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

So if you look at the only competitor we have in IDH1 glioma, it's vorasidenib. And if you look at their INDIGO study, which is the study upon which they received approval in their Phase III study vorasidenib had 11% response rate in low-grade glioma and a 0% response rate in high-grade glioma. When we announced our Daiichi data, we showed that if you look at in low-grade glioma, safu, whose response was 44%. And in high grade, it was 17%, but 1/3 of that 6% or complete responses, which means the tumor disappears. We had a GBM patient whose tumor disappeared for 3.5 years, another high-grade oligo that's been gone for about 2 years. So very, very, very robust responses. If you look at progression rates in the vorasidenib trial in INDIGO, at 1 year, there was a 23% progression, we had 4%. And in the INDIGO study at 2 years, they had 41% progression and we had 12%. So again, pretty big. Now we both vorasidenib and safu both announced recently a 3-year follow-up. And at 3 years, if you look at the non-progression rate for the safu arm now. It's 79% at 3 years out. So it is really just not really been seen before. So that's a very, very durable response for a brain tumor that has had no therapy really until vorasidenib. If you look at our adverse event profile, 8% or 7% of our only 7% drug discontinuation due to drug-related adverse events, which is pretty well tolerated. So I would say that, that efficacy and that tolerability, we feel is going to be a winner for us. This is a huge market because even though the actual number of patients with glioma is about the same as ROS1, low-grade glioma patients can live for 20 years plus without drug. And even high-grade patients can live 4 to 7 years. So we're talking about the worst patients still having a potential DOR longer than IBTROZI in first line. And the low-grade glioma was having a potential DOR 5x of IBTROZI if that materializes, that would be one of the largest commercial opportunities ever see in oncology. So I said that IBTROZI, if you look at the TAM there with RNA testing, it could be $5 billion a year maximum TAM. Well, in low-grade glioma, it could be 5x that because it's just 5x longer DOR, right? So if you look at vorasidenib pricing, they're priced at $40,000 a month, so 30% higher than IBTROZI. So just looking at that, that makes the TAM of this opportunity dwarf ROS1. And we think ROS1 is already big.

Are there lessons learned from the Servier launch. I know we don't have a lot of visibility on that. But from a commercial setting, right, like can you look at that to have a proxy for awareness. Can you look at your clinical plan maybe to try to pull the trigger a little earlier? I know you mentioned response rates...

Right. So we can only glean Servier sales from Royalty Pharma's royalties. But when we look at the Royalty Pharma royalties in the last quarter, vorasidenib is on about a $2 billion a year run rate after only 18 months on the market. So it's done great. It's the only glioma drug approved. So it's done great and the market is there. And there are no conflicting practices like IO chemo or something because no one does that for brain tumors. So I think the vora launch has taught us that the market is exactly what we think it is. It's there. It's for -- there for the taking. We think that -- I just -- I mentioned that at 1 year vorasidenib expression rate is 23%, which means that in the 18 months since launch -- as of last quarter, they had treated over 5,500 patients, which means 1/4 of those have already progressed or are progressing. So that's well over 1,000 -- 1,250 patients that are already progressing and in need of another agent. So that market is there. So we think that safu will fulfill that need.

I guess what sort of KOL feedback are you receiving regarding safu and the opportunity there?

We received shockingly positive KOLs feedback. Most of these KOLs are reluctant to call a drug better than another without a head-to-head trial. And almost every killer you spoke and you said, yes, your drug is better than vora. So that's something we don't see very often. We just had a major KOL, one of the large institutions here make that comment to us. So I think the data are hard to compare because it's, as I said, when you have almost 80% of your patients still on drug at 3 years, there isn't anything close to that. So I would say that our KOLs love this drug. I mean our trials are enrolling exactly on track because people like the drug.

Great. Yes. You mentioned data 2029. Can you maybe walk through the trial design and maybe what we can see.

Yes. So this is a maintenance study for -- it's called the SIGMA trial, and it's the patients who fail standard of care therapies, and it's against a standard of care, and it's a progression-free survival endpoint. So that will just -- it's a slow when you wait for events to look for progression. You have to wait for progression if you have a drug that has a really long time to progression, it's going to take a while. So we think that, that study will read out in 2019, shouldn't be long within that. It's been on track for enrollment. But I think that what's maybe more exciting to investors and also in some ways to us because we want to get this drug out as quickly as we can. We're looking at a number of studies, populations that are amenable to an end point that's a little sooner to read out. So one example of that would be Grade 3 oligaldendlioma. Almost all of these patients have measurable disease, unlike the SIGMA patients who don't always have measurable disease all the Grade 3 [indiscernible] have vegetable disease, which means that they have a tumor that can be assessed for size and response when you treat it. So that should be a response rate that we can see. We have another study, which is maybe even more exciting, which is the post for [indiscernible] trial. These patients, as I said, 1/4 of them will fail or in the first year. Once they fail, they don't really have a lot of options. And we can show responses after failure. And we know these tumors are there because they're growing because they're failing, right? So they're actually growing. Safu can shrink those tumors, I think that will have a huge halo effect on people's perception of the drug to work or something is failed, I think, always makes it drug look superior. So I think that we can show changes in response compared to vora, I think that's going to be a very positive trial for us. The second thing that I mentioned on last quarter earnings call, is that we're also looking at something called tumor growth rate because -- when tumors are growing, their slope is positive. When tumors are shrinking their slope is negative. You cannot go from a positive slope to a negative, so without changing your slope. I mean -- so that has to reflect the change in tumor growth rates. So we've actually now looked at our data and have shown that in every one of our cases where people were patients respond to therapies, there is a change in tumor growth rate. The growth rate slows and then it goes from positive to negative. And we think that's clinically meaningful. Now the FDA doesn't currently accept that as approval endpoint. But we -- as we accumulate more and more data, we intend to continue to pursue that conversation with them because I don't think anyone's going to argue that a growing tumor is less good for a patient than a shrinking tumor, and that's reflected by the TGR tumor growth rate. So response rate is still a gold standard endpoint, but we think tumor growth rate can and should be another endpoint to consider, and that would be even sooner to read out than response rate.

Quick question on the development plan. Is there a switch study maybe to do over the long term I know obviously, you're going after patients that are refractory and and that's a tangible population. But do you think, eventually, you could do something to that degree or maybe an earlier line, what are the challenges, I guess, of having vorasidenib as the standard of care.

Yes, I do think that it's interesting that even today, we're getting a lot of calls from low-grade patients who are contemplating Vora, we would rather be on safu. And they're asking if they're eligible for our trials because they've seen the data and they think the data are better. So we do think that if we show responses in any of these populations, SIGMA, the Grade 3 algo, the post-FEO study. We think that, that would be compelling for patients to receive it earlier and earlier because as good as Vora is, their data doesn't really compare to safu. And I think that our hope would be that patients don't even switch. They just start safu matter what they have because I think it's probably the better drug they have low-grade or high-grade disease.

Geoff, what's important to keep in mind is that, of course, we are talking about several trials, but they hope, at the end, accumulate to build a whole German population, right? You have the low-grade glioma. We're doing that ex U.S. in places where you have no access to vora. So that puts us into approval there and to be used exactly in the same place in vora can be. But then with the post vora, evidence of further efficacy is a great free oligandroglioma, evidence of first efficacy and with a high-grade glioma evidence that we work even when vora doesn't. And I think when you sum all of that together, it becomes pretty clear that feel successful for all those trials, we are going to grab the whole market because why would you pick something which is less efficacious, especially for something like a brain tumor.

Great. Yes. I guess, could we talk a little bit more about the global opportunity. I guess, how is awareness ex U.S.? And just how are you looking to expand?

This is a disease, which is obviously everywhere in the world and everybody will treat it. So I think from the point we are making earlier, we still [indiscernible] it's a very different proposal because to some extent, ROS1 can be missed. This will not be missed. And this will be only in centers that are very strong, doing brain cancers. You don't do that everywhere, right? So I think in terms of promotion, a number of places we need to go and to where it works, it's a very easier to some extent, population to reach, if that's your question. Then vorasidenib today is in the U.S. I think they just got a pricing in Japan, which was relatively high, which is good news for the value that we put in that market. They are in negotiation in Europe. We will develop something for the whole world, just like we did.

Yes. As Philippe said, it's really hard to miss a brain tumor because the brain is confined by the rigid skull. You can't grow without causing so much pressure that you get clinical symptoms. So no one misses a brain tumor. It's a diagnosis is pretty quickly. So I think that, that the market is there. We've already seen Devora uptake they're selling a ton of drug they have extremely high uptake. And in fact, they're even getting uptake in patients who are even on their label, a testament to how desperate these patients are and how much they need some therapy. So we can show what we hope to show in these populations. And we think that we -- safu could and should take the entire glioma market.

Great. I guess any other safu, we can move over to DTC. Great. Yes. Let's talk a little bit about the DTC platform. Maybe could you walk us through the technology here and how it could be differentiated?

So the idea behind the DTC is -- so we certainly all know about ADCs, but the problem with ADCs is the A part is really big. So it doesn't allow that molecule to cross sell membranes very well. Many of those ADCs have to be cleaved to release their ore head when they released the ore head, that work is no longer actually targeted. It can diffuse elsewhere, you get initial pneumonitis, you can get lots of systemic side effects. So the idea ADCs is taking -- making the targeter and the warhead both small molecules or combining 2 heads. You can mix and match your payloads in multiple ways. But because they're all small molecules, they're in order of magnitude smaller than ADCs and now readily can access intracellar compartments and go into the cell and get into the tumor. So we think there are real advantages there. When we started our program a year ago, we had a candidate that we took into the clinic and when we got into humans, we learned a lot of things about how these -- this is a first-in-man study. So when we learned a lot of things about how 1511 work when we were in patients. And while we actually did see responses, it wasn't perfect. We learned things that we thought we could improve and our idea is that if we take a program into into the clinic, our hope is to take it into pivotal studies, but if we're going to commit $100 million plus to a pivotal study, we want to make sure that molecules as fine-tuned as we can make it. So we decided to do that. We decided to redesign some of our molecules with some of the considerations that we learned from our first study. And we've been doing that. And so hopefully, later this year, we'll be announcing an update to that program.

And just to be very clear, this is really hard to do, right? Don't take it the wrong way. Because it's very easy to combine 2 molecules to make something that doesn't do anything at all. That's relatively easy. But to combine 2 molecules to make sure that it retains both properties that made those molecules very successful when other in oncology. That's a hard part. And that's why we've been really building a lot of understanding of the way that works, and that gives us a potential of having really this strong platform where we can come up with more and more molecules in that space. And if you can combine them and on top of that, make them synergetic, then it's really the holy grail because what we see in ROS1 or IDH1 disease that are driven by a single mutation to some extent, very strongly by a single mutation. So that's easy. But that's unusual in cancer. In most cases, you have several processes going on at the same time. But you can combine your agents, make them synergetic so that you're blocking several parts of the several processes going on, then you can hope towards the same kind of super long efficacy we've seen in ROS1 and IDH1. And that's the promise of our DTC platform.

Phillippe is right. It took us 5 years to figure out the chemistry. It's really, really tough. But when we do see activity, and we managed to make a molecule active on both ends we see activities we see profiles that we don't see with any other agent. So it is exciting, but it's been challenging.

I guess final question. When you think about Nuvation, looking to next year, maybe talk about what you think the most compelling part of the story would be, is it the commercial adoption? Is it potential data?

So next year, I think there are a couple of things you'd like to see. Number one is IBTROZI really starts to take off with the first line in revenue stacking. We think that we are clearly going to be the leader in that area. So we're excited to see that finally take hold and testing increase and IO chemo use go down. We think safu should have some -- we're going to start to see some data from our trials next year. So it's hard to know when. Our shortest time, the response in a safu is a response in 2 weeks, but our longest time is over a year. So that's why we can't really tell you when we think we're going to see those responses. But we know we do see responses and when we start to get those, I think that's going to be super exciting because as soon as we see any significant responses, we're going to be going to FDA ask them, what do you need to approve this drug. As I said, Chimerix had 11 responders to get approved. So it's not a lot of patients. And then hopefully, we'll have DDCs chugging along, and we'll still have a ton of cash. And we're also looking out always for exciting business development opportunities. And so that's something else that we also keep focusing on.

Okay. Thanks, guys.

Thanks so much, Geoff.

Thank you, everyone.