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DATE
Monday, May 4, 2026 at 4:30 p.m. ET
CALL PARTICIPANTS
- Chief Executive Officer — David Hung
- Chief Commercial Officer — Colleen Sjogren
- Chief Financial Officer — Philippe Sauvage
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TAKEAWAYS
- Total revenue -- $83.2 million, including both product and collaboration/license revenue sources.
- Iptrozy net U.S. product revenue -- $18.5 million, showing 18% growth versus the prior quarter, attributed to a higher proportion of first-line patient starts and sustained therapy duration.
- First-line patient starts -- For the first time since launch, more than 50% of new Iptrozy patients were TKI-naive, compared to about 30% in the third quarter last year, demonstrating a clear shift in patient mix.
- New patient starts -- Approximately 200 new patients initiated Iptrozy for the third consecutive quarter, bringing total starts to over 600 since launch.
- Median duration of response in TKI-naive patients -- "In TKI-naive patients in TRUST-1, as recently published in the Journal of Clinical Oncology, median duration of response and median progression-free survival have both now increased to approximately 50 months, or more than four years."
- Adverse events leading to discontinuation -- 6.5% of 337 pivotal-study patients discontinued Iptrozy due to any adverse reaction, with only 0.3% stopping because of the six most common adverse events.
- Gross-to-net discount -- Gross-to-net discount increased a few percentage points at the start of the year, now expected to stabilize in the high-20% to approximately 30% range.
- Collaboration and license revenue -- $64.7 million, including nearly $60 million upfront from Eisai and $1.7 million in royalties from partnerships in Japan and China.
- Operating expenses -- $73.5 million, consisting of $35.0 million in R&D (driven by SIGMA and TRUST trials) and $38.3 million in SG&A (primarily from commercial launch).
- Cash position -- $533.7 million in cash, cash equivalents, and marketable securities at quarter end, with $50 million undrawn from an existing term loan facility.
- Iptrozy adoption -- 100% of the top 50 historical TKI accounts in the country have prescribed Iptrozy. Broad account adoption is an important indicator of launch strength, and, when paired with favorable placement on pathways and formularies, reinforces the belief that institutions recognize the differentiated clinical profile of Iptrozy.
- Iptrozy physician awareness -- Aided awareness among target physicians reached 97%, supporting breadth of commercial reach.
- Safusitinib Japan rights -- Exclusive rights to safusitinib in Japan were acquired from Daiichi Sankyo, allowing planned expansion of the pivotal SIGMA study and reinforcing global program control without altering the cash runway.
- China commercial uptake -- Sales from Innovent’s Iptrozy launch in China increased rapidly after January NRDL listing, with new patient starts and net revenue exceeding internal expectations.
- Upcoming clinical data -- New data on patient-reported outcomes from the TRUST program and results from the ongoing TRUST-4 study will be presented at ASCO in June.
SUMMARY
Nuvation Bio (NUVB 1.78%) reported expanding first-line use of Iptrozy, with new starts now predominantly TKI-naive, supporting increased durability and revenue stacking. Management confirmed operating expenses reflected increased investment in ongoing pivotal programs, while royalties and upfront payments from global partners contributed substantially to total revenue. Commercial penetration of Iptrozy was reinforced by full adoption among the top TKI accounts and almost universal physician awareness. China revenue and patient starts outperformed internal expectations following national reimbursement access. Safusitinib’s Japanese expansion further consolidated ownership of global rights, enabling integrated late-stage development in high-need glioma populations.
- Management noted an expected decline in late-line patient starts as earlier-line usage rises, attributing the trend to both clinical outcomes and underlying patient diagnostic dynamics.
- Total U.S. addressable market for advanced ROS1-positive NSCLC patients remains constrained by low community molecular testing rates, with improvement initiatives directly targeting these gaps to support future volume growth.
- Net product revenue growth continued despite a higher gross-to-net discount, driven by increased first-line duration and a shrinking late-line patient pool.
- Collaborations and milestone structure, including a $30 million anticipated Eisai payment for future European approval, are factored into ongoing liquidity planning without the expectation of further external financing needs.
- Company plans to shift external reporting focus from new patient starts to realized revenue as first-line therapy drives longer-term cumulative growth.
INDUSTRY GLOSSARY
- TKI-naive: Patients who have not previously received a tyrosine kinase inhibitor as cancer therapy.
- Gross-to-net (GTN): The percentage difference between total product sales at list price and actual revenue realized after discounts, rebates, and allowances.
- TRUST program: Nuvation Bio’s pivotal trial series evaluating Iptrozy in ROS1-positive non-small cell lung cancer across various settings.
- SIGMA study: The Phase 3 pivotal trial evaluating safusitinib for maintenance therapy in IDH1-mutant glioma.
- NRDL: National Reimbursement Drug List; the official listing of drugs covered and reimbursed nationally in China.
- CNS guideline: Clinical recommendations from the National Comprehensive Cancer Network for the management of central nervous system metastases in cancer patients.
Full Conference Call Transcript
David Hung: Thanks, J.R. Good afternoon, everyone, and thank you all for joining us. Today, I am excited to discuss the progress we have made across our business in the first quarter. Following the line-agnostic FDA approval of Iptrozy in June 2025, we entered 2026 focused on continuing to build a successful commercial launch in ROS1-positive non-small cell lung cancer, with specific focus on educating physicians, supporting patients, and generating new clinical evidence that reinforces Iptrozy’s differentiated profile. Overall, we are very pleased with our continued execution, highlighted by strong demand for Iptrozy and our ability to significantly increase the percentage of new patients treated in the first-line setting.
We successfully treated approximately 200 new patients with Iptrozy in the first quarter, which makes three consecutive quarters of about 200 new patient starts, bringing our total to over 600 since launch. We see a growing trend of more new patients coming from the first-line setting and, in turn, a lower percentage of patients coming from the third-line setting or later. In fact, for the first time since launch, more than half of the new patients who started Iptrozy in the quarter were TKI-naive.
Given the changing dynamics of patient mix and moving from later-line to the first-line setting, and considering the significantly increased durability of Iptrozy in earlier versus later-line settings, we are just beginning to see revenue stack in this quarter, as Philippe will shortly discuss. This revenue dynamic is the most important metric for the launch going forward. Therefore, at some point in the future, we will focus on revenue and no longer report new patient starts.
This has meaningful implications for the long-term opportunity for our brand, especially now given that based on a recent new analysis presented at AACR, Iptrozy has now extended its median duration of response to 50 months in TKI-naive patients in the pooled results from the pivotal TRUST studies. When patients are treated earlier in their disease course, they are often in a better position to realize increased benefit from a therapy with durable efficacy and generally favorable tolerability. Over time, we believe this can build a larger, longer-duration base of active patients on Iptrozy and support more substantial revenue growth. Since launch, our discontinuations have been driven primarily by disease progression in later-line patients.
This is expected in any oncology launch as these patients have already progressed through other approved therapies. From the data that we see, discontinuations in earlier-line patients or for adverse events are consistent with clinical trial results and remain relatively low. As a reminder, and as detailed in Iptrozy’s prescribing information, 6.5% of 337 patients with advanced ROS1-positive NSCLC in our pivotal TRUST studies discontinued therapy due to any adverse reaction. And as we have previously presented, only one of these patients, or 0.3%, discontinued treatment due to any of the six most common adverse events, including liver enzyme elevations, diarrhea, nausea, vomiting, or dizziness.
The feedback we continue to receive from both key opinion leaders and our sales organization has been highly consistent. Physicians are impressed with Iptrozy’s clinical profile, citing the durability and tolerability, and the real-world experience is giving physicians increased confidence to both keep patients on therapy longer and to choose Iptrozy when considering a preferred first-line treatment option. This response further supports our belief in both consensus net revenue estimates for Iptrozy in 2026 and its long-term potential. We are also encouraged by the addition of Iptrozy to the latest NCCN CNS guidelines as a systemic therapy option for ROS1-positive NSCLC patients with brain metastases.
We believe this is an important recognition of Iptrozy’s demonstrated intracranial activity and further supports its differentiated position in the ROS1 treatment landscape. Turning to our recent abstracts and publications, we were thrilled to present updated pooled results from the August 2025 data cutoff of the TRUST-1 and TRUST-2 studies at the American Association of Cancer Research congress, or AACR. These updated data continue to reinforce the strength of Iptrozy’s profile. In TKI-naive patients in TRUST-1, as recently published in the Journal of Clinical Oncology, median duration of response and median progression-free survival have both now increased to approximately 50 months, or more than four years.
As presented at AACR in TKI-pretreated patients, the median duration of response was nearly 20 months in TRUST-2, and the overall survival in the pooled TKI-pretreated population showed a median of nearly 30 months, which is unprecedented in this space. And with this longer follow-up, Iptrozy continued to demonstrate a manageable and consistent safety profile, including lower rates of neurologic adverse events and no new safety signals. We believe these durability data matter not only clinically but commercially. Drugs that combine deep and durable efficacy with a favorable tolerability profile are well positioned to become the therapy of choice for TKI-naive patients, and that is exactly the trend we are seeing in our launch.
With approximately three years of follow-up in the pooled analysis, and more than four years of follow-up in TRUST-1, we believe these data further support Iptrozy as an effective, durable, and tolerable treatment option for patients living with advanced ROS1-positive NSCLC. At AACR, we also presented preclinical work which continues to build on our broader scientific understanding of Iptrozy’s differentiated profile. As I discussed on our last earnings call, Iptrozy is designed to achieve deep and durable inhibition of ROS1 while maintaining measured activity against TRK-B. Our presentation showed two important points. First, talotrectinib has nearly complete coverage of ROS1 fusions at clinically relevant concentrations and is effective against ROS1 resistance mutations.
Second, talotrectinib has partial, yet biologically meaningful, inhibition of TRK-B, while being sufficiently balanced to avoid significant CNS-related adverse events as seen in our clinical trials and real-world experience. Of note, in the same experiment, a TRK-sparing agent failed to control tumor migration and markers of invasion and metastases, which were well controlled by talotrectinib. These data support the concept that some degree of TRK-B inhibition may be required to inhibit systemic progression, prevent the migration of lung cancer cells, and protect against metastases to the brain. This analysis showed that our medicine may have a mechanistic profile which we believe leads to a potential impact on tumor invasiveness and metastatic behavior in patients, while limiting neurologic adverse events.
This balanced approach and ability to prevent resistance could ultimately play an important role in the long-term durable control of ROS1-positive lung cancer, as demonstrated in Iptrozy’s median progression-free survival of over four years. At ASCO in June, we will be presenting additional data from our TRUST program on patient-reported outcomes and our ongoing TRUST-4 study in the adjuvant setting. Turning to safusitinib, we remain very excited about the potential of this program and the opportunity it represents for patients with IDH1-mutant glioma. Beyond its potential clinical importance, we believe safusitinib could address a broad segment of the glioma market and therefore represent a meaningful long-term value opportunity for the company.
Safusitinib is currently being evaluated in the ongoing Phase 3 SIGMA study for the maintenance treatment of patients with IDH1-mutant astrocytoma who have high-risk features following standard of care, and in a non-pivotal cohort with grade 3 oligodendroglioma following surgery. In Phase 1 and Phase 2 single-arm studies, safusitinib has shown very encouraging efficacy signals, including durable responses and prolonged progression-free survival across both low- and high-grade IDH1-mutant gliomas. We think about the glioma market as a pie with four parts: low-grade low-risk, low-grade high-risk, high-grade low-risk, and high-grade high-risk tumors. Today, the only approved glioma drug, vorasidenib, is approved in the low-grade, low-risk glioma setting, and prior data have shown limited activity in enhancing or high-risk, high-grade tumors.
In contrast, safusitinib has shown significant activity in clinical studies across all four subgroups of IDH1-mutant glioma. The safusitinib SIGMA pivotal trial will target three of the four pieces of the glioma pie, enrolling high-grade high-risk, high-grade low-risk, and low-grade high-risk IDH1-mutant glioma patients. We are also exploring potential studies to further develop safusitinib in the final piece of the pie, low-grade low-risk glioma, and we will provide an update on our plans later this year. I would also like to highlight that a November 2025 publication in Neuro-Oncology summarized the Phase 2 study of safusitinib in patients with chemotherapy- and radiotherapy-naive grade 2 IDH1-mutant gliomas as of a 03/10/2023 data cutoff.
Strikingly, as of February 2026, 12 of the 27 patients evaluated in this study remained on treatment with a median follow-up of more than five years. We believe these data continue to support the potential of safusitinib in patient populations with significant unmet need and limited or no FDA-approved targeted treatment options. Importantly, in April, we acquired exclusive rights to safusitinib in Japan from our partner Daiichi Sankyo. With that agreement now complete, we plan to expand the pivotal Phase 3 SIGMA study into Japan, continue to advance the global development program, and pursue presentation and publication of longer-term Phase 2 data so the scientific community remains current on these findings.
Finally, we remain on track to provide an update on our drug-drug conjugate platform by the end of the year. Overall, the first quarter confirmed important points in our 2026 outlook. We are seeing solid new patient demand, improving mix toward first-line use, and continued confirmation of Iptrozy’s encouraging efficacy and tolerability profile in the real world. We believe these trends position Iptrozy well for long-term success while we continue to advance a broader pipeline designed to address significant patient needs and create additional future value. With that, I will turn the call over to Colleen.
Colleen Sjogren: Thank you, David, and hello, everyone. We continue to see strong momentum in the launch of Iptrozy, and we are particularly encouraged by what we have accomplished in just three quarters, especially when viewed against relevant targeted therapy launch analogs. Based on our internal data, we have generated more new patient starts than the prior ROS1 launches combined over the same time period. We believe this early success reflects the compelling clinical profile of Iptrozy and the focused execution of our commercial team. In addition, it represents a strong foundation for long-term value creation.
As David mentioned, new patient starts remained robust at approximately 200 for the third quarter in a row, and this included a greater proportion of patients initiating treatment in the first-line setting. Importantly, our internal data sources indicate that for the first time, over half of new patient starts in the quarter were TKI-naive, compared to approximately 30% in the first full quarter following launch. This continued shift from later-line to frontline use is one of the clearest indicators of the strength of the launch and is in line with what we would expect based on typical uptake trends with new oncology agents.
This gives us confidence in Iptrozy’s long term because these patients respond at a higher rate, have the potential to remain on therapy for years, and contribute to a more durable active patient base over time. This dynamic is also important in understanding the discontinuation patterns we have observed, as we are encouraged by how Iptrozy’s clinical profile has translated to the commercial setting. Discontinuations continue to be concentrated among later-line patients, which is expected given the more advanced disease in this population and exposure to multiple prior therapies.
As we discussed last quarter, most discontinuations are driven by disease progression in later-line patients rather than tolerability, and this dynamic can introduce some variability in near-term revenue even when new patient demand is steady. Importantly, adverse event-related discontinuations remain low and in line with what we observed in clinical trials, reinforcing the strong overall clinical profile of Iptrozy, including its favorable tolerability. Taken together, these observations, along with feedback from both patients and physicians, reinforce our view that Iptrozy is well positioned to serve patients across the ROS1 lung cancer treatment landscape and has not changed our view of the potential for Iptrozy in this setting.
This increasing strength in patient mix and positive real-world feedback on Iptrozy’s treatment profile is matched by expanding adoption across both academic and community settings. We are especially encouraged by the pace of uptake we are seeing, particularly given that ROS1 is a rare disease and the prescriber base is relatively broad. Our commercial efforts continue to translate into strong physician awareness, which we believe is a meaningful indicator of successful launch execution. Based on our most recent market research, aided awareness of Iptrozy among target physicians has reached 97%, underscoring the breadth of our commercial reach and the growing visibility of Iptrozy in the market.
We understand that academic and community customers have different needs, and we have been deliberate in aligning our commercial strategy with the distinct value drivers for each setting. As a result, 100% of the top 50 historical TKI accounts in the country have prescribed Iptrozy. Our broad account adoption is another important indicator of launch strength, and when paired with favorable placement on pathways and formularies, it reinforces our belief that institutions recognize the differentiated clinical profile of Iptrozy. We believe the launch progress we have seen to date also reflects the strength of a team that knows how to win in targeted oncology.
We are seeing our efforts translate into meaningful account and physician traction, the result is an appreciation for the durability that Iptrozy has to offer and the openness to partnering with Nuvation Bio Inc. Taken together, we believe this positions us well to continue building momentum in the full ROS1 market over time. Lastly, we believe there is meaningful opportunity to increase the number of ROS1-positive patients who are diagnosed and treated with a ROS1 TKI today. Publications and data from the field suggest there should be approximately 3 thousand patients with advanced ROS1-positive non-small cell lung cancer diagnosed annually in the U.S. based on DNA testing.
As the field shifts to using RNA- and DNA-based testing together, which may detect an additional 30% of fusions, the annual addressable population could expand to approximately 4 thousand patients. Unfortunately, although effective testing is better in most academic centers, it is currently significantly lower in parts of the community, including below 50% in some centers. To combat this, we have implemented several initiatives to partner with and educate the community on the importance of testing for oncogenic drivers. We strongly believe all patients should have the opportunity to benefit from the prolonged durability and high response rates Iptrozy has shown in the first-line setting, consistent with the NCCN guidelines issued last year.
Improving patient identification is the right thing to do for patients and will be a key driver of long-term value for Nuvation Bio Inc. Overall, we are encouraged by the level of demand we are seeing, the shift towards earlier-line use, and the strength of the launch execution to date. The medical community recognizes that Iptrozy’s long durability gives physicians an important tool and offers patients the potential for long-lasting benefit with a generally favorable safety profile so they can stay on therapy for years. With an experienced commercial team, a clear strategy, and disciplined execution across the launch, we believe we are well positioned to continue building momentum and the long-term success of Iptrozy.
Now I will turn it over to Philippe.
Philippe Sauvage: For detailed first quarter 2026 financials, please refer to our earnings press release which is available on our website. I will highlight a few key points from the quarter. In the first quarter, we generated $83.2 million in total revenue, including $18.5 million in Iptrozy net U.S. product revenue. This represents 18% growth in net product revenue from the prior quarter, which was not only driven by yet another quarter of about 200 new patient starts, but importantly, from a growing population of active patients remaining on Iptrozy due to increasing frontline use.
As you can see on this slide, the number of patients starting Iptrozy in the last three quarters has been consistent; however, due to the percentage of first-line patients increasing from approximately 30% in the third quarter last year to approximately 40% in the fourth quarter last year to now more than 50%, net product revenue has grown from $7.7 million to $15.7 million to now $18.5 million, in spite of an expected uptick in gross-to-net. We expect this trend to continue and also expect the number of new patient starts to increase as more U.S. physicians become aware of Iptrozy and testing rates in the community continue to improve.
As previously mentioned, our long-term success will be driven by the exceptional duration of response with Iptrozy in the first-line setting. We are pleased that the growing number of TKI-naive patients have started our medicine since the early months of our launch. This trend, combined with our ability to grow revenue despite later-line patients dropping off Iptrozy, demonstrates the potential impact of revenue stacking going forward. Lastly, as noted, we did see an expected uptick in gross-to-net discount at the start of the year; we still expect our gross-to-net expansion to gradually stabilize from here.
In addition to product revenue, we recognized $64.7 million in collaboration and license revenue in the quarter, including an upfront payment of nearly $60 million from Eisai pursuant to our partnership, which was announced in January. We also received approximately $1.7 million in royalty payments from our partnerships in Japan and China, both of which are exceeding initial expectations on a new patient starts and net revenue basis. As a reminder, talotrectinib was listed in China’s National Reimbursement Drug List, or NRDL, in January and, since then, sales from Innovent’s launch have increased rapidly.
We believe this significant commercial uptake is due to a greater appreciation for effective testing in China, and we also believe this rate of adoption will translate to the U.S. market as patient identification improves over time. We continue to invest in our business and in our programs, resulting in total operating expenses of $73.5 million for the quarter. R&D expenses were $35.0 million, driven by increased investment in the SIGMA and TRUST clinical studies, and SG&A expenses were $38.3 million, primarily driven by commercialization activities. Turning to the balance sheet, we ended the quarter with $533.7 million in cash, cash equivalents, and marketable securities.
In addition, $50 million remains available under our existing term loan agreement with Sagard Healthcare Partners through June 30. We also expect to receive a milestone payment of approximately $30 million from Eisai upon the approval of Iptrozy in Europe in 2027. Lastly, on the business development front, we announced our partnership with LSI in January to commercialize Iptrozy in Europe and other territories outside of China and Japan, which we discussed on our previous earnings calls. In April, we also announced the agreement with Daiichi Sankyo to acquire rights to safusitinib in Japan.
This transaction made sense to us from a strategic and financial perspective, as it allowed us to fully secure global rights to safusitinib, including ownership of all clinical data and rights to future publications and data generation, without changing our expected cash runway. Acquiring full global rights will reinforce our speed of execution and now allow us to expand our commercial reach to Japan. I would like to thank Daiichi Sankyo for their efforts in developing safusitinib and for their confidence in us to take the program forward to potential global regulatory approvals.
Overall, our capital position continues to provide us with the flexibility to support the Iptrozy launch, advance our pipeline, evaluate additional strategic opportunities, all while maintaining a disciplined approach to spending. We continue to believe we are well positioned to execute on our priorities without the need for additional external financing, even on our current trajectory and operating plan. I will now turn it back to David for closing remarks.
David Hung: Thanks, Philippe. As we move through 2026, we remain focused on disciplined execution, continuing to build on the momentum of the launch, advancing our clinical and scientific understanding of Iptrozy, and progressing our broader pipeline. I want to thank our team for their continued commitment, our investigators, partners, shareholders, and, most importantly, patients and their families for their ongoing support. We will now open the call for questions. I will now ask the operator to open the line.
Operator: We will now begin the question-and-answer session. Please limit yourself to one question and one follow-up. If you would like to ask a question, please press 1 to raise your hand. To withdraw your question, press 1 again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please standby while we compile the Q&A roster. Your first question comes from the line of an analyst with Jefferies. Your line is now open. Please go ahead.
Analyst: Thank you. Congrats on the progress, and thank you for taking my question. Can you comment on whether the growing first-line patients are coming from the academic or the community settings? And then what specific educational field force initiatives have been implemented to accelerate adoption in the high-volume community setting? Right, adoption and basically use over the chemo-IO agent.
Colleen Sjogren: Hey, Farzin, it is Colleen. I will take that one. First, we are very encouraged. We have about 97% awareness right now, and this is uniform adoption of Iptrozy across both academic and community. Most importantly, when we look at historically the top ROS1 accounts—which we have a historical list of about 50 of those accounts—100% of them have prescribed Iptrozy. So we are seeing broad adoption across all channels: academic, IDN, and community. We believe that speaks directly to oncologists being driven by the clinical evidence and TRUST data. It is so compelling that, in each channel, we are seeing really good uptake and adoption.
On your question about specific initiatives to accelerate adoption over chemo-IO, one of the things we are really focused on is testing rates. This is a real challenge, and we are not dismissive of it, but we are also not passive about it. The gap between academic and community testing is very well documented, and, frankly, in some community centers, we are seeing testing rates that still remain below 50%. In our opinion, that is unacceptable from a patient care standpoint and represents a really meaningful community opportunity. What gives us confidence is that we have a targeted strategy in place.
We are partnering directly with community oncology practices, investing in educational initiatives, and directly working with testing platforms to make sure comprehensive molecular testing is the standard of care and not the exception. We believe in the size of this market, we acknowledge the testing issue, and we are addressing it directly.
David Hung: Hi, Farzin. This is David. To add a little more precision, the ability to get first-line patients really depends on them being diagnosed. While we have great awareness in both community and academic centers, testing rates are currently higher in academic centers than community centers. Therefore, the diagnosis of new patients is right now higher in academic centers because that is where more testing is being done. But we have already seen significant improvement in multiple community centers, and we are very heartened by that improvement in testing rates and the awareness that there is a drug that is highly efficacious, durable, and well tolerated to use when those diagnoses are made.
We are excited about the change we have seen in first-line percentage—from about 30% in the first quarter after launch to about 40% and now to over 50%. That is a pretty exciting growth trajectory for us because we think it will allow us to meet our consensus expectations for the year if that were to continue.
Analyst: Thank you so much. Congrats.
Operator: Your next question comes from the line of an analyst with RBC Capital Markets. Your line is now open. Please go ahead.
Analyst: Thanks for taking my question. I wanted to follow up on that a little bit, trying to better understand the dynamics of the new patient starts. It seems like it has been 200 for the past three quarters, and you have laid out a lot of reasons why there should be growing awareness and better testing. I am trying to understand why that has not pulled through into more new patient starts yet. For example, why the proportion is changing towards first-line, but you are not necessarily also seeing more of the later-line patients coming on as well. Is there a bottleneck somewhere?
If this is something that can be helped by expanding the salesforce and hitting more prescribers, please talk about that dynamic. Thank you.
David Hung: It is a great question. The main reason is that, in our early quarters of launch, we were getting mainly late-line patients—third-, fourth-, and fifth-line. Those patients can discontinue therapy in literally a month or two. Very late-line patients drop out very quickly, unfortunately, to pursue other therapies or they pass away. The reason it appears to be a plateau is not that demand is plateauing; it is that the late-line patients are dropping out very quickly. We are getting first-line patients, but those are incident cases.
The prevalence pool has already been diagnosed—those are easier to find because they have already had a ROS1 diagnosis and have been on therapy—but they do not stay on very long and drop off quickly. The first-line patients have to be newly diagnosed, and that incidence pool obviously takes longer time to build. The fact that we have gone from 30% to 40% to now over 50% first-line shows we are finding those first-line patients, while the third-, fourth-, and fifth-line patients are dropping off rapidly. That should stabilize because eventually we will deplete that pool. We think we have already captured a significant amount of the late-line patients. That is why we are really focused on first-line.
That is what really matters given that we now have a PFS or DOR of more than four years—50 months—which no drug is even within a year of. We think that is going to lead to revenue stacking that will really start to kick in, and we are just seeing that this year. So even with roughly the same number of new patient starts, and in spite of an increase in gross-to-net, revenue still went up 18%. If we keep the same growth rate in first-line patients that we have seen from Q3 to Q4 and Q4 to Q1, we think we should make our consensus for the year comfortably.
Operator: Your next question comes from the line of an analyst with Clear Street. Your line is now open. Please go ahead.
Analyst: Good evening. Thanks for taking my questions. Maybe a question on repeat prescriptions and distribution. Previously you mentioned a 70% versus 30% academic versus community split, but today you also mentioned that 100% of top 50 accounts have prescribed Iptrozy, which I assume are mostly community-based. Any insight you can provide there? Also, how does the NCCN CNS guideline inclusion help you get more first-line adoption? And on the lower testing rates in the community, are these rates lower because of lack of awareness, or are there other hurdles that could take longer to change?
Colleen Sjogren: A couple of things to keep in mind. Across the top historical accounts—100% of those 50 accounts have now written Iptrozy—we see much greater usage now across community, IDN, and academic. You are right: when we first launched, we saw very fast uptake in academics. Now we are seeing just as much strength in uptake across other channels, especially in the community. Academic oncologists are driven by clinical evidence, and the TRUST data speaks directly to that. Community oncologists need practical support—reimbursement pathways, patient support programs, and confidence that their patients can tolerate therapy over time. They are now seeing all of that: the surround sound of Nuvation Connect, reimbursement pathways in effect, and our patient support programs.
We believe that is directly linked to increasing uptake in the community. On testing, our accounts are increasingly prioritizing flagging mutation status. As RNA-based testing gains ground alongside DNA, more ROS1-positive patients are starting to be identified each month and year. We are laying the groundwork in education, positioning Iptrozy to benefit as identification rates improve. We are also educating on effective testing—making sure oncologists wait until they get all oncogenic driver testing back before making a treatment decision.
David Hung: On the NCCN CNS guidelines, that is important because one of the most widely used previous TKIs in ROS1 was crizotinib, and crizotinib does not get into the brain. The new NCCN CNS guidelines specifically call out the CNS profile of Iptrozy, which contrasts starkly against crizotinib’s complete absence of brain penetration. About 36% of ROS1 cases have brain metastases at first diagnosis, and another 50% will progress in the brain upon first progression. It would be inappropriate to give a drug that is not CNS-penetrant. Not only is Iptrozy highly CNS-penetrant, but even in the second-line setting—often the most difficult-to-treat patients—our intracranial response rate is 66%, the highest recorded so far of any TKI in the pretreated space.
That is independent of our unmatched first-line durability. We think the new NCCN CNS guidelines make it even more imperative that doctors select the right therapy.
Colleen Sjogren: And, Kaveri, to add to David’s point, we have already received early feedback from HCPs that this will enhance Iptrozy’s profile and impact treatment decisions.
Analyst: Very helpful. This has a lot of exclamation points. Thank you so much.
Operator: Your next question comes from the line of an analyst with Truist Securities. Your line is now open. Please go ahead.
Analyst: Good afternoon, David and team. Congrats on the progress and results, and thanks for taking my question. A competitor recently presented data suggesting activity in patients previously treated with talotrectinib. How would you expect treating physicians to interpret such results? Would you see this influencing sequencing decisions or Iptrozy’s positioning compared to competing or potential agents in the market?
David Hung: It does have implications. First, we are delighted that new treatment options are becoming available for patients as they fail therapy. But if you look at Iptrozy’s efficacy—with a response rate of 90% and now a PFS of about 50 months—there is nothing close to it in the first-line space. Repotrectinib’s PFS is about 36 months, so you are still talking about almost a year-and-a-half difference. In the second-line setting, with our DOR approaching 20 months and a response rate of 56% without excluding any oncogenic drivers—and an intracranial response rate of 66% without excluding any oncogenic drivers—there are no agents today that can claim numbers that match those.
When a competitor has data in the third-line setting showing response after Iptrozy fails in the second-line setting, we are delighted that patients have another option in the third line. The competitor you are referring to received Breakthrough Therapy designation in the third-line setting, while Iptrozy received Breakthrough Therapy designation in the first- and second-line settings. We think things are playing out as the FDA initially saw them: Iptrozy will be used in the first- and second-line settings; other agents are needed in the third line, and we welcome that because that is what patients need.
Operator: Your next question comes from the line of an analyst with B. Riley. Your line is now open. Please go ahead.
Analyst: Good afternoon, team. Thanks for taking our questions. Building on the prior point of how Iptrozy is now considered relative to crizotinib and how entrenched positions could shift with additional market education—how relevant is the development of new CNS meds to the clinicians you talk to? And could you comment on dose interruptions or reductions tracking in frontline patients versus later lines? And on a go-forward basis, since new patient adds may not be a very relevant metric, what should we focus on—updates on first-line proportion, durability, gross-to-net—to think about modeling beyond 2026?
David Hung: CNS is highly relevant. ROS1 NSCLC is aggressive not only in tumor growth but also in where tumors go. More than a third of patients have brain metastases at diagnosis, and in 50% of cases, upon progression, the brain is the first site of metastasis. That makes it imperative to have CNS coverage as early as possible with an agent that has proven long-term efficacy. Our intracranial response rate in the second-line setting is 66%, our duration of response in second line is about 20 months, and overall survival approaches three years—no other agents have published data close to that.
In first line, the difference is even more pronounced: there is no agent remotely within Iptrozy’s 90% response rate and 50-month PFS. Regarding dose reductions and interruptions, the drug is well tolerated. We are not seeing anything new in the real world that we did not see in clinical trials. Dose reduction and interruption rates in practice are essentially what we saw in clinical trials. On efficacy, it is early to quantify real-world durability, but we expect similar performance to trials—about 50 months in first line and roughly 20 months in second line—based on what we see so far and physician feedback.
Philippe Sauvage: On the forward-looking metrics, the key driver is the build-up of first-line patients and the resulting revenue stacking. We grew first-line patients by roughly 35% from Q3 to Q4 and again by about 35% from Q4 to Q1. If we keep increasing at that rate from Q1 to Q4, we will hit consensus; if we do better, we can beat consensus. The apparent stability in total new starts reflects two opposing dynamics: first-line patients increasing quarter after quarter, while the finite pool of late-line patients drops off faster. Looking ahead, we will keep talking about first-line build, given the incredible tolerability and durability that help patients stay on therapy a long time and help us progress quarter after quarter.
On gross-to-net, Q1 typically sees an uptick due to price changes and mix effects such as 340B and Medicaid. Our gross-to-net increased a few percentage points this quarter as expected. We continue to expect stabilization around the high-20s to roughly 30% over time. There are no surprises here—no surprises on GTN, patients, or operating expenses—everything is tracking as we anticipated.
Operator: Your next question comes from the line of an analyst with TD Cowen. Your line is now open. Please go ahead.
Analyst: Thank you so much, and thanks for all the detail. As the proportion of first-line, treatment-naive patients rises from 30% to 40% to now over 50% of new starts, can you give us a sense of what percentage of total on-therapy patients are treatment naive at this point? And on gross-to-net, should we assume you will be in the high-20s and stabilize there this year, given it was around 25% last quarter?
Philippe Sauvage: On your first question, yes, the proportion of first-line patients among new starts is increasing quarter after quarter, and we expect that to continue. We have limitations on exact real-time data for the full on-therapy base, but you can estimate based on first-line growth rates and the drug’s favorable tolerability profile, plus the late-line versus first-line discontinuation dynamics we described. On gross-to-net, it is fairly mechanical. Increased 340B and Medicaid exposure and the inflation-linked price dynamics drive gross-to-net higher by roughly the amount of the price increase for those segments. We expect to stabilize around ~30% as the mix normalizes and inflation dynamics flow through. This is aligned with what we said previously.
Operator: Your next question comes from the line of an analyst with JonesTrading. Your line is now open. Please go ahead.
Analyst: Thanks for taking my questions. How is the duration of therapy in first-line patients comparing to your expectations based on clinical trials? And with the recent NCCN additions, do you expect a noticeable inflection, or is that more of a background tailwind?
David Hung: It is still early, but first-line patients are clearly staying on longer, which is reflected in revenue growth and the growing active patient base. We expect an average of over four years, consistent with trials, and so far discontinuations are predominantly in late-line patients, as expected.
Philippe Sauvage: Side-effect profiles are aligned with clinical trials, so there is no reason for adverse events to drive early discontinuations.
David Hung: On the NCCN updates, there is usually some lag. The first NCCN change a year ago—clarifying that IO is contraindicated—took time to shift practice. The CNS guideline may be appreciated sooner given high awareness that ROS1 is brain-tropic. In any case, it is a positive tailwind consistent with Iptrozy’s profile. On issuing annual sales guidance, now that we have hundreds of patients and a clearer growth trajectory, we would be willing to consider providing guidance at some point in the future.
Operator: Your final question comes from the line of an analyst with Citizens Bank. Your line is now open. Please go ahead.
Analyst: Thanks for taking the question, and congrats on the results. We have gotten a lot of color on CNS efficacy. Could we get the team’s perspective on comparing talotrectinib’s CNS profile to emerging clinical candidates rather than already approved ones? And does the NCCN CNS guideline reinforce the benefit here?
David Hung: The nearest not-yet-approved competitor has reported an intracranial response rate of about 45% in the second-line setting, with exclusions. Our intracranial response rate is 66% without excluding oncogenic drivers. Against approved TKIs, Iptrozy’s intracranial activity is also higher. So, based on available data today, Iptrozy’s CNS activity compares favorably, and the NCCN CNS guideline does reinforce that benefit.
Operator: Your next question comes from the line of an analyst with UBS. Your line is now open. Please go ahead.
Analyst: Hey, thanks for squeezing us in. A quick one on the IDH1 program. Could you remind us of the standard of care in the high-grade glioma setting? And what PFS or ORR would be clinically meaningful in the broader population and in the subset that could read out next year? What would a good result look like, and what could the next steps be?
David Hung: The SIGMA trial is a placebo-controlled study. There is absolutely nothing approved for the management of high-grade IDH1-mutant glioma. Management today is surgery for tumor debulking, radiation, and chemotherapy, with limited effectiveness. For response rate, anything north of 20% would be clinically meaningful in an indication with no approved therapies, and we would go to the FDA to discuss an approval pathway. For grade 3 oligodendroglioma—less aggressive than grade 4 astrocytoma/GBM—we would expect higher response rates, and again anything north of 20% we believe would be of strong interest to the FDA given the lack of options. We feel good about this based on data presented so far.
Operator: There are no further questions at this time. I will now turn the call back to David for closing remarks.
David Hung: Thank you all for your support. We are really excited about what we are seeing with the Iptrozy launch—it has gone pretty much as we had hoped—and we cannot wait to report our next quarter’s results. Thank you very much.
Operator: This concludes today’s call. Thank you for attending. You may now disconnect.
