Greetings and thanks for joining us. To this next fireside chat, I'd like to welcome Mr. Dan Paterson, the CEO of Verastem . Verastem is developing a range of novel therapies against cancer, and just earlier this month, the company's lead combination therapy, avutometinib/defactinib, has received accelerated approval from the FDA for the treatment of low-grade serous ovarian cancer. To learn more about the progress that the company has made and the business strategy going forward, I welcome Dan. Good day, Dan. I'm glad to see you, and I appreciate you accepting our invitation to speak at this conference. Glad to be here.
To start us off, and for the benefit of the audience members who may not be familiar with the company, could you provide us with a brief intro to Verastem? What are some of the key facts people should know about this combo and the recent approval in LGSOC?
Sure, sure. Our strategy is to develop small molecules to target the RAS pathway. The first program that we had is a combination of defactinib now with the brand name AVMAPKI FAKZYNJA CO-PACK. It's a mouthful. Holding up to remember when both generic names and brand names are easier to say. They've gotten more complicated. We did get approval recently. We had a PDUFA date of the end of June, and it was very clear from the interactions we had with the agency, starting with the acceptance of the NDA back in December. We had done a rolling submission because it was actually two drugs. Even though the data was mature late last year, and that was the last module that went in, we wanted to make sure we gave them enough time because it was two actually full CMC packages to review.
It was very clear when we got the acceptance of the NDA, they started signaling that this would go quicker than the PDUFA date. We did have breakthrough therapy designation. This is an area of high unmet need where there was no prior approved therapy. Based on the signals we're getting, we moved forward all of our hiring, and we had the salesforce hired and trained and everything in place when we did get the letter. We're deep in the launch right now. You know, it feels like we're reaping the benefit of the two to three years we've spent working with both the HCP and the patient community.
There seems to be a fair amount of awareness, excitement, and we're just happy to be out there and working through all the things you work through with individual institutions, the things they have to do to be able to start using a drug, and starting to work on getting it in formulary, getting standard orders in place and all the things they need. That activity is going on. At the same time that we're doing that launch, we've got a very exciting ASCO coming up. We'll be reporting data on our frontline metastatic pancreatic study, which will be really the first time that we've got really exciting data in a larger indication. Our partner, GenFleet, we have a G12D inhibitor as part of a larger collaboration with them.
We reported some really cool data at AACR that I think shows that at least preclinically, it has a best-in-class profile. We will have the initial phase I experience from China will be reported to ASCO. A lot going on for us.
Thanks. Great to hear. To stick with the avutometinib/defactinib first before we move on to the frontline products. Now it's been about 10 days since the approval. Can you provide us with any anecdotal examples of what responses have you seen so far from the physician community? Also, has the launch been going as you planned? Have you had some learnings from this early launch that you can share with us?
I wouldn't say any learnings yet. I would say it's early days, but it's gone at least as well, if not better than we would expect. We incidentally had an event planned with 25 physicians the day of approval, and it went from introducing ourselves to actually talking about the drug. That was great for the salesforce to really hit the ground running. We have drug in the channel. It's been ordered. We actually have patient orders where I'm aware of a handful, if not more, of patients that are in the process. They have to go in and get appointments and get labs done and all that that are kind of working towards going on the drug. Very excited.
I would say the inbound interest is a bit of what has surprised me, is we're getting people calling in and saying, "Okay, what do I have to do to be ready to do this? How do I get the information?" So far, so good. I'm sure we'll have our bumps along the way, you always do. It feels like it's going quite well.
Sounds great. Certainly looking forward to the next couple of earnings calls. Regarding the commercialization, would you say what are the next steps for the company? Do you have specific goals in mind that you hope to achieve by the end of the year or the next 12 months, let's say?
I would say by the end of the year, we want to see a good trajectory on uptake. And we've had a number of strategic objectives. The first one is make sure we remove any barriers. So we've been working proactively with payers, with the large GPOs, all the large systems to make sure that any barriers are out of the way. When we talked about the label, we had talked about the most likely label being KRAS mutant low-grade serous ovarian cancer. We got that as a label. Our breakthrough therapy designation was for patients who had had at least one prior platinum-containing therapy. The label actually ended up being at least one prior therapy. The reason that's important, there are a couple of key studies going on that may eliminate platinum as a frontline therapy. And so it's nice not to have that restriction.
As we've talked for quite a while, we do believe that the data in the KRAS wild type compared to other options that these patients have is quite attractive. The day we got approval, we did put in our package with the NCCN to be able to get included on their guidelines. That process is underway. For those who aren't familiar, in the U.S., the thing that really dictates whether insurance companies pay for a treatment in oncology is the NCCN guidelines. They're kind of a national organization. Most of the other organizations adopt some form of their guidelines as the guidelines they use. One of the things we've learned from past launches is for the large physician practices that are affiliated with the group purchasing organizations, they tend to be very guideline-driven.
It is very important to get into their guidelines. They actually embed them in their electronic medical records. It pops up as the therapy you use. That, plus the in-services that you do as part of your contracting with the GPOs, is how you educate those physicians, as opposed to the old way of going out and having salespeople do one-on-one detailing. That does not work as well in the community now. Obviously, you have concentrations of physicians who see a lot of patients. In this particular market, about 100 sites see about half of all the patients. That will be where we concentrate the salesforce. It is really the other parts of our organization, the medical science liaisons, the market access folks. We have nurse educators. Those get deployed to help with all the other aspects of the market.
I know that very recently you guys announced a companion diagnostic as well for the drug. I was wondering, how important is this companion diagnostic for the combination? What proportion of the LGSOC patients are already being tested?
Yeah. To address that first, in a way, it's a bit of a box-checking exercise because it is required, and it was a post-marketing commitment, and we will do it, and we're developing, and we're well into that development. There are KRAS tests out there. In this country, you tend to have large companies develop the tests, and then the large institutions kind of have their own versions that they like to do. It's broadly available. In ovarian cancer, we did some market research before we launched. We were pleased to see roughly 80% of patients are probably already getting a KRAS test. I think part of that is driven by the fact that in high-grade ovarian cancer, a lot of the therapies are patients who have either a BRCA mutation or other types of DNA damage repair defects.
They've gotten used to doing testing, and you tend not to do the testing as a one-off. You do a next-generation sequencing panel. They've adopted the panel. We do not think that's really going to be a barrier. We will have our own companion diagnostic in the not-too-distant future, but that's not needed to market the drug or to even start.
Good to know. For the last question on commercialization, looking beyond the U.S. to the other major international markets such as Europe, Japan, Canada, what are your plans there?
I would say our next approval will be most likely in Japan. Part of that is because we can do a relatively small bridging study and get what's called conditional approval, and then we'll roll those sites over to participate in our global confirmatory study. That is a relatively straight path. Even before today's announcement about most favored nation pricing, which we'll get into today, Europe had its own challenges. We are talking to the regulators over there. We got our pediatric waiver recently, which is required. We are working on orphan drug designation in Europe. We will be having scientific discussions on whether we can get approved based on the current study, which there's a chance we can, or whether we have to have the confirmatory study, which is a randomized study done before we can do that.
Even if we're able to get approval in Europe off the original study, reimbursement's likely to follow the confirmatory study. We'll be pushing forward with that. Approval will be done by the end of the year. Again, the most favored nation, I don't know how real it's going to end up being or whether there's some upfront bluster, but that could impact the willingness of companies to, frankly, go to Europe.
Yeah, that's a wait-and-see type of thing. Yeah. All right. Moving on to the clinical programs then. Beyond ovarian cancer, the company is also testing the avutometinib/defactinib combo for a variety of other solid tumor indications such as lung cancer and pancreatic cancer. Could you highlight some of the key focuses for the company in these areas and what are the most important results achieved so far?
Sure. Sure. We recently announced that on the lung cancer, this is KRAS mutant G12C. It's a collaboration we have with Amgen taking sotorasib. We originally combined it with avutometinib, and we recently added in defactinib, which was always the plan because the triplet looked really good preclinically. We did recently announce we've gotten through the safety portion of that, and now we're expanding. Importantly, we'll be expanding into sites in Europe where accruals should really pick up. The European regulators wanted us to develop some data on the triplet before they'd let us open that study. That's a nice milestone. Probably our next most important thing beyond the current approval is we will have updated data on frontline metastatic pancreatic cancer. You may recall we reported initial data on that at ASCO last year. It was a relatively small cohort.
It was six patients, but we had confirmed responses in five out of six patients and 83% response rate, which is just astounding in that disease, which it's been one of the hardest diseases to really develop regimens against. We'll be reporting on 60 patients, so a larger data set, and be able to get into really what our go-forward dose would be. In today's era of Project Optimus, we had that exciting data last year. We did have one dose-limiting toxicity. It was febrile neutropenia, most likely due to the chemo regimen because this is combining with standard chemo and PDAC, so gemcitabine plus avutometinib and defactinib. We explored a number of different doses to optimize around the chemotherapy. We think that was a critical step before we go forward into a larger study. We've been picking the dose to go forward and reporting what we think is pretty exciting data.
I'm certainly looking forward to the updated ASCO. I think in the earlier, you also mentioned that we can expect to see the phase I results from VS-7375, which is a KRAS G12D, remember?
Yes. Yeah. I think that'll set up right very nicely after the data we had at AACR. We had a presentation at AACR. There was a preclinical presentation, but it really highlighted both the preclinical profile of the drug and did some head-to-head comparisons with the RevMed molecule, which arguably has clinically set a benchmark in pancreatics so far. Following that on, our partner GenFleet will have their phase I experience from China at ASCO. Very excited about that. Obviously, G12D is a very hot space. Frankly, I was surprised there won't be more clinical data at ASCO because there's been so much activity preclinically. This will be really, I think, a nice data set to show how this sets up. There's always a difficulty in cross-study comparisons, Chinese data versus U.S. data, differences in the patient populations, all of those.
I think it'll give folks enough excitement for our phase I/II that's coming down the pike. We've guided New Year this year. We'll be starting in the U.S. We've got a number of very prominent institutions with investigators that are very experienced, both with G12D inhibitors, but just RAS inhibitors in general. We're going to take advantage of all the expertise of those investigators to really optimize our program going forward.
I'm certainly looking forward to the GenFleet results because this is the first time we've seen what the drug can do in humans.
Yes.
For your phase I/II , that's kind of related this year. Do you have a specific indication in mind already, or is it going to be a sort of a basket study to test in different tumors?
Yeah, we're starting out just really defining the dose. The good news is when we submitted the IND to the FDA, we submitted some of the Chinese data, and we're actually able to start at effective doses. This isn't a traditional phase I where we're going back to the beginning. This is really focused on, I would say, more Project Optimus, choosing the right dose to then go into the phase II or the expansion phases. What we've said is we are going to do PDAC, so we'll go into pancreatic. We're going to go into non-small cell lung cancer. We're also quite excited about colorectal cancer. Revolution Medicines reported about a 9% response rate as a single agent. It looks like you're probably going to have to combine with something like Erbitux. These are relatively high rate of rash, which might be a challenge.
We think that's maybe an area where we can go where maybe they won't go as aggressively, but we are going to go into pancreatic and lung as well, look at a number of combinations. John Pachter, our CSO, who's here, his group has been doing a whole bunch of combination studies preclinically to say what direction to go into. We're really gearing that program up and excited to really move it forward very quickly.
Makes sense. Yes. All right. What are the next steps then for these programs? Looking beyond ASCO, are there any other clinical milestones that we can expect in the second half of this year?
Yeah. For the second half of this year, obviously, everyone's going to look at our sales trajectory. We will, by the end of the year, have additional data on the sotorasib combination. Then really disclosing more plans around where we go after these initial studies and what that looks like.
Great. In the last couple of minutes to close it off, what is the company's cash position looking like, and what is your expected cash runway? Do you have sufficient resources to support the launch? Also, what are your commercial plans for the rest of this year, I guess?
Yeah. So we just reported quarterly earnings, and we had roughly $193 million in cash. That was bolstered by the $75 million raise that we did recently. We had a lot of debate around, do we wait until after ASCO and do a larger raise when hopefully the stock goes up? In looking at the unknown external environment, and as we were debating what to do, our stock went down to like four, and now it's recovered to like eight. We decided the prudent thing to do was do that $75 million raise because it did a couple of important things for us. We had done a raise last year that came with some cash-only warrants that had a short expiration date. They expire in January. They've been well in the money for a while. This gets us well past that. It unlocks that.
It was not just the 75. It is the 75 plus 62. You take those two together, gets us well into the back half of 2026. What I would say is we funded the base LGSOC business. It is really any future investment is likely to be funding these larger programs, which we would only fund after we see good results. That allows us to progress. Importantly, the 75 allowed us to really fund the launch in the base business.
Great. Thank you very much, Dan, for joining us for this very informative chat.
All right.