We are going to get going. We're getting down to the end here at the BofA Annual Healthcare Conference. Jason Gerberry here from the biotech team, pleased to be introducing Mirati Therapeutics. We've got Benjamin Hickey, Chief Commercial Officer, and we've got Ryan Tse from IR in the crowd. Ben, thanks for joining us. Sure. It's great to be here. Thanks, Jason. Yep. You know, I guess, as CCO, you get to preside over a new launch, and we've got our first quarter update recently. Maybe if you wanna start with just sort of how you see the launch going, and then we'll go from there. Sure. We're very happy, I would say, with the first quarter. As we reported our earnings earlier this week, we've already seen a third of new patients, new, naive to KRAS G12C therapy, choose KRAZATI. We're very excited about that and on the right, the right pathway to hopefully being market leader, and that's certainly something we firmly believe in. We delivered $6.3 million for net sales in the first quarter. Mm-hmm. We are, I think, very promising penetration. We've also seen adoption of the product in the top 50 accounts, 80% of the top 50 accounts. We're also seeing great execution from the field teams and being able to actually access accounts which represent about 90% of the opportunity. Very good execution, very good early results, we are, you know, very confident of the, of the path forward and being the number one KRAS inhibitor. you know, there's mention obviously about, I think, genotyping occurring in like 70% of patients, that other precision oncology categories like EGFR are trending at like 85%. Thus, there's an opportunity if you get those percentages up. I think there's also some commentary about perhaps some of those 70% being genotyped and that being lost as they get to second line. If you can just talk about those dynamics, how that's an opportunity for you guys to grow this category? Sure. The numbers are correct. It's about 70% of genotype testing currently at diagnosis. What we are seeing that unfortunately today, only about 25% of the time is there a structured field in the EHR, which means that it's very easy for a physician to identify that that patient has a marker for G12C. Keep in mind, these patients are doing well on frontline therapy and could be taking, you know, 12- 24 months to progress into second line. At the moment, it's only about one in four patients are in a structured field. A lot of the time there is a pathology report, which is appended to the EHR, and about 25% of the time it's just unknown, and they may have to search through their own notes to find it. We've built a lot of, in-depth community-level account plans, and then we're also partnering with some of the EHR companies to see how we can actually accelerate the adoption of these fields, so it's easier for the physician to actually identify and recognize the patient. Got it. Maybe one other complication is this is predominantly a smoker population, which previously has not been a population that's had great access to targeted therapies. Just another hurdle to overcome, which is why we think the market is still very immature and has a long way to run. What drives that convergence? Is it just another pharma company out there in the field, creating awareness and that ultimately drives it? If you look at maybe other analogs. It's certainly part of that. We've effectively doubled the promotion in the market. We've, you know, we've built for success. We have an extensive field sales access and field medical teams, which we think has increased the level of noise there. We also were very specific and thoughtful around our focus on community oncology, which is where, you know, close to 80% of lung cancer is treated. That's where we studied the drug. Our pivotal study, our cohort A, about approximately 40% of the patients came from the community, so they already had experience. We also think with the profile of KRAZATI, with over 14 months of survival, as well as, you know, strong CNS penetration, that is another reason to believe on why we're actually seeing a number of physicians write KRAZATI that haven't even previously written a KRAS inhibitor, which gives us another, you know, some hope and optimism, I would say, that the market will grow at a rapid rate moving forward. Yep. A couple things caught my ear on the one Q call about how this launch is going with KRAZATI. One being that there are actually some switches occurring off of LUMAKRAS. I guess it seems like the most common pattern there is somebody develops brain mets, and then they're gonna get moved over to KRAZATI, just given that you at least have, you know, demonstrated-. Yep a clinical signal there. I imagine that a switch patient probably is not gonna be that much revenue because, like, the duration therapy is not that long. Over time, I imagine, like, perhaps oncologists may just go, "Why am I not just using KRAZATI?" Like versus having to do this sort of switch. Yeah. I think what we guided to on the call was that we see about 20% of patients which are either switching off of sotorasib or are coming from very like lines of therapy. To your earlier point, may have a shorter length of therapy. Now, we don't know. It's too early to understand those dynamics. The two reasons we hear of the of physicians moving to KRAZATI if they're already being treated with a KRAS inhibitor, one is around CNS mets, as you'd mentioned. I think our data, both in previously treated around 33% and then showing data in active and untreated, which looks very much like our systemic response rates, is a reason for that. How much of that continues in the future, we'll see. The other part is really this dynamic around hepatotoxicity, where a lot of physicians, particularly in the academic centers, are aware of our frontline data. Mm-hmm ... where we've shown a combine, you know, where we can concurrently combine and have a path forward in frontline.They're taking solace from that, and in their experience, at least anecdotally, they're seeing less of that hepatotoxicity with adagrasib than they are with the competing KRAS inhibitor. Got it. On the latter point, I guess the concern is not enough clarity on how much of a washout period you may need with your IO agent, and thus am I gonna trigger more severe DILI or drug-induced liver injury versus... That's correct. To your earlier point, Over time, I do think that we'll see that as a reason to believe, not that we promote it's not on our label, we certainly wouldn't promote that, but that it could be a reason to believe on why we think that physicians will, even more than the 1/3 already, within just 3 months of the year, that more of those physicians will begin to choose KRAZATI as their go-to in second line. Yep. Okay. You talked a little bit about the community academic dynamics, and that the community is really can drive the lion share. It's probably early to break out sales splits and things like that, but just in terms of where the marketing effort is, I mean, obviously, sales reps can't get into most academics' hospitals anyway to promote to those physicians. Is the bulk of the effort really at the community? The bulk of the effort is, we are seeing the early adoption is, I would say, about 60/40 academic to community, which is very promising for us because it shows that actually that the thought leaders and academic centers are beginning to choose KRAZATI over the competition. That's really a leading indicator for future adoption in the community. We, I would say, are disproportionately focused in the community with our field teams, but that doesn't mean we don't have a big presence. If you remember, we've already had, you know, two New England Journal articles, actually three New England Journal, two Journal of Clinical Oncology as well. We have a big medical presence from field medical as well as from a publication standpoint. Mm-hmm ... and then engaging with the academics as well. I would say we see the opportunity for growth is really in the community. That's because of the testing dynamics and this patient identification issue. Yep. Okay. Look, I, I get it's way too early to talk duration of therapy with KRAZATI, but you could probably learn a lot from LUMAKRAS at this point. PFS, you know what, six, seven months with these agents. Rule of thumb in Wall Street tends to be discount that by a third, you kinda get, like, four months. I guess that's been one of the pushbacks on the 12C story is that, like, durations of therapy aren't that long and we're gonna need to see combinations to really unlock the value of these agents. Is all that sort of. I don't know if you pushed back on it, on any of those data points. Yeah. I think a couple of things. We would expect you'd said the street gives it a certain haircut as it were in a real world. That's not our expectation. Okay. It's too early to assess that. Keep in mind two things. One is we recruited our pivotal study in the community, so it is a very community-like population. A number of our patients in the pivotal study were on three or four lines of therapy. We do think that our PFS and OS results actually are very. The read-through that for what we will see in the post-launch phase is pretty good. Number two is that we launched with a tablet, and our label and early studies are in the capsule, and we've heard absolutely anecdotally that the tablet is more tolerable, which gives us, you know, confidence and optimism that we'll begin to see patients being able to stay on therapy and hopefully benefit from KRAZATI. Okay. Maybe just, you know, you talked a little bit about CNS activity, just sort of the plans, you know, to potentially get this in the label. You've got the NCCN recommendation, which I think is helping, right? Do you envision, you know, any additional efforts to kind of amplify that potential advantage in the marketplace? Sure. We were very excited to hear from the NCCN that we were the only KRAS inhibitor to be listed and given that designation, from a CNS standpoint. That's only been relatively recently, so optimism that that could lead to further growth in the market. number two is that for our KRYSTAL-12 study, that we'll look at measures in terms of delaying progression- Mm-hmm ... from a CNS met standpoint. We look forward to that readout next year, and we think that could be another opportunity to differentiate our profile. Thirdly, we'll continue to publish our data, particularly in the active and untreated population, and that should be in the relatively, you know, very short term, in regards to getting another publication out there and articulating what the active and untreated, both response rates and durability of response looks like. Yep. Okay. Ultimately, to your point, we would look to look at the, you know, the composite of the data and engage the FDA ultimately with how that would look from a label standpoint. Understood. Okay. Just 2 more questions before we go to first line, and any opportunity there. Your 400 mg BID monotherapy study, I think you've expected a readout, you know, of that study sometime this year. Just if you can confirm that? For the KRYSTAL-7, the combination in frontline, is that what you're saying? No, I thought the 400 milligram BID study in second line. Oh, the 400... Yeah. Thank you for clarifying. We have a post-approval commitment that we agreed with the FDA, looking at both the monotherapy of the 400 and 600 in second line. We're just in the phases of initiating that study, so we won't have a readout this year. That's just in the early phases. Okay. It sounds like perhaps the company's amenable to an ex-US or EU partnership. How active are those discussions going? You know, a lot of times biotech companies don't wanna, you know, fracture off the rights- Yeah ... you know, to different, key geographies. You know, obviously, you know, capital is important as you kind of advance. A lot of the focus, I feel like with Mirati has shifted to the early-stage pipeline. Yep. I'm just curious. Yeah, I think the good news is we have a lot of optionality because we have not only with adagrasib in second-line colorectal and then moving to front line, but we also have the pending readout with sitravatinib, which is also in lung cancer. That means that there's a lot of interest in our pipeline in regards to an ex U.S. potential partnership. We have engaged or are engaged in those conversations. There's a great deal of interest, we have a great deal of flexibility. We'll, you know, take the actions which will generate the most return for our shareholders. It's just good to have those options, certainly a great deal of interest, and we're with it in those discussions currently. Yep. Okay. Just help us think through as we think about the frontline opportunity, you know, how to think about the development path forward here. It sounds like from the most recent you know, earnings call, we just need to see more of the durability data to make a more informed decision. Part of it's powering, part of it could be, you know, making sure we don't see anything you don't like. It's a complicated development pathway 'cause there's a lot of different subpopulations and different. Sure. -go-to-market pathways there. We tend to think of the market in two segments, which is the greater than 50 PD-1 expression and the less than 50 for the most part. The comparator in a greater than 50 would be a Pembro monotherapy, and in the less than 50 would be a 189 like regimen, which includes chemotherapy. We'll have data later this year about 150 patients with extended follow-up. We'll be able to see not just response rate, but durational response and early looks at PFS, which to your point, puts in a very strong position to be able to choose, is it one study or the other, also articulate what the appropriate powering of that study would be. You know, and as you think about, you know, having a, you know, potentially market in the frontline setting, Merck has set a very high bar. I mean, what do you think it takes with, you know, these studies from a precision oncology perspective? We oftentimes hear if I've got an all-comer based approach that works just as well- Yeah. It's gonna be hard to move off of that. It seems like the cost of admission is OS superiority in all these segments and, you know, there's been a bit of a shift to the KRYSTAL-17 approach, looking at a triplet in the... I think you said the under 50s or the, or the negatives. In the less than 50, we tend to look at that segment. Okay. Yeah. Yeah, just the evolved thinking there, as it pertains to the end market that you're dealing with and just sort of what it takes to differentiate. I think from an endpoint standpoint, we would be thinking about PFS, in addition to OS. You know, I think we feel pretty comfortable in terms of the engagement we've had with the FDA around the study being led by a PFS endpoint. The comparator for the study is pretty clear. In the greater than 50, it would be monotherapy. We see if you look at KEYNOTE-024 and KEYNOTE-042, response rates are in kind of the mid-40s, and in the less than 50, they're in the mid-30s. I think the bar is relatively clear. We have looked at the KRAS population, looked at real world data. The net of that looks like the KRAS population looks like it does slightly worse in less than 50, and similar to the all comers, maybe a little bit better in the greater than 50. We think with a targeted therapy, with the right, you know, the right power in the study and the right clinical benefit that we'll be able to infer from our current K- 7, we'll be in a very strong position. I would say that the enthusiasm for physicians, around this frontline study, whether it be the less than or greater than, is very, very high. Okay. You mentioned CRC a little bit. Just, you know, can you talk a little bit about the FDA interactions? Is the agency still amenable to these single arm studies as we think about a potential third line opportunity? I mean, mindful third line's obviously smaller, and the second line indication is probably where you derive, you know, more value. Yeah. You know, maybe just... 'Cause that is an event that's coming up. Yeah. The third line outcomes are very poor for patients. You're talking about low single-digit response rates and potentially even worse from a, you know, for those who have a G12C genotype. Our discussion with the FDA has been very positive. We received breakthrough designation. They've been very responsive, and turnaround times are very quick with the FDA. We expect to file this year. We expect the data that we've provided so far, and it will continue to mature, is certainly supportive of an accelerated filing. Our confirmatory study, something that the FDA wants to see is that confirmatory study is well underway. Our K-10 study, which is in second line, is in recruiting and enrolling very, very well. I think that further de-risks our approach in third line. You know, we'll be in third line for a small period of time and hopefully then jumping into second line. As far as we understand, the competitors are only playing in the third line space at the moment. A good quick to market opportunity. To solidify that and be the only KRAS in second line is, as you say, is the bigger opportunity. Not just within colorectal, but then thinking about the total dataset that we'll be able to talk about with KRAZATI, and particularly in the community where they are treating all sorts of tumors to be able to be in a pancreas NCCN, have a colorectal approval, have data in, you know, industry-leading data in the second line, and then be able to be combinable in the front line. We think we've got a pretty good story to tell in the medical community. Is it possible we get an interim from the second line study, in advance of the accelerated approval decision for third line? I think that's unlikely given that we're running pretty quick at the third line. I'd expect us to be able to, you know, file in the third line and work pretty closely and quickly towards approval. I think that we read for K-10 probably subsequent to that. Mm-hmm. Um- You know, before we move topics, I mean, anything else like specifically just on the KRAZATI launch that you feel like we haven't touched upon that you feel like it's important just in terms of how investors are thinking about that opportunity versus, you know, it seems like there's a lot of weight and anticipation on sort of frontline updates ultimately. I think the key is we are hyper-focused on both taking market share and being the leading KRAS inhibitor, and we're off to a great start. I think people sometimes forget that we only launched the product and got approval in mid to late December. Right. This really is our first few months on the market. To be at a third of the market already, I think is a super positive indicator of where we'll be in the future, and that ramp will continue. I think that's number one. Number two is the market will continue to grow, and I think probably at a greater rate than maybe people are expecting. You know, we saw annual growth in Q1 of about 20%, and we believe that will continue on a kind of a linear basis to continue at a pretty high clip. That's number two. Number three is we have a very energized, focused organization that eats, lives, sleeps, you know, KRAS. To have that focus and have that belief that you have, you know, a differentiated profile gives us a lot of belief in terms of what we'll be able to do in the market moving forward. I think, you know, a lot of room to grow in second line and then, you know, next year we'll be talking about the readout, the pivotal study, hopefully approval in colorectal, as well as the advancements we're making in frontline. Just a, you know, a lot to come from KRAZATI. Yep. makes sense. In terms of SAPPHIRE, that's the next thing, it's obviously a potentially substantial opportunity. I think some of the obvious pushbacks are very obvious here, right? We've seen a few IO-TKIs in this setting being unsuccessful. There's some competitor data in the second line setting Trop-2 that, you know, looks like it could be competitive. Just like, what do you think is the bar? Could some middling overall survival, PF or OS hazard ratio of like 0.8, 0.1, is that gonna cut it? Do you feel like you really need to show something more compelling to be able to get traction in the space with the approach? Yeah. I think there's a huge unmet need in second-line lung cancer post-IO progression. Physicians are not comfortable with using docetaxel or ramucirumab or the whole collection of other chemos, so the bar is relatively low, I would say. That's number one. Number 2 is that if you look at the other data readouts that we've seen so far, keep in mind we designed our study differently. We required at least four-month stable disease prior to enrolling in the study. Mm-hmm. You're talking about a population that has some immunogenicity already. We think we've given ourselves the best chance of success. You know, it's a large study. It's over, you know, 550 patients, and it's powered for a overall survival benefit, which if you think about how sitravatinib works. Mm-hmm ...which is really more focused on the TAM receptor than the VEGF, that's a reason to believe that we are re-stimulating the immune system. I think with a longer follow-up, we are, you know, cautiously optimistic, but like you say, we, you know, we'll have the data readout in Q2 and we'll see. I think the unmet need is high, the clinical bar is relatively low, and we are, you know, hopeful that we can help these patients. Yeah. The trial design tweak that you talked about versus competitors, that sort of was effectively like a washout period so that patients who get randomized to the docetaxel arm don't have some sort of like benefit from the frontline IO that they got ultimately. Is that? I would think about it in almost an inverse way, that the patients that are coming on have shown that they have shown some IO benefit. Mm-hmm. We think that, given how sitravatinib works, was the right way to design the study and give it the best chance of success. We, you know, docetaxel has done slightly better in recent studies post-IO, we'll have to see. Again, we've given ourselves room within the study. It's a pretty big study. We've put, you know, a lot of the alpha on the final analysis for OS, we'll know the data this quarter, fingers crossed. Practically speaking, if that trial is positive, do you think that that drives more of a utilization in an IO-sensitive population? How does that sort of segment the market, opportunity? I think it could potentially. Keep in mind, we've already built the infrastructure from a commercial standpoint. It really wouldn't be a significant additional investment, right? We could reallocate spend. We've built all the infrastructure, the back end, the front end, the field teams, the marketing team, the access team, etc., the medical team. There's not a big commercial or medical-related build. That's important to understand. In regards to how the market may break down, I think if there are other drugs which are successful, like the Trop-2s, I do think that it would be rational for the market to break down to this kind of, you know, prior immunoresponsiveness- Mm-hmm ...versus non-responsiveness, which I think from a commercial standpoint would be a good thing because we would expect that immunoresponsive population to potentially have a longer length of therapy over time. Yep. Okay. You have about five minutes to go here. Maybe just, you know, a lot of focus on Mirati's early-stage pipeline. Not sure, you know, in your role, how involved you are in the discussions with be it G12D or PRMT5, but maybe just curious, you know, what excites you about what's going on, you know, beyond just sort of the mid to late-stage development programs. Sure. I tend to annoy all the other executive team members and get very involved with D and PRMT5 Yeah. And so on, 'cause it's that important to the company. You know, we've made great progress with PRMT5 and look forward to showing them, you know, a fulsome data update later this year. We, you know, we like what we're seeing pre-clinically. We like what we're seeing from a dosing standpoint in that study. It's probably about a year ahead of G12D 'cause we've been in the clinic for quite a while. Yeah. You know, I think we'll have more data on that in the short term. I would say our scientists are, you know, are very excited about what they've seen early in that study. We're just not seeing some of those dose-limiting toxicities that the earlier generation of PRMT5 unselected agents had seen. Keep in mind, we are, you know, specific to the MTAP deletion. We are getting to therapeutic even above the levels that we believe that were therapeutic from a pre-clinical standpoint. We like what we're seeing on PRMT5. G12D, the enthusiasm around that program is just immense. You know, we get a lot of calls from physicians and centers that wanna be part of that we've had to hold off because we just need to get through the initial dosing cohorts. We're very early. We've literally been in the clinic just a few weeks. We've guided to, you know, first half of 2024. With that, where we'll be able to show, you know, a pretty robust data set, including not just PK profile, but looking at early clinical re-response as well as the safety profile. I guess the last point I would make on that is this is the same discovery research team that brought, you know, KRAS G12C to the forefront. A very experienced team. They've had a great deal of learnings, from the C space that they're now applying to the D space. We, you know, we're very optimistic and hopeful. Yep. I guess with PRMT5, the comment, Terry, is moving close to a recommended phase 2 dose. That's at therapeutically active levels. Your commentary regard, A, the selectivity of the approach, we feel like we're decoupling from the tox that maybe plagued other efforts in this space. There's still an open question because we haven't fully elucidated with any really approach in this pathway exactly what single agent activity means in a lot of these different tumor settings or if it's going to be a single agent approach or gonna require combination strategies. Yep. to ultimately, you know, bring a medication like this to market. Yeah. Our intention is certainly to see single agent activity here. Depending on what we see there's always, you know, as we did with KRAS G12C, we'll always move to combinations quickly, because that's just the nature of oncology development. We, you know, unlike SOS1, where we may be looking at more a synergistic effect with a KRAS inhibitor, we think PRMT5 has the opportunity to stand alone and show monotherapy activity. The update in the back half is likely more than just safety PK. You know, the hope is to have some sort of clinical response data. The hope would be, you know, enrollment has gone well there, so we'd be hopeful to be able to characterize the molecule appropriately. Okay. maybe with G12D, curious, you know, historically, the challenge was always bioavailability, IV versus oral. How comfortable should investors be just sort of that you guys have sort of solved for the bioavailability piece of this? We've been at this for a while, and the team feels that we can crack the code here as regards to bioavailability. As you've mentioned, you know, we've looked at a couple of different formulations. We have the oral is our lead program. One of the reasons to keep looking at IV is actually more a push from the commercial side and because of IRA, that we wanna make sure that we are actually considering the longer term value of the asset and consider both an oral and IV. Mm-hmm. That's part of the drive behind that. We, you know, we like what we've seen pre-clinically, and we hope to be able to replicate that in the clinic then, but we'll see. Do you feel like there's room to optimize with next-gen G12Ds based on, at least on the early properties that you can kind of see there in animals or pharmacologically speaking, mindful that, you know, data can drive, you know, revisiting that? I think it's too early to tell. There's very little data in the space. Mm-hmm. We like the selectivity of our program. That means that we're not hitting, you know, off target where we may be seeing other molecules may run into toxicity issues. We are highly selective. We're hopeful if we hit the target high enough, hard enough, and we get the right bioavailability, that's the, that's the optimal path. Yep. That it sounds like that may be versus the PRMT5 update second half of this year. First half of next year, it seems like you guys are very clear. We expect to be at recommended Phase II dose, and we expect to have a very fulsome update that, you know, can allow and enable next step decision-making. That's right. As an organization, we don't want to get into a play-by-play with every patient type. We think it's more appropriate to give a more wholesome, fulsome update, across a number of parameters and really shape the path and be able to articulate what that path looks like going forward. Okay. Well, we're up against our time, thanks, Ben, for joining us. With that, we can wrap up our session. Thanks.