Are we good? All right, we are good. Kicking off the next session here with Mirati Therapeutics. It's my great pleasure to welcome Laurie Stelzer, our Chief Financial Officer. Laurie, welcome, and thanks for joining us. Thank you. Mirati obviously had a very exciting, and busy last 12 months. KRAZATI is now approved and presumably launched in the U.S. Maybe just to set the stage, could you just give us a quick overview and, especially as we think about how the next 12 months will unfold for the company? Certainly, certainly. Thank you for having us. I appreciate it. Mirati is now a commercial stage targeted oncology company with KRAZATI recent approval and launch. KRAZATI is approved now for patients with KRASG12C mutation non-small cell lung cancer who have received previous systemic treatment. We are a, you know, kind of leader in KRAS with a, you know, experience and expertise in KRAS mutations and programs such as KRASG12C, KRASG12D, new, you know, new generation KRAS as well as KRAS-enabling programs such as our SOS1. We also have a synergistic and lung cancer portfolio. This lung cancer portfolio, starting with KRAZATI, and KRAZATI's launch, is scalable and synergistic, and we should be able to see value across our portfolio as we launch into that therapeutic area. That should drive a lot of value. We're also, we've got a innovative company with a very productive discovery research and preclinical team. This has really provided the robust portfolio that we have that's gonna drive long-term growth in the company. We're in a great cash position. We had $1.1 billion at the end of the year. We've got cash into 2025. We're taking a very disciplined and data-driven approach to deploying our capital. You know, I think we're in a great position from a resource, a people capability, pipeline perspective to really drive growth going forward. For the catalyst coming in the next 12 months, we've got sitravatinib. This is a phase III SAPPHIRE study in non-small cell lung. That final analysis will read out in the second half. On adagrasib, we've got an additional data readout in our first-line data, KRYSTAL-7. This is our phase II first-line non-small cell lung study. That readout will happen in the second half of the year. It's an additional read of that ongoing data. We also expect to have approval in Europe in the third quarter for KRAZATI, that'll be a big milestone. For MRTX1719, this is our PRMT5 program. We will have some preliminary data. We'll have safety and tolerability data in the second half of the year with some potential to have some efficacy read as well. For MRTX1133, this is our KRASG12D program, we expect that study to start. It's an extremely exciting program for us, that study should start here imminently. We've got, you know, a terrific pipeline, some terrific, you know, readouts coming, you know, imagine we'll talk about some of that as we go through the chat. All right, great. Well, thanks for the overview. Maybe kicking it off with KRAZATI. You know, the drug is now on the market a little bit over a month. You know, can you talk a bit about how the early commercial experience has been as the drug has rolled out and, you know, how has it tracked relative to expectations? Yeah. It's early days, super early days, but we've been getting feedback from healthcare providers, that's, you know, been really terrific, a very encouraging, very positive feedback. You know, we are, you know, our team's been able to hit the ground running. We've had our commercial team, and our field-facing team, on board. They've really hit the ground running. We've had some, you know, early successes. Couple of examples. You know, we were able to get on the NCCN guidelines within, you know, the first week. We're also seeing, drug get to patients really within 5 days after the, you know, the physicians are prescribing. Some really early wins. You know, and I think we'll continue to see success. We've got, you know, kind of more, feet on the ground and, you know, certainly increasing share of voice and, competitive products. you know, we're pretty excited about the potential for success here. How is the drug used, relative to Lumakras? Any initial signs on how that is playing out? Yeah, they're both, you know, KRASG12C inhibitors, both, you know, in second line. We see our product as differentiated. You know, I'd say on three fronts. One is efficacy. We have an ORR of 43% and a median overall survival of 14.1 months in the pooled data. We believe that, you know, we've got a differentiated efficacy story. I think the second point of differentiator is really around CNS Mets. We've been able to show that we are CNS penetrant, and this is important for physicians. The physicians, you know, 40% of patients that have non-small cell lung will either present with CNS Mets or develop CNS Mets. We're being told by physicians that this is an important factor in choosing KRAZATI over the competition. I think the third major factor, you know, is around the fact that we are combinable with Pembro. You know, we've been able to demonstrate that with the data that we presented at ESMO IO. This is important for physicians. You know, as patients progress from first line, and they've had the KEYNOTE-189 regimen with Pembro, and they progress to second line, knowing that we're combinable, a physician won't hesitate to prescribe KRAZATI, you know, in second line almost immediately, where, you know, with the competition, they may want to wait. I think that's another point of differentiation. You know, as we think about the launch of the rest of the year, to what degree do you think KRAZATI can expand the existing market versus, you know, taking share from Amgen, essentially? Yeah, I think it'll be both. I think we, you know, with the differentiated profile that I just discussed, you know, I think we'll start to see KRAZATI take share. We do anticipate being a share leader at some point, you know, in the coming months. I think you know, with the share gain. I also think we'll be able to grow the market. You know, only about two-thirds of patients today are getting tested in first line, some of those patients are lost by the time, you know, in the EMR system by the time they present in second line. There's still work to be done there. I think testing rates in the smoker population and in the community setting is low. You know, we see that those are the KRAS G12C patients predominantly, increasing testing rates will be important. Our team, you know, kinda hit the ground running, adding, you know, to the share of voice, adding to the message about testing. I think we'll see that go up over time and, you know, kind of increase the market itself. I think it'll be on both fronts that we'll grow. Great. You know, the CNS activity, as you mentioned, is a unique feature of KRAZATI. How important has that been for physicians? Yeah, physicians are saying it's very important. you know, as I mentioned before, about 40% of patients will have CNS mets. you know, to be able to prescribe a drug that's CNS penetrant, we've been told is an important part of their decision on what to prescribe. I think that will play out to be, you know, quite important. Okay, great. you know, we talk about some of the trials. The KRYSTAL-7 is, KRYSTAL-12, I'm sorry, is your confirmatory phase III trial. We've seen the Amgen data at ESMO last year, you have obviously recently upsized the study to include an OS endpoint. Maybe just remind us, you know, what led to the decision to amend the trial protocol and how impactful, how important is that to differentiation of KRAZATI? Yeah. The differentiation is really why we did that. Being able to be the only KRAS G12C with an OS data on the label, I think will be important. We did amend the study to have a dual primary endpoint between OS and PFS. Positive readout on either of these primary endpoints will allow us to file. We do expect to have PFS readout in the first half of 2024. We won't have mature OS, but we'll be able to take a look at OS at that time. If PFS is positive, then we'll be able to file on that data for final approval. Again, another, you know, important point of differentiation for us. Okay, great. Then maybe touching upon some of the label expansion opportunities. You know, you talked about planned randomized phase III trials of adagrasib with KEYTRUDA last year in the first-line setting. You know, how confident are you at this point in, you know, in the combination data that we've seen so far to start those studies? Or do you need to see more KRYSTAL-7 data to adequately power those trials The data we've seen so far gives us the confidence to move forward in first line non-small cell lung. First of all, we clearly demonstrated that adagrasib could be combined with pembro in the data that we presented at ESMO IO. I think that was an incredibly important question to resolve. The fact that we're combinable will allow for adagrasib pembro to perhaps become the backbone for further combinations. You know, that's an important point. We will be looking at another cut of the KRYSTAL-7 data in the second half of the year. We'll be using a data-driven approach to the design of our study. So more mature data will be important. We've got more than 100 patients on the KRYSTAL-7 study now. You know, that data's just been maturing. I think that will be important to inform that phase III design. We'll take a very, very data-driven approach as we progress in that study. You know, I think another positive note, we will be starting a phase II study looking at pembro plus ada plus chemotherapy. You know, the pembro plus chemo is standard of care and adding ada to that standard of care, I think it'll be important to understand the safety and tolerability of that combination. We're starting that work this year as well. All right. That makes sense. You obviously do have the monotherapy first-line lung cancer cohorts enrolling as well. We haven't seen any data yet. Actually, you did include some data recently, in December, but, you know, remind us of the status of the monotherapy cohorts and, you know, potential avenues of registration here. We are continuing to enroll that monotherapy in the less than 1 as a cohort of our K 7 study. When we present that K 7 study in the second half of this year, expect to see some more data in that monotherapy arm. You know, that monotherapy arm could be a path to accelerated approval. We do intend to have conversations with the FDA around that data and whether or not we've, you know, reached the bar on the efficacy front to get accelerated approval. That is certainly a pathway that we're exploring. Makes sense. Okay. If you think, more near term, in terms of more near-term updates, I think you talked about, having regulatory interactions with the FDA about the colorectal filing strategy. Yeah, maybe talk about what you think the hurdle is for single arm, registration, in CRC and where you are with your, you know, discussions at this point. That is what we're talking to the FDA about in Q1 this year. Whether or not we have reached that hurdle. We haven't disclosed what we think that hurdle should be, but we certainly think the strength of the data in CRC, especially compared to standard of care today, we believe that, you know, that we will have reached that hurdle. That is the discussion we're having with the FDA, whether or not we've reached the data hurdle and the number of patients needed for accelerated approval. We should have that answer here very shortly. Is there a bull case where you could file with the data that you have at this point? There is. Okay. Yeah, there is a case. Okay, great. You're obviously doing a combination with Erbitux in the second line setting. Maybe just update us on how that study has been enrolling and whether you think, you know, it will be viewed as perhaps being substantially enrolled to support accelerated approval? Yeah, exactly. in a monotherapy setting. Yeah. This is our KRYSTAL-10 study. Our preliminary data is in third-line plus. This KRYSTAL-10 study is a phase III enrolling second-line plus CRC patients. Since we've presented the data, you know, that just continues to enroll incredibly well. We do see that as the confirmatory study if we were to get accelerated approval on this third-line plus dataset. You know, continue to improve or continue to enroll and perhaps we'll have data, but we haven't said when we would have that next cut of data on it. All right, great. Then you did talk about pancreatic cancer as well. We've seen some data here last year as well. I know you've been considering a registration trial here. Just update us on where you are with those activities. Yeah, that study continues to be an ongoing study. We should present some of that kind of pan-tumor data in the second quarter. We'll be taking another look at that then. Okay. What exactly should we expect here in terms of the update? Is it a pancreatic focus predominantly, or are we thinking about other tumor types as well? It'll be pancreas plus, the other tumor types that we've been studying in that kind of cross-tumor cohort. Okay, great. Yeah. Maybe switching gears and talking about MRTX1133, your G12D inhibitor, where, you know, I know you've done some work to improve bioavailability, and as the drug is now, phase I ready, I believe. Maybe just talk about, maybe what you've done, around BA and your confidence that you can achieve sufficient drug exposures, in a study. Yeah, maybe starting there. Yeah, that's a good question. Yes, we had some bioavailability issues with that program. We've taken a very novel approach, very novel proprietary approach, so we're not talking much about it given the competitive landscape. But we believe that we've, through that novel approach to formulation, that we've solved the bioavailability issues. We've increased bioavailability more than 10 times. That's the formulation that we'll be moving ahead in the phase I study and do expect that study to be starting imminently. Okay, great. Yeah. Looking forward to that. You did mention your SOS1 inhibitor as well, which is in phase I now. Maybe talk about how we should think about the opportunity for SOS1, maybe relative to SHP2, and, you know, any differences that one might expect here in terms of the clinical profile or the development opportunity. Yeah. SOS1 is our, kind of an enabling, program. We believe that it, when combined with KRAS and, you know, kind of other, targeted therapies like EGFR, you know, that it could enhance the performance of those programs. We are in the phase I, you know, dose escalation portion of that study. We do expect to move into, combinations with adagrasib, here in the second half of the year. More to come on that. We do see that as a, an incredible opportunity and combination and, you know, that's continuing to progress quite well. Okay, great. On 1719, your PRMT5 inhibitor, you did mention earlier that, you know, you might reach activity potentially this year in a phase I study. Just again, remind us, you know, what are you trying to achieve here in phase I? You know, what types of patients are enrolling, and what should investors expect in terms of updates later this year? Our MRTX1719, which is our PRMT5 program, we believe that, you know, this is a second-generation program, you know, different than the first-generation programs in that it is targeting the MTAP gene deletion. This program will, this product or this molecule will go targeting the PRMT5 MTA complex. There's a high amount, an abnormal amount of MTA in the tumors where the MTAP gene is depleted. By targeting MTA, and this MTA complex, the PRMT5 or our PRMT5 will impact the tumor cells to a much greater extent, and leave kind of normal cells alone. We believe that we'll be able to reach the therapeutic levels, where the first generation, you know, had too much toxicity to be able to reach therapeutic levels. That's the theory of this, of this program and why we think it will be different than, you know, than the other first-generation products. We do expect to be able to present safety and tolerability in the second half. At that point in time, we would expect to see some clinical efficacy, some early reads on potential efficacy. We're extremely excited about the potential of this product, and we find it very different than the first-generation products and, you know, have full reason to believe that we can be successful here. Okay, great. Maybe, you know, one final question circling back to KRAZATI. You know, what is your latest thinking about the rest-of-world commercialization? Are you know, planning to take it on in-house? Are you still considering partnerships? You know, what are your plans there? Again, a reminder, we should have approval in the third quarter in Europe. You know, so we have time to, you know, continue to contemplate our plans in Europe. We do intend to start to think about an ex-US partner, a rest-of-world partner. We think that could be the, you know, the right path to exploring adagrasib and really getting the most benefit outside the US. We're starting those partner discussions now, but that could certainly be the right path for us going forward. Okay, great. Laurie, thank you so much. Oh, thank you. With that, we'll wrap up. Really appreciate the time. Thank you. It was my pleasure.