Good afternoon, 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. 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. 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. This is an exciting time for us. We're 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 a third at presentation, another 50% upon progression progressed in the brain. This is a disease that's very aggressive. The average progression-free survival on what used to be standard of care IO-chemo was 6-12 months.
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. Just to note that that response rate and progression-free survival have not been matched by any other drugs in any solid tumor. 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 1 trials. This drug first entered clinic about nine years ago in one of our earliest trials, our Phase 1 study of 15 patients.
Today, we learned that one patient was out seven years, one out eight years, two out nine years, one of those with a complete response, so no visible tumor left. It is just extraordinary to think that that could be an outcome for a disease where just a few years ago, IO-chemo could offer 6-12 months of progression-free survival. We think this is a very exciting time for us, and we are really excited to launch this.
That's fantastic. 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 June 23. We frankly have seen even some early approvals that have come down from FDA in the last couple of weeks. Maybe just touch on, and by the way, this is in the backdrop of some trepidation when it comes to regulatory friction. Maybe just bring us up to speed on that confidence that we are certainly interpreting and where you are with FDA.
Sure. 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. When our NDA was submitted, it was accepted with priority review. Clearly, it has been a priority for the FDA. I can tell you that in our interactions with them over the last six months, they have just been extraordinarily responsive and efficient. We really commend the agency on their responsiveness to try to bring this drug to patients as quickly as possible. We are very confident that the latest that this approval will happen will be on the PDUFA date, if not before.
Okay. Fantastic. 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 has shown for taletrectinib relative to the standards of care, the other ROS1s in the marketplace, whether they're approved or in development.
We published these data recently in the Journal of Clinical Oncology. We have, as I mentioned, in the first line setting, PFS of 46 months, DOR, duration of response of 44 months, overall response rate of 89%. 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. If you look at patients, even in the second line setting, the intracranial response rate is 66%, which is still really exciting given the fact that that's such a common site of disease progression. We think that that combined with a very tolerable safety profile, we think this drug will be very attractive to patients. We think that this is going to be a pretty significant alternative for patients seeking therapy for this really aggressive disease.
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 repotrectinib. Maybe it's some modest performance there, but I think that there are some interesting reasons and learnings that you can leverage from that. 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 taletrectinib once it reaches market?
Interestingly, today, the vast majority, as recently as the end of last year, the vast majority of ROS1 patients do not appear to have been getting a ROS1 therapy. Some of that is due to logistics. 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 two to three weeks. These patients, on average, are 50 years old, still raising families, still in their careers. They're really anxious, and they want to be on some therapy. Many of them go on to IO-chemo, which is commonly used in lung cancer. You might think that two or three weeks later, when they get the NGS back and it is ROS1, they would switch. That actually does not happen for a couple of reasons.
Number one, if you look at the old NCCN guidelines until the end of 2024, the NCCN guideline said if you had a ROS1 mutation right up front, of course, they recommend a ROS1 agent. If you've already started another systemic therapy and are subsequently found to have ROS1, the NCCN recommended two options. Option one is finish that systemic therapy, IO-chemo, including maintenance. Option two is to switch. 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. I think that it's sometimes hard to overcome momentum. All of that changed significantly on January 7th of this year. Just four months ago, the NCCN updated their guidelines.
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. 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 contraindicated. 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. I think that's going to change the dynamics of medical practice significantly.
Great. Now to talk about maybe some flex in the approval date, and granted, it is just coming up, but 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, many case studies that I think provide an enhancement to reassurance, but maybe provide what you're doing. You've been in 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. 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's Colleen Sjogren. She was one of my superstars at Medivation, and we're super excited to have her at the helm of this launch. Many of my other senior leadership and commercial are also from Medivation. Dan Thompson, head of sales, was also a Medivation alum. We're ready to go. We've been there and done that before. As you might remember, we launched XTANDI against J&J then, against ZYTIGA. Even though they were 18 months ahead of us with the ZYTIGA launch, we overtook ZYTIGA within eight quarters. Today, XTANDI does well over $6 billion a year in sales. We feel very comfortable with commercial launches.
We've been there. I think we've learned a lot since Medivation days. I think we're even more prepared to do this launch, and we're super excited to launch this drug.
Yeah. We and investors, of course, are just taking interest in trying to better understand what a trajectory can 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. Maybe help us develop that framework a bit as far as that uptake, as far as getting that market traction.
Yeah. You know, I think the launches, no matter how you look at them, no matter what tailwinds you have, are always challenging. 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 four 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 would amount to almost $1 billion of new patient starts per year.
Because our PFS is nearly four years and because of revenue stacking, by the fourth year, the theoretical maximum market opportunity is nearly $4 billion a year. That is 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 fusions than the DNA test. If that market is close to $4 billion on DNA testing, we think that when RNA becomes a standard, it is going to be over $5 billion a year. We think that with our profile, we should command the majority of that market. We think that with some time, this will be a very successful commercial opportunity.
Just helping us think about that, Matt, you've referenced RIPO and that pricing. Is it fair for us to assume parity pricing at this point?
We'll announce that next month. We aren't making any comments on it at this time, but we'll kind of just keep that for now.
As you talk, of course, the guidelines are very important. We walked through that. You also mentioned just testing, just the concept of ROS1 and maybe being underdiagnosed. How does a plan perhaps to boost the diagnosis and treatment rates, I should say, that boost that awareness and that patient identification play into the strategy?
Clearly, testing rates could improve, especially in the community. They're pretty high right now in academic centers. I think that lung cancer just a few decades ago was considered to be a death sentence, a really difficult-to-treat disease. 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. I think that that's a rising tide that'll 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 the 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. That'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. It is important to identify those mutations. I think that will increase continually.
Certainly also the luxury of taletectrinib 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 a launch in the United States?
Yeah, I think the launch in China, from my understanding, has been good. I think that this is a, again, ROS1 is a cancer that's more prevalent in Asian populations. I think that our partner will do well in this deal. We think that the U.S. market is also very, as I said, really attractive commercial opportunity. I really can't wait to get out there.
Yeah, that.
What we've seen in China as well is a clear endorsement of the medical value of the product. Like really a message from the Chinese oncology organization saying this is really a first-line therapy, et cetera. In terms of launch dynamic, it's a bit early in China because of the near and the early timeline, so it's not reimbursed yet. The medical endorsement has been incredible. I think this is really a testament to the medical value of the product and how it changed the landscape.
As you talk about the interest in the commercial opportunity, there are also potential arrival or at least development of those competitors behind you. Maybe help us put that into context a little bit. Certainly small market, high opportunity, but several others interrogating the space as well.
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. I just think that we feel very confident. This drug has a long experience. Our safety database is comprised of more than 400 patients. One of the largest ROS1 data sets assembled to date. Our follow-up time for some of these patients is nine years. We started dosing these patients nine years ago, and some of those patients are still going at nine years. We have no idea how much longer they could go, but it looks very exciting for us.
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 and stuff with 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 this IDH1 inhibitor.
Yeah. Safusidenib, which is our mutant IDH1 inhibitor, inhibits mutant IDH1 like vorasidenib. When we look at the data, to us, they appear pretty different. Vorasidenib's response rate in the Phase 3 INDIGO study in low-grade glioma was 11%. In our first DAIICHI study, safusidenib showed a response rate of 33%. We're going to show even more data later this year, not only on ORR, but for the first time PFS. We think that these drugs are very differentiated. If you look at high-grade gliomas, vorasidenib's response rate is zero. Safusidenib has shown a 17% response rate, and a third of those have been complete responses. We have one 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.
We started to try to characterize what might be the differences between safusidenib and vorasidenib, but we've done a number of preclinical experiments. What we're finding is that safusidenib has immune-enhancing activities that we don't see with vorasidenib. Interestingly, if you look at the adverse events with safusidenib, of the top eight adverse events, five of them are immune-related, where vorasidenib doesn't have these immune-related side effects. We think that safusidenib, on top of being a mutant IDH1 inhibitor, is a potentially new generation of oral IO agent. If that's the case, it is possible that safusidenib might have activity even beyond IDH1 mutant mutations.
We're actually now conducting a number of preclinical experiments to see whether or not safusidenib with cytanib can be coupled with other IO agents to further enhance the immune response. If so, that would be potentially a much, much broader opportunity than just IDH1 mutant glioma. We're intrigued by this molecule. We're excited about the data we already have. We've just finished a meeting with the FDA. Very shortly, we'll be rolling out on clinicaltrials.gov the design of our pivotal study for safusidenib with cytanib in glioma. We're also going to be exploring preclinically right now how safusidenib with cytanib might fit into IO therapies for other kinds of cancer.
Just in the 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?
1511 is our first drug-drug candidate from our DDC platform. It's kind of like an ADC, but without the A. These are now two small molecules that have been fused together to create a bispecific small molecule. We've seen really interesting activity in preclinical models. We are now in the clinic. We've been in the clinic for well over six months. We're testing 1511 in five different very difficult-to-treat cancers. Women who failed in HER2 or TRDLV 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. We've been 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.
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 taletrectinib on the existing pipeline. When you think of additional capacity, your resource position, how do you envision that being allocated?
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, more royalty financing, and then a $100 million debt. 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's been so difficult. I just learned recently that of the 700+ biotech companies out there, 65% of them have less than two 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. David.
Yeah, 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. If you do the math, it's actually less than 5.5% because there are 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. 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.
Appreciate it. Thank you.
Thank you.