Nuvation Bio Inc.

Good afternoon, and welcome to the NovationBio first quarter 2025 financial results and business update conference call. Please be advised that today's conference call is being recorded. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for questions. I would now like to turn the call over to J.R. DeVita, Executive Director of Corporate Development and Investor Relations at NovationBio. Please go ahead.

Thank you, and good afternoon, everyone. Joining me on today's call are Dr. David Hung, our founder, president, and chief executive officer, Colleen Sjogren, our chief commercial officer, and Philippe Sauvage, our chief financial officer. Certain statements we make during this call will be forward-looking. These include statements about talent directives, expected FDA approval, U.S. commercial launch, and potential benefit for patients, our commercial teams launch readiness, and our cash runway. Because such statements deal with future events that 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 Ford 10Q that are filed with the U.S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended March 31, 2025, and provided a business update. The press release is available on the investor section of our website at nuvationbio.com. These statements are subject to risks and uncertainties that could cause actual results to differ materially. For more information, please refer to our filings with the SEC. Now, I'll turn the call over to our founder, president, and chief executive officer, Dr. David Hung. David?

Thank you, JR, and thank you all for joining us this afternoon. I'll begin with an overview of our company and programs, near-term focus, and strategic priorities. Colleen will then share our commercial preparedness for teletracting them. and Philippe will summarize our financial results and outlook. We've entered a transformational period for Novation Bio. With the PDUFA date set for June 23 for teletrekinib, our next generation ROS1 inhibitor for non-small cell lung cancer, or NSCLC, this quarter serves as a key inflection point as we prepare to become a commercial stage company. We believe the potential approval of teletrekinib could be one of the most significant moments in our company's history. Over the next several weeks, our team will continue executing with discipline and focus, ensuring we are prepared to deliver a meaningful new treatment option to patients living with ROS1-positive lung cancer. From the beginning, Innovation Bio has been driven by a simple but powerful idea. To challenge the status quo in cancer treatment, especially in particularly difficult-to-treat cancers. I always tell my employees our company mission is rooted in the premise that patients don't need more drugs. They need better drugs, drugs that impact important metrics for patients and doctors, like efficacy, safety, and convenience. Rothwind positive lung cancer represents a well-characterized but particularly aggressive subset of non-small-cell lung cancer. The median progression-free survival, or PFS, of this disease prior to the advent of targeted therapies ranged from 6 to 12 months and treated with chemotherapy and or immuno-oncology agents. First-generation ROS1 tyrosine kinase inhibitors, or GKIs, chrysotinib and intratenib, changed the treatment landscape significantly. providing an overall response rate, or ORR, of approximately 70% with a median PFS of about 18 months in the first-line setting. Resonance, however, does not cross the blood-brain barrier, and intracranial metastases in ROS1 lung cancer are common. About 35% of patients newly diagnosed with metastatic ROS1-positive lung cancer have tumors that have already spread to their brain. and the brain is the most common site of disease progression, with about 50% of patients previously treated developing brain metastases upon progression. Second-generation Repatracnib provides an ORR of 79% and a median PFS of 36 months, a significant improvement over first-generation agents. Unfortunately, Both intractative and reproductive have CNS toxicity that has limited their use in some patients. The CNS toxicity of reproductive in particular is potentially due to the fact that its affinity for ROS1 is similar to its affinity for TREC-B, a neurotrophic receptor in the brain that is associated with CNS side effects. We believe telotrectinib has the potential to become best in class in a space where patients, physicians, and payers are still struggling with the challenges of current ROS1 therapies. In our clinical trials across different lines of therapy, telotrectinib has demonstrated consistent, durable responses, strong intracranial activity, and a favorable safety profile, including a low rate of discontinuation and tolerable CNS effects. In pooled data from our pivotal trials that we recently published in the Journal of Clinical Oncology, teletractin had a confirmed ORR of 89% in treatment 90 patients and a median PFS of 46 months. We also observed a median duration of response, or DOR, of 44 months. I'd like to put this into context within the broader oncology treatment landscape. In my long career in oncology, I have not seen any approved agents in any solid tumor where I have observed response rates and durability like those in telotrectinib. Osimertinib, one of the most successful lung cancer drugs ever, with over 6 billion in annual sales, has an ORR of 77%, median PFS of 19 months, a median DOR of 17 months. Enzalutamide, the most successful prostate cancer drug worldwide, which Pfizer acquired from my prior company Medivation, with over 6 billion in annual sales, has an ORR of 59% and a median PFS of 20 months. Additionally, virtually all cancers eventually escape targeted therapy through the emergence of resistance mutation. Drugs with extremely prolonged PFS and DOR metrics in the metastatic setting must be particularly effective at preventing the emergence of resistance. We view calotractinib's 46-month median PFS and 44-month median DOR as reflections of the potential for calotractinib to delay or prevent the development of ROS1 TKI resistance mutations. We're also seeing consistent intracranial activity with telotrekniv, including a 77% confirmed intracranial OR in treatment 90 patients with measurable brain metastases. In the second line setting, telotrekniv had a confirmed OR of 56% with a median PFS of 10 months and a median DOR of 17 months. Perhaps even more importantly, In the second-line setting where brain metastases become particularly prevalent and problematic, calotrectinib demonstrated a 66% confirmed intracranial ORR. Intracranial response rate is critically important in this disease since seen as progression has the greatest impact on long-term survival. Finally, Telattractive has demonstrated a favorable safety profile. Most adverse events have been low-grade, transient, and manageable. This includes low rates of significant neurological issues. For example, Telattractive's rate of dizziness in our pivotal studies was 21%, and 90% of this dizziness is grade 1 and transient, lasting about three days. We believe telotreknib's well-tolerated CNS profile is driven by its 11 to 20-fold selective inhibition of ROS1 over TREKB, enabling potent ROS1 inhibition while reducing dose-limiting CNS toxicity. Importantly, we believe there are subtleties to the amount of ROS1 versus TREKB inhibition that is beneficial for patients. TREKB is believed to play a role in brain metastases. Published studies suggest that high TREC-B expression is linked to CNS progression in lung cancer, breast cancer, and other solid tumors. These data suggest that you do want to inhibit TREC-B to some extent, just not to the extent that it compromises tolerability. Talotracnib is well tolerated, but not entirely devoid of TREC-B activity, which we believe contributes to its 21% busyness rate, more than 90% of which is grade 1. However, we believe that telotracnib strikes the right balance between potent ROS1 and milder trach B inhibition, and we further believe that this balance plays a role in telotracnib's high systemic and intracranial response rates and long durability of response. The most common adverse events with telotracnib is elevation of liver function tests, or LFTs. Elevation of LFTs is well understood with TTIs, and oncologists are accustomed to managing these, generally by dose reduction, interruption, or, if necessary, drug discontinuation. The overall drug discontinuation rate due to treatment emergent adverse events, or TEAEs, for telotretinib is just 6.5%, which is low in this space. Additionally, while diarrhea is the second most common GI side effect with telotretinib, The vast majority of this diarrhea is grade 1 and transient. Finally, we believe that by far the greatest threat to any ROS1 lung cancer patient is disease progression, especially in the first-line setting when particularly effective ROS1 therapies can otherwise mean years of PFS. Recall that prior to the advent of precision oncology drugs, non-small-cell lung cancer patients generally progress in IO chemo in six to 12 months. As an example of how calotrectinib has affected the lives of some patients with advanced ROS1-positive lung cancer, we have recently learned that of the 15 patients dosed in a phase one study of calotrectinib in the TKI-naive setting, one patient received treatment for seven years, one patient has now exceeded eight years, and two others have now exceeded the nine-year mark. As a reminder, the FDA has granted calotractinib breakthrough therapy designation in both the first and second line settings, the only ROS1 drug in development to receive such designations. Our calotractinib new drug application, currently under priority review, is supported by one of the largest datasets in the ROS1 space. including a safety database of more than 400 patients. The review of our MDA is progressing on time with all planned inspections now completed with favorable outcomes. Our level of engagement with the FDA is high and our interactions have been timely and as expected. We are confident in the strength of our data package and that approval will be achieved on or before producing it. Importantly, what stands out to us most is the potential for teletractive to positively impact patients' lives. These patients are typically younger, non-smoking individuals who unfortunately face an aggressive disease with limited long-term treatment options. To give them not just a new but a highly durable, efficacious, and tolerable option would be profoundly meaningful. We believe the market is ready for new alternatives. With strong and durable efficacy and a favorable safety profile, We believe teletractinib, if approved, is well-positioned to reshape the ROS1 landscape. And our commercial team, many of whom have successfully launched leading oncology therapies at Medivation, Variety, and other success stories, is ready to deliver. We're entering this next chapter from the position of strength, with a deeply experienced commercial team and a focused market strategy. And with our recently announced $250 million non-diluted financing agreement with Cigar Healthcare Partners, we expect to have the flexibility and funding to launch teletracting and advance our broader pipeline without the need to raise additional capital to achieve profitability. Just as importantly, we see the same kind of transformative potential across our broader pipelines. Saccucitinib, our mutant IDH1 inhibitor, is being developed for diffuse IDH1 mutant glioma, a devastating brain cancer with very few treatment options, and a market opportunity that is materially larger than the Rothland positive lung cancer measure. Early clinical data suggests that Saccucitinib may offer deeper responses in both low-grade and high-grade glioma than what's been seen with other agents in this class. This includes data that has shown complete responses in high-grade glioma patients lasting years. With its high blood-brain barrier penetrance and the potential immune-based mechanism of action, we're preparing to move this program into pivotal development this year. NEV1511, our first clinical candidate from our drug-to-drug conjugate platform, represents a completely new modality in targeted cancer therapy. We look forward to providing an update for our phase one dose escalation study in difficult-to-treat solid tumors later this year. And NEV868, our BD2-selective VET inhibitor, demonstrated the tolerability and target selectivity we had hoped for. With nearly 1,500 volts of activity for BD2 over BD1, it stands out as the most selective agent of its kind. We've completed phase one dose escalation and are evaluating multiple strategic options, including continued internal development or potential partnership opportunities. Each of these programs shares the same design principles, deep biological rationale, differentiated profiles, and a commitment to real patient unmet needs. We remain focused, mission-driven, and confident that we have the team, strategy, and mindset to launch Teletrakniv successfully and build lasting value. With that, I'll turn it over to Chief Commercial Officer Colleen Shogren to walk you through our commercial strategy and launch preparedness. Colleen?