All right. Good morning, everyone. Thank you to those of us in the room, as well as folks dialed in on the webcast. My name is Faisal Krishnath. I'm one of the senior biotech analysts here at Jefferies. We're here live from the Jefferies Global Healthcare Conference in New York. We're really pleased to have with us this morning the management team of Verastem Oncology, Jonathan Pachter, the Chief Scientific Officer, as well as Daniel Lyons, the Chief Commercial Officer. Interesting company at an inflection point with both a commercial-stage asset as well as a compelling G12D program. Lots to talk about across both of those two topics. I think we'll do the commercial-stage asset first, and then we'll talk about the G12D. Before we dive in, John, could you just start by giving us a quick overview and intro to yourself and the company?
Sure, my pleasure. It's a very exciting time for Verastem Oncology. We're a commercial-stage multi-asset company focused on small molecule oral drugs targeting RAS/MAPK pathway-driven cancers. We've successfully launched AVMAPKI FAKZYNJA CO-PACK, the first ever FDA-approved therapy for a rare ovarian cancer called low-grade serous ovarian cancer. By every measure, the launch has been successful, with more than $50 million revenue generated since launch and consistent quarter-over-quarter growth. We also have a blockbuster opportunity with our KRAS G12D inhibitor, VS-7375. It's also a small molecule oral therapy. It's very selective for KRAS G12D, which is the most common KRAS variant driving human cancers, including pancreatic, colorectal, lung, et cetera. We look forward to giving several updates during this year.
Excellent. Thank you. Thank you, John, for the introduction. Let's dive into CO-PACK, and Dan, I know you'll have a lot to say here, but can you talk to us a little bit more about some of the things that John mentioned in terms of the growth seen so far and how you feel about the launch so far?
Sure. First, thanks for having me. I joined Verastem Oncology just over a month ago. Prior to this, I was at SpringWorks Therapeutics, as coming in the opportunity I saw specifically with COPAK to serve these patients in a rare oncology with a targeted treatment was very exciting. I think when you look at where we were in Q1 and where we're going in Q2, I think what we've committed is that the growth you saw Q4 - Q1, we would exceed that in Q1 - Q2. We're in June, I think we're right on track for that. I think there's tremendous opportunity, just in my brief time here, to continue to do three things really, really well, this is where we focus the commercial organization. We have to be able to maintain consistent new patient starts, I think we're doing that.
That's sort of the feeding at the top of the funnel as we bring patients in and as more physicians get experience, the second thing we need to do is move this up in line of therapy. In oncology, generally what you see, especially in rare oncology, is using a drug that's been recently approved in patients who are at later lines. That is, I think, what we saw in the first year with AVMAPKI FAKZYNJA CO-PACK, is that gynecologic oncologists had patients coming in, they were mutated, and they may have been fourth, fifth, sixth line.
Moving up in that line of therapy as this being the treatment for the first or next occurrence is where our commercial team is focused right now, and I think that's going to be fueling that growth as we go forward, and we can talk about some of the changes made there, not only myself, but just in the brief time across the commercial organization. The third thing we have to do is keep patients on therapy. This is a novel treatment, one of the first approved novel. I think it might be the first approved novel treatment.
Yes.
Because of this, physicians have to get comfortable with it and also comfortable treating side effects. That's where we're focused as well. These are not new adverse events. They may feel new. They may seem new because they haven't used this medicine before. Overall, those three things are where we're focused. We're excited about the growth. We think that obviously we're going to see more in Q2 than we saw in Q1 and then propel that through the rest of the year.
Got it. You kind of alluded to this, but the growth was fairly modest in terms of revenue growth from the fourth quarter of 2025 to the first quarter of 2026. What were the factors that contributed to that?
Yeah. When you think about Q1, seasonality plays a very important role, especially in the first year of oral oncology launches, right? I've seen this in the prior companies I've worked at. We launched right around mid-year, as you get to January, you have patients who have to have their insurance reverified. You have patients who have to go through that maximum out-of-pocket cost. All of those things don't necessarily mean that a nurse or a nurse practitioner or the finance department at an oncology office are going to just immediately go to your free drug. They're going to say, "Well, we can wait a week or two. We just refilled you in the third or fourth week of December." That generally ended up delaying some starts. It delayed some refills. This is very common. We saw that.
That is what in Q1, I think, held us back a little bit in January. February and March recovered really well, and we're seeing that momentum continue through April and May, and we expect to see it more in June.
Got it. I think as it also mentioned that some of the duration of therapy metrics were not up to the average that you would hope to achieve for the launch. Can you talk to us about that and how you intend to address that?
Yeah. I think just to my earlier comment, the patients in the launch were seeing ECOG performance status that was much higher than what we were seeing in the real world, mostly because physicians were using this drug for patients who were fifth line, fourth line, beyond. This was an alternative outside of going into hospice. Of course, you're not going to see duration of therapy that high. This is very common, though, in oncology. As they get more comfortable, they move it up into line of therapy. This is also a slow-growing disease. Patients who were diagnosed and got their first line of treatment in, let's say, late 2024, early 2025, they are now just starting to recur.
This is now an option for that first or next recurrence, and that means we'll get those patients who are a little bit healthier, and they'll be able to stay on. We also, in our clinical trial, we did see some dose pausing or some treatment pauses along the way. I think it's important for us to remind physicians that that doesn't necessarily mean that you go into a dose reduction. You should be, at least for most patients, restarting them at the initial dose and then deciding whether they're going to take it down. There's a lot of teaching that needs to go on and that our sales team and our medical affairs team is focused on, and I think that is where we think we're going to have that driver.
Got it. For investors, part of the struggle is that the two statements seem at odds with each other, that it is a low grade, more slower growing indolent disease, but at the same time, you guys are saying that you had patients who were coming in very late line with very poor status and low time on therapy. Can you help reconcile those two things and explain?
Yeah
to investors how both can be true?
I think there's the prevalent population pool that had this disease, and there was nothing approved. They were getting off-label treatments wherever they were in their treatment journey. This disease people live with for decades. If you have a patient who's currently on therapy and you're treating them with something and they're doing fine, in oncology, generally, you don't do a switch at that point because you're running out of options for patients that you have in your armamentarium. We were getting patients that were next, and a lot of them were much later line. If you look at where we are positioning ourselves, once they have experience, they will generally feel more comfortable using it in earlier line. It just takes some time.
I just got back from ASCO, just like you did, and in nearly all of the conversations I had, it was, "We are looking for this patient for when all my patients recur next.
If you're a KRAS-mutated patient with LGSOC, I know that this has now very clearly become one of the next options that you're going to have and likely wanting to get experience with it. We're confident there.
Got it. As you talked about, you mentioned a couple of times this idea of having stronger growth into the second quarter now than what you saw in the early part of the year. Can you maybe help quantify that a little bit for us and help us understand the type of growth cadence that we should expect through the year?
Again, I was just asking our CFO, Dan, over there exactly where we are with consensus. I think we're going to land close to consensus right now, where we're trending in June.
You mean on the quarter or on the year?
On the quarter. Then for the year, I think we're on that trend as well, but we have to see how June goes. June's critical. I mentioned we made some changes from a commercial perspective. One is we added a couple sales reps. We brought in some new leadership on the sales side. We've refocused. We launched our reimagined recurrent LGSOC campaign to really help us move up in line of therapy. As we're pulling all these strings, there's always some change. Now we're moving forward. Our field force is fully out there. We've got talking points around those three priorities that I laid out. Obviously I'm optimistic that we're going to be moving towards those numbers, but right now we're in June, and we're going to focus on the next four weeks.
Yeah, makes sense. Dan, understanding that you've been involved in multiple commercial launches in your career, as you've come into the company and have tried to understand the situation and what went into the launch in the early days of it, what are the key things, I know you just mentioned a couple of them, but what are the other key things that as you've come in have been able to feel like, "Oh, this company is doing XYZ. They need to be doing ABC." What are the other tweaks and fixes that you're making?
Yeah. It's a good question, and again, it's only been four or five weeks. What I would say is the company has done a nice job in starting using the data to help find patients, and I think we're just being able to action that right now, whether it's through site alerts, whether it's through patient-finding efforts. They're all not created equal. I think many of you know in oncology, there is multiple different electronic health record systems. The ability to look longitudinally at patients can be challenging. We are pulling on all of those strings right now and putting some urgency behind it to help find those patients.
I think additionally, the focus around what we're doing, I think we want to help reframe the conversation with our customers around helping find those patients, but also that putting some urgency around that first or next, where it was more along the lines of, if you see this patient, think about this treatment. Where we're going now is that this is the only approved treatment for this disease. These patients are very specific with their KRAS mutation. It's time to get that experience with the medicine. Again, I think I was very impressed when I got here with a lot of the work that was being done after just 10 months of launch or 11 months. I think that there's a lot of opportunity as we go forward.
Got it. You have the big expansion opportunity for RAMP 301 reading out next year. Can you talk to us, at least just from the commercial perspective of how big the opportunity for this drug is, both with and without that expansion?
Sure. I think with the expansion, we've already got KRAS mutated. If we do have an indication with wild type, that would be a significant increase on the target population. It's not commensurate to being the additional two-thirds, but it is probably double the ability, probably double the number of patients that we would be able to see with wild type eventually in that line. It doesn't change what we would do, though. These are the same customers. These are the same gynecological oncologists. This may expand more into the community because you've got just a broader indication. We're doing all the right things now. It doesn't change those three things. We're looking forward to that opportunity to continue this treatment to more patients, but it doesn't change our initial focus.
Yeah. How should we think about peak revenue opportunity for the drug with and without that expansion?
I don't think we're giving guidance there. I'll wink at Dan over there. I think it's early to say.
I think analysts have been somewhere from $300 million-$600 million.
Yeah.
Yeah. That's with the expansion into wild type or without?
I think with wild type is kind of the top of that range, and without is the bottom of that range.
Got it. Okay. You guys are comfortable with the range that the Street is at?
We are today.
Got it. Okay. I want to shift gears to talk about your KRAS G12D.
Great
to co-pack if there's time allowing. John, can you start with just giving us a quick intro and background on the program that you guys got from GenFleet?
Yeah, I'll start with the fact that it was a really great collaboration with GenFleet, who's in China. We spent a couple of years with them selecting the agent around the dual on/off profile and excellent pharmacokinetics, which turned out to be critical. GenFleet has China rights. They've treated over 300 patients. We have ex-China rights. We're moving extremely quickly with the phase I and now launching phase II programs in lung, colorectal, and pancreatic. It's really, I think, best in class. It's very selective for KRAS G12D, which is the most prevalent KRAS mutation in human cancers. I think that as I just also got back from ASCO, and all the investigators are saying that if your cancer is driven by a specific variant, KRAS G12D, they would give a selective agent for KRAS G12D before they would give a pan-RAS inhibitor.
A pan-RAS inhibitor will bring other side effects that are on target for that agent but not on target for ours, such as rash and stomatitis, which are really problematic for patients. I think in preclinical models, it's really been better than other agents we've compared to, and we ascribe that to this dual on/off activity of the drug, very potent against both.
Got it. Just to clarify that comment, that's super interesting. You're saying that docs are telling you that they would prefer to use If they know a patient, let's say, pancreatic cancer driven by G12D, they would prefer to use a G12D selective over a multi-RAS inhibitor?
Absolutely. Yeah. I think that if you think about where we started in treating cancer with chemotherapy, we're hitting the cancer, we're hitting everything all around it. Now in the age of RAS inhibitors, which is really exciting, and the talk at ASCO given on trastuzumab deruxtecan is really exciting, moving the field forward, targeting RAS for pancreatic cancer. I think that as you go from chemotherapy, now you have pan-RAS that hits the target that's driving but also hits peripherally wild-type RAS, so normal RAS, hitting normal tissues, and that's why you get rash and stomatitis and other things that are on target for that broad thing. In 2026, patients deserve something that you know which mutation is driving their cancer. You target only that mutation. It's as clean as possible.
Not only is the safety better, but you can just hit that target much harder than you can with something that's not as selective. We're really excited about the efficacy potentially being much better. Our Chinese colleagues, GenFleet, have shown data in both lung and pancreatic, which the response rates are better than anything that's been out there from others.
Got it. Just to kind of play devil's advocate a bit, I think the multi-RAS camp would argue that you actually want some of that wild-type activity to help with resistance. That's kind of, I think some would argue that it's a feature, not a bug. I'm curious, given that you've selected and developed this molecule, your G12D, how you think about that.
Yeah, it's a fascinating question. I think G12C inhibitors did find that resistance mutations in the clinic could be other RAS mutations, and that's where that idea came from, that you might want a pan-RAS inhibitor. In preclinical pancreatic cancer models that we use and others use, we're seeing a lot of resistance mechanisms that affect the pan-RAS inhibitors, but not our drug, conversely. We find that, for example, you get loss of cyclophilin A in these models, which is critical for the pan-RAS inhibitors to work. Doesn't affect our molecule at all. We find upregulation of upstream receptor tyrosine kinases with the pan-RAS inhibitors, or actually also with zoldanrasib, which is a tri-complex G12D inhibitor. We don't see that at all with our agent.
Really the answer is that cancer will find a way around any drug you give it, and it just might be different in terms of resistance mechanisms for different drugs. The idea that there won't be resistance to pan-RAS and there will be to variant selective has been dispelled.
Got it. You characterized your G12D as a potential best-in-class program. At least from the China data, it looks like the response rates seen by GenFleet are indeed above the other G12Ds, but that there's also some pretty notable toxicity. Can you talk to us about that?
Yeah. It was fascinating. There were 3 G12D inhibitors out of China presented at ASCO, you probably went to the session, including a GenFleet presentation. For some reasons we understand and some we don't, the toxicity of these agents in China seems to be much worse by far than what we're seeing. In terms of GI side effects, we're managing it intelligently. We're giving the drug to fed patients. GenFleet is giving it to fasted patients. We know that food helps. We also are mandating for the first two cycles prophylactic antiemetics, which we've learned from other RAS inhibitors in our investigation. That helps tremendously. If patients have diarrhea, for example, the investigators are very proactive, giving over-the-counter antidiarrheals, and it's just been managed really well. We don't see any liver side effects. We don't see any high-grade neutropenia.
All the things that have been seen with these inhibitors in China, really in all of those presentations, we don't see in the U.S. It's really been a beautiful tolerability profile. We don't see any rash, which lets us combine well with cetuximab, and the lack of cytopenias had predicted, and now we know that we can combine very well with, for example, gemcitabine Abraxane for frontline pancreatic cancer. It's been a really exciting profile.
Yeah, I know you're talking about the U.S. study that you guys.
Yes
have been enrolling. Can you clarify for us, how long have you been enrolling that study? Where are you at in number of patients? Should we still expect a data update within the month?
Yeah. We started about a year ago. We are especially focused on pancreatic, lung, and colorectal. We've enrolled over 100 patients. We will absolutely give an update before the end of this month. I think that what's important, though, is I think investors want to see a good denominator. They want to see intent to treat rather than just evaluable.
Ideally, at the go-forward regimen, the go-forward dose, and we've been thrilled that we can clear the 900-mg dose with good tolerability. Remind me that GenFleet is moving forward with a 600 mg dose, and we see much better efficacy at 900. We're really excited about that.
Got it. On the earnings call, you guys had emphasized that the first half 2026 update would focus more on safety and case studies. Is that still the case, or should we expect to have a comprehensive look at efficacy?
Yeah. I think because it's so important to have a large denominator, especially at the go-forward dose, I think it would be a mistake to put out response rates that are going to change. In pancreatic cancer, for example, we've seen and others have seen that with multiple scans, you get deepening of the response. We've seen patients that start with a small reduction in their tumor burden and with pancreatic cancer, for example, and then get down to a partial response with a few scans.
I think for that reason, we'll give an update on our safety data with more patients and more time. We'll give an update on our pharmacokinetics, showing again that 900 mg is delivering more drug than 600 mg, and by the way, we've also started dosing at 1,200 mg, but we think 900 mg will be the move forward a dose. Then we'll probably present case studies both as monotherapy and in combinations to give a flavor of what we've been seeing.
Got it. Just to be clear, investors should not expect to see things like a waterfall plot, swimmers plot, proper ORR tables, and such like that?
Yeah, we're excited about sharing that in the second half of the year.
Got it. Just to kind of push you on this because I get asked this from investors. What is the reasoning for that? What you say in terms of you don't want to present an ORR that might change, but that's typical in early-stage oncology drug development.
Yeah. First of all, it's a very competitive landscape, and I think when RevMed first came out with erdafitinib they had about a 20% response rate, and that was fine because it was the only agent out there.
Yeah.
Our agent will do much better than that, but the response rate will deepen over time, and you need enough patients to really assess. The other thing that we didn't expect is that the tolerability has been so excellent that whereas we were at 600, we've gotten to 900 more recently. It was just the end of last year that we started into 900 mgs. We're really aggressively going forward with the 900 as monotherapy. We've cleared 900 with full-dose cetuximab, which you can't do with another agent like erdafitinib, and we're moving forward now. We've cleared 600 with gem Abraxane, but we're now testing 900 as well. It's a matter of getting to that move-forward dose, which takes time.
Yeah
Getting enough patients that it's meaningful for investors.
Got it. When you say enough patients, can you clarify what you mean by that? You mentioned 100 patients into the phase I already. I understand a portion of those will be evaluable, but when investors hear this, they think, "Oh, they have 100 patients enrolled. At least half of them must be evaluable. I don't understand why they're not showing full efficacy data.
I think, for example, in a given cancer, having 20 patients that are efficacy valuable, preferably with more than one scan, at 900 mgs would be ideal. That would give a true sense of what we're seeing in the clinic. I think if we show a couple patients at 400 where we started and a couple at another dose, it really just doesn't help anyone to understand the efficacy that we're seeing.
Got it. Why are you setting 900 mgs as the level that you want to be able to show that, given that GenFleet has shown that 600 mgs is a very active dose?
Yeah, it's a fantastic question. We've seen from pre-clinical models that the dose that gives us 30% or greater in every single mouse in every single model, we can get the equivalent of that in terms of steady state AUC at a certain steady state AUC. 600 mgs, both in China and the U.S., and again, they're fasted, we're fed, but we're seeing similar PK between the two, which is good.
Yeah.
When you look at that, the average is at that line that gives you maximal efficacy, but you're leaving half the patients behind and below that line and half are above. At 900 so far, we've seen that every single patient is above.
We don't want to leave any patient behind. We think that that's why we're seeing such great efficacy at 900 mgs.
Got it. Should we expect that the U.S. experience at the 600 mg dose would on efficacy look like the China experience at the 600 mg dose?
I think nothing seems identical between the U.S. and China studies. Our focus is on 900 and showing that it's really best in class.
Yeah
versus other RAS inhibitors, and that's where we're heading.
Got it. Okay. We have about five minutes left. I want to make sure we talk about a really important topic, is the phase II strategy that you guys disclosed. Can you remind us what your phase II pivotal plans are?
Yeah. That's also very exciting. We had submitted our phase I design, we were looking to upsize the lung, pancreatic, and colorectal cohorts, the FDA responded that it looks like you're trying to pursue marketing authorization, and if so, we recommend that you break out separate phase IIs in each indication. We took that as a very positive sign that they didn't suggest, for example, randomization versus a control.
To be clear, was your interaction with the FDA what would support a pivotal study, or was it that you had suggested expanding these cohorts and they said, "We recommend separate phase IIs?
Right. They said, "If you have marketing authorization in mind, then" We took that as Accelerated Approval could be a possibility given the extremely strong responses that we'd shared the Chinese data with them.
We've moved really quickly with that. We've opened the pancreatic phase II. The lung and colorectal phase IIs will open extremely soon as well.
Got it. Can you remind us the design of each of these phase II studies?
Yeah. In the case of lung cancer, we're testing single agent. The focus will be on 900 mgs. In the case of colorectal and pancreatic, now we're testing both single agent, again at 900, we're also testing in combination with anti-EGFR, not just in colorectal, where everyone expects that, also in pancreatic cancer. The other thing that's exciting is we have activity of the molecule in intracranial models, we talked to a lot of lung cancer investigators at ASCO. They said that if we have activity against brain mets, that'll be extremely important. In our phase II, there's also a cohort of lung cancer patients with asymptomatic brain mets. We're really excited to see that as well, that would really bring it out as best in class as well.
Got it. It seems like the FDA in the past few years has made a bit of a U-turn, away from single-arm Accelerated Approvals, especially for combinations, as we saw with a notable example in melanoma. What gives you guys the confidence that you'll be able to go down this path, especially when the other RAS players like RevMed and Incyte have chosen not to pursue an Accelerated Approval strategy?
Yeah, I think that just very strong efficacy. It's all in the data. If our efficacy is extremely strong in terms of response rate and duration, then I think that the agency will consider that. Part of our confidence is that we just did it. With a novel combination, we got single-arm Accelerated Approval. I think it's the recent experience of how we've done that, and we look to replicate that.
Got it. Based on your interactions with regulators, do you guys have a sense for what the minimum threshold is that you must show on response rate across the three indications?
It'll be a review issue. I think that we do. I think certainly more than 30% response rate is a minimum price of admission, I think that we also have thoughts that we're developing on what will constitute best in class. The agency won't ever give you a threshold and say, "You win if you're over this number.
Yeah. In pancreatic, presumably daraxonrasib will have a full approval in second-line all comers pancreatic cancer probably within a few months. Does that change your ability to pursue an accelerated strategy in pancreatic?
First of all, so they had the 33% response rate. I think first of all, in terms of enrollment, we're opening the phase II now. As I said, investigators have said that we'll have no trouble enrolling relative to a pan-RAS.
I think it's really about the efficacy, again. If we have best in class efficacy, we already know that the safety is tremendously better for patients than the pan-RAS inhibitors, then I think that we have no concerns.
Got it. Even if a drug has full approval in a patient population overlapping yours?
Yeah, overlapping is an important part of that. I think that we don't yet know what their efficacy is specifically.
Yeah
in KRAS G12D, but it's therefore not an identical population.
Got it. We're just about at time, but I wanted to ask, can you remind us the cash position of the company and whether you believe that you're funded to profitability?
Sure. Yeah. We had $182 million in cash as of March 31st. We have a cash runway through the first half of 2027.
Got it. All right. Excellent. Thank you guys so much. Thank you, John. Thank you, Dan. Really appreciate you taking the time.