Good afternoon, everyone. Tyler Van Buren here, senior biotech analyst at TD Cowen. Anyways, welcome to the 43rd annual TD Cowen Health Care Conference. For our next session, we have a fireside chat with Mirati. It's my pleasure to introduce David Meek, Chief Executive Officer, and Ben Hickey, Chief Commercial Officer. David and Ben, thank you very much for being here. Thanks, Tyler. Glad to be here. Before we get started, if you guys have any questions in the audience, feel free to raise your hand, and we'll do our best to get it asked. Before we get started on some more specific questions on KRAZATI and the pipeline, David, maybe you could provide a general overview of the business. Sure. Thanks, Tyler. We're real excited to be here today to talk about the Mirati story. The Mirati story is this. We're a target oncology company, we discover, we develop, and we now commercialize target oncology therapies with a primary focus on KRAS. We've got our KRAS G12C program, our KRAS G12D program, our KRAS enabling program, a SOS1 inhibitor, and we have a PRMT5 inhibitor and a sitravatinib. We'll talk about each one of these later on during this conversation. That's what we do, target oncology. We've got, we ended last year with an approval of KRAZATI. It's our first approval, and we're real excited about the launch of KRAZATI or adagrasib. Our approval is in second-line plus non-small cell lung cancer for patients that harbor a KRAS G12C mutation. We believe this is a best-in-class KRAS G12C inhibitor and will be the market leader in the KRAS G12C inhibitor space. Our initial launch is in second-line non-small cell lung cancer. We've got an extensive lifecycle management plan that we'll talk about today. We're real excited about the future that adagrasib and KRAZATI do have for Mirati. On top of that, you know, looking at our pipeline, we have in the past 15 months, we've put three programs in the clinic. We'll talk about those, and we've got a phase III readout with sitravatinib, the SAPPHIRE trial, which we'll read out next quarter. We have multiple catalysts that are upcoming for Mirati. We're real excited to talk about the Mirati story. Let's get into it. Starting with KRAZATI, on the earnings call, you guys mentioned that the initial launch experience was very positive. Can you elaborate on that and, what are your expectations for the launch? Sure. As a reminder, we launched and were approved in the second half of December. Obviously I'll, you know, kinda contain my comments to the Q4 for the most part. We were, and have been very excited. I mean, the way that the team has got out there, started educating physicians very, very quickly. We had products in the channel within the week. We were educating physicians within 24, 48 hours. It's been going very, very well. Our access has been going well from a coverage standpoint so far. Lots of interest in our patient hub. So far, so good. We've got a super energized team out there, which is really enjoying it so far. Is there anything in particular that you guys are doing different than what Amgen did for the LUMAKRAS launch? How are you measuring success over the first year or two? Yeah. We think the market has a long way to grow. It really is in its, you know, infancy at the moment in regards to both the testing rate, which we still see is only in the 60s, probably high 60s at this stage, and that's at diagnosis. Those patients are still coming through to second line. We still think there's an opportunity for those second line patients to be identified within the EHR systems. There's still a large gap there, particularly in the community. As a reminder, we've had people out there for over a year in the field. We've been able to really understand the local dynamics, really understand the flow of patients coming in from first line into second line, establish the right relationships, establish the right level of access, and are actually beginning to look at real-world studies where we identify patients that could benefit from a KRAS G12C inhibitor. We expect both the market to grow and for us to be able to penetrate in terms of market share and ultimately, over time, become the number one prescribed KRAS inhibitor. Are you seeing any switches from Lumakras, or do you expect to start with G12C naive patients, at least for the initial phases of the launch? Yeah. The, the vast majority will certainly be those naive to class second line patients. We, we do get questions anecdotally and through medical information around various patient types, whether it be patients with a CNS metastases or patients with hepatotoxicity or something like that. Some more anecdotes around that, but certainly the majority we expect to be new to the class in the second line. Okay. I understand that you're gonna wait till Q1 earnings when you have your first full quarter of launch to give more specifics about it, but can you help us understand generally what type of metrics you might be tracking? Sure. First of all, we're obsessive about the level of service that we give to physicians, so we actually track what that experience looks like and things like our patient hub, our services we provide, our out-of-pocket support to patients. We'll provide some color around that. The number of physicians that are beginning to write the product, we think that's an important surrogate marker, I should say, for success in the future. Access formulary coverage on the payer side is obviously an imperative of ours. We'll begin to show some of the anecdotal experience about patients being on therapy and what physicians are seeing, as they get, you know, initiate patients in their first few weeks. Those are some of the things we think are important in the early parts of the launch. Okay. I guess just a nuanced question, but why are prescriptions, KRAZATI prescriptions not being tracked by IQVIA or Symphony when they are for LUMAKRAS? 'Cause for competitive reasons, we decided that we would be blocking some of that data. You know, historically there's been some of the data has come through a little bit, but moving forward, there'll probably be less and less. That's really is because we are very focused on local account plans, and we think that could be a competitive advantage where we really understand not just the testing dynamics at the local level, but also the adoption, whether it be of LUMAKRAS or of our own assets. Really for competitive reasons. Got it. Okay. I guess how confident are you that this second line plus setting will continue to grow as you guys launch? Very. We think there, again, when you look at the testing rate, which is ticking up quarter-on-quarter, the feedback we've heard about physicians and seeing the actual eligible population, we still think there's a lot of room to grow there. Keep in mind that the level of promotional noise in the market, we've now just doubled. We have a significant field force out there. We've got significant efforts on the digital side. We were able to build our custom model in the time of COVID, so we didn't always assume that everything would come back to normal. We have extensive efforts around our CRM platform and how we engage with people digitally. We think actually that surround sound and with the profile that we have with over 14 months of overall survival response rates in the mid-40s and CNS penetration, that we have a really unique differentiated profile to bring to physicians. With that, we really do see both the market growing as well as penetration from a market share standpoint. Yeah, I would just add, Tyler, that it's pretty common when the second, you know, program or product enters the market and other organization is out there educating the physicians, you do see the market grow. This is pretty common. Yeah. ex-U.S., you guys are expecting a potential approval in the third quarter, right? Yeah. Are you guys gonna be prepared to launch on day one of approval? What's the strategy ex U.S. gonna be? Sure. We are, we expected approval in the 3rd quarter of this year from the EMA. We have a very small team in Europe right now that is doing the preparation for market access and so on to prepare the market for the launch of KRAZATI. We also, just to be clear, we have our KRYSTAL-12, which is our confirmatory trial. This will read out in the 1st half of next year. This confirmatory phase III trial will have. It's for PFS, and it will have an OS endpoint as well. That's gonna be important for the payers in Europe. We'll launch sometime in 2024 in Europe, you know, taking a look at all this data that emerges for KRAZATI. That's what we're going to prepare right now for the launch in Europe as well as the rest of the world. Got it. Okay. How are you guys educating physicians on the, on the clinical front about the differentiation with CNS Mets? Sure. I'll start, and you can jump in. As a reminder, we did a sub-analysis of the cohort A data, our registrational data set, where we saw CNS response rates in the low to mid-30s. We were excited about that. We'll actually have additional published data coming out in the not too distant future on that front. We also have an active and untreated CNS Mets cohort, which is currently not in the label. We're continuing to enroll that study. We presented data earlier last year at ASCO, where we've seen response rates again in the mid-30s range, which really are reassuring to physicians to show that while you're getting systemic response rates in the 40s, you're also getting CNS penetration and intracranial responses in those 30s. We expect to see more data from that cohort. We're able to talk about the cohort A data. Obviously, through medical channels, we'll be publishing more data around that active and untreated. We've also shared our preclinical data and KPU levels, which clearly show that we penetrate the CSF. Do you think it's likely that physicians are going to choose KRAZATI preferentially over LUMAKRAS for patients who have existing Mets? Do you think there are some physicians out there that'll be like, "Look, I can't tell which one out of three patients are gonna get a CNS Met, and I'd rather have drug in the CNS than not. The value proposition for KRAZATI is one of overarching efficacy. We have over 14 months of overall survival, we have response rates in the mid-forties, and we have the CNS penetration. It's not just one thing, and we're very clear to make sure that we educate around all of the benefits of the drug and including our safety and tolerability. It's not just about the CNS. That's part of a broader picture around efficacy. As a reminder, that's from our cohort A, our single-arm study. When we get into next year, we'll be also showing data from our KRYSTAL-12, where we actually envision our ability to differentiate further because of the like population that was enrolled between our study and CodeBreaK 200, that that will probably be another clear delineating opportunity for us on the relative profiles of KRAZATI versus the competition. Okay. You guys are did a great job executing with respect to the tablet formulation and being able to launch with the tablet. Are you seeing any early feedback, I guess, from those who are familiar with KRAZATI or adagrasib, maybe the investigators, in terms of using the tablet in the commercial setting? As a reminder, we did all of our studies for cohort A in the capsule format, and then we were actually approved given the bioequivalence in the data we provided to the FDA with a tablet formulation. So it's probably too early to tell, but anecdotally, the physician, it's not been an issue that comes up at all. They're happy that the FDA approved the tablet. We're encouraged by that, and we expect to exceed probably, you know, better GI tolerability over time. Keep in mind that our pivotal study, our confirmatory study, almost 100% of that population is all in a tablet, which again will be an opportunity for us to differentiate both on efficacy as well as safety. You both mentioned, KRYSTAL-12. I just wanna follow up on that. I guess, what type of reductions in GI adverse events do you think you could see in that trial? Is it possible that we see reductions in other sort of adverse events? Yeah, I'll start. Yeah, we'll see in the trial. As Ken mentioned, the trial now is enrolling or for the, basically almost the past year, has enrolled only patients with the tablet formulation. We would expect to see, you know, reduced GI side effects. That's not all. Not just reduced side effects, but, you know, we hope this plays out for dose intensity, overall efficacy as well. We'll see in the trial. It's not just for safety, but also we think will play out for efficacy as well. We'll see in the trial. We're optimistic. I think we already have a good handle on the patient population. As Ben said earlier, KRYSTAL-12 is just a larger patient population than our phase II trial was and more as a confirmatory trial. We're pretty excited about it, and we're excited it is in a tablet formulation too. We'll see. First half of next year, we'll have the PFS data. What we're able to file with the PFS data is we'll file with the FDA, and we'll definitely have an early look at OS at that point. Okay, great. Let's move to, potential frontline use. You gave the first-line pembro combo update at ESMO in December, and I guess reflecting back on that, what do you think are some of the biggest misconceptions that investors had from the update and how, do you aim to fix that, or how might that change over time? Sure. It certainly wasn't the reaction that we were hoping for from the marketplace. You know, we feel the data really showed that the combination of adagrasib plus pembrolizumab in the frontline setting, that the combination is safe and tolerable and combinable. That was clearly what we wanted to demonstrate with that cohort of patients from the ongoing trial. I'd like to think that we've cleared that up, that folks were looking specifically at ALT and AST, liver enzyme elevations of grade 3, grade 4, of, you know, we have 8% and 9% in there, so not even at the double digit range. I think we felt good about that, and I think the Street has realized, okay, that's great, this is combinable at this point in time. It was an early look at durability. You know, still, you know, the number of patients that we had greater than six months therapy was early. We were always clear that this is gonna be an early look on the durability. What we're gonna do is later this year, we'll give an update which will have more patients in the trial, the ongoing KRYSTAL-7 trial. More patients by TPS level. The TPS score is greater than 50%, the TPS score is less than 50%, TPS at less than 1%. We'll have greater patient numbers in each one of those. We'll have longer durability for each of those cohorts as well. If you remember, we, the patients that were greater than six months that we shared, in December, the response rate was 55% in that patient population, so it was better than the shorter, duration of patients. In TPS greater than 50% of the 10 patients, eight out of 10 were responders. You know, we're pretty optimistic about, you know, what we'll show later this year, but we'll see, you know, the data later this year. That's where we'll. Stay tuned for the second half of the year. Okay. I guess with respect to that update, what should expectations be for the six-month landmark PFS analysis? Will there be more data that comes out throughout the course of the year that helps you kind of set a bar for these patients? Yeah. We haven't set the bar for this right now. You know, this will be our first look at landmark PFS data for the ongoing KRYSTAL-7 trial. If you look at the TPS less than 50%, there's real world evidence that we talked about at ESMO, this real world evidence would suggest for patients with TPS scores less than 50%, that they do less well than the allcomer patient population. We have data from our monotherapy data with adagrasib, that over time, the response rates actually improve over time. Let's see how this continues to play out. We'll see where the real world evidence data publishes later this year. We'll see our next data update that we'll publish at the second half of the year. For the TPS greater than 50%, we'll continue to play that out. That's a different patient population because that patient population, if there's a phase III trial, that would be a phase III trial of adagrasib plus pembrolizumab versus pembrolizumab alone, versus the less than 50%, it'll be adagrasib plus pembro versus the KEYNOTE-189 regimen, which is pembrolizumab plus chemo. Got it. I guess on that topic, can you just provide a brief overview of the phase III program in the frontline and the various trials that you intend to execute on? Sure. The phase III program, and it's a good point, Ty, like how you said program, right? It could be more than one trial. We think of the patient population, we talked about TPS greater than 50%, and the control arm there would be pembrolizumab monotherapy. Adagrasib plus pembrolizumab for the greater than 50%. We've already had this conversation with the FDA, and that would be that trial. For the less than 50%, we've got a couple of different pathways. The one pathway where we have the most amount of data right now is adagrasib plus pembrolizumab versus the KEYNOTE-189 regimen today. That's for the TPS less than 50%. For the TPS less than 1%, it could be that patient population, it could be adagrasib plus pembrolizumab, or it could be adagrasib monotherapy, which is also being studied in the ongoing KRYSTAL-7 trial. There's one other pathway that could play out over time as well, and that is, we just started this phase II trial, adagrasib on top of the KEYNOTE-189 chemo-immunotherapy regimen that is a standard of care today. We're now starting that trial. Yeah, we're feeling optimistic about that now that we know the adagrasib plus pembrolizumab can be combined. We do not think there's overlapping toxicities with chemotherapy and adagrasib, so now we need to prove this out in a clinical study. That could be another pathway in the frontline setting over time for us as well. When could we get data from that KRYSTAL-7 chemo combo trial, and how intent are you ultimately deploying it in the phase III, right? Some would argue in, you know, the lower than 50% that they're more comfortable with the triple versus the double as opposed to a double versus double. Yeah, good question. The timing, we're just starting. We're just starting, so it's gonna take some time. What we're really looking for in the first couple cycles will be safety and tolerability of the combination of adagrasib on top of the KEYNOTE-199 regimen. We're gonna have to get through a couple cycles. I think we'd all agree it's going to be an active, you know, drug and a drug in a combination, but, you know, is the safety and tolerability gonna be there? You know, we're cautiously optimistic that let's see what happens with this, but we're just starting enrollment in that trial, in that program. The adagrasib plus pembrolizumab for the less than 50%, we also feel very good about that as well, so we could take that pathway first, and start that program. Okay. Maybe we'll move to colorectal. You guys recently spoke about a potential third line plus Accelerated Approval in combination with cetuximab. Can you talk about the timeline there, and then also a timeline to potential approval in the second line indication? I can start. We recently had, you know, positive discussions with the FDA. As a reminder, we have a breakthrough designation for this indication, so it will be adagrasib plus cetuximab in 3rd line colorectal cancer. We have had, you know, strong enrollment to date in that setting. We would expect to file by the end of the year. We just need to see more durability of that data. We intend to move up lines of therapy with our K10 study, which has been enrolling very strongly, and that would move us up to the 2nd line setting with a confirmatory study versus chemo dealer's choice. We have very robust plans in place for colorectal. How do you think of the magnitude about the magnitude of the opportunity, right? It's obviously not G12C in lung, do you guys still view it as a meaningful opportunity? Sure. The epidemiology, the rate of the G12C mutation is obviously lower in colorectal. We're not stopping there, and we're looking beyond colorectal as well, and I'm gonna talk about that in a moment too. Particularly in the community oncology, where they're treating a multitude of tumor types, having a drug which is approved in multiple tumor types, we think is very helpful. I think our data really does stand out in this setting in particular. We've seen very strong monotherapy response rates here, and then really outstanding synergistic results with the addition of cetuximab. We, we think we'll have a, hopefully a quick path to approval and pretty fast adoption. We hear, you know, anecdotal requests for that data even today or that for patients looking for coverage the odd time as well. Obviously a clear amount of interest from physicians and patients in this indication. Okay. Yeah, I would just add that we should be the, if not the first in the third line plus CRC, the first for second line plus in colorectal cancer. We do see this. To Ben's point, it's a meaningful opportunity for adagrasib in the relatively near future. Yeah. Ben, you mentioned beyond CRC, so maybe before you go to G12D, you could just discuss that and if that's something that you guys are, you know, truly focused on. We've seen some compelling data across tumor types, so we'll be discussing with the FDA a pan-tumor approach, using monotherapy adagrasib across a number of tumor types, such as pancreas, appendiceal, and many others. We think based upon historical norms that we've seen response rates and durability in a range that the FDA has previously approved, but we need to engage with them and see what the path looks forward. That would be, I think another compelling opportunity and just shows the, almost the complete program with adagrasib across a number of tumor types. Okay. Let's move to G12D. You guys just started the phase I program. You're gonna begin dosing patients. You've said that you could reach therapeutically active levels within the first few cohorts. Should we expect an update later in the year? What do you think you guys need to show in that first update, or what are you looking to show? I appreciate the suggestion of later this year. Thanks, Tyler. That's what they all want, so. Exactly. We are, just to be clear, we've communicated first half of next year for that data. With that being said, we're starting, the first patient should be dosed this month. We said in Q1. In March, we should have the first patient dosed, and I think that's pretty rapid considering with the IND cleared in January, and we're already gonna have first patient dosed in a matter of weeks. From the IND clearance, clearing. We do think we're starting at a pretty reasonable dose. Dose escalation will happen, of course. And, you know, we're gonna move as fast as we can. We have the sites all teed up. They're great phase I sites by the who's who out there that does phase I trials. We know they have patients teed up as well. We're gonna move as fast as we can and we want to get PK data out there, PD data out there, safety data, and also, you know, the phase I trial is in patients that have the G12D mutation, so it's important as well to see activity. We've committed to first half of next year, we're gonna do everything we can. We are going as fast as possible in the program. To be the first oral KRAS G12D inhibitor. Yeah. There's apparently several other G12D inhibitors out there. I guess, how do you view your compound as differentiated? I'd also be curious to hear if you have any comments on a data set we saw from a competitor the other day with a couple of G12D responses as well. Well, it's certainly an exciting space, the KRAS space, period. The KRAS G12D patient population is about three times greater than the KRAS G12C population. The prize is big, right? There's a lot of patients out there, about 180,000 patients just at the U.S. and Europe, so a significant opportunity. These patients in pancreatic cancer, colorectal cancer, lung cancer and so on, you know, outlook isn't very good, so the unmet need is very high. There's no doubt there's folks like Mirati and others that want to develop assets for G12D patients. I'd like to think we are. If anyone's gonna develop a KRAS inhibitor, it's us. Look what we did with our KRAS G12C inhibitor with adagrasib. Look what we're gonna do with our G12D program. We think with our half-life and our real time on target, we need that maximal penetration on the target. Based on what we know, we're real excited about our MRTX1133, our G12D inhibitor. Okay. We'll see in the clinical trials. Yeah. We're motivated by what we see. Yeah. with ours. Pre-clinically, are you seeing similar results to what you saw with G12D? 'Cause obviously it's technically, a lot more challenging. Similar to your point, yeah. There's a lot of redo from the G12C program into the G12D program. We certainly learned a lot with adagrasib and those learnings. It's the same team that's doing our G12D program. You know, we've learned many good things and things to not do as well. Now moving to PRMT5 or 1719. You guys started the trial, I guess a little over a year ago, we're gonna have a durability update in the second half of the year. What should expectations be for that update? Sure. The phase I trial is recruiting well. We're in the dose escalation phase. You know, what we're gonna see is typical later this year, PK data, PD data, safety data, early signals of efficacy. The phase I trial is in patients that have the MTAP deletion, so they are real patients. You know, that's what we'll be sharing in the second half of this year. Okay. What we're, you know, seeing so far, it is early and again, we're still in dose escalation, but I think we're feeling optimistic about what we could see later this year, but we've got to let the data unfold. Fair enough. The patient population here too, you know, this patient population, up to 10% of patients with solid tumors have the MTAP deletion, so a huge unmet need in this patient population. We just talked about G12D, talked about PRMT5. I mean, think about it. If either or both of these programs are, you know, we see clinical activity, these are major value drivers for Mirati. Yeah, yeah, for sure. You guys have the SHP2 and SOS1 programs ongoing as well. What's your latest on those two programs and how they might be incorporated into the later stage pipeline? Sure. We our SOS1 inhibitor, MRTX0902, we started the phase I program in the second half of last year. Again, in Q3, we started that program. This is a KRAS enabler. The real utility for this over time will be in combination with a KRAS G12C inhibitor, a KRAS G12D inhibitor, EGFR inhibitor. Not, not a monotherapy story. We're in the dose escalation phase as monotherapy, and the goal is by the end of the year, put this into a combination program with adagrasib to increase the efficacy of adagrasib beginning in the second line setting. That's, that's where the program is. Our focus right now is on the SOS1 inhibitor combination. Okay. All right. It's being prioritized over SHP2? It is. Okay. All right. Okay. I guess on, what's the latest on cash runway and your efforts to optimize the cash balance that you currently have through value-creating events? Sure. We ended the year with $1.1 billion in cash. That takes our cash runway into 2025. When we looked at what our cash OpEx and the burn was in the first, sorry, 2022, was around $570 million. We're saying we'll have a similar cash burn this year. We also have revenue this year that we've talked about from the launch of KRAZATI, that revenue will increase over time as well as into 2024. When you add all that up, what our burn is, what it, with the revenue that we have, it's about two years at this point in, into 2025. We, like everybody, we're taking a very disciplined approach. We'll let the data decide, you know, when we, you know, pass that next gate of clinical development. If we see first-in-class, best-in-class programs, you know, we're going to aggressively pursue those. If we don't, we're not going to invest our capital there. Should we expect activity on the business development front over the next year or so? Are you guys just so focused on your internal pipeline? It's hard. I'd say we're really focused on what we have. You know, we have adagrasib, sitravatinib and three phase I programs. We're really focused so on delivering these programs, not to mention we're launching adagrasib right now. You know, not to say we would not be opportunistic and, you know what, I would also say on the BD side, and we continue to do this, and we announced two partnerships last year, one with Aadi, with their mTOR inhibitor, and then with Incyte, with the PDL1 inhibitor. These co-development opportunities are out there. They're real, not just with adagrasib, but the rest of our portfolio. There's truly combination opportunities that are there. We did mention that, you know, with sitravatinib, we'll see how that there could be an opportunity with sitravatinib. Maybe there's a royalty opportunity, something like that we would take a look at. That would, you know, further help our cash runway. Let's see how that unfolds here. Okay. We're up on time, but David and Ben, maybe I'll ask you both. What do you believe is the most underappreciated aspect of the Mirati story? I'll start. Maybe just to maybe, you know, put a bow on the capital. You know, we are in, we're in good shape with our capital right now. We're not going out there tomorrow and raising money. You know, folks need to understand that and appreciate that we've got sufficient runway. We have multiple catalysts over time, that we have ahead of us in the not too distant future as well. That's one thing I would say about the story. I think the value for the pipeline is not being realized at this point in time. You know, I'd just ask folks to take a look at the data and the data that we have emerging later this year. We've got real opportunities for, you know, first and best-in-class assets with MRTX1133 and PRMT5, just as two examples. Of course, adagrasib full potential is not realized at this point. We've got a great story, and I think tremendous value to unlock for shareholders and patients alike. I think you covered it. Cool. David and Ben, thank you very much for your time. Thank you, Tyler. Thanks, Tyler. Thank you.