following the NCCN guideline changes in the community setting or community practices? And what factors or initiatives could further drive first-line use of Epcrosy there, and I have a couple after that for—

David Hung: Sure. So we did note that if you look at the other TKIs before we were approved, we actually did see an increase in switch 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 Introzy to the market after our approval, we have seen, you know, clear growth, and from the little glimpse that we see, we have been seeing increasing first-line use, but, again, our glimpse into that window is so limited at this point. I do not, you know, I cannot really speak in detail about it.

We will 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. You know, just the amount of IO/chemo used before those new guidelines was significant, and even after the guidelines, we still think that is a challenge, but I think that now that IO is actually contraindicated, I think that is only going to help drive the appropriate therapy. And as I have said earlier, there is no other therapy that can match our metrics on efficacy or even tolerability.

So I think that we are well positioned to capture this, and I think the NCCN guidance will be a significant tailwind. But, you know, I think the greatest tailwind we have is just the strength of our label.

Barry Coleman: Alright. That is helpful. And for the phase 3 astrocytoma trial, what efficacy outcomes would be considered both clinically meaningful and commercially attractive? And what is the kind of, like, estimated market opportunity or value that it can provide? And, for, you know, 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? Thank you.

David Hung: Yeah. That is 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 on each side, both the low and high grade have low-risk and high-risk features. Currently, vorasitamab is only approved in one of those pieces of that pie. It is 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. So the phase 3 study that we are doing targets three of those boxes, three pieces of that pie.

Instead of the vorasitinib one piece, our phase 3 trial targets three of those pieces. So we think that is a very significant unmet need for patients. It is clearly a much larger commercial opportunity. And so to get that drug approved in those three pieces of that pie, we have to do a progression-free survival study, which is why we just need to enroll a certain number of patients. We have to follow them for a certain amount of time, which is why the readout is 2029. Now that said, we also think that it is important for us to get this drug out to patients as quickly as possible.

And there is yet another piece of that pie that is not currently being adequately addressed, which is if you look at all your grade 3 oligodendroglioma patients, these patients are a little bit different because unlike the phase 3 study patients which I talked about, those patients have completed surgery and radiotherapy and somewhere between six and twelve cycles of temozolomide. So as a result, they do not tend to have measurable disease. When you do not have measurable disease, you have to use PFS. You cannot use response rate. Well, clearly, ORR is a much faster readout than PFS. So the grade 3 oligodendroglioma study is important because those patients have measurable disease.

These are patients, you know, who have not had a resection, not a recent one, have in general significant measurable disease, and they just cannot take—because these patients can live 15-plus years—they just cannot take chemotherapy or radiotherapy every day for the next 15 years. I am going to—would just be impossible to tolerate that. So we think it is a huge unmet need. But because now these patients have measurable disease, we can use overall response rate. Unlike the SIGMA phase 3 study, which is a PFS readout, this will be an ORR readout, an overall response rate readout by RANO 2.0 criteria.

So we think that if we can see a significant response rate in that study that we have guided to reading out by 2027, clearly, that is a much earlier readout. We know there are examples of other glioma drugs being approved on a very small dataset with response rate. We know that a glioma drug was approved on fewer than 80 patients with an overall response rate. So clearly, if we see a really robust response rate, we think that would justify discussion with FDA as to what it would take to get this drug approved to get it to patients a lot sooner than our readout in 2029 for the phase 3 study.

So I think that it is important to do the study as, number one, it is a really important unmet need. These patients just cannot take chemo and radiation for 15 years. That is just not tenable. They need something that is much better tolerated, much more convenient. And secondly, it gives us an opportunity to see the activity of this drug in an area where nothing else works. For vorasitinib, in this high-grade population, the response was literally 0%. We think that it will give us an opportunity to look at the response rate of this drug and potentially initiate a discussion with FDA to figure out how to get this drug to patients even earlier.

We also think that generating data in this subset where nothing works and even has a 0% response rate will compel physicians and patients to think, hey, this is a drug that has activity where nothing else does. Is this a better drug? Is it a more powerful drug? Is it doing things that other drugs cannot do? And we think that could potentially influence the glioma market and the practice of what physicians and patients decide to use or attempt if they are treating a disease that has relatively few treatment options and is still, at the end of the day, an invariably lethal disease.

So we think that the second study is a very important study for all of those reasons.

Operator: The next question comes from the line of Mayank Mamtani with B. Riley Securities. You may proceed.

Mayank Mamtani: Yes. Good afternoon, team. Thanks for taking our questions, and congrats on the progress. Appreciate the level of detail on 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 those 200-patient quarterly run rate to sort of continue in the coming quarters, including perhaps when there is a competitor entrance later in the year? And also, what is the real-world discontinuation you are seeing in earlier line? I know you gave the 75% discontinuation rate in later line, but was just curious if you had something in frontline. I understand the sample size would be small there.

Then I will follow up.

David Hung: So, you know, we have said since the first quarter that we reported sales that we would continue to look at new patient starts. I think that is an important metric. It is 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, if you are a third-line patient and you discontinue in a month or two, you are not going to have the kind of revenues that you would expect in the first-line setting.

So we think it is 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 I think that is the best metric: are patients using this drug; do physicians want to prescribe it? And over time, what you will see is that—we have said there are only about a thousand or so TKI-experienced patients—so if you continue to see 200 patients per quarter, and we know that at some point we are going to have captured the majority of that thousand patients, that means any growth at all in that 200 number has to be in first-line patients.

And while that revenue may not appear immediately, if it takes you a year to get stacking, when you start to see that growth in first line, you will see, over time, revenue stacking, and you will also see significant increase in revenue. It is just not going to happen immediately, because those third-line patients are going to come off. Some of them, you know, discontinue within a month. And we think those first-line patients will be on for 50 months. So, you know, I think that for the next couple quarters, we still think NPS is important.

But, you know, by a year into our launch—so by third quarter of this year—we will have been doing this for a year. If we continue to get 200-plus patients per quarter, and the majority of those are TKI experienced, that means we will capture the majority of the TKI-experienced market. So any growth at all in that NPS number has to, by definition, be in first line. So I think that is what you should be looking for. I think the revenues will catch up to NPS with a few more quarters. It is just not going to do it right away, but that is what you would expect.

Mayank Mamtani: On the discontinuation on the earlier line—

David Hung: Oh, yeah. Sorry. So 75% of our discontinuations came from late-line patients. So very late—oh, for the patients that we know of—

Philippe Sauvage: And as David said, a subset of patients, the ones that were going through the hub. So for 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, yeah, the main patients who will discontinue are purely later-line patients. If you go back to our clinical trial, rate of discontinuation was very low, as you know, 6.5%. Right? So this is really what we are going to see. We are 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 is true in oncology.

And what we have seen in our subset going through the hub is that those are the most discontinuations we see.

David Hung: By far.

Mayank Mamtani: 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 actual approval discussion? Sorry if I missed that. Thank you for the—

David Hung: Yeah. I think that we have seen ORR anywhere north of 20%. I mean, this is a population, as you said—the biggest glioma drug in the world, rorasidenib, has a 0% response rate in that population. So, you know, could it be lower? Maybe. But certainly at 20% or higher, I think that would be extremely interesting.

Mayank Mamtani: Got it. Thank you.

Operator: The next question comes from the line of Gregory Renza with Truist. You may proceed.

Gregory Renza: Great. Thanks. Good evening, Dave and team. Congrats on the progress. Thanks for taking my question. David, just maybe on your current resource position. As you have commented on the current financial structure and also the path with the TROZI launch, maybe providing that path to potential profitability. Just wondering if you could provide a finer point on maybe what that horizon looks like. And related to this, as you have spoken about business development, you have mentioned the complementarity that the Abtrozi and Saphu provide for the pipeline. How are you thinking about adding to that mix, especially in light of that focus or that mention of profitability? Thanks so much.

David Hung: So 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 $150,000,000 with Sagard with another $50,000,000 in debt. And then since then, we have done a deal with Eisai where we got another million, and we will have yet another $30,000,000 upon European approval submission or approval next year. So, you know, we stand by that statement. We have certainly far more cash than we need to get to profitability now. If we do a significant business development deal, that would, you know, certainly take some cash.

But we are aware of the importance of getting to profitability without having to need additional financing. These are still difficult markets. I think that, in general, we have been relatively conservative on that front. So, you know, we will carefully weigh the upside of a deal, and certainly, any deal we do would have to be what we consider a good deal—as, you know, as we consider the Anhara. We think that was a great deal for us. So any further business development will have to be a great deal for us, and we have to weigh the benefits and cons of using our cash and cutting into our runway to profitability.

But we feel very, very confident that we will get to profitability right now, easily with what we have on hand. We do believe that, given what we have, we think that further business development is important. It has always been an important part of our company growth historically. And we think we will continue to look for opportunities that we think are particularly compelling for us, especially if they can capture some of the synergies that we already have within our company.

Gregory Renza: That is great. Appreciate the 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 in the year. Just maybe remind us of your conviction on the platform as you invest in that area of the business.

David Hung: So we are absolutely convinced that platform is real and has real potential. We know that 1511 was a first-in-class compound—it is effectively a first-in-history compound, actually—so we, you know, we learned a lot with 1511 and it was not that we did not see any responses at all. We did see responses with 1511. They just were not consistent enough for us to invest $100,000,000, ultimately, in a phase 3 study. You know, we look at all our drug candidates as: would this be worth spending $100,000,000 on, or should we make it better? And it is something you always have to balance in early-stage programs. So the answer for 1511 was probably not.

And we learned enough to figure out how to make it better or to make a DDC better. And we are hard at work doing that. But 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, and we will update you all hopefully by year end this year. Great. Thanks again.

Operator: The next question comes from the line of Yaron Werber with TD Securities. You may proceed.

Yaron Werber: Thank you very much, team, for the question. This is Steven on for Yaron. On the Intrusive 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 use? Have you engaged regulators to try to perhaps get a preference in the 1L setting in the NCCN guidelines? And if so, how is that going? And secondly, any update or perhaps any news on the DET 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 is no longer the case. Can you maybe update on the thinking there? Thank you very much.

David Hung: Sure. Let me take the first couple questions, and I will hand to Colleen. So crizotinib is still used a significant amount 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 malpractice to use crizotinib in the first-line setting when you do not really know which patient is going to go on to develop a CNS event. First of all, 36% of them present with a brain met. But even if they do not, we know that 50% of them will go on to get a brain met.

I cannot tell which one of two is going to do that. And to give a drug that does not have any CNS coverage, in my opinion, as an oncologist, is malpractice. I think that is inappropriate for patients. So I cannot comment on, you know, how long crizotinib will be entrenched. I think that KOLs and patients appreciate the importance of CNS coverage, and I think that is part of our job, and Colleen’s team is—you know, that is one of our main messages. I think we have to continue to do that.

So I cannot tell you that crizotinib will go away, but I do think that 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 do actually believe that our drug is differentiated, and we are looking at strategies to have that captured within the NCCN guidance. So on that, I would say, you know, stay tuned on that. But we are well aware of the difference in performance metrics of our drug against other drugs.

So we think that Iptrozy is an extremely compelling choice for patients and physicians, and we think that should be adequately reflected in all the sources that are available for patients and physicians. And so, you know, that is not lost on us. Colleen?

Colleen Sjogren: Yeah. Hey, Steven. And I just want to elaborate a little bit more. So David spoke about the patients that we are receiving that have been pretreated and, obviously, progression, toxicity, as you just spoke to, brain penetrance. So in addition to those patients, we are also looking to expand the market. And you asked what else can we do? I will tell you that it is our personal mission—that we take it very personally—that these patients that have ROS1-positive non-small cell lung cancer are going through their patient journey in the appropriate way. And one of those ways is to ensure that they are being tested before a treatment decision is 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, and I spoke about also earlier DNA testing being very, very important to understand the actionable mutations before a treatment decision is made. So in addition to us getting patients that are being switched off other TKIs, we are definitely growing the market and helping to educate more on the importance of understanding the entire picture before a treatment decision is made.

Steven (for Yaron Werber): And then on 868? And then the European approval?

David Hung: So on the European side, we do not believe that any additional clinical trials will be needed, and we will give you more details once the MAA is submitted. On 868, you know, there has been some interest in that compound, so I think we are looking at all our options.

Operator: The next question comes from the line of Silvan Tuerkcan with Citizens. You may proceed.

Silvan Tuerkcan: Yeah. Good afternoon, and thanks for taking my question. I just wanted to ask, did the gross-to-net, the pricing, stabilize at this point? And then can you share where that is coming out? And if you have any idea where that will end up? Thank you.

Philippe Sauvage: Yeah. Thanks for your question, Silvan. So 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 bit beyond that. To say exactly when it is going to stabilize is always a very difficult question, because it all depends upon negotiation with payers, obviously. But, yeah, we think that we are in a very good place in terms of access, which is what we wanted.

We really wanted to make sure that all patients that needed that access before the end of the year were covered, and we think that doing all of that will take us probably a little bit further up, but not so high. I will not probably give you much more detail than that. But, yeah, we are still going to increase that gross-to-net a little in the coming quarters.

Silvan Tuerkcan: Great. Thank you.

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: Thanks so much. We want to thank you for all your support. You know, launches can be anxious. I think everyone has been looking at our numbers. We have gotten some feedback that some people might have been disappointed with the gap they perceived—we perceived—between new patient starts and the revenue number. This is to be expected, as you know, in launches, especially in oncology, and as an oncologist, I can tell you that, you know, late-line patients get started first. They are the ones that are out of options, but that pool is already identified. This is a prevalence population. It is hard to find a new patient.

So when you get those late-line patients, they are going to discontinue faster. I would say just be patient. It is all going to happen. We are 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. So I want to thank all of you for your continued support, and we look forward to updating you further on our next call.

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

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