Nuvation Bio Inc. (NUVB) Earnings Call Transcript & Summary

Everyone, welcome back to the 2025 RBC Global Healthcare Conference. My name is Greg Renza, one of the biotech analysts here at RBC, and we're pleased now to be joined by Nuvation Bio. And representing the company is the Founder, President and Chief Executive Officer, David Hung; as well as the Chief Financial Officer, Philippe Sauvage.

Gentlemen, it's great to see you. There's a lot going on in Nuvation. This is actually a great time, David, to talk about the story, what you've been up to, really important event coming up. But let's maybe take it from the beginning and just have you walk us through Nuvation Bio, the pipeline, your focus on ROS1 inhibition with the regulatory decision underway, but also a lot of exciting things happening.

Sure. Thanks, Greg, and thanks all for coming. So this is an exciting time for us. We are on the verge of receiving FDA approval for our first drug, taletrectinib. This is a ROS1 inhibitor for ROS1-driven non-small cell lung cancers. We submitted our NDA last year and it was accepted with priority review. Our PDUFA date is June 23. So we anticipate approval imminently. We're very excited about this drug because the ROS1 lung cancer is a very, very aggressive subset of lung cancer. On average, these patients are young, 50 years old on average. A significant number of patients have developed brain metastases early, about 1/3 at presentation, another 50% on progression, progressed in the brain. So this is a disease that's very aggressive. The average survival -- progression-free survival on what used to be standard of care, IO chemo was 6 to 12 months. And we're very excited that if you look at our recent publication in the Journal of Clinical Oncology with our pivotal studies, there we announced last year an overall response rate of 89%, progression-free survival of 46 months. And just to note that, that response rate and progression-free survival have not been matched by any other drugs in any solid tumor. So we're really excited about what that potentially means for patients. We've seen very, very long-term PFS with some of our patients. We just got a recent update on the very first 15 patients in one of our Phase I trial. So this drug first entered clinic about 9 years ago in one of our earliest trials, our Phase I study of 15 patients. Today, we learned that 1 patient was out 7 years, 1 out 8 years, 2 out 9 years, 1 of those with a complete response. So no visible tumor left. It's just extraordinary to think that, that could be an outcome for a disease where just a few years ago, IO chemo could offer 6 to 12 months of progression-free survival. So we think this is a very exciting time for us, and we're really excited to launch this.

That's fantastic. And even with your recent disclosures on your first quarter earnings, just a couple of weeks ago, I think that the market and we just saw the confidence that's potentially exuded with respect to your FDA interactions and with respect to the PDUFA date that you're touching on, on June 23. We frankly have seen even some early approvals that have come down from FDA in the last couple of weeks. So maybe just touch on -- and by the way, this is in the backdrop of some trepidation when it comes to regulatory friction. So maybe just bring us up to speed on that confidence that we are certainly interpreting and where you are with FDA.

Sure. So the first thing to mention is that taletrectinib is actually the only ROS1 agent in development that has been granted breakthrough designation in both the first- and second-line setting. And when our NDA was submitted, it was accepted with priority review. So clearly, it's been a priority for the FDA. I can tell you that in our interactions with them over the last 6 months, they have just been extraordinarily responsive and efficient. So we really commend the agency on the responsiveness to try to bring this drug to patients as quickly as possible. So we're very confident that the latest that this approval will happen will be on the PDUFA date, if not before.

Okay. Fantastic. And you touched on some of the data. I just wanted to ask you to elaborate a little more just on the TRUST-I, the TRUST-II studies. Just what it's shown for taletrectinib relative to the standards of care, the other ROSs in the marketplace, whether they're approved or in development?

So we published this data recently in the Journal of Clinical Oncology. We have, as I mentioned, in the first-line setting, PFS of 46 months, DoR, the duration of response of 44 months, overall response rate of 89%. And in the second-line setting, we still see extremely robust activities because one of the main sites of progression for ROS1 patients is in the brain. And if you look at patients, even in the second-line setting, intracranial response rate is 66%, which is still really exciting, given the fact that, that's such a common site of disease progression. And we think that, that combined with a very tolerable safety profile, we think this drug will be very attractive to patients. So we think that this is going to be a pretty significant alternative for patients seeking therapy for this really aggressive disease.

Yes. And as we track the ROS1 space, maybe Nuvation is in a luxury position of having the ability to learn from Bristol's AUGTYRO launch with repo. Maybe some modest performance there, but I think that there are some interesting reasons and learnings that you can leverage from that. So to that, David, what are you learning from the landscape from a competitor launch? How are you applying that to potentially improve the positioning of tale once it reaches market?

So interestingly, today, the vast majority -- as recently as the end of last year, the vast majority of ROS1 patients don't appear to have been getting a ROS1 therapy. And some of that is due to logistics. So if you look at -- let's say, a patient gets a biopsy on a Monday, they get their pathology back very quickly, let's say, Tuesday, but they may not get their NGS testing back for 2 to 3 weeks. These patients, on average, are 50 years old, still raising families, still in their careers. They're really anxious so they want to be in some therapy. So many of them go on to IO chemo, which is commonly used in lung cancer. And you might think that 2 or 3 weeks later when they get the NGS back and it's ROS1, they would switch. But that actually doesn't happen for a couple of reasons. Number one, if you look at the old NCCN guidelines until the end of 2024, the NCCN guidelines said if you had a ROS1 mutation right upfront, of course, they recommend a ROS1 agent. But if you've already started another systemic therapy that are subsequently found to have ROS1, the NCCN recommended 2 options. Option 1 is finish that systemic therapy, IO chemo, including maintenance. Or option 2 is a switch. And so because the NCCN recommended as one of the options to continue and finish IO chemo, that's what happens in a significant number of patients. And I think that it's sometimes hard to overcome momentum. So all of that changed significantly on January 7 of this year. So just 4 months ago, the NCCN updated their guidelines. And now if you've started IO chemo or another systemic therapy for what ends up being ROS1 lung cancer, now the recommendation is you need to stop that therapy, you need to switch to a ROS1 agent. And in fact, if you now look at the guidelines carefully, at the bottom it says, if you're found to have a ROS1 mutation, IO is now contraindication. So not only is ROS1 therapy now being recommended for ROS1 lung cancer as it should be. But specifically, ROS1 fusion is a contraindication for the use of IO. And I think that's going to change the dynamics of medical practice significantly.

Great. And I was talking about maybe some flex in the approval then granted, it is just coming up. I want to talk a bit about your launch preparations, clearly leveraging your and your team's prior experience across successful development and commercialization. Just many case studies that I think provide an enhancement to reassurance. But maybe provide what you're doing, you, Philippe and the team to prepare and that activation and launch readiness.

Sure. So my commercial team is fully in place. We were ready to go May 1. So we are anxiously waiting for the approval, but we are ready to launch immediately. My Chief Commercial Officer, I've known since Medivation, her name is Colleen Sjogren. She was one of my superstars at Medivation, and are super excited to have her at the helm of this launch. Many of my other senior leadership in commercial are also from Medivation. Dan Thompson, Head of Sales, was also in Medivation alum. We're ready to go. And we've been there and done that before. We -- as you might remember, we launched XTANDI against J&J then, against Zytiga. And even with -- even though they were 18 months ahead of us with the Zytiga launch, we overtook Zytiga within 8 quarters. And today, XTANDI does well over $6 billion a year in sales. So we feel very comfortable with commercial launches. We've been there. I think we've learned a lot since Medivation days. And so I think we're even more prepared to do this launch, and we're super excited to launch this drug.

Yes. And we and investors, of course, are just taking interest in trying to better understand what a trajectory could look like, of course, throughout the 2020s and beyond, but also near term and just giving us a framework to think about the patient set, the activation of the patients, not just the flow of revenues, but also those important operational metrics. So maybe help us develop that framework a bit as far as that uptake as far as getting that market traction.

Yes. I think the launches are no matter how you look at them, no matter what tailwinds you have are always challenging. So just to be very straightforward, I think that all launches never go as fast as you want, but we are very confident in our team. We think this drug is a great drug. We think that the value proposition is clear. We think this is a really big commercial opportunity. If you look at our PFS now of nearly 4 years, what that means is that even though you might have only 3,000 new patients per year, if you were just to multiply that times the current repotrectinib price, that amount to almost $1 billion of new patient starts per year, but because our PFS is nearly 4 years and because of revenue stacking by the fourth year, the theoretical maximum market opportunity is nearly $4 billion a year. And that's based on current DNA testing. The new RNA test was introduced just about a year ago, and RNA is about 30% more efficient at identifying ROS1 infusions than the DNA test. So if that market is close to $4 billion on DNA testing, we think that when RNA becomes a standard, it's going to be over $5 billion a year. We think that with our profile, we think that we should command the majority of that market. So we think that with some time, this will be a very successful commercial opportunity.

And just helping us think about that math, you've referenced repo and that pricing, is it fair for us to assume parity pricing at this point?

We're going to -- we'll announce that next month. So we're not making any comments on it at this time, but -- so we'll kind of just keep that for now.

Yes. And as you talk -- of course, the guideline is very, very important. We walked through that. And you also mentioned just testing just the concept of ROS1 maybe being underdiagnosed. How does the plan perhaps to boost the diagnosis and treatment rates, I should say, boost that awareness and that patient identification play into the strategy?

So clearly, testing rates could improve, especially in the community. They're pretty high right now in academic centers. But I think that lung cancer just a few decades ago was considered to be a death sentence. It's a really difficult to treat disease. And now with the advent of precision oncology agents, lung cancer has become one of the most treatable cancers on the planet. If you look at EGFR, ALK, RET, and now ROS1, these precision agents for those mutations lead to extraordinary outcomes really, really different from what used to be standard of care. So I think that, that's a rising tide that will float all boats. I think that when people have seen what's happened in the EGFR, ALK and RET spaces, I think that will spill over to ROS1. I think awareness of testing is now increasing significantly. I recently learned that in Louisiana, they actually have legislation now that requires NGS testing for lung cancer. It's a great development. I think that should hopefully go on to other states. I think that's the right thing to do for lung cancer patients because it is so treatable if you have a mutation, so it's important to identify those mutations. And I think that will increase continually.

And certainly, also the luxury of tale being approved across other regulatory bodies with China approval, what have you learned? What are the insights just from the partner there from that launch that could potentially inform or support your thesis as far as the launch in the United States?

Yes. I think the launch in China from my understanding has been good. I think that this is -- again, there's -- ROS1 is a cancer that's more prevalent in Asian populations. So I think that our partner will do well in this deal. And we think that the U.S. market is also very, as I said, really attractive commercial opportunity. So I really can't wait to get out there.

And what we've seen in China as well is a clear endorsement of the medical value of the product, like really message from the Chinese oncology organization saying this is really a first-line therapy, et cetera. In terms of launch dynamics, it's a bit early in China because of the NVL time lines, so it's not reimbursed yet. But the medical endorsement has been incredible. And I think this is really a testament to the medical value of the product and how it changed the landscape.

And as you talk about the interest in the commercial opportunity, there are also potential arrival or at least development of those competitors behind you. So maybe help us put that into context a little bit. Certainly, small market, high opportunity, but several others interrogating the space as well.

So as I mentioned, we are the only ROS1 agent in development that's been granted breakthrough designation in the first- and second-line setting. We're launching with a line-agnostic label. We have priority review. Our competitors are a number of years behind us. We think that -- and we have not yet seen any data from any competitor that can match the numbers that we've posted. So I just think that we feel very confident this drug has a long experience. Our safety database is comprised of more than 400 patients, so one of the largest ROS1 data sets assembled to date. Our follow-up time for some of these patients is 9 years. We started dosing these patients 9 years ago, and some of those patients are still going at 9 years. So we have no idea how much longer they could go, but it looks very exciting for us. So I think that we feel very, very confident in our position and our profile. And so we just can't wait to get this to patients.

Great. Great. I want to spend some time in the last few minutes on the pipeline in safusidenib. I think the investor interest is brewing. I think there's brewing here actually at this conference, believe it or not, but also in the last several weeks and months and especially since you took in the asset with the AnHeart deal. Maybe just walk us through your hypothesis on the underlying mechanism when it comes to the H1 inhibitor.

Yes. So safusidenib, which is our mutant IDH1 inhibitor, inhibits mutant IDH1 like vorasidenib. But when we look at the data, to us, they appear pretty different. So vorasidenib's response rate in the Phase III INDIGO study in low-grade glioma was 11%. And in our first Daiichi study, safusidenib showed a response rate of 33%, and we're going to show even more data later this year, not only on OR, but for the first time, PFS. And we think that these drugs are very differentiated. If you look at high-grade gliomas, vorasidenib's response rate is 0, safusidenib has shown a 17% response rate and 1/3 of those have been complete responses. So we have 1 GBM that's now been in a complete response for 3.4 years. We have a second high-grade glioma that's been in a complete response for 95 weeks. It's unusual. So we start to try to characterize what might be the differences between safusidenib and vorasidenib, but we've done a number of preclinical experiments. And what we're finding is that safusidenib has immune-enhancing activities that we don't see with vorasidenib. And interestingly, if you look at the adverse events with safusidenib, of the top 8 adverse events, 5 of them are immune-related where vorasidenib doesn't have these immune-related side effects. So we think that safusidenib on top of being a mutant IDH1 inhibitor is a potentially new generation of oral IO agent. And if that's the case, it is possible that safusidenib might have activity even beyond IDH1 mutations. So we're actually now conducting a number of preclinical experiments to see whether or not safusidenib can be coupled with other IO agents to further enhance the immune response. And if so, that would be potentially a much, much broader opportunity than just IDH1 mutant glioma. So we're intrigued by this molecule. We're excited about the data we already have. We've just finished the meeting with the FDA and very shortly, we'll be rolling out on clinicaltrials.gov, the design of our pivotal study for safusidenib in glioma, but we're also going to be exploring preclinically right now. Our safusidenib might fit into IO therapies for other kinds of cancer.

And then just in last moment as we think about the legacy of Nuvation and the history and the drug-drug conjugate platform, maybe just remind us of the status of 1511 and what should investors be looking for from program updates later this year?

So 1511 is our first drug-drug candidate from our DDC platform. It's kind of like an ADC, but without the A. So these are now 2 small molecules that have been fused together to create a bispecific small molecule. We've seen really interesting activity in preclinical models. So we're now in the clinic. We've been in the clinic for well over 6 months. We're testing 1511 in 5 different -- very difficult-to-treat cancer. So women who failed Enhertu or Trodelvy with breast cancer, women who have HER2-negative metastatic breast cancer, men who failed XTANDI with prostate cancer, women who failed platinum for ovarian cancer and then, of course, one of the worst tumors of all advanced pancreatic cancer. So we are -- we've been in the -- in dose escalation. We have now hit our maximum tolerated dose, and we are expanding those cohorts and hope to report data sometime in the second half of this year.

And David, as you think about the future of Nuvation and certainly, you and the team lauded for your drug-hunting capabilities, what's next for Nuvation, of course, the focus on tale on the existing pipeline, but when you think of additional capacity, your resource position, how do you envision that being allocated?

So right now, we had as of our last Q, $462 million on the balance sheet, but we just announced a deal with Sagard where upon approval, we'll have access to another $250 million in capital, non-dilutive capital from a royalty financing and then $100 million debt. So we have -- we'll have over $700 million to develop our programs and to look for new stuff. I think this is a really, really unprecedented time in our industry. I think that the market has been so difficult. I just learned recently that of the 700-plus biotech companies out there, 65% of them have less than 2 years of cash. I think that puts them in a very difficult position. We've looked at hundreds of opportunities to date. And we'll continue to look at hundreds more, but we think that there are a lot of potentially really exciting deals out there to further bolster our pipeline, and we're looking forward to talking about that in the future.

Great. Well, David...

Yes. Maybe to add just something. When you think about it, we bought AnHeart less than a year ago for $260 million in stock. Keep that number in mind, $260 million in stock. And the Sagard financing that David was talking about was $150 million for 5.5% royalty of the U.S. sales of one of those products. So if you do the math, it's actually less than 5.5% because there is levels of royalties that go down and all the rest. You're talking about 5%, let's say, royalty, $150 million, that's $3 billion more or less for a deal that we made for $260 million stock last year. So it's pretty impressive in terms of value creation.

That's certainly worth noting. David, Philippe, thank you so much. We look forward to the June PDUFA and all the progress. Appreciate it.

Thank you very much. Appreciate it.

Thank you.