Nuvation Bio Inc. Cantor Global Healthcare Conference

Hello everyone. Welcome to day 2 of the Cantor Global Healthcare Conference. My name is Lee Wozniak, a biotech analyst here at Cantor. It is my great pleasure to welcome our next company, Nuvation Bio, for a fireside chat. With me today is David, CEO, and Philip, CFO. Thank you for joining me. Maybe David, I will turn it over to you to give us a 10,000-foot view of the story before we get into the pipeline.

Great. Thanks, Lee. Thanks for having us. Nuvation Bio, I think we are on really solid footing. We launched IBTROZI, our ROS1 inhibitor, a little over a year ago. I think with now all competitors' data out in the open, I think it is pretty clear that IBTROZI is the best drug in class. If you look at our efficacy, 90% response rate, 15-month duration of response on the first-line setting. That is actually never been matched by any drug in any indication in oncology. So I think we are clearly the best ROS1 drug. Our tolerability, again, with an overall discontinuation rate of 6.5%. Discontinuations for any of our top 6 adverse events at 1 in 337 patients. Again, extremely tolerable drug. The reason that this opportunity is so unique and underappreciated is that very few drugs in oncology have durations of response that are even close to 50 months.

Because of the 50-month duration of response, that leads to revenue stacking that you generally just do not see. Even though the epidemiology tells you that there are 3,000 ROS1 patients newly diagnosed in the first-line setting every year, if we were just to multiply that times the current drug price, that would be $1 billion a year. For every year thereafter, up till 4-plus years, you would expect an additional $1 billion. So $2 billion in the second year, $3 billion in the third year.

$4 billion in the fourth year. So that is where you can see the revenue stacking leads to a significant number. That is with the epidemiology based on DNA testing, which is 30% less sensitive than RNA testing. When RNA testing becomes standard of care, we could even see that potential $4 billion market exceed $5 billion. Where are we with relation to that? As I said, 3,000 new patients a year by DNA testing, that is 250 patients per month. If you look at the number of first-line patients, in our first quarter of launch it was 70, second quarter was 80, third quarter was 100, fourth quarter was 140. If you just look at where we are right now, at 140, that is almost 50 patients a month. The market is 250 patients per month by the epidemiology.

After a year, we are already a fifth of the way to capturing the entire pie. We think that with other new changes, like the NCCN guidelines changing to now contraindicate IO, that will further increase the adoption of ROS1 agents. Then with a general increase in testing, that will further increase the uptake of drugs like IBTROZI. I think we are doing extremely well on that launch, and we look forward to updating you with every quarter that we announce our sales for the quarter. Safusidenib is our IDH1 drug for gliomas. I would say that that program is really exciting because we just recently announced 3-year follow-up data with that program.

If you look at our only competitor in the space, which is vorasidenib, if you look at safusidenib's non-progression rate of 79% at 3 years, so only 21% progression at 3 years, we would say that that has just not been observed before in gliomas. Our response rate at 3 years has increased from 44% to 52%. Again, not observed before. I would say that program looks extremely promising. We are going after all four pieces of the glioma pie.

So low risk, low grade, high risk, low grade, low risk, high grade, and high risk, high grade. You have four clinical trials that are targeting all four pieces of that pie. The SIGMA trial is a PFS study that will not read out until 2029. We have a study against placebo that will also be a PFS trial that will read out in 2029. But we have two other trials that have response rate endpoints that could read out significantly sooner. One is a grade 3 oligodendroglioma trial. Because these patients all have measurable disease, we will be using response rate as the primary endpoint. If we look at Chimerix, which got their drug approved in DIPG on the basis of 11 responses out of 50 patients, we think something around a 20% response rate is potentially approvable. Then we are doing another study, which is in post-vora failures.

These are patients who failed vorasidenib, and if we show responses with safu in those patients, we think that is really exciting, because now these patients have no other treatment options today, and we believe that would allow us to capture the entire vorasidenib market. Again, VORANIGO has treated more than 6,000 patients since launch. We know that the progression rate for vorasidenib at 1 year is about 23%, so about a quarter of those should have failed by now. We think we need to get something like 50 patients and show roughly 10 responses.

to potentially have an approvable package. We are pretty excited about that. Our drug conjugate platform is our 2-small-molecule conjugate platform, which is kind of like an ADC without the A. We are using 2 small molecule drugs. We are going to announce an update on that in the second half of the year. From a cash standpoint, we have $700 million on the balance sheet, so we are very comfortable, far more than we need to get to profitability. With that, I think we are feeling very comfortable where we are.

Yeah. That is a great overview, David. Let us start with the Yervoy launch. As you mentioned in your Q2, you had a very nice frontline patient mix in terms of percentage. It is about 85% in new patient starts. How should we think about the long-term growth trajectory from here as you guys shift more Yeah towards the frontline?

Yeah, so that is a great question. As I mentioned, we started with 30% of our patients in frontline to 40%. Now it is 85% in the frontline setting. With that, we have still only captured, right now, 20% of the theoretical 3,000 patients per year in the frontline setting. So where else are we going to get it from? First of all, we are already the market leader among our competitors but there's still more to be had.

There's still some Repatha sales. There's still some crizotinib sales. We hope to eventually cannibalize all of that. Number 2, in spite of NCCN guidelines, we know that especially in some community centers, IO chemo is still being used. In some centers, as much as 40%. We think that as NCCN guidelines kick in and people start to really realize there's a many-year difference in survival between IO chemo and a ROS1 agent, we think that we will start to convert that IO chemo use to ROS1 use.

And that's going to also potentially even double our sales. Then on top of that, we know testing rates, while they're high in the academic centers, in some community centers can be as low as 30% to 40%. So we have potentially even double sales based on just improvement of testing rates in the community. We're at 50 patients now. If we were to double from IO chemo, that would take us to 100, and if we were to double that from testing, that could take us to 200. And that'd be closer to the 250 theoretical patients that are maximally available in the frontline setting.

we are going to continue to just educate physicians on the vast difference in outcome between IO chemo and a ROS1 agent. We'll continue to take market share, we believe, from other current ROS1 agents. And testing in general has increased because many precision oncology tests now have turned lung cancer into one of the most treatable cancers on the planet if you know you have one of these mutations.