... So, welcome to the Cantor Fitzgerald Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst with Cantor. With us, we have Verastem, a company we cover, and I'm pleased to introduce Dan Paterson, our CEO, and Jonathan Pachter, our Chief Scientific Officer. So, welcome, and let's just start off with a brief introduction of yourselves and a brief description of the company for those who may not be familiar.
Sure. So, we develop small molecules targeting the RAS pathway. We had our first approval earlier this year in a rare form of ovarian cancer, low-grade serous ovarian cancer. A couple notable things about the approval. It was, as far as we know, the first total novel approval in oncology, so it was two drugs at the same time that had never been approved for anything before. It was also the first drug or drug combination ever approved specifically for low-grade serous ovarian cancer, which is a form of ovarian cancer that tends to strike younger women, resistant to chemo, very poor outcomes, and so very excited to have that approved. And then, in today's current environment in Washington, also surprised to get approval about two months before our PDUFA date. So, you know, that's our first program.
We have another program targeting KRAS G12D, which it's partnered with a company in China called GenFleet. They've developed quite a bit of data in China. Some will be reported this weekend, actually, at World Lung. We've had high response rates as a single agent, both in pancreatic and lung cancer, and then we're progressing that here in the United States. We started our phase one in June, but we started with a very abbreviated dose escalation schedule because of the data that had been developed in China so very excited. You know, this is a transformative year for us, both with very exciting data on a potential best-in-class, potential blockbuster, and then we got out of the gate pretty quickly with our first partial quarter of revenue on our launch so excited about that.
Yeah. So first of all, congratulations on the approval, you know, for low-grade serous ovarian cancers. Many years in the working, and nice to see, but also nice to see, like you mentioned, it being approved earlier than expected.
Yeah, and John and I have been working on it for about 10 years. We started working on it before we even had the drug. We had one of them, defactinib, and then we sponsored a combo trial with the two drugs, and that was the lever we used to be able to actually get the drug. And so, you know, it's been a pretty long journey for both of us, so very excited.
A lot of history, so... can you just walk us through some of the data and meaning, you know, how they actually work together mechanistically, and why this combination matters clinically for KRAS mutant LGSOC patients?
Sure. John, you wanna-
So mechanistically-
Take the mechanism?
Yeah. Mechanistically, avutametnib is unique in its own right, so it's a RAF/MEK clamp, so a dual inhibitor of RAF and MEK. When you inhibit MEK only, the cancer is addicted to the pathway, so it feeds back and activates RAF and tries to drive through the blockade, avutametnib gets around that, so it's really best in class from that perspective. But it's also been seen that the FAK inhibitor, FAK is sort of a central node of resistance to various anticancer drugs, including MAP kinase pathway inhibitors. So we know that that's why FAK inhibition gives you broader inhibition of the signaling t hat's driving the cancer growth.
That's just, you know, if it's helping avutametnib, now one of the things we're very interested in is how the FAK inhibitor might also help some of the newer KRAS inhibitors, including our own.
All right, so this is sort of the concept of vertical and horizontal?
That's right.
You hit both of them, I guess, with.
That's right, with just two agents.
Right. So, you know, you've now had a few months of real-world, you know, prescriptions for avutametnib, defactinib, gem, sorry. You reported about $2.1 million in revenue in just the first six weeks of launch, with only two specialty pharmacies online. So what are your plans to add additional specialty pharmacies, and especially and specialty distributors and GPOs?
So, the two months early, you know, we got some key things done early, so we were able to launch. We were able to get drug into the channel, but we didn't have everything in place. So we launched, as you said, with two specialty pharmacies. We've now added three specialty distributors, and the important thing there is they serve different audiences. So a small practice, you know, is likely to use a specialty pharmacy. The much larger practices, as we saw oncology move from purely infusion to oral, have figured out a way to actually make money off the oral drugs. They have their own pharmacies, and so we weren't able to service them without having our specialty distributors that then ship to their pharmacy. So that's now all up and running.
Also important in all of that is these large practices belong to group purchasing organizations. You contract with the group purchasing organizations once you have your specialty distributors in place. So it's a long way of saying, now that we're into the second quarter of our launch, we have everything in place, and so we're able to service the market. And then, importantly, the other thing that we didn't have at launch was our peer-reviewed publications, because those were timed to come out with the approval. We were going to have them by the PDUFA date. Once a lot of that's in process, it's hard to accelerate it. So now we have the peer-reviewed publications, which are important for a couple things. One, they allow us now to apply to the NCCN to get included in their guidelines.
We're automatically included in the guidelines on our label upon approval for the KRAS wild type. It turns out that in low-grade serous ovarian cancer, a KRAS mutation is actually a positive prognostic factor. Unlike a lot of cancers, they actually do better with a KRAS mutation. KRAS wild type is a poor prognostic factor in this disease, and that's not just with our drug, but across all drugs, so those patients just don't do as well. A patient who has a KRAS mutant tumor will live on average 12 years. A patient with a KRAS wild type LGSOC tumor on average lives only seven years, and so we're on the market. We're in the NCCN guidelines, which is very important for reimbursement for the KRAS mutant.
Well, now that we have our publication, we have applied to NCCN to be considered to be included in their guidelines for KRAS wild type. They've accepted the application, and have told us it'll be reviewed at their October meeting that's coming up.
October.
Now, having said that, we are to date seeing usage in both wild type and mutant, because if you look at the data in our publication, it's better than standard of care in both of them, and we are getting reimbursed to date with both of them, so off to a good start, but it'll be a nice accelerator to get into the NCCN guidelines, and then also now being in the specialty distributor channels, having our GPO contracts in place. We can now work more proactively with these large organizations to help promote the use of the drug, so they'll invite us in when they have... You know, typically, the way they work is they're very guideline driven. They tend to have these in-service meetings, where their physicians get together, and they teach them about the newest drugs.
That's frankly a much more efficient way to get to these physicians out in the community than trying to have a salesperson go out one-on-one to meet with every single physician. We get a big group of them in the room, and then it's worth sending our heavy guns like John and John Hayslip, our CMO, to talk to them instead of a medical science liaison or a salesperson. It's a very efficient way to get the word out about the drug more broadly.
In terms of wild type, you know, KRAS patients, is that sort of being driven? There are scripts there, you mentioned. Is that being driven by, you know, the centers of excellence, or is that also within the community?
We've seen it both in the community and the centers of excellence, and I think a lot of that is a result of the work we've been doing over the last couple of years. We've had our medical science liaisons out in the field for a couple of years, and so once the data came out at some of the key meetings, we were out educating about it, educating about the disease, and now we're out educating on how to use the drug.
Okay. Just to continue, as we were speaking a little bit earlier, you know, as additional specialty pharmacies, distributors, and GPOs, you know, do come online and, your education program ramps up, you know, how do you see the trajectory, of uptake in the second half of 2025 and in 2026?
It should continue to increase, and I think an important dynamic here that you don't see in a lot of oncology launches is the LGSOC patients on our clinical trial, the patients with a KRAS mutant tumor were on treatment for an average of 18 months, and the wild type on average for 11 months. And so if you think of the dynamics of a launch, and typically in an oncology launch, like a typical cancer drug, they may cycle patients through every three to six months. And so this allows us to build a bit of an annuity, almost like a rare disease model, where over time, every month we'll report more continuing patients.
We'll obviously add new ones on, but the impact is, every time we bring on a patient, we're hoping to have them for a long time, and so it should build nicely over time.
Okay, so I understand the strategy, but investors want to know numbers, and so do you have any numbers in terms of what you're aiming for?
No.
All right.
You know, one of the things, you know, as much as you want to give guidance until you really establish a pattern, it's not a great thing to do. You know, what we've done is, you know, try and educate a lot of the analysts to make sure we don't have some over here and some over here, and that there's more consensus. But over time, the history itself will speak for itself, and you know, we're hoping to continue with the success. So far, it seems like our strategy and the tactics we're applying are working, but it's early.
All right. You know, so, you know, you mentioned that you are getting scripts from both, you know, from centers of excellence as well as the community, but where are you actually seeing the bulk of the uptake? Primarily among your, you know, among your high-priority target physicians, academic institutes, or more broadly?
I'd say it's more broadly. It's very much a split. My commercial team never likes to hear this, but we have a fair number of prescriptions from doctors who haven't been visited yet. And, you know, it's early.
Yeah.
But you know, it's been relatively broad, and now, having said that, we do have physicians with repeat prescriptions. We've had a number of patients, as you would expect, being you know, a couple months into the launch, where we're getting refills, and so that's all tracking well, and then now it's a matter of you know, just accelerating as we go.
Right. So, you know, what are you learning from, you know, the early organic pull-through, and how is that sort of shaping your, your future targeting and resource allocation?
Yeah, I'd say we haven't learned anything to date that's changing our targeting or our allocation. You know, we still believe that there are certain centers that are Centers of Excellence that see a lot of these patients, and they'll obviously be a big focus. But also, those tend to be the centers that are most familiar with the drug anyway, and so we don't have as much education to do there. So it really is a mix of our sales force itself, which is relatively small, 16 to 18 what I would characterize as sales folks or oncology account managers. They will focus on the bigger accounts because, you know, there's both talking about the drug itself, but also talking about logistics, and how t o get it, and how to work through their system.
And then, as I mentioned, the large national practices, which are made up of many smaller practices, so you don't want to call on every physician individually, but they have the infrastructure and the relationships with the GPOs, where we can now go in and speak to them en masse, really, as a group. And then, a lot of the focus there is the ... as I mentioned, they tend to be very guideline-driven, so making sure we get on their individual guidelines, which then get embedded in their electronic medical record. So when they put in that they have a patient with low-grade serous ovarian cancer, we'll pop up as the likely choice because we're in their guidelines, and it just makes it easy because there are pre-made order sets and everything all set. So it makes it very frictionless when they want to give the drug.
Our goal really in the community with the physicians who may not see a lot of these patients, yet half the total volume is out in the community, is to make sure that we've done enough so that they know there's a drug specifically for this disease, and there's plenty of ways to go look up what it is. They can Google it. They can ask us to have a rep come in. But all we want them to know is there's a drug specifically for this disease now, so I need to think differently.
Just out of curiosity, you know, you mentioned these large meetings. Are they done in person, or are they done, you know, via Zoom? Because, you know, I'm just asking because there are some people at Cantor that are stuck, you know, with in person, you know-
Yeah.
And there are other people who like to leverage technology.
I would say the bigger meetings we'll do in person. Now, we have some people that are the same, myself included. You know, getting me to go out on a non-deal roadshow face-to-face is always harder than, you know, because you can do so many by Zoom in a given day. So there's always that to come through. But you know, there's the social aspect of it, too. You get invited to these meetings, and you're talking to people in the hall, and I'm sure that's the same pitch-
I get it.
... you make to the Cantor. You know, 'cause as an industry, you guys have been much more aggressive with the back to work than some of the other industries, but...
All right, sorry, I had to throw that in there.
Yeah.
So, you know, you mentioned, I believe on the Q2 call, you know, minimal use of a bridge drug, and a zero copay program. You know, how should we be thinking about gross to net, you know, sort of trending over the next few quarters or a year or so? You know, especially as Medicare patients start coming online under the IRA cap.
Yeah. So there's a whole bunch layered in there. You know, we're thinking, you know, it's, it's too early to establish a trend of our own. You know, we've guided that we think the 15% to 20% gross to net that you see in these products is probably correct for us. I think the biggest thing that will impact that will be our Medicare commercial mix, and we're still establishing that. It's early. I will say, we've given away very little free drug and, you know, so we have programs, whether it's a starter program, a bridge program, where if it's taking a little while to get the insurance company on board, we can give a month of free drug.
Now, when you have patients who are going to be on therapy for eighteen months, that's a very cost-effective way to get a patient started. Because typically, if you do this in oncology, again, if you're cycling every three to six months and you've given away a month of free drug-
Yeah
... that's gonna hit, you know, in a different way. But I will say, we're not utilizing those programs very much because we are finding that reimbursement's working well. What we are using much more aggressively is a zero copay program. So as you probably know, under IRA, for Medicare patients, their maximal out-of-pocket is $2,000 a year.
Mm-hmm.
That's huge because we could never help Medicare patients, by law, while we could always help commercial patients, and our goal is for commercial patients, for most of them, and that's been our experience to date, to have pretty much close to a $0 copay. 'Cause there's well-established metrics that show the abandonment rate of a prescription goes up as the out-of-pocket burden goes up for a patient, and so we want to always try and minimize that.
Okay. You know, and I guess, you know, what are you sort of seeing in terms of, payer mix and, prior authorization, timelines? Is there-
Yeah, so we are seeing almost universal prior auth, which is not a surprise. We're not giving specific metrics on the time to payment, but I will say it's been a lot shorter than we would have anticipated.
Okay.
And I think it's because of the strength of the data. We typically use the same data packet we submitted to NCCN, and, you know, when you look at that, and you look at the treatment options for these patients, it's quite compelling. And so we are getting reimbursement. We're getting reimbursement for off-label things I wouldn't have expected, and I think it just shows that, you know, some of these patients, they don't have other options. I think insurance companies are spending a lot of their time on Wegovy and things like that, and we're never gonna move the needle for an insurance company. We're really important to an individual patient, so that's why we're, where we're putting our effort.
But, you know, this isn't a disease where there's hundreds of thousands of patients, and it's really about just making sure they're taken care of and can get on the right therapy.
... So, you know, LGSOC, it's not considered a bolus to a switch-driven market. Just sort of walk us through that, even though you said-
Yeah, we got that question a lot, and when we launched a number of years ago, we had a drug called Copiktra, which is in the CLL and FL space. In that space, you tend to do watchful waiting and things like that. You know, you get the disease under control, and it's basically blood levels that tell you that the disease is coming back, and so they'll wait. In instances like that, you can have patients waiting until a new drug comes. In LGSOC, they tend to be symptomatic. It's a constant battle to make sure the tumor doesn't grow. 'Cause when the tumor grows, there's not a lot of free space in the gut, and it does bad things.
Mm-hmm.
So it interferes with your intestines and your GI tract, and all of that. And so they tend to be under active therapy to control symptoms. And so what we're seeing, and what we would advise... You know, I would never advise a physician taking a patient who's on a therapy off because they think ours is going to be better, because eventually they're going to need it. And it really is a marathon, not a sprint, and it's how long can I keep a patient on today's therapy to then avail myself of the next therapy and win the long game? And so that's what we're seeing as a dynamic, is patients will have, you know, regular visits with the physician. If they have an increase in symptoms, they may schedule an unscheduled visit, and then they get a scan, or they're not tolerating their current therapy.
Because a lot of the other therapies, the side effect profiles aren't great. And so, you know, we've talked to a lot of women, and we actually have a video of this conference that we sponsored at the FDA with a lot of patients, and you listen to them talk about their experience on these drugs, and it's just, it's heartbreaking. And so it really is a situation where either you can't tolerate it anymore or the tumor is progressing, then it's time to switch. And so, you know, we didn't expect a big bolus of patients at the beginning. We're not seeing that. We're seeing an acceleration as we go through, but that's just natural penetration into the market.
Okay. You know, then you just mentioned, you know. So, you know, basically discomfort in the GI area, and so forth, you know, with tumor growth. And, I guess one of the KOL calls that we hosted, you know, the physician said, you know, tumor shrinkage is not the overall objective all the time, and it's actually stabilization.
Stable disease. Yeah, I mean, I've been working in oncology a long time, and, you know, the hallmark has always been, you know, the early indication is tumor shrinkage, and then you look at progression-free survival, and obviously survival over time. In this disease, stable disease is a win, and we have a number of patients that have been on our clinical trials, and I've met a number of them, that have been in stable disease for a couple of years. And that's a win. As long as you're tolerating the drug, the tumor isn't growing, that's what all you can ask for.
Okay, so you know, going back to the market dynamics, you know, what leading indicators are you actually tracking internally to sort of forecast long-term uptake and growth consistency?
So the leading indicator we track, and we're having to do this because there isn't an ICD-10 code for low-grade serous ovarian cancer. So it's not easy to go look in claims data and say that there's this many patients here and this many there. Our salespeople and our MSLs are having conversations with individual physicians to understand how many patients do they have. And so it's not just patients coming in looking for a new therapy, but we're tracking how many active patients do they have that are on something else that will eventually need our drug, and that's probably the best leading indicator.
Okay. So you, your field team remains, I think at about 16 reps.
Yeah.
So what are the, you know, the KPIs that you're using to measure efficiency and saturation?
Yeah, and to be clear, we've got the sales reps.
Mm.
We have our medical science liaisons, then we also have national accounts managers, and different. There's probably forty people touching the field overall. The leading indicators are, you know, first and foremost, I would say awareness. So, you know, we had pretty good awareness going out. We're measuring to see that that's increased. You know, looking at, again, surveys of physicians with intent to treat, so they're ready to use it. Then obviously, there are performance metrics or, really, volume metrics on the individual reps and MSLs, you know, measuring, how many visits do they have? For the medical science liaisons, it's really measuring podium presence. So are there people other than us out there talking about our drug? And really basic things like that.
Okay. And then, do you foresee any need to sort of expand the sales force, you know, once you actually have a wild type approval, or-
Um
... is this sufficient? I mean-
It's the same target physician, so I don't see that as something that we would do. I think if we were going to expand anything, it would probably be, first and foremost, our oncology nurse educators. So one of the things that, you know, we've got as really a strategic imperative, you know, the first one is obviously people knowing about the drug, and then people going on the drug. As important is people staying on the drug. And so we've got oncology nurse educators that, when we get a first patient at a practice, we get that person an appointment to go in and meet with the staff to educate on how to use the drug, how to educate the patients. So one of the side effects that we see is a transient disturbance in eyesight, kind of like a blue aura.
It goes away in a couple days, but if you don't know it's coming, it can be very disconcerting, so we need to make sure that the nurses are saying, "Hey, this might be happen. You can get rash," and in our protocol, we used a prophylactic regimen, where for the first couple of cycles, they used a cream and an antibiotic. We educate them on that, so it's all the things to help, you know, the nurses and the physicians know what to expect, but also to help them in educating the patients, so you can get through that first couple of cycles, and then hopefully stay on long term.
Okay. So, you know, you mentioned you know other people speaking about your drug other than the company. When I was doing sort of a search on ClinicalTrials.gov, I did come across one Sloan-sponsored study, Sloan Kettering, with aromatase inhibitors, and so I think they're going after the front first line.
That's combining-
In combination
... our drug with aromatase inhibitors.
Yes.
Yes.
And so, how are you thinking about moving to the front line, then?
Yeah, so, we didn't do a front-line study for our confirmatory study because it would've taken too long. So even though once a patient's relapsed, you know, progression-free survival on some of the standard of care is, like, six, seven months. Front line, it can be for quite a long time, and so it would've been too long of a time to outcome to do our confirmatory study, 'cause the FDA wants to have those done in a certain period of time. So we're doing this investigator-sponsored study. Memorial Sloan Kettering is the lead. We're doing that to develop the first, you know, proof of concept data front line, and then we'll likely either go to one of the large cooperative groups or sponsor one ourselves to eventually get a front-line label.
But right now, you know, we think there's plenty of business after first line, 'cause pretty much everybody eventually-
Becomes
... relapses and will become a customer, so that work's ongoing, but we do want to develop the evidence really to be able to do that. 'Cause, you know, one of the things that we have heard from the KOLs is intervening early with the best drug kind of prevents the tumor from growing for the longest. Because one of the end goals here is to prevent having to do another debulking surgery.
Yeah.
You don't want to have to keep going back, 'cause every time they go in, you create more adhesions and scars and things, and so we do think earlier is better. It's just going to take a while to develop that evidence.
Okay, we are running out of time, but I do want to ask one question on RAMP 301 .
Sure.
It's your confirmatory Phase 3.
Right.
Enrollment completion expected by the year-end.
Yes
... with an IDMC , a sample size re-estimation in Q4, correct?
Correct.
So, you know, just any details that you can provide, What will trigger it? You know, is this event driven, or is, you know, after a certain percent of patients reach a certain time point on drug? And so that's one question.
Yeah, it, it was really triggered by finishing accrual, so having the patients on. And the reason we did it was we didn't have great comparators for the standard of care. When you looked at the studies that were done with standard of care, they either had less prior lines of therapy, or our study was the first one that ever prospectively separated mutant and wild type. And so the other studies, there was some post hoc analysis of a subset of patients who'd had a KRAS test.
Mm-hmm.
It's a long way of saying we did our best at estimating the sample size. We had the sample size large enough that we thought would be a positive study, but we felt it prudent, kind of belt and suspenders, to say, "You know what? We can actually take a look and increase the sample size if we think we need to," and that's why that was built in.
Pete, maybe if time's running out, maybe I can highlight a couple other things that are really...
John wants to talk about our G12D.
Exciting as well.
Sure. Go ahead.
Yeah, and before I talk about G12D. With avutametnib and defactinib, seeing a 44% response rate in KRAS mutant low-grade serous ovarian cancer, which is what you're talking about, that brings up KRAS is such an important driver in other cancers. avutametnib, defactinib with standard gem or Abraxane chemotherapy, we've seen in front-line metastatic pancreatic cancer an 83% response rate. Ten confirmed responses out of the first 12 patients. We've now expanded to 29 patients. That's unheard of to have response rates like that in pancreatic cancer. The other thing to highlight is we have a KRAS G12D inhibitor, which we think is really best in class preclinically and clinically. At ASCO, it had a 52% response rate in KRAS G12D pancreatic cancer again.
And then this Sunday, at the World Lung Meeting in Barcelona, there'll be a presentation. They're seeing a 69% response rate in KRAS G12D lung cancer. So these are new numbers for KRAS inhibitors that are higher than ever seen before. We have a lot of preclinical head-to-head data relative to Revolution Medicines' KRAS inhibitor, which is the other leader in the space, and these clinical numbers seem to be trumping that as well. So very exciting days for Verastem. I'm glad I got to say a couple words.
All right, we are out of time. Thank you very much-
Thanks, Pete
... for-
Thanks, Pete
... joining us at the Cantor Healthcare Conference, and looking forward to the progress.
All right.