Great. Good morning, everyone. Thanks for joining us. I'm Salveen Richter, biotechnology analyst at Goldman Sachs, really pleased to have the team from Mirati. We have David Meek, CEO, and Alan Sandler, CMO. Maybe to start, David, you're now several months into the KRAZATI launch in second line, you know, KRAS G12C metastatic non-small cell lung cancer. Can you give us an update on how the launch is progressing and the metrics you're paying attention to, and how you think that the forward is going to progress? Great. Well, thanks, Salveen, thank you to Goldman Sachs for, you know, the invite to the healthcare conference. Just a couple of things before I get to your question. Alan and I are real excited to share the Mirati story, give the update on the KRAZATI launch, which the headline is going very well, and to talk about our pipeline as well. You know, we're excited about this conversation this morning. Going to your question specifically, the launch is off to a really good start. We're thrilled with the first few months of the launch. We talked about this in our Q1 earnings call. The reaction from the physicians has been very positive, listening to the efficacy story that we have, and I'm sure we'll go into more details there, but the overall efficacy stories, response rates, survival, CNS activity, the safety profile, it's all going really well at the physician level. We also reported, you know, just in the first few months of launch, market share, new-to-brand market share of about 1/3 of the new patients are going to KRAZATI. That was very encouraging news in the first few months. A couple other things, I'd say. We've had very strong penetration in our key accounts. We've reached over 90% of the accounts in the first few months of the launch, which represent over 95% of the potential for KRAZATI or the G12C inhibitor class. Reimbursement is off to a very good start as well. We have reimbursement where we need it, we're very excited about that. A couple of things to say: How is this happening? I'd say part of our secret sauce is our team. We've hired a commercial team where the average tenure is about 19 years in oncology. They've got biotech experience, they have pharma experience. They've launched all of the, you know, major oncology drugs that have been launched in the last few years. They know their accounts very well. They know their territories, their physicians. We're really thrilled with that team. It's not just the commercial team, it's the medical affairs team, it's the market access team, all just doing a remarkable job getting that early market share gains that we're excited about. What are we going to look at going forward and how do we measure our success? New to brand share is one of the leading indicators that will drive sales. Market access, very important when the physician is prescribing KRAZATI, that there's reimbursement for the patient. We've done a really nice job there. That's another leading indicator we're looking at as well. Just the qualitative feedback from the physicians, you know, through market research, advisory boards, one-on-one interactions with physicians is something else that's very important to us well. The breadth and depth of the prescribers. You know, with thinking of the total prescriber base, how many are prescribing KRAZATI already, repeat prescribers. Those are some of the leading indicators we look at, but as I said, we're off to a real good start with the launch. You've talked about the need to focus on patient identification and testing. Help us understand, you know, the work that's being done on that front. Sure. Yes, especially with a target oncology medicine, it's really important that the physician, you know, does conduct that NGS testing so they know it's an actionable, you know, biomarker. Where we are currently in the marketplace with KRAS G12C testing at the account level, it's about 70% of the patients have NGS testing upon initial diagnosis, and that's diagnosis of when they're initially diagnosed with first-line non-small cell lung cancer before they go into therapy. It's about 70% there. It'll grow to where we think close to 90%. If we look at the ALK inhibitors or EGFR inhibitors, it'll get to about 90%. It should be 100, but I think we'll settle for about 90. We're already seeing linear growth there. It's increased from the time Sotorasib launched till now. Now we have two organizations educating the community about the need to test for and look for KRAS G12C. That is improving. We will see it pick up. At the EMR, this is what's most important, is what's happening with the electronic medical records when the physician and patient are interacting, is it's getting that NGS test to those 70% today all the way through the EMR, the physician understands as a patient's progressing in the frontline setting, they do have an actionable mutation, and then they can connect those dots. That number is still too low, physician education is happening there. Overall, this is good for market growth. The market is not fully penetrated. We see an opportunity to grow the market, and very importantly, market share penetration with KRAZATI, which will lead to really peak potential over time. How are physicians deciding whether to put their patient on your drug versus Amgen's drug? Physicians, oncologists. It's efficacy, and efficacy. We've got a great story with efficacy. It's a data-driven story, so physicians are looking, you know, at the response rates, at survival, at PFS. They're looking at all these factors, the CNS activity. We're real excited that we were added to the NCCN Guidelines a couple of months ago. We're the only KRAS G12C inhibitor in the Guidelines. That's just all differentiation on the efficacy front. It's also really important, too, on the safety profile of the two drugs. The combined ability with pembro data that we released last year, that's also very reassuring to physicians that, you know, while the drug is not indicated to be prescribed with pembrolizumab, it's also a sequential therapy. Patients coming off the frontline regimen with pembro, with the KEYNOTE-189 regimen, knowing a physician can initiate therapy early with KRAZATI in a second-line setting, that's also a differentiator for us. It's a great value story we have. The physician reaction is very strong to the efficacy story that we have. Any updated thoughts at this point as to how large the second-line market is? There's about 7,000 patients are new to the second-line setting every year in the United States. That's the patient population we're going to the new-to-second-line setting. They're coming off the KEYNOTE-189 regimen. That's the real sweet spot. That's where we're indicated. That's where we have the data, in that patient population of 7,000. There are some third-line and fourth-line patients. If for some reason, they don't go to a KRAS G12C inhibitor in the second line, some patients could progress to third and fourth line, and there's an opportunity there, but the real sweet spot is those 7,000 patients. Okay. Remind us as to the ex-US commercialization strategy? Sure. Our plan ex-US, we are currently exploring partnerships for the ex-US opportunity for us. I should say, we do have a partner with Zai already in China. I, you know, want to make sure that we don't forget that. It's really not China, not the US. We're looking for those partnerships right now, and we think that's an opportunity to help out with, you know, overall capital, also, you know, help with the risk of future clinical development and share some of those clinical development costs. We're exploring those as we speak. You talked earlier about the combination with KEYTRUDA as you look at the frontline setting, you're taking a multipronged approach here when you look at the pivotal style studies in the various populations. Could you just help us understand where you stand with, you know, KRAZATI and KEYTRUDA and TPS less than 50%, and monotherapy and TPS less than 1%, based on your ESMO IO data? You know, where does your confidence lie at this point? Sure. Maybe I'll take even a step back and include the greater than 50% as well, because as you pointed out, the frontline patients is not, it's not just one population. There's actually two, if not three, as you pointed out. We will have an update on the data coming up the second half of this year, which is rapidly approaching. With that, we'll have additional patients, about twice as many patients that have been treated with the doublet. We'll also have those patients that were initially treated and have longer time on treatment. We'll be able to have some discussion and some data to talk about durability, including PFS. Based on that data, will help drive what direction we're going. I think a key point and why the greater than 50, less than 50 is that key decision point is the greater than 50% pembrolizumab is accepted standard of care, and that would be the approach for the control arm, and that would be the doublet versus pembrolizumab. You're looking at a nice, clean study of pembro plus minus adagrasib. You'll recall from the ESMO IO, in the patients that were on study for more than six months, not on treatment, but on study for more than six months, we had eight out of 10 responders. We're looking very forward to seeing how that data matures and take that approach in the greater than 50. The less than 50, coming back to your question, in that, there's a couple of different approaches. We do have a monotherapy that we're looking at, in that, less than 1%. Another opportunity is adagrasib in combination with cetuximab. We're gonna be looking at that data as well the second half of the year. In addition, another opportunity is to look at adagrasib in combination with the KEYNOTE-189 regimen of chemotherapy plus pembrolizumab. We'll be looking at the data coming forward with the doublet. I think there was a little misunderstanding of the data from ESMO IO early on, where the doublet may not have shown enough activity to beat the triplet, but it did show significant activity that we were encouraged and excited about. Now having the opportunity to look at it by adding chemotherapy to it, having an opportunity to see if you can add to standard of care, we think is a very exciting opportunity, and that's our KRYSTAL-17 study, right? The KRYSTAL-17, where we're looking to see how can we add adagrasib to that. We're excited about it, and we'll have data, at least safety data, coming up toward the end of the year, we believe. Okay. If you go from the doublet to the triplet, I guess that is the question, right? How do you think about the safety profile? Maybe you could talk to us on the work you've done with the doublet towards getting to the triplet there. Also, what are these efficacy bars now? Yeah for these different populations? Right. safety is gonna be the initial aspect. I think, you know, there was Amgen had data where looking at adding chemotherapy to SOTO. that actually looks as a in our view, as a positive. It provides additional confidence for us that you can add again, chemotherapy to Ada because of the non-overlapping toxicities. We don't believe there's going to be any drug-drug interactions either. we see that as a positive, and we, of course, have the ability to add pembrolizumab to that. we'll look at that safety toward the end of the year. The next is the bar that you mentioned. we believe it's either you can look at it as what KEYNOTE-189 was in that particular setting. There's also emerging data as to how do the KRAS G12C mutant patients actually do as compared to the overall population or the wild type. As you know, there are multiple institutions such as the Dana-Farber, Memorial Sloan Kettering, Tempus, that are looking at that data, and it, right now, it appears as if in the less than 50, that those patients may do a little less well than the overall population. The way to look at it is we're gonna need to be when we look at our data, we're gonna need to be better than what that is. At least better than, you know, the overall population, and by roughly 25-30% or so, you'd like to see that, 'cause that's what you're gonna need from a regulatory perspective to have a chance at a registrational trial ultimately. As a former mentor said, "There's only one reason to do a Phase II study, and that's because you have the Phase III study in mind." It's a proof of principle. We have that, the plans are set, and we're just waiting for the data to mature so that we'll follow our direction. Great. Let me just add one thing to what Alan said is, you start off with the combinability safety profile, Salveen, is I think we've demonstrated through a robust set of clinical data, and we'll just add to that there is a combinability profile with adagrasib and pembrolizumab. If we could not have that combinability, the opportunity, the front line would be, you know, nominal for us. Whether it's a greater than 50% combined with pembro, or the less than 50% combined with pembro and/or chemotherapy, you know, that was a big breakthrough that came out of the ESMO IO update, and we'll give a much larger data set throughout the year. This is really about market leadership. As a KRAS G12C inhibitor, one needs to be able to show they can be combined safely, in this case, with IO and pembrolizumab. That's what we're all excited about, the frontline opportunity, and as the year goes on, we'll share the update. This whole data set will come at one time, and I don't know if you've disclosed the medical meeting. Well, yeah, we just said second half. We haven't been specific yet on the venue. Okay. I guess when we see this data set, do you think it'll be interpretable, that we will, you know, given the number of patients and follow-up, we'll be able to understand the full profile at this point? Yes. I think that we will definitely, you know, you'll have a nice, robust data set, we'll be able to look at response rate, and then those early indications at durability, which is important because the primary endpoint most likely will be PFS. This will be our first opportunity to take a look at that. We did have a little bit of a look in ESMO IO with the spider plots and whatnot, it was obviously very early. We'll have that opportunity now to do that, we should be able to define our strategy moving forward. I should add, that, you know, we're working at risk from an administrative perspective to try and get those studies ready so that we'll be able to push the button and get the study started at the end of the year when, the direction is clear. You're pursuing an accelerated approval in colorectal cancer. Could you just walk us through where that stands and how you view that data set in the context of the need in the patient population? Sure. Yeah, I'll take that. Alan can jump in. With CRC, we think this is another market leadership opportunity. Even going back to the launch, you know, this data set in colorectal cancer, and, you know, pancreatic, and, you know, the tumor-agnostic data that we shared recently at ASCO, this is all about the halo effect of adagrasib. It actually helps physicians today when they think about what's the most effective KRAS G12C inhibitor across tumor types. The CRC data is another exciting opportunity. The plan right now in the third-line-plus setting for colorectal cancer, we will submit that sNDA by the end of the year for CRC there. We also have our ongoing trial, the KRYSTAL-10 trial, that's underway right now. This is a phase III trial in the second-line setting, both in combination with cetuximab. That'll be our path forward, combination of adagrasib plus cetuximab. That second-line trial, that will finish enrollment this year. We will see PFS and interim OS next year, that would be the basis for a confirmatory trial for the third-line-plus setting, then a new indication for the second-line-plus setting. We would, from what we know today, we would be the only KRAS G Twelve C inhibitor in the second-line setting. You know, we're excited about this opportunity. For this patient population, the response rates are in the single digits, and the PFS is less than two months. There's a significant unmet need for these colorectal cancer patients that harbor a G Twelve C mutation. We saw some early data at AACR and ASCO from some competitors, from Lilly and Roche. How do you see yourselves as positioned relative to those assets? We feel really. Yeah good about our data. Yeah. I mean, I think that, you know, it's good for patients that there are other agents that are out there. We believe that we have the best agent that's there, and we're in the lead, which is always a good thing. Yeah. Could you speak to your strategy in other tumor types at this point, and your learnings that kind of inform how you're gonna look at that? For adagrasib? Yeah. Yes, or maybe the tumor-agnostic. I'm sorry, I missed the beginning of the question. Just the strategy in other solid tumors. Other solid tumors. Thank you. We have conversations already going on, formal conversations with the FDA. We'll be submitting a package looking at the potential for a tumor-agnostic approach. You know, we've looked at our data, we've looked at the data of other agents that have been approved in this setting, and we believe we're competitive in that, both with respect to response rate, patient numbers, and durability. Those are the key issues that the FDA is looking for. That said, we also have an opportunity, depending on how the conversation goes, we have exceptional data in previously treated pancreatic cancer as well as biliary tract cholangiocarcinoma. We had a 33% response rate in pancreatic, 42% in the BTC as well, with significant PFS. It was a little over five months, five and a half months for pancreatic cancer, which as you know, is remarkable in this heavily pre-treated population. It was over eight months for BTC. Those are possibilities as individual indications, or again, the tumor-agnostic approach that we'll be looking at. We're confident that either of those directions will be available to us. Just a couple months ago, we were added to the NCCN Guidelines for pancreatic cancer. That was a, you know, another good indication of the opportunity that adagrasib has beyond lung cancer, beyond colorectal cancer. Great. Let's move to KRAS G12D. You've initiated a phase III trial here. Remind us where this stands and how we should think about, well, also the trial design, and how we should think about what we might see by year-end. Right. For the G12D, we're talking about probably having data available the first half of next year, this is a study that started in March. It's accruing very nicely. It's a traditional phase I study with dose escalation. It's not tumor-specific to start. We're just looking for G12D mutations so that we can accelerate as quickly as possible to find the dose. PK and pharmacodynamic parameters are gonna be key. We'll be evaluating that. Safety is always something that you're looking at in these types of studies. We will be presenting the data... As we said, we're looking toward the first half of next year, but it will be predicated on when we have enough data to show that we can make some sort of statement about those key parameters moving forward. We're very confident and excited about about this molecule. It has some very important key differentiating factors. It works both in the on and off aspect of KRAS G12D. It is, you know, extremely potent, has a very, very long half-life. We think that, plus the formulations that we have in the oral setting, should provide enough bioavailability that we'll be able to saturate the receptors throughout the dosing interval. We're looking forward to that study moving forward. When you look at the patients in various tumor types, what learnings can you take from, you know, KRAS G12C and apply here to this study? Sure. Preclinical models, a little bit less for G12D than C, but the data that's there, again, suggests a nice correlation between preclinical and the clinical efficacy. That's one of the beauties of targeted therapy, as opposed, say, to, you know, cancer immunotherapy, where the models don't necessarily correlate well. We're looking forward to that, and we anticipate, you know, seeing activity, once we've established the PK and pharmacodynamic principles. What are the risks that investors should be aware of when you think of the translation from the preclinical models? Well, I think, you know, we've always, you know, you look at the history of drug development, there's always... It's not 100% correlation between preclinical and clinical. The correlation is best with targeted agents that have a specific target. I think there, although there's always risk, I think for us, we think the target is validated. We also believe that this is an area that what we need is to show that we have the right oral formulation, although we're working on an IV as a backup, but with the right oral formulation to be able to get the drug into patients at an appropriate dose level for efficacy. Got it. Just remind us, you talked about these bioavailability challenges in the past. Like, how did you kind of optimize, or why do you feel confident at this point that you've addressed those? Right. I think I can't speak to the specific recipes as to what we're doing, but, I think given what we've seen preclinically, there's enough evidence to suggest that we're moving in the right direction. Again, of course, with all of the patients, we're testing for pharmacokinetic and pharmacodynamic parameters, and we'll be evaluating those in the near future as well. Any indications where you feel most confident at this point? Indications? Mm-hmm. You know, I think, it'll be interesting. I believe this is another potential opportunity for a tumor-agnostic approach, of course. As you know, G12D is about three times as many patients as the G12C. Specific tumor types, pancreas, certainly seems to be one that, again, given what we've seen with G12C having activity, we think the eleven thirty-three should have activity in pancreas as well, along with colorectal cancer and lung. We kind of mirroring what we're gonna see maybe with the G12C. Could you walk us through the SOS1 inhibitor and the strategy, in combination with KRAZATI? Sure. We're excited again about the SOS1 inhibitor because of the fact it could be first-in-class, best-in-class.... we're doing what we believe to be an interesting Phase I approach, where we're going to establish initially the single agent dose, and then rapidly, once we're comfortable with that, initiate the combination with adagrasib. We're not waiting for the Phase II dose for the SOS1 inhibitor, but we're able to look at the combination data that much quicker. We're not anticipating single agent activity with the SOS1 inhibitor, but are you know, believe that in combination should be very effective, as it maintains KRAS in the off position, which would certain to modulate and enhance the effectiveness of adagrasib in this setting. also should be able to work with KRAS G12D inhibitors, with the MRTX1133, as we establish that. There's an opportunity for EGFR TKIs as well, looking forward. We're excited about that moving forward. If you were to see monotherapy activity, and then you do the combo in, I guess, where would you start that combination trial, and how would you then kind of evolve it through the portfolio? I think what we'd do is, since it's modulating the activity of another molecule, in this case, say, adagrasib, what we would do is look for it in those areas where adagrasib has already shown efficacy and/or already has an indication. We'd be looking at it in combination in non-small cell lung cancer. Wonder if you could add it to cetuximab and adagrasib in colorectal cancer, the SOS1 and adagrasib in pancreatic cancer. That type of pattern. Yeah. Think about a patient today that would be prescribed KRAZATI. They're in the second line setting and is working as monotherapy, and then if they progress, you could consider adding a SOS1 inhibitor then. It, you know, it actually extends the length of therapy for KRAZATI. In our long range plan, you know, we see, you know, KRAZATI being prescribed with other agents like SOS1 inhibitors. There's others as well, again, it just extends the duration of therapy. Yeah for KRAZATI because the patient's benefiting then from that combination approach. Another approach might be to actually start to look at the combination in the very beginning to see if it's actually better than the single agent activity. Yeah it enhances the adagrasib. That's another approach. Both of those are approaches looking forward to. You have an MTA cooperative, PRMT5. Maybe you could speak to that program and when we might get some insight there. Yeah, MRTX1719? Yeah, that's our PRMT5 inhibitor. And, you know, we're excited about all of these opportunities we have. You know, let me begin with the patient population in the U.S. and Europe is about 200,000+ patients, a larger patient population than the G12D population that Alan spoke about, which is three times larger than the G12C population. It's more than 10% of solid tumors patients have MTAP deletion. Significant opportunity. We think we have an opportunity maybe to be first-in-class as well with our PRMT5 program. Later on this year, you know, we've committed that we will disclose the Phase I data that we have. We'll share, you know, safety, we'll share pharmacokinetics, we'll share biomarker data that we have, for PRMT5, and then early signs of clinical activity. That would be update in the second half of 2023. Far, early on, what the team saw pre-clinically, you know, we're seeing in the clinic. We're encouraged by what we see, from the safety side and as we've gone through dose escalation. We'll share all that data in the second half. Maybe just remind us with these latter two targets we've talked about, where challenges have been in the past with regard to development here? For the MTAP deleted patients and for the PRMT5 inhibitors, the challenge has been toxicity because the drugs were not specific for the tumor cells. With the design of our agent, which is about 70-fold more selective than the first generation, this is an opportunity to get to a target that we believe has been validated already, and to be able to get there without the toxicity. Our Phase I data to date, we're seeing the ability to escalate, so we're encouraged by that as well. Another aspect of this that's just as important is, although we're confident that there should be single agent activity for this agent based on preclinical data, it's always important to see whether or not you can combine an agent with others. That enhanced safety profile that we have, would appear to allow us to do that. We're already thinking about, even though we're still in the monotherapy dose escalation, we're already looking at which of the diseases that one would think about, of course, you know, pancreas, non-small cell lung cancer, and mesothelioma come to mind. There are others, such as bladder and breast. The design of this phase I study looks at the three major cohorts that I mentioned, but also a basket study, we'll have a sense of what it does in some of the other malignancies. Also thinking, what is the best approach for combination therapy? Jamie and the group are looking at preclinical models to see what might be the best approach. There's also an amount of empiricism in terms of how does it combine with standard of care? Once you've looked at the efficacy in monotherapy, and understand where you might be headed from a disease perspective, then you look at the standard of care and see how that reacts, how that works, both pre-clinically, as well as clinically moving forward. Okay. David, a last question for you. The company has clearly evolved, you know, at this point, you have a commercial footprint, that's going to grow. You've got these assets in the clinic, and you have an R&D pipeline with early-stage assets. Where do you think Mirati or who is Mirati in five years? Well, the transition from an R&D organization to a commercial organization was a great transition and really part of a new era for Mirati. You know, we're excited to have a best-in-class KRAS G12C inhibitor. We've talked about ways to manage that life cycle over time. It's already in a blockbuster plus space, and we think that can grow even more. We see KRAZATI being a very important drug for, you know, a very long patent life for KRAZATI across multiple tumor types. The pipeline, too. When you think of the pipeline, as a targeted oncology company, and that is what we are, we've talked about three of the programs that are in phase I. The opportunities are just tremendous. You know, patient sizes of populations of greater than 200,000 with MTAP deletion, patient size of greater than 125,000 with the G12D population. We see ourselves in five years of being a multi-asset commercial organization with a very strong discovery engine. We didn't talk about that and, you know, that'll be another day. We've got a great discovery engine, a great development organization, and now a great commercial organization. I think we can look back in five years, and in five years, you know, we're probably, you know, knocking on the door of a few of these products, you know, by way of accelerated approvals and so on, of having a multi-asset commercial organization, too. We're real excited about the future, and our team is real excited about it. Great. Thank you. Well, thank you so much. Thank you, Salveen. Thanks very much. Thank you.