This session, Fireside Chat with Nuvation Bio. I’m Soumit Roy Head of Healthcare Research at Jones and with me , we have the CEO of Nuvation Bio, David Hung, and the CFO, Philippe Sauvage. Really appreciate you coming here, despite of the challenging times [in biotechs too much as] but you have seen the [cycle] many times so really appreciate you coming here. David is well-known in the [biotech space], he has lead the development and [inaudible], which is now the standard care for prostate cancer and successful acquisition of Medivation by Pfizer for $14,000,000,000. He has seen developing a drug from ground up all the way to [inaudible] acquisition, so definitely it is [inaudible] to learn from.
Nuvation Bio is a global oncology company solving some of the toughest challenges in cancer treatment by developing therapeutics that create a positive impact. The company's lead programs are two potentially best-in-class drugs for lung cancer and glioma. Compared to peers, both drugs are showing durable responses and prolonged survival. We really believe these are potentially two best-in-class drugs. Nuvation is on the cusp of becoming a commercial stage company by mid-2025. The PDUFA date is June 23rd, and we'll ask something about how the FDA is doing in that regard for certainly. The company's ROS1 inhibitor for ROS1-positive non-small cell lung cancer. To begin with, David, maybe if you can give a brief intro on the Nuvation Bio and what we should be focusing on in 2025.
We have four drugs in our pipeline. The most advanced one is Taletrectinib, which is a ROS1 inhibitor. We anticipate FDA approval on June 23rd. This is a drug for a kind of lung cancer driven by a mutation called ROS1. It's extremely aggressive. A normal standard of care, which is IO chemo, generally gives you a progression-free survival in the range of 6-12 months. Our drug, our median progression-free survival is 46 months. It's almost four years. We've had patients on our drug that are still on drug approaching eight years now. We think it's an extremely robust benefit.
That should get FDA approval in June. We've gotten priority review, and we were already granted breakthrough designation by FDA, and we anticipate a line-agnostic full approval. We're excited about that. We have a second drug in development called Safusidenib.
It's the only other drug currently being developed for a kind of glioma, brain tumor, called IDH1-mutant glioma. The one drug approved in that space is Vorasidenib, made by Servier. About six months ago, Royalty Pharma did a deal paying almost $1 billion for a 15% US-only royalty of Vorasidenib, which values Vorasidenib at around $6 billion. Vorasidenib's pivotal study showed an 11% response rate in low-grade glioma and no responses in high-grade glioma. In our first study with our partner, Daiichi , Safusidenib showed a 33% response rate in low-grade glioma, triple the Vorasidenib 11% response rate in their pivotal study.
In high-grade glioma, Safusidenib has now shown 17% responses. A third of those responses are complete responses. Complete response in oncology means the tumor has disappeared. One of those tumors that disappeared was a very high-grade aggressive brain tumor known as glioblastoma.
These are virtually untreatable. That patient's tumor has been gone for now 3.4 years. We have a second patient with another high-grade glioma, and that patient's tumor has now been gone for 95 weeks. We think this drug is extremely promising and are now in discussions with FDA to take that into a pivotal study in 2025 as well. We have a third program in something we call a drug-drug conjugate program. It's kind of like an ADC without the A. It's two small molecules fused together. We've shown activity that appears quite interesting, and we anticipate further data in 2025 as well. Three major things. We have Taletrectinib approval in June. We have Safusidenib entering pivotal studies in glioma and potentially more data on our DDC program this year.
It's very exciting, especially a lot of people are looking forward to launch of, which is kind of the name of the session, is launching a drug in a crowded space. We have three approved ROS1s, one getting off-label used by Pfizer's drug. In the Pfizer, you know, Xalkori sells, but at the same time, Roche has pulled back, BMS has pulled back. Really curious when you reach out to clinicians if you have done some kind of survey to gauge their level of interest and what are the key points you try to focus on and any pushback you get?
Yeah. We have done extensive market research. If you look at, and it will make sense, this is common sense. If you look at a patient or a doctor, the number one attribute of a drug that they care about and that determines prescription and use is your progression-free survival. That is by far number one. The second most important number is your response rate. Our progression-free survival of 46 months is, you know, and our response rate of 89% is actually unique. In the history of oncology, there are no drugs in any solid tumor that have been able to match an 89% response rate and 46-month PFS. Even Xtandi, the drug we developed at Medivation, which is almost a $7 billion a year drug today, Xtandi's response rate was 59%, PFS was 20 months.
With an 89% response rate and 46-month PFS, we think this is just an extremely promising drug, and we think it'll do very well.
The data that supports, like you mentioned, you're going for the line-agnostic label from the two of these phase two trials. Any risk you see? I'm curious about the conversations that when you showed the data, they're like, "Yeah, go for line-agnostic." I'm like, "You know what? File first, let's see, and then maybe you will get later lines and front line you have to do.
Yeah. The FDA has been extremely helpful and positive. In fact, despite all the turbulence in Washington, I would say the FDA has been incredibly responsive to our application. We've been really, really happy with the amount of attention we've gotten and the efficiency with which they've interacted with us. As I said before, you know, if you look at our response rate and PFS, there are no drugs in solid tumors ever that have been able to match that. We think that their responsiveness is appropriate for the potential that we could be offering patients with this therapy. We've been very, very pleased with our FDA interactions. We are going to get a line-agnostic full approval. That is clear. You know, as I said, our PDUFA date is June 23rd. We should be approved on schedule.
You're ready to go hit the market right after.
We have our commercial team fully hired. Many of them are from my Medivation days. I know them well. They know me well. We are ready to go.
Yeah. That is exciting. Going back to the previous surveys you did with the physicians, have they talked about the sequencing of the drug, how they want to handle, where should.
You know, if you think about the value proposition of our drug for patients, right now, if you look at first-generation TKIs for ROS1 -positive lung cancer, there's only two, Crizotinib and Entrectinib. Entrectinib is the only one that gets in the brain. That's important because brain metastases are a common place that this cancer appears. The average PFS of Entrectinib is 16 months. If you start with Entrectinib as a first-generation TKI and you fail in 16 months on average, and you go to Repotrectinib, the only approved second-generation agent, you get another nine months of PFS. Sixteen plus nine gives you 25 months. If you start with Taletrectinib, you get 46 months as a median PFS, which means that if you just start with Taletrectinib, you get almost two years longer PFS. That's what the data show.
I think that's a very compelling argument for physicians and for patients.
At the hospitals, do you see Roche or BMS a major competitor, or is still Pfizer the main drug you have to beat?
You know, I think certainly Pfizer's drug was the first drug to get approved, Crizotinib, but Crizotinib and Entrectinib are both coming off patent shortly. They're not being actively promoted. As you know, BMS's Repotrectinib has struggled because of the really high incidence of CNS toxicity with that drug. We know from IQVIA scripts that 30% of Repotrectinib scripts are not being refilled every quarter. They're falling off every quarter. We think that Taletrectinib is very well positioned. Our CNS side effects in our pivotal studies have been very manageable. Our efficacy, as I've mentioned, is 46 months and an 89% response rate. We think that this is a really robust choice for patients when it becomes available.
What do you say to the market? Because as you're, you know, this is a billion-plus dollar drug at the least, and it feels like line-agnostic is baked in, approval is baked in. You will launch, and it will be at least second or third drug in the market.
You know, I think the markets are, you know, right now, it's a very difficult time in the markets. I think that, you know, it's probably a lot of distractions. I'm sure we're not at the top of the list for attention in markets as turbulent as these. We're, you know, we're fine. We have, as you probably all know, we had over $500,000,000 on our balance sheet as of last quarter. We just announced a deal with Sagard where we raise another $200,000,000 when we get approval of the drug in June and option for another $50,000,000 to draw down on top of that. It gives us access to about $750,000,000 in cash, which should be enough to take us through to profitability, to easily take us through to profitability.
You know, I think our stock is really, you know, we're trading below cash. I just am not, there's a forum for went out last night. I just bought $500,000 shares myself last night. One of our directors also bought shares last week. You know, we think we're not raising money. We're happy to just let things calm down in the markets. We're going to launch our drug. We're very confident that we'll do well. We're not really at all swayed by what's going on in these markets.
Any pushback you get from investors in terms of safety concerns?
No, as I said, you know, we think our drug is incredibly well tolerated. If you look at the discontinuation rate of our drug at 7% with treatment emergent adverse events leading to discontinuation, that's really an extremely tolerable profile for any cancer drug. We feel, you know, we feel very, very good about that. If you look at our 337 patients in our efficacy database, only eight had adverse events that were related to our drug. So we think it's a very well tolerated drug. As I said, you know, on the safety side, another point I should make is that by far the greatest safety risk to any patient is progression of their cancer. Once their cancer comes back and progresses, it doesn't matter what other safety events you have, because you don't have any options.
If you look at our PFS of almost four years, you know, that's a year. I mean, if you look at Repotrectinib's PFS, it is 36 months. If you look at Entrectinib, 16 months. We think that by far the most important safety concern should be, can you keep that cancer away? And we think Taletrectinib's profile is a really good answer to that.
Switching to the IDH1 inhibitor, you acquired it last year. Interesting because you found something in the rough at the pricing and showing remarkable data. Tell us a little bit of the backstory of finding the product and what really attracted you. Like, you know, first comment I get is, does the world need another IDH1 mutant? And then I look around, there is only one approved.
Yeah, I mean, you know, so we, you know, if you look at my career, I, you know, made most of my career made, you know, acquisitions. Xtandi was an acquisition. You know, we tried to find diamonds in the rough. You know, we looked at over 200 opportunities over the last few years. We really did not like anything. Finally, we found this company in China in the middle of, you know, COVID lockdown China.
It is a private company, had a couple of assets that we really thought were promising. We reviewed, we did scorched earth diligence on them. We reviewed the FDA correspondence. We really liked it and decided to buy the company. Our first two offers of the company were all cash offers. They were both rejected because they wanted stock because they really liked our other program.
We ended up doing an all-stock deal. Anytime a company wants you to pay for them in stock, it's also further validation of their assets. You know, we ended up paying for AnHeart with $280,000,000 in stock. With that, we now have Taletrectinib that's launching in June and Safusidenib, which is entering a pivotal study. We think, you know, that was a great return. If you look at the deal we just did with Sagard, you know, we just raised, you know, up to $250 million. Our royalty is 5.5%.
Yeah.
$150,000,000 of synthetic royalty for only 5.5%, up to $600,000,000 of sales. If you think about the price we paid for the acquisition of $280,000,000, we already got $150,000,000 back for 5.5%.
That was value.
Sales.
That would value Taletrectinib well over $2 billion.
You can see the value creation here. It's pretty explicit. I think to your earlier point about what there is a lot of turmoil in the market, and it's probably hard to pay attention. Analysts or investors that really pay attention to us see the value. That's true of Sagard. We need to do a lot of due diligence to make that deal. That's true of all the analysts that follow our stocks that all have price target way above where we currently sit, right? That's the reason why we're here, right, talking to everyone, making sure that everybody gets the story because we believe we have something very compelling here in terms of value creation for any investor, just like David yesterday.
Right. Touching a bit on the phase two data that you already have with the IDH1, is there any particular differences we should think about the trial you're running versus the data you have, the mutation profile or tumor subtypes, location, because once you get into that range?
You know, if you look at our data, we have two data sets, two trials, with Safusidenib so far. One has been made public. It's with Daiichi. That's the one where we reported a 33% response rate in low grade, 17% response rate in high grade with those two CRs. We have a second data set coming out this year with Daiichi, which is even more important in some ways because it's now only one dose. It's much easier to interpret. It's only in low grade. For the first time, we're going to present not only our response rate, but we're going to show progression-free survival. That was the basis of approval of Vorasidenib. We're going to show numbers this year, which we think really justify why we're investing in this program and taking it to a pivotal study.
You know, I can't talk about what the design will be yet because the FDA hasn't finished their feedback with us. We want to make sure we are, you know, completely make sure we have everything designed the way what we need for approval. We are still finishing our discussions with FDA on that. As soon as we finish those discussions, we'll announce the pivotal design. We anticipate starting that trial this year. We think this drug is, you know, there's only an N of two of competitors in the space. We think that our drug looks pretty promising from the data we have already so far.
If you peel back a little bit, in the data, I don't know if it's a function of a smaller cohort size, there is more activity in the enhancing tumor types versus the non-enhancing. There was no CR versus Vorasidenib. When we look at it, it's like they work in non-enhancing type rather than enhancing.
Yeah, so Vorasidenib's response rate high grade. So enhancing means high grade, non-enhancing means low grade. So Vorasidenib had a 0% response rate in high grade, and we had 17%. In low grade, their response rate was 11% in their pivotal studies. Our first study showed 33%. So whether it's low grade or not, enhancing or not, we think Safusidenib shows a higher response rate, which is why we are so excited about taking it to a pivotal study. We're going to present, as I said, more data this year, which we're going to give you for the first time a glimpse, not only at another data set for response rate, but for the first time progression-free survival, which we think is an important metric.
As I said earlier, at the end of the day, the thing patients and physicians care the most about is how long can you keep the cancer away. We think this is a huge, hugely important metric, and we're going to present that this year.
Is that a small timeline?
We have, you know, we're still working with our partner Daiichi to figure out a time frame to present it in, but we'd love to put it out, you know, as soon as possible. We think it's an important data set.
In terms of the genome mix up population, there's going to be pretty similar.
Yeah, so if you look at subtypes, you know, you know, I think the R132H variant is 98% of our glioma in our trial. That's the most common type. There are other variants. We don't, you know, we don't really pay attention to that. This is our bread and butter glioma study.
Really would love to get a sense from you in the last couple of minutes, since you're in close touch with the FDA, with the recent changes and, you know, timeline. Usually, it used to be a month or even two months ahead of PDUFA, there will be decisions made, the positive decisions. Anything?
You know, I don't know if it'll be early. I mean, it could be. As I said, we've been really impressed and grateful how responsive FDA has been. We think they're doing a great job. We think the review team has been extraordinary, actually. You know, we feel really, really good about where we are. We anticipate approval at the latest at our PDUFA date, but could it come earlier? You know, it's always possible.
I think that the NDAs that have already been submitted are getting the appropriate attention. I think it may be more challenging for companies that have not yet submitted NDAs. You know, there is a big layoff. At some point, it's going to be some impact of that on future applications. For this application, we've seen absolutely no evidence at all of any slowdown at all.
In fact, to the contrary, we've been really impressed with the efficiency of our interaction with FDA.
Of course, we're making sure, I'm sorry, that our commercial team is ready in any case. We've hired the commercial team. They're getting ready, even if we were approved earlier.
Yeah, we're ready to launch.
We're ready to launch.
Yeah. In terms of the ex-US territory, Europe or something you have indicated, likely going to be partnered out. You don't want to manage that aspect of it.
Yeah.
Is that a 2025 event we should expect, or there's going to be?
Yes, we're in current discussion with multiple partners right now. We've been very pleased with the quality of the interactions. For a biotech of our size at our stage, launching in Europe is a bit too complicated. We don't want to bother ourselves with that, even if there is good value to be created there. We are looking for the right partners, somebody that can help us out there with strong experience and strong local footprint. We're already partnering in Japan and China, like David was saying earlier. We've had great interactions with Innovent in China and with Nippon Kayaku in Japan. We were actually there last year, and we met them with David. We are looking for somebody of that quality for Europe.
That's great. Thank you again for joining us.
Thank you so much.
This is great for us to present your story. If we can't sell this, I don't know what we can.
Thank you so much.
Thank you. Thank you again.
Thank you so much. Thank you.
Next session is with another very exciting area, Wave Therapeutics. Catherine Novak will be moderating the session. Please stick around. Looking forward.