Nuvation Bio Inc.

Hello and welcome to NuvationBio's third quarter 2025 financial result and corporate update call. Today's call is being recorded and a replay will be available. All participants are currently in a listen only mode. A brief question and answer session will follow the prepared remarks. Now I'd like to turn the call over to J.R. Devita, Executive Director of Corporate Development and Investor Relations at NuvationBio. Please go ahead.

Thank you and good afternoon, everyone. Welcome to the innovation bio third quarter 2025 earnings conference call. Earlier today, we released financial results for the quarter ending September 30 2025 and provided a business update. The press release is available on the investor section of our website at innovation bio.com. And a recording of this conference call will also be available on our website following its completion. I'd like to remind you that today's call includes forward-looking statements, including statements about the therapeutic and commercial potential of Iptrosi and Sapucitinib, the components of our anticipated product revenue, expected milestone payments, and our cash runway. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the US Securities and Exchange Commission. Joining me on today's call to discuss our quarterly results 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 business updates. Colleen will provide details on the commercial launch of Introsi, and Philippe will discuss our financial and operating updates. David will then conclude with closing remarks. Now I'll turn the call over to Dr. David Hung. David.

Thanks, JR. Good afternoon, everyone, and thank you for joining us. I'm pleased to share our third quarter results with you today. As a reminder, our lead product, Ibtrozi, received full approval from the US FDA on June 11th, making the third quarter our first full quarter as a commercial stage company. We are thrilled to report that momentum from the US launch of Ibtrozi continues to build in a meaningful, steady manner. On our last earnings call, we announced that 70 new patients had started Ibtrozi between FDA approval and the end of July, which represented approximately 10 new patient starts per week. Going forward, we will report key performance indicators and sales on a quarterly basis. This allows for a direct apples to apples comparison of quarter over quarter growth, regardless of when we report our results. Today, we can tell you that 204 new patients started Iptrosi in the third quarter. which represents over 15 new patient starts per week during this period. We are seeing and hearing strong physician appreciation and support for the durable efficacy, robust intracranial activity, and excellent tolerability profile we've discussed previously. Importantly, what we're seeing in the field reflects exactly the cadence we were hoping for at this stage, supported by real-world, real-time patient treatment needs. While rare disease launches are always complex, we are quite encouraged by the number of patients we have been able to help with Ibtrosi at this point in our launch. To put our performance in context, Reprotrectinib, or Octiro, was approved by the FDA on November 15th, 2023. Per retrospective IQVIA data, just 34 new patients started Octiro during its first three full months after approval. While we realize IQVIA does not capture all patients that start therapy, this represents less than three new patient starts per week from December 2023 to the end of February 2024. As evidenced by the volume of new patient starts to date and defining characteristics of its product profile, we believe that IPTROSI is on track to become the new standard of care in ROS1-positive non-small cell lung cancer. This sentiment is already reflected in the practicing physician community as evidenced by a recent article published last month in Cure Today by Dr. Jeffrey Liu, one of the most prominent KOLs in the RAS1 lung cancer space, on the data we recently presented at the 2025 World Conference on Lung Cancer, or WCLC. Since its launch, Acuvia data also shows that Actiro has been unable to displace crizotinib, or zalkori, and become the standard of care in this disease. We believe zalkori should not be the standard of care because it does not cross the blunt brain barrier. About 36% of newly diagnosed patients with advanced ROS1-positive non-small cell lung cancer have tumors that have already spread to their brain, and another 50% of patients previously treated develop brain metastases upon progression. This viewpoint has been echoed by multiple KOLs we have interacted with in the field. Per data published in the Journal of Clinical Oncology, or JCO, Ibtrozi demonstrated a confirmed overall response rate, or ORR, of 89% and a median duration of response, or DOR, of 44 months in TKI-naive patients, and importantly, a 66% confirmed intracranial response rate in patients with brain metastases who were TKI pretreated. Data published in JCO was based on pooled analyses from the TRUST-1 and TRUST-2 studies using a June 2024 data cutoff, and today we are delighted to report that the median DOR of TKI-naive patients treated with Iptrosi in the pooled analyses has now increased to 50 months from 44 months with additional follow-up from a more recent data cutoff date of August 2025. These new data are being prepared in a supplemental MDA to support a label update that we plan to submit in the coming weeks. And we also plan to provide a more fulsome update from the August 2025 data cutoff at a medical conference in 2026. These long-term data appear to represent the greatest patient benefit to date in ROS1-positive non-smell cell lung cancer. It is also important to note that unlike ongoing studies of other ROS1 TKIs, our pivotal studies did not exclude patients with other concomitant oncogenic mutations, making the results with Ibtrozi, we believe, representative and applicable to real-world patients. To our knowledge, we have not seen any approved therapies in any solid tumor oncology indication that have shown efficacy data like those of Atrozi's combined response rates and durability in the first-line setting. Only lorlatinib, or labrena, for ALK-positive non-small cell lung cancer has shown a longer median PFS of greater than five years in its crown study, but per its label, labrena's confirmed ORR is 76%. Just as it would be a challenging and significant investment over many years to achieve, much less surpass, the medium PFS of LABRAINA and ALK-positive non-small cell lung cancer, we feel it will be equally difficult and lengthy an investment to demonstrate durability data close to that of Ibtrozi and ROS1-positive non-small cell lung cancer. We also published important new data at both WCLC in September and the European Society of Medical Oncology, or ESMO, in October. At WCLC, we shared updated Iptrosi data from both the pivotal TRUST1 and TRUST2 studies that supported the data in our label. This included both additional details, which emphasized the consistent durability of Iptrosi's efficacy profile and a more thorough characterization of Iptrosi's well-tolerated safety profile. Specifically, while our presentation did not summarize all adverse events detailed in our prescribing information, it instead focused on the six most common adverse events seen in clinical studies of Iptrosi. These were increased aspartate aminotransferase, or AST, increased alanine aminotransferase, or ALT, followed in order by diarrhea, nausea, vomiting, and dizziness. Of note, Out of the 337 patients with ROS1-positive non-small cell lung cancer treated with diptrosy in our pivotal studies, the number of patients who discontinued diptrosy for any of these top six adverse events was one. This represents a discontinuation rate of just 0.3% for the six most common adverse events. In addition, The published data show that Ibtrozi's clinically apparent adverse events, diarrhea, nausea, vomiting, and dizziness, were transient, majority grade 1, and resolved in 1 to 3 days. Again, the combined efficacy, durability, and tolerability of Ibtrozi are unprecedented in this disease. Additionally, at the ESMO conference, He presented data on Ibtrozi's efficacy in patients who had failed rosletrex or intractinib, the only CNS penetrant first-generation ROS1 TKI. Ibtrozi's confirmed ORR post-intractinib failure was 80%. We are not aware of any ROS1 agents approved or in development that can match this response rate. Also notably, All 10 patients who failed intracnib in this study failed for progression, not tolerability. This is an important distinction because showing an 80% confirmed ORR after progression is a much higher bar to achieve than an 80% ORR in patients who failed intracnib for tolerability but whose tumors are not progressing on intracnib. This data is particularly important because, as I noted earlier, Intracranial metastases develop in 50% of patients progressing with ROS1-positive non-small cell lung cancer, and Rosletrek was previously the most tolerable of the currently approved earlier generation brain-penetrant ROS1-PKIs. We believe these results following progression on Rosletrek help solidify Ibtrozi's differentiated profile and activity in the central nervous system. We believe that Ibtrozi's robust and durable systemic and intracranial response rates may be due to its unique combination of activities against two important targets, ROS-1 and TREC-B. As we have previously mentioned, Ibtrozi is 11 to 20-fold more selective for ROS-1 over TREC-B. It is strikingly potent against ROS-1 with picomolar level inhibitory activity. However, we believe that modest and tolerable inhibition of TREC-B by Abtrose may also contribute to intracranial disease control. For published studies, TREC-B signaling has been associated with larger tumor size, higher clinical stage, higher probability of distant metastases, including in the CNS, and worse survival across multiple solid tumor types, including lung cancer. Our view is that Ibtrozi strikes the right balance between potent inhibition of ROS1 combined with measured and tolerable TREC-B activity. Interestingly, as I just mentioned, the only other approved TKI with a PFS longer than that of Ibtrozi is Labrena, used in ALK-positive non-small cell lung cancer, which also inhibits TREC-B to a measured extent. We do not believe this is a coincidence. ALK-positive non-small cell lung cancers also frequently metastasize to the brain, and Lebrano's TREC-B activity may be one of the key features in striking durability. We believe that Ibtrozi's ability to hit ROS1 very hard and TREC-B modestly may drive its unique systemic and intracranial response durability and its tolerability profile. We also continue to execute on Ibtrozi's life cycle management. We recently dosed the first patient in TRUST4, our randomized placebo-controlled Phase III study evaluating telotretinoin as adjuvant therapy for patients with resected ROS1-positive early-stage non-small-cell lung cancer. Surgical resection remains the standard of care for early-stage lung cancer, yet recurrence is unfortunately common, and patients with ROS1 infusions have no approved targeted therapy options in the adjuvant setting today. Trust4 is designed to address this gap, building on the proven efficacy and safety profile of trozine-advanced disease with the goal of delaying or preventing disease recurrence after surgery. We are the first approved ROS1 therapy to initiate a clinical trial in the adjuvant setting, providing an important opportunity to address a key unmet need for patients. The fact that we and the dedicated investigators participating in our adjuvant study believe Iptrosi's safety profile is well tolerated to the point that we can help patients earlier in the disease is a particularly positive reflection of this program. Finally, in partnership with Nippon Kayaku, we were pleased to receive regulatory approval of Iptrosi in Japan, further expanding access to patients with ROS1-positive non-spellful lung cancer outside the U.S., We view this milestone as an important step in bringing Ibtrozi to patients and providers around the globe following its approval in China earlier this year. In short, we believe our large performance, the latest updates reconfirming Ibtrozi's efficacy and tolerability profile, and the additional development and regulatory achievements all show why Ibtrozi is poised to be the new standard of care for patients with ROS1-positive non-small cell lung cancer. We also made important progress on the rest of our pipeline. Allow me to turn briefly to Saccucitinib. Saccucitinib is a mutant IDH1 inhibitor being developed for diffuse IDH1 mutant glioma, a devastating brain cancer for which there are very few treatment options available today. Each year, there are approximately 2,400 new cases of IDH1 mutant glioma in the US, split almost evenly between low-grade including grade 2, and high-grade, including grades 3 and 4. An important difference from RAS1-positive non-small cell lung cancer is that patients newly diagnosed with low-grade and high-grade IDH mutant glioma live approximately 10 to 15 and 3 to 7 years, respectively. Therefore, patients may benefit from an approved therapy for many years, and as a result, the market opportunity is materially larger. The only treatment option available for patients with IDH1 mutant glioma is voracitinib, which was approved by the U.S. FDA in August 2024 for only grade 2 patients. In its pivotal indigo study, which again included only grade 2 patients with non-enhancing disease, voracitinib demonstrated a median PFS of 27.7 months and an ORR of 11%. Strikingly, the launch of Oracitinib has greatly surpassed analysts' expectations by approximately 20-fold. For background, Oracitinib is commercialized by Servier, a private company who acquired the program from Agios. Although Servier does not report sales of Oracitinib, they can be gleaned from the royalties received and reported by Royalty Pharma, who in May 2024 paid Agios $905 million dollars for a 15% royalty on net sales of Oracitnib in the US. Royalty Pharma recently disclosed in an investor update that US net sales of Oracitnib were over $550 million since launch compared to analyst projections of approximately 30 million over the same timeframe, including $223 million in net revenue in the second quarter of 2025 alone. Based on this, boracitinib is quickly approaching an annual run rate of $1 billion in U.S. net sales. We believe this is consistent with what we have said is a significant commercial opportunity for our IDH1 inhibitor, sapucitinib. As a reminder, boracitinib is approved in grade 2 IDH1-2 mutant glioma, and there are no therapies approved in the IDH1 mutant high-grade or high-risk lower-grade settings. While we acknowledge the complexity of cross-trial comparison, in a clinical study run by our partner Daiichi Sankyo, sathucytinib showed an ORR of 33% in patients with recurrent low-grade IDH1 mutant glioma, which is three times the ORR voracitinib showed in its pivotal indigo study. More importantly, sathucytinib demonstrated a 17% ORR in high-grade IDH1 mutant glioma including two complete responses lasting multiple years. These complete responses include a GBM, or glioblastoma multiforme, the worst of all gliomas, which is now referred to as grade 4 astrocytoma. To our knowledge, no other IDH1 inhibitors have demonstrated responses of this kind in high-grade IDH1 mutant glioma, and we believe this speaks to the emerging and promising clinical profile of Succutinib. Based on data generated to date, we have begun dosing patients in a global randomized study evaluating the efficacy and safety of sapucitinib versus placebo for the maintenance treatment of high-grade IDH1 mutant glioma following standard of care treatment. Specifically, we defined the population as patients with newly diagnosed IDH1 mutant grade 3 astrocytoma with certain high-risk features or grade 4 disease. Following a successful meeting with the US FDA, we're actively preparing a protocol amendment to modify the trial into a pivotal phase three study by increasing the size to approximately 300 patients, which should support potential regulatory approvals. Please refer to clinicaltrials.gov for additional details on the study design. Other important elements coming from the FDA meeting include agreement on PFS as the primary endpoint which could support full approval, agreement on the dose of 250 milligrams BID without further need for dose optimization in this setting, and agreement on the defined patient population with the potential to also include patients with IDH1 mutant high-risk grade II or low-grade gliomas, a patient group that might not be best served by voracitinib given its pivotal indigo study design. For example, The indigo study excluded grade two patients with enhancing disease. Enhancing disease is known for having a higher risk of progression. Considering the high unmet need and the exciting profile of sapucindib, we are optimistic about the speed of recruitment in this trial. That said, we want to be transparent on the length of this study. Given the agreed upon PFS endpoint and natural history of disease, this study will take years to complete. In addition, I'd reiterate that the blinded protocol will prevent us from disclosing public updates until enough events have occurred. We estimate that the study will be completed in 2029. Finally, we want to share an update on our discussions with FDA regarding development of sitinib in grade two IDH1 mutant glioma where ruracitinib is approved. These discussions were incredibly collaborative but it was clear that to receive approval, we would need to demonstrate a PFS benefit of sapucindib in a single randomized study with sufficient representation of U.S. patients. This would naturally result in including voracidinib as a control arm, given any other control arm in the U.S. would be considered unethical. While voracidinib may be approved or achieving approvals in ex-U.S. regions, accessibility and reimbursement is highly variable. and it would take too long to enroll a study supported by a PFS endpoint solely in the U.S. An alternative is for us to supply voracitinib, but the cost would easily exceed $100 million, which is simply not a financially prudent business decision. Therefore, we've decided not to pursue a head-to-head low-grade Leoma study on our own at this time, and to instead focus our resources and efforts on the high-grade maintenance study, However, as we've alluded to above, some grade two subsets were excluded from the voracitib-indigo pivotal study, such as high-risk grade two patients, which are still low-grade gliomas. We will therefore likely enroll grade two or low-grade subsets with high-risk features, which still represents an unmet need with no approved therapy. We will continue to explore whether there are other pathways to pursue development in a portion of the low-grade population, or other IDH1 mutant glioma patient subsets that could potentially benefit from sapucitinib and also remain flexible around further partnerships in the development of this program. Lastly, NUV1511 is the first clinical candidate from our drug-drug conjugate or DDC platform and represents a new modality in targeted cancer therapy. We plan to provide an update from our phase one dose escalation study and difficult to treat solid tumors in the near term. We remain confident that we have the team, strategy, and mindset to execute our program successfully, build lasting value, and most importantly, serve patients. With that, I'll turn it over to Colleen.