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 Khashid. I'm one of the senior biotech analysts here at Jeffries. We're here live from the Jeffries Global Healthcare Conference in New York. Really pleased to have with us this morning the management team of Verisem Oncology, Jonathan Pachter, the chief scientific officer, as well as Dan Lyons, the chief commercial officer. Interesting company at an inflection point with both a commercial-stage asset, as well as a compelling G12D program, so 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 Veristim Oncology. We're a commercial-stage multi-asset company focused on small-molecule oral drugs targeting Rasmap kinase pathway-driven cancers. We've successfully launched Avmapki vaccine Jacopac, 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. But we also have a blockbuster opportunity with our KRES-G12D inhibitor, VS7375. It's also a small molecule oral therapy. It's very selective for KRES-G12D, which is the most common KRES variant driving human cancers, including pancreatic, colorectal, lung, et cetera. And we look forward to giving several updates during this year.
Male Speaker 1 Excellent. Thank you, John, for the introduction. Let's dive into COPEC, and Dan, I know you'll have a lot to say here, but can you talk to us a little bit more about, I mean, some of the things that John mentioned in terms of the growth scene so far and how you feel about the launch so far?
Sure. So first, thanks for having me. I joined Veristem Oncology just over a month ago. Prior to this, I was at SpringWorks Therapeutics, and as coming in, the opportunity I saw specifically with Copac 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 to Q1, we would exceed that in Q1 to Q2. And so we're in June, and 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, and this is where we focus the commercial organization. We have to be able to maintain consistent new patient starts, and I think we're doing 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. And so in oncology, generally what you see, especially in rare oncology, is using a drug drug that's been recently approved in patients who are at later lines. And so that is, I think, what we saw in the first year with that map effects in Jacopac 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 and next recurrence, 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. And then the third thing we have to do is keep patients on therapy. This is a novel, novel treatment, one of the first approved novel. I think it might be the first approved novel, novel treatment. And because of this, physicians have to get comfortable with it and also comfortable treating side effects. And so 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. But overall, those three things is where we're focused. So 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.
So you kind of alluded to this, but the growth was, you know, fairly modest in terms of revenue growth from the fourth quarter of 25 to the first quarter of 26. What were the factors that contributed to that?
Yeah, I mean, when you think about Q1, right, seasonality plays a very important role, especially in the first year of oral oncology launches, right? and I've seen this in the prior companies I've worked at. You know, we launched right around mid-year. But as you get to January, you have patients who have to have their insurance re-verified. You have patients who have to go through, you know, that maximum out-of-pocket cost. And 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. And so that generally ended up delaying some starts. It delayed some refills. This is very common. We saw that. And so 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. As you, I think you guys had also mentioned that some of the duration of therapy metrics were not kind of 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 my earlier comment, right, you know, 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 patients who were, you know, this was an alternative outside of going into hospice. And so, of course, you're not going to see duration of therapy that high. This is very common, though, in oncology, right? As they get more comfortable, they move it up into line of therapy. This is also a slow-growing disease, right? So patients who were diagnosed and got their first line of treatment in, let's say, late 24, early 25, they are now just starting to recur. And so 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, you know, 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. So 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.
And can you help? Because for investors, part of the struggle is that the two statements seem kind of at odds with each other, that it is a low-grade, kind of 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 kind of like reconcile those two things and explain to investors how both can be
true yeah i think you know there's the prevalent population pool that had this disease and there was nothing approved so they were getting off-label treatments at wherever they were in their treatment journey right i mean this disease people live with for for decades and so 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 a switch at that point because you're running out of options for patients that you have in your armaterium. And so we were getting patients that were next, and a lot of them were much later line. And then if you look at where we are positioning ourselves, once they have experience, they will generally feel more comfortable using it in earlier line. And this just, it just takes some time. But 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. And so 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 wanted to get experience So we're confident there.
And then as you talked about, you mentioned a couple times this idea of having stronger growth from 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?
So I think we're – again, I'm not – 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. And then – You mean on the quarter or on the year? On the quarter. And 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, right? 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. And so as we're pulling all these strings, there's always some change, right? And now we're moving forward, right? Our field force is fully out there. We've got talking points around those three priorities that I laid out. And so 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, it makes sense. And then, Dan, understanding that you've been involved in multiple commercial launches in your career, as you've come into the company and have kind of, you know, tried to understand the situation and kind of 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 you kind of, as you've come and have, like, oh, like, this company is doing X, Y, Z, they need to be doing A, B, C, and, like, 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's multiple different electronic health record systems the ability to look longitudinally at patients can be challenging we are pulling on all those strings right now and putting some urgency behind it to help find those patients I think additionally you know the focus around sort of what we're doing I think we we want to help reframe the conversation with our customers around helping find those patients, but also 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, and it's time to get that experience with the medicine. So, again, I think I was very impressed when I got here with a lot of the work that was being done after just, you know, 10 months of launch or 11 months, and I think that there's a lot of
opportunity as we go forward. Got it, and you have the big expansion opportunity for RAMP 301 reading out next year. Can you talk to us, at least from the commercial perspective, of, you know, how big the opportunity for this drug is, both with and without that expansion?
Sure, so I think with the expansion, right, 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 an 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. And so 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. But we're doing all the right things now. It doesn't change those three things. And so we're looking forward to that opportunity to continue this treatment to more patients, but it doesn't change our initial focus.
Yeah, and 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 stay.
I think analysts have been somewhere from $300 million to $600 million.
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. And you guys are comfortable with the range that the street is at?
We are today.
Got it, okay. So I want to shift gears to talk about your KRS-G12D, and then maybe we'll circle back to Kopech if there's time allowing. But, 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. And so Genfleet has China rights. They've treated over 300 patients. We have ex-China rights. We're moving extremely quickly with the phase one and now launching phase two programs in lung, colorectal, and pancreatic. It's really, I think, best in class. And so it's very selective for KRSG12D, which is the most prevalent KRS 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, KRSG12D, they would give a selective agent for KRSG12D 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. So 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
Got it. So just to clarify that comment, that's super interesting. So 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 Derrickson RASP 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 RAS 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 and not only is the safety better but you can just hit that target much harder than you can with something that's that's not as selective so we're really exciting excited about the efficacy potentially being much better and our chinese colleagues gen fleet 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. And then just to kind of play devil's advocate a bit, you know, I think the multi-RAS camp would argue that you actually want some of that wild-type activity to help with resistance and to get kind of, and that's kind of, you know, I think some would argue that it's a feature, not a bug. I'm curious, you know, given that you've selected and developed this molecule, your G12D, how do 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. So we find that, for example, you get loss of cyclophiline 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, actually also with zoldan-ras, which is a tricomplex G12D inhibitor. We don't see that at all with our agents. So 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. But the idea that there won't be resistance to panrests and there will be to variants selective has been dispelled.
Got it. And you characterized your G12D as a potential best-in-class program. But 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. So there were three 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. So 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 investigators, and that helps tremendously. And then as patients, if patients have diarrhea, for example, the investigators are very proactive giving over-the-counter antidiarrheals, and it's just been managed really well. But 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. So 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 cytopedias had predicted, and now we know that we can combine very well with, for example, gemcitabine, abraxane for frontline pancreatic cancer. So it's been a really exciting profile.
Yeah, and I know you're talking about the U.S. study that you guys have been enrolling. So could you clarify for us how long have you been enrolling that study? Where are you at in number of patients? And should we still expect a data update within the month?
Yeah, so we started about a year ago. So 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. We will, 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 valuable, ideally at the go-forward regimen, the go-forward dose, and we've been thrilled that we can clear the 900-milligram dose with good tolerability, reminding you that GenFleet is moving forward with a 600-milligram dose, and we see much better efficacy at 900. So we're really excited about that. Got it.
And then on the earnings call, you guys had emphasized that the first half 26 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?
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. And 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, you know, reduction in their tumor burden with pancreatic cancer, for example, and then get down to a partial response with a few So 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 milligrams is delivering more drug than 600 and by the way we've also started dosing at 1200 but we think 900 will be the move forward a dose and 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 so just to just be clear
so like investors should not expect to see things like a like a waterfall plot swimmer's plot like proper, like, ORR tables and such like that?
Yeah, we're excited about sharing that in the second half of the year.
And then just to kind of, you know, push you on this, because, you know, I get asked this from investors, what is kind of the reasoning for that? Because what you say in terms of, like, you don't want to present an ORR that might change, but that's kind of typical in early stage oncology drug development.
Yeah, I mean, first of all, it's a very competitive landscape. and I think when RevMed first came out with Derrickson-Rasiv, they had about a 20% response rate, and that was fine because it was the only agent out there. Our agent will do much better than that, but the response rate will deepen over time, and you need enough patients to really assess. And 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 milligrams. So we're really aggressively going forward with 900 as monotherapy. We've cleared 900 with full-dose cetuximab, which you can't do with another agent like Derrickson Rassiv. And we're moving forward now. We've cleared 600 with gemabraxane, but we're now testing 900 as well. So it's a matter of getting to that move forward dose, which takes time, and then getting enough patients that it's meaningful for investors.
Got it. And then when you say enough patients, can you clarify what you mean by that? Because you mentioned 100 patients into the phase one already. I understand, you know, a portion of those will be valuable. But, you know, like when investors hear this, they think, oh, they have 100 patients enrolled. Like at least half of them must be valuable. 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 milligrams would be ideal. So that would give a true sense of what we're seeing in the clinic. I think if we show a couple of 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. And why are you setting 900 milligrams as the level that you want to be able to show that given that Genfleet has shown that 600 milligrams is a very active dose?
Yeah, it's a fantastic question. So we've seen from preclinical 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 milligrams both in China and the US, and again, they're fasted, we're fed, but we're seeing similar PK between the two, which is good, but 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 or above. At 900 so far, we've seen that every single patient is above, so we don't want to leave any patient behind. We think that that's why we're seeing such great efficacy at 900 milligrams. Got it.
But should we expect that the U.S. experience at the 600-mig dose would, on efficacy, look like the China experience at the 600-mig dose?
I mean, I think nothing seems identical between the U.S. and China studies. I think our focus is on showing, well, I mean, our focus is on 900 and showing that it's really best in class versus other RAS inhibitors, and that's where we're heading.
We have about five minutes left, so I want to make sure we talk about a really important topic, is the phase two strategy that you guys disclosed. Can you remind us what your phase two pivotal plans are?
Yeah, that's also very exciting. So we had submitted our phase one design and we were looking to upsize the lung pancreatic and colorectal cohorts, and the FDA responded that it looks like you're trying to pursue marketing authorization, and if so, we recommended that you break out separate phase twos in each indication. We took that as a very positive sign that they didn't suggest, for example, randomization versus the control.
But to be clear, was your interaction with the agency what would support a pivotal study or was it that you had suggested expanding these cohorts and they said we recommend separate phase twos?
Right. They said if you have marketing authorization in mind, so we took that as accelerated approval could be a possibility given the extremely strong responses that we'd share the Chinese data with them. So 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.
And can you remind us of the design of each of these phase II studies?
So in the case of lung cancer, we're testing single agent. The focus will be on 900 milligrams. In the case of colorectal and pancreatic now, we're testing both single agent, again at 900, but we're also testing in combination with anti-EGFR, not just in colorectal where everyone expects that, but also in pancreatic cancer. The other thing that's exciting is we have activity of the molecule in intracranial models, and we talked to a lot of lung cancer investigators at ASCO. they said that if we have activity against brain meds, that'll be extremely important. In our phase two, there's also a cohort of lung cancer patients with asymptomatic brain meds. So we're really excited to see that as well, and that would really bring it out as best in class as well. Got it.
So it seems like, you know, the FDA in the past few years has kind of made a bit of a U-turn away from single arm accelerator approvals, especially for combinations, as we saw with, you know 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 Insight have chosen not to pursue an accelerated approval strategy? Yeah I think the just very strong
efficacy I think if we it's all in the data if our data if our efficacy is extremely strong in terms of response rate and duration then I think that the agency will consider that and we part of our confidence is that we just did it so with a novel novel combination we got single single arm accelerated approval so I think it's the recent experience of how we've done that and
we look to replicate that got it and then based on your interactions with regulators do you guys have a sense for what the kind of minimum threshold is that you must show on response
rate across the three indications it'll be a review issue I mean I think that we do I think certainly more than 30% response rate is kind of a minimum price of admission, but I think that we also have thoughts that we're developing on what will constitute best in class, but the agency won't ever give you a threshold and say you win if you're over this number.
Yeah, and then in pancreatic, presumably Dirac and Rasta will have a full approval and second-line all-comers pancreatic cancer, you know, probably within a few months. Does that change your ability to pursue an accelerated strategy in pancreatic?
So, first of all, well, so they had a 33 percent response rate. I think, first of all, in terms of enrollment, we're opening the phase two 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 PanRAS 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 they probably, we don't yet know what their efficacy is specifically in TRSG-12D, but it's therefore not an identical population.
Got it. And we're just about out of 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, so we had $182 million in cash as of March 31st. We have a cash runway through the first half of 2027.
Well, thank you guys so much. Thank you, John. Really appreciate you taking the time.