Good afternoon, everybody, and thank you once again for joining us for our 6th Annual Oncology Innovation Summit. It's a great pleasure to moderate, actually, the last session of our 2-day conference. I'm Jerome Warber from the TD Cowen Biotech team, and it's a great pleasure to have with us today the Nuvation Bio management team. Really needs no introduction: David Hung, founder, president, and CEO; and Philippe Sauvage, who's Chief Financial Officer. Gentlemen, thanks so much for joining. We appreciate it.
Thanks for having us, Jerome.
Thanks for having us, Jerome.
This is, a, very much a special time and important time for Nuvation Bio, hopefully in about 25 days from now. You have an important PDUFA coming up. We'll talk about it for taletrectinib, and of course we're gonna, see you at the upcoming ASCO meeting as well. Let's start with that. At ASCO, you're gonna present the comparisons in safety and efficacy from your pooled TRUST-I and TRUST-II data sets. Recall for everybody, TRUST-I was, a study that was conducted in China in patients with ROS1 mutations and lung cancer. TRUST-II was global. They were essentially pooled, and the FDA granted the Breakthrough Therapy Designation. The PDUFA is coming up on June 23, 2025. What they are gonna show at ASCO is the upcoming analysis based on racial subgroup, between Asians and non-Asians, showing specifically that the data is, frankly, indistinguishable.
It's essentially identical, regardless of where you are geographically around the globe and by ethnic group as well. Specifically, 83% of patients in the combined finding were from Asian geographies, and again, the response rate looked pretty much the same. It was 89% versus 84% in TKI-naive. In patients who are pretreated, it was 52% in Asians and 68% in non-Asians. Then specifically within the global TRUST-II alone, response rates again were fairly indistinguishable between 83% and 86%. Safety also looked comparable. What new data can we expect from ASCO?
I mean, I think the data you just cited really speaks to what we've been saying all along, that our data sets are very consistent with each other. I think that's always a concern when you have studies done in different geographical, you know, jurisdictions. I think that what we're showing here is that regardless of ethnicity, regardless of geographic region, our data are really very consistent, which we think adds to the strength of our data set.
In terms of, is there gonna be any more safety analysis at ASCO as well that's brought in from the abstract and even looking at CNS tolerability?
I think, you know, when you speak about differences in regions, I think historically one criticism has been that, perhaps Chinese patients might be more deferential to their physicians and under-report adverse events compared to Western populations. What you'll see from our data set is that we've said they're very consistent. That was not the case. We saw very consistent safety reporting as well as efficacy reporting regardless of ethnicity or jurisdiction. We just think that the data are, you know, very clear. The drug is clearly active, clearly well tolerated, and regardless of where patients receive their therapies, their benefits were similar.
Yeah. By the way, for the audience, if you have any questions, feel free to either email me directly, and happy to read it anonymously on our behalf, or you can also go on the Wall Street Webcast, Webcasting, chat and just put that in there. Again, happy to take it for you. At ISPOR, you presented, and this is literally just a few weeks ago, presented what's known as MAIC. It's a matching adjusted indirect comparison data set looking at taletrectinib against the standard of care or the available drugs. Now, Rozlytrek from Roche specifically, in TKI-naive patients, taletrectinib showed a 58% reduction in risk of disease progression, and also a 52% reduction in risk of death compared to Rozlytrek. At ELCC, you actually did the same analysis against crizotinib from Pfizer, also in the first line.
You know, Rozlytrek is even better than crizotinib, and taletrectinib even beat that. Obviously, against crizotinib, the data looks very good too. It was a 52% reduction in PFS and a 66% reduction in risk of death relative to crizotinib. Maybe when you're thinking about your marketing efforts, how much of that data can you use in your marketing efforts?
I mean, those are published studies. So, certainly we can reference published studies. But, you know, it's always hard to compare patients across different studies, even with the MAIC methodology. I think, you know, we're really focused on just the numbers that we've posted for taletrectinib by itself. If you look at our JCO publication, an 89% overall response rate, 46-month PFS, a 44-month DOR. And we've made the point previously that no matter what drug you look at in any tumor, there are very few drugs in oncology history that have been able to post numbers that match an 89% response rate, 46-month PFS, and 44-month DOR. So, you know, I think that we have to always be very careful across trial comparisons.
If you just look at the magnitude of the numbers that have been posted for taletrectinib just by itself, they're striking. These patients are getting significant and durable benefit. We repeatedly go back to the fact that taletrectinib studies first started in patients a little over nine years ago. We recently had a look back at some of the earliest patients to ever take taletrectinib, going back to our phase one study. We cite the fact that in the first 15 patients on taletrectinib, three of them are still on taletrectinib eight, nine, and nine years out. You know, that's 20% of those first 15 are still taking drug, you know, approaching a decade out.
For a disease as aggressive and relentless as ROS1 non-small cell lung cancer, I think those are numbers that we certainly would not have dreamed of nine years ago. And are really pleased that we are seeing that kind of durability and response.
When you're looking at, you know, the data on the intracranial ORR, it was 77% in naive, 66% in previously pretreated patients. The data obviously looks really, really good. You know, because of the great CNS activity, do you have a sense what percentage of patients have CNS mets at baseline or well-developed CNS mets?
ROS1 lung cancer is particularly aggressive. About 36% of people will have brain mets at presentation, and another 50%, when they do progress, will progress with the brain as the first site of progression. Very, very high rate of CNS involvement, which is why high CNS activity is one of the greatest determinants of long-term survival and something that you really look for in how well a drug has the potential to benefit a patient with the disease. You know, when you look at our intracranial response rate in first line of 66%, that's really, really good. And if you look at just our, again, our PFS and DOR, you do not generally get a PFS and DOR of any significant magnitude if you are not covering the avenues through which these cancers progress and shorten the lifespans of patients.
The fact that we are having such long PFS, and duration of response really speaks to how effective this drug is at addressing resistance and covering the CNS.
Yeah. So let's talk a little bit about, you know, Octiro and Rozlytrek together. Rozlytrek obviously launched about three to four years ahead of Octiro from Bristol. You know, together they're selling just under $200 million or so. What have their recent launches taught you? I mean, crizotinib, just to give the audience, you know, Xalkori before it went generic was selling globally around $400 million. It's thought that probably most of that was in ROS1 because there's obviously other good ALK inhibitors out there. You know, now since it's generic, it's, you know, kind of around $150 million or so on the branded side. What can you do differently is the question to really grow the market?
Right. I think the fact that first-generation TKI sales being even what they are speak to the fact that there is a market out there, even though our own research suggests that a large number of patients who have ROS1 mutations are actually not getting treated with a ROS1 agent. We know that the previous NCCN guidelines actually recommended as one of the treatment options for patients with ROS1 lung cancer, actually IO chemo as one such recommended therapy, the other being ROS1 agent. We know that first-generation TKI sales, even what they are, were in the face of NCCN guidelines that have now changed. As of January 7th, those guidelines have changed. We anticipate significant changes in practice to reduce the use of IO, especially now that IO is contraindicated. We think ROS1 agents will pick up.
Now, if you, and in fact, what we've learned in the last three months is that sales of TKIs has increased about 20% since the introduction of the new NCCN guidelines. I think that Octiro's sales probably suffer from some of the tolerability issues that have been seen with Octiro, specifically in the CNS. I think that if we look at the IQVIA data, they suggest that about 30% of patients are dropping off per quarter, about 10% a month. You know, by the fifth month, about half of Octiro patients are not continuing therapy. It's very hard to build any sales minimum with that, especially in a story which really matures into a revenue stacking story if you do have significant PFS.
I think that the fact that tolerability has been an issue for Rozlytrek stresses or underscores the importance of good tolerability if you want to get long-term use. We think that, given the fact that our treatment-emergent adverse event discontinuation rate is about 6.5%, we think that, you know, speaks volumes about how well tolerated taletrectinib is and why we think that, if you're looking at our PFS numbers, we think that revenues for this drug will stack over about 4 years and make it a very commercially attractive opportunity.
And maybe, Yaron, to come back to your point about market dynamics, I mean, if you think about close examples to the ROS1 market, like ALK and EGFR, those markets were always with NCCN recommendations that were close to what is now ROS1 recommendation. When new agents came, you saw those markets literally explode, like go 3 times, 4 times growth in a matter of years, like a few years. These dynamics that we expect to see in the ROS1 market, we've seen it before in ALK and EGFR. There is no reason to believe it's not going to happen for the same reason, because now recommendations are clear, because drugs have longer duration of treatment, because that's what patients need. Do you anticipate the patients are going to be switching?
If a patient is on IO, IO chemo, would they switch right away to TKI now?
I mean, the NCCN guidelines now have, you know, stated that IO is contraindicated. So that would not be an appropriate therapy for patients. I would think that if they have a ROS1 fusion, they need to be taking a ROS1 agent.
Yeah. Do you have a sense, are patients typically getting care in the community based on NGS, or are they doing the NGS and then sending them to a tertiary center?
The majority of patients are still in the community. We think that about two-thirds, one-third community versus academic center. Still the majority in the community. While the rates of NGS testing may not be quite as high in the community as they are in the academic settings, given the fact that now there are so many precision oncology drugs, especially in lung cancer, that has really increased awareness of the importance of genetic testing. We have seen, you know, NGS testing increase throughout the community with multiple other mutations like EGFR, ALK, RET, and now ROS. We think that is probably a rising tide that should float all boats. I think that we should see significantly improved genetic testing going forward.
By the way, the other point I want to make is that if you look at the current incidence and prevalence numbers of ROS1 non-small cell lung cancer, those are based on current DNA testing. The new RNA test was introduced last year, just about a year ago. It is anticipated that will become the new standard of care. That's important because RNA-based testing detects about 30% more ROS1 fusions than DNA testing. The market is probably about 30% bigger than has, you know, previously been stated. You know, of that 3,000 patients a year with RNA testing, that should be close to 4,000 patients.
Rate case should grow. Okay.
Yeah.
And we've also seen, you know, a conversation in the past few months that many community aggregators have already changed their recommendation to take into account the new NCCN guidelines. We've seen what we would as patients expect to see, which is that, you know, they're changing the guidelines. They're making sure that the guidelines are appropriate for patients. NCCN guidelines come out, they listen, they change. There is a really, really strong dynamic going on right now, which is very positive.
How, you know, Roche is a fairly big company, so is Bristol. And again, these have not been historically big products. It's big enough for them. How aggressively have they been really marketing these drugs?
You know, I can't really speak to that. I think that the challenges that Octiro has had in the marketplace are probably as much attributable to the tolerability of that drug.
Yeah.
As any potential efforts. I think that, you know, Rozlytrek and crizotinib are old drugs and probably not at the top of the priority list for their manufacturers. I think that for Nuvation Bio, taletrectinib is our only commercial product. We will be devoting all of our effort to launching this drug well. We have a very, very experienced team, many from Medivation. You might recall, you know, we were up against J&J, with Zytiga, with our Xtandi. You know, we did very well on that launch. I think that, you know, this will be the only focus of our commercial efforts. We are going to be making that an incredibly high priority. We feel like we have the team to do it well.
Yeah. Can you maybe just remind us how many patients have been on drug in the U.S.? I'm just trying to get a sense kind of what's the potential immediate conversion and maybe a little bit the EAP launched, I believe, in February. You know, how fast has that sort of taken off?
We do have an EAP up and going, you know, because we're in the, you know, we have to be very cautious. We can't really promote that trial. We've been just, you know, for those who have inquired about it, we have informed about the availability of that program. It's not something that we have been able to go out and actively market. We calculate that there's something somewhere between probably 1,000 and 1,500 patients on another TKI already out there. You know, given now the, you know, given the fact that if you look at the average PFS of first-gen TKIs, it's about a year and a half. After about a year and a half, you would expect those patients on average to progress in that timeframe.
For those who are having difficulties with tolerability, you might expect those patients to switch to a drug that they might be able to tolerate a little better.
Okay. So initially it could be, you know, a switching dynamic and then a new patient diagnosis and onboarding dynamic.
I think it's always hard to switch patients because oncologists do have a mindset of generally not making switches unless patients are progressing. I think that unless they're really having adverse events that are intolerable or seeing progression, in general, it's hard to switch patients. I think if they do have tolerability problems or they are progressing, I think a next-generation TKI is the appropriate thing to use.
Yeah. So beyond progression, wanted to maybe just get a little bit of an update. Cedar has been relatively stable within the sea of change at FDA. How has the interactions with FDA been under your breakthrough designation?
You know, they've been incredibly responsive. I have to say they've just been fantastic. We've had incredibly efficient and, you know, very frequent interactions with the agency. We feel that they're placing a very high priority on this drug. We think that's appropriate because, as I said, the profile of this drug hasn't really been seen in many oncology drugs in terms of its efficacy and tolerability. We are very, very pleased with the priority they've given this program. We do anticipate approval no later than our PDUFA date, which is just a few weeks away.
Yeah. If you can, can you comment whether you've been in labeling discussions?
We are.
Okay. And there's no, obviously, you've said there's, you know, they're not, they're not calling an ODEC.
There's no advisory committee.
Yeah. Your breakthrough again is for, it's including front line and second line. So we.
We anticipate a line agnostic label, but our Breakthrough Therapy Designation was granted in first and second line. There are actually no other drugs in development right now that have been granted BGD in first and second line. We think, again, the FDA fully appreciates how unique this profile is. We think that it's going to receive, you know, approval imminently.
Yeah. And so it can be taletrectinib for the treatment of ROS1-positive lung cancer.
Correct.
Essentially, anything in the data that's that we should be expecting to class effect, anything like that that should be called out on the label?
I don't think so. I mean, nothing that is really nothing that you are not already aware of. I mean, we've said all along that, you know, LFTs elevation is a common feature of many TKIs. It's the most common adverse event we've seen. Again, as you look at our discontinuation rate, which to us is the bottom line of how tolerable a drug is, you know, our discontinuation rate is 6.5% for TEAEs, which is excellent. I think that, you know, our CNS tolerability is excellent. We've talked about, you know, a dizziness rate that is very, very manageable and is finished within about three days. Again, a very tolerable profile. I think, you know, no surprises on that front.
Yeah. I want to ask a little bit about, on the conference call, the Q1 call, you mentioned also a few metrics that we should all pay attention to that are going to be important sort of launch metrics. Time to reimbursement, they're essentially leading indicators of upcoming prescriptions. Can you maybe run through some of those, you know, and then kind of in the first few quarters, sort of what should we expect, in this type of a market in terms of sales? I know you don't give guidance, obviously, and you're not even approved yet, but just thinking ahead.
I think what we've been very clear about is that the metric of success for us is patient on therapy. That's where we're going to start. That's where we're going to inform the market after that. I think for us, things like, you know, time to reimbursement are more like internal topics. Obviously, they are important to us. The really more important metric is how many patients can benefit from taletrectinib. That's what we're really working on. I mean, like David said, we have an incredibly, you know, experienced sales team. I think the youngest is a team that's probably 20 years experience in cancer. They know they've done that before. They know what is important.
What is important is to drive those patient numbers higher and to put patients on what we believe is the right treatment, which is taletrectinib for them. That is really what we are going to look at. Obviously, it is a mutation, which is not the most common one. You are talking about 2% of patients. We know there are limits to the kind of information we will be able to gather, but we will be trying to follow up how many patients also potentially are still on IO chemo. David mentioned there is still a big pool of patients there and monitor what is happening with those TKIs as well. That is the kind of things we are going to look at. As you said, we are not providing sales guidance yet.
Yeah. Okay. And then what about European plans, European filing or European partnership plans?
Yeah. We have been very, very transparent about that. We have a partner already in Japan, Nippon Kayaku, and we expect Nippon Kayaku, I should say, to negotiate its price and potentially launch by the end of the year. We also have a partnership in China, Innovent. Innovent, the drug has been approved first and second line in China, but Innovent has not finalized an RDL negotiation yet, so price negotiation in China. The dynamics are a bit different there. We are very actively looking. We're in discussion with multiple parties for a partnership in Europe as well.
Okay. And when you're thinking about pricing in the U.S., I mean, we should assume we should take the cues from the way Rozlytrek or Repotrectinib are priced, right?
We're so close. I mean, you know, we can't comment on it now, but we will, you will have the answer within really just a matter of weeks.
Okay. Let me ask maybe a different question, just factual. What's the price of Octiro monthly and Rozlytrek?
It's about $30,000 a month.
Okay. And again, your median duration is 44 months.
Duration of response is about 44 months.
Yeah. Okay. So EMA looking for a partnership. Okay. I want to talk, I know we're at time, but, safusidenib is very important. This is your IDH1 mutant product for glioma. You are running a phase two study currently in the U.S. with a global expansion plan. This is an open label study, 95 patients. Part one is evaluating PK safety, initial efficacy at different doses between 125 and 500 mg. And then part two is going to be the expansion, looking specifically at grade 2 and then grade 3 gliomas. The study is already fully enrolled, I believe, as of November of last year. So that's ongoing. But separately, your partner, Daiichi in Japan, I believe, ran a phase two. And that phase two looked at dosing.
I believe it was in low-grade glioma or maybe glioma grade 2, maybe some grade 3, but it was low-grade mostly. I think we're hoping and you're hoping to be able to present that data this year. It sounds like that dose is going to be probably the relevant dose that you will take into a phase three that will start by the end of the year. Can you give us a little bit of a sense what should we expect from that data?
That data set will be important because this is a study with only low-grade glioma and only one dose. It will be much clearer what the results are. We're going to show ORR as we've done before. As you might recall, our previous ORR in low-grade glioma was 33%, which is about three times the Indigo low-grade response rate of 11%. We're going to show ORR again in this trial, which is a little bit clearer because it's only one dose and only low-grade glioma. For the first time, we're also going to show PFS. You might recall that vorasidenib was approved in the Indigo study based upon improving PFS from 11 months to 27 months, so a 16-month improvement in PFS.
In spite of a relatively modest response rate, the PFS improvement of 16 months was significant and the basis of its approval. We're going to show data on PFS for the first time in the second Daiichi study later this year. We're excited to share that data. We think that speaks further to why we're investing the investment we are into taking this drug forward, in gliomas.
The phase two that you're running right now, it sounds like you're not waiting for that data to move to phase three.
We are moving to a pivotal study. We have been in discussions with the agency, and, you know, we will be making that disclosure relatively soon about what the design of the pivotal studies will be for high-grade and low-grade glioma.
Okay. So you'll do, it sounds like you'll do both, right? High and low. And I, one would imagine, would be two different studies.
Certainly, high-grade is a completely unmet need since there's really nothing that has shown any response rate in high-grade glioma. With low-grade glioma, you know, there is vorasidenib that's already approved. That does make the potential approval pathway a little bit more complicated. We are in discussions with the agency about what the best path forward is there. Once we've reached agreement on what that path is, we'll make that disclosure publicly available.
Yeah. Does it make sense to go head-to-head against Repotrectinib?
You know, these are all discussion points that we all will probably talk about after we finish our discussions with the agency.
Yeah. And just for the audience, you know, vorasidenib does not have any activity. I think it's literally 0% in high-grade. You had 17% in your high-grade, so at that point, you can go head-to-head against chemo, presumably. Chemo usually gives you about 5% or.
I mean, pretty poor responses in general. And more striking than the 17% response rate in high-grade is the fact that we've had about a third of those responses have been complete responses, lasting, you know, years. One patient about two years, one patient about almost three and a half years. Those are responses you just generally don't see in high-grade glioma. So we're, you know, we're very confident this drug has real activity. And we're just trying to figure out, you know, the fastest and shortest path to get this drug to patients.
Yeah. Terrific. I know we're running a little bit over, but thank you so much. Good to see you as always. I'm looking forward. We're going to see you over the weekend.
Thanks so much, everyone.
Pleasure. Thank you, John. Take care.
Thank you. Thanks, everybody, for joining us. We really appreciate it. We're doing several events at ASCO. Hopefully, we can see you and have a good trip into ASCO.