Good afternoon, everyone. Thanks for joining us on day two of our Global Biotech Conference. I'm Andrew Berens, Senior Biotech Analyst and Head of Targeted Oncology for SVB Securities. We are very excited today to have Mirati join us. We have David Meek, the CEO, and Ben Hickey, Chief Commercial Officer. Thank you, gentlemen, for spending a few minutes with us to walk through the Mirati story. Thanks, Andy. Thanks for the invitation. Great. Well, before we get started, maybe just a brief overview, David, from you about Mirati, where you are in the company in terms of, you just launched a new drug, KRAZATI, and maybe a little bit about the pipeline. Sure. We have a lot of exciting things to talk about in 2023. Our mission, for those of you not too familiar with Mirati, is to discover, develop, and now deliver our target oncology medicines to patients with significant unmet need with cancer. At the end of 2022, we received approval for our first asset, KRAZATI or adagrasib, in the second line setting for patients with non-small cell lung cancer who harbor the KRAS G12C mutation. This is a big breakthrough for cancer patients. It's a big breakthrough for Mirati as well. We're in the launch phase, and I'm sure we'll get into some of those, you know, questions and comments here very soon. A real big opportunity for Mirati that we're excited to speak about. We think we have a best-in-class asset with KRAZATI, and over time, we'll be the market leader in this space, but give us some time to get there. Also, we've got a very differentiated pipeline at Mirati of target oncology medicines, and I'm sure we'll get into some of those conversations as well. You know, beginning, we're a KRAS company. We have expertise in KRAS G12C, KRAS G12D, next generation KRAS, as well as KRAS enabling programs. It's a key platform for us. Secondly, we think about the synergies we have in Mirati, especially in lung cancer. adagrasib is an asset that's initially launched for lung cancer. sitravatinib, we'll talk about that later too. We will have a data readout for a final overall survival analysis in the second quarter of this year. If positive and filed and approved, that's an opportunity, another opportunity for a lung cancer drug for us in the second line setting for non-small cell lung cancer. Significant opportunity, significant synergy story for us in the lung cancer space, as well as our development expertise and commercial expertise in the lung cancer setting. The third thing I'd say is we're well capitalized at Mirati. We ended last year with $1.1 billion in cash. We've got cash runway into 2025. We've got a disciplined and data-driven approach to how we do our allocation of resources here at Mirati. With the number of upcoming milestones we have, we have the capital to get to those milestones. We think about some of the catalysts we have coming up this year. adagrasib in the launch, we're certainly very focused on that. Adagrasib, the lifecycle management plan in the frontline setting for adagrasib in combination with checkpoint inhibitors, adagrasib for colorectal cancer. Sitravatinib, I mentioned the data readout in 2Q this year. We think of our PRMT5 MTAP deletion program. We'll have more data later this year. Of course, MRTX1133, our KRAS G12D inhibitor, where we just cleared the IND. We'll begin that phase I program here very soon. Real excited about Mirati and excited to have a conversation with you, Andy. Great. Well, thanks for the overview, David. I know, I know you'll be limited on what you can say about the launch. It's early days also, but, you know, I'd say Amgen's launch, was probably not as robust as what some investors had expected. I believe personally, some of that is, you know, related to some attributes of that drug, that hopefully KRAZATI can capture some market share. I guess, what are you looking for in these early days as success in the, in the launch trajectory? Like, what, you know, in terms of market share, prescribers, you know, what are some of the things we should look for in these early days that things are resonating with physicians and a good leading indicator? You know, we're fortunate. We have Ben Hickey, our Chief Commercial Officer, here with us today. Ben, I'll hand it over to you. Yeah, sure. Thanks for the question. Number one, we need to generate unrestricted access and affordable access for patients. You know, we hired a lot of the team back in 2022 and had a lot of engagement on the access and payer side to ensure that people have access to the drug. We also launched a very robust patient services hub, which we've seen, you know, good utilization to date. That's really important, and we get a good positive experience. We hired a very experienced lung cancer team. These are folks that have launched multiple drugs, the majority of which have been in the lung cancer space, have very good relationships, and we're able to access offices very quickly. I think some of the metrics that we'll really be tracking are things like, you know, are we able to get access to all of the accounts? Are we seeing positive, early experiences from physicians? That's really a key inflection point for us. Access coverage will be another metric we look at very closely, ensure we get that unrestricted and affordable access. Then over time, we'll be looking at kinda new to brand share, because I think that really measures your competitiveness. Maybe the final one I would say is that we do think that the market has quite a lot of space to grow. So overall class growth, I think, is an important one, which I think we can grow both with increased testing as well as increased patient identification in second-line KRAS. Okay. I think that, one of the things that struck me was, you know, Amgen obviously had a first-mover advantage, but the clinicians really, I think you mentioned their anecdotal experiences are important, and my sense was their anecdotal experiences, with Lumakras were not that great, especially in patients that, you know, had got a checkpoint inhibitor in close proximity to where Lumakras was started. Are there signs that the doctors are willing to switch to the next, you know, the next G12C drug? Or are you finding that there's been a lot of stickiness and brand dedication from, you know, the clinicians, or is it too early to tell that at this point? The latter, which is, it's too early to tell, but I'll say positive signals to date. I think you're referring to, you know, the data that we presented in frontline at the end of last year, ESMO IO, where we showed that we could concurrently combine with an IO backbone, such as Pembrolizumab. I think that data was very well received by physicians. While we don't obviously promote that's outside of our label today, we have heard, you know, anecdotal support, and positive feedback around that dimension of the profile. I think it really just talks to how, you know, the Mirati team designed the molecule in a different way. Clearly, we compete the same class, but these are two very different molecules. I think over time, that will be more and more realized and more appreciated by our customer base. Do you expect to see patients that, let's say, they drop off of Lumakras because of some toxicity, let's say hepatotoxicity, for example? Do you expect to see some switching to KRAZATI or is it really gonna be just new patients, you know, to second-line therapy and beyond? We think the vast majority will be that naive to second line. Those 7,000 patients which are progressing through front line. Whenever you launch a new product, there's always anecdotal experiences, and physicians will try it in a variety of different ways. Over the long term, we think that the majority of the patients will come from those naive to therapy. That's the over time will be the key metric that we look at from a competitiveness standpoint. Okay. Yeah, we it's interesting 'cause we hosted a dinner, and one of the clinicians referred to Lumakras as a hospice waiting room, which was a pretty strong comment. It was in the context of, you know, we would really like to have a better G12C drug than Lumakras because it seems like as soon as I put my patients on Lumakras, they end up getting hepatotoxicity and dropping off of therapy altogether. How, you know, how important do you think that this ability to combine with checkpoint inhibitor concomitantly is gonna translate into the second line and be a value proposition there? When we presented the frontline data at ESMO IO, our physician base, you know, we had a number of advisory boards and so on. They were very positive around that data and the path to frontline. We do think there could be and will be a kind of a spillover positivity halo around that. Again, not something that we talk about a lot, but we have heard about that from physicians. We are laser-focused on our second line indication, our overall survival, our CNS penetration, and our response rates. I think, you know, that dataset, the data we presented previously in CRC and in pancreas cancer, again, are parts of the, you know, almost the mosaic, as it were, that paints the picture of differentiation for us. I think more of that to come in the future. Right. Do you get the sense of the CNS activity? We haven't seen a lot from Amgen yet, but do you get a sense that that's resonating also with clinicians in terms of a differentiated profile? We believe so. Again, very early to speak to direct physician feedback post-launch, but even in the pre-launch setting, that was something that we heard a lot in our market research. Just keep in mind that, you know, up to 40% of patients, unfortunately, will develop a CNS metastases over the course of their treatment and the course of their disease. It is a big population and one that is of concern. We did see increases from a prescribing standpoint, that this is a really important driver, and having CNS penetration is very important. We'll have to see how that plays out now we're actually in the market and commercially available. Okay. Are you guys gonna be I know you get prescriber-level data that's not available to the investment community, you know, in terms of physicians that might be high prescribers of Lumakras starting to write for KRAZATI. Is that something that you plan to update us on, during the course of the launch? Over time, we'll be sharing a few metrics as we, you know, around the breadth of prescribing and by setting, academic and community and so on. We'll give some color to that over time. Okay. Let's see. We're also expecting European approval in the third quarter, I believe. How do you think that that's gonna be received by the healthcare authorities not having the control arm in KRYSTAL-1? Is that, has that become less of a focus of the MAA at this point, or are they still, you know, very much dead set on having a control arm? I think you've got to think about it two ways. There is a regulatory hurdle where we think that the conditional marketing authorisation and our Cohort A from KRYSTAL-1 will meet that bar because of the level of response rates and durability responses. There is, you know, head to the ex-US markets and getting pricing reimbursement, which is a different hurdle and one which we think that we would be better served to wait for the 12 results potentially before we seek, you know, expansive pricing and reimbursement. We have the opportunity again to get the regulatory filing. We did initiate an EAP in Europe. I think broader coverage will really be dependent on the 12 results, which is our pivotal confirmatory study in second-line lung cancer. Okay. There may be a gap. If you get approval, you may wait to actually start seeking the reimbursement. There'll be a little bit of time between the two. I would add, it's not a big gap, Andy. You know, when we, you know, we'll start to see PFS data in first half of next year for KRYSTAL-12. Having that data will be important. If we have approval at the end of, you know, talk, third quarter this year, it's not that big of a gap, really. You begin having conversations with the payers country by country. Yes, that's a reality that we will, you know, confront. Okay. In terms of the front line, I know you've alluded to the possibility of maybe getting a monotherapy accelerated approval in patients with PD-L1 status less than 1%. Is this something that you've discussed with the FDA? Are you still optimistic that that's a possibility? The reason I ask is, we had some panels yesterday and lung cancer has just the bar seems to have gotten higher and higher and higher. You have checkpoint inhibitors, you know, across the whole spectrum of TPS scores having OS benefits. There's definitely some concern that the FDA may not be willing to grant an accelerated approval based on response rates, you know, or even an interim PFS if you do a randomized trial, with like, Project Front Runner. You know, I guess, what is your level of confidence that that's still an available pathway for you potentially? I'll start. It's gonna depend on the data, Andy. You know, we're still enrolling in this patient population. As we have this, you know, data, and if we think the data is compelling, we'll certainly have a conversation with the agency. We That's interesting. That's a smarter way to do it because the activity is done significantly more than what they're seeing, so it should support a accelerated pathway, and then maybe also an earlier line of therapy. You'll get approved before them, and then you'll move ahead of them at the same time that they would probably get approval, if they can get approval. Interesting. Another question came in just, because you don't have, I guess, the CNS benefit of a label, how will you get that message across to clinicians? Obviously we've published some of the data or presented some of the data that in regards to the active and untreated CNS mets, but that's through the medical channel. From a promotional standpoint, we don't talk about that data because it's not in the label. What we do talk about is within Cohort A, which is with the previously treated or previously radiated patients, where we see about a third of patients get a robust response. We are able to talk about and promote that data. Okay, great. Why don't we shift gears to the G12D program? This definitely seems to be getting a lot more attention again with investors. Can you just remind us, I think you initially presented some data from the G12D program back at maybe the Triple meeting two years ago. At that time, I think it was, you know, I think you had some bioavailability issues, and you were delaying, I think, advancing it until you worked through some of those. Can you just, I guess, give us an overview of what you showed back at the Triple meeting and where the program is now? Sure. You maybe start at the higher level. We're, you know, very excited about our MRTX1133, our KRAS G12D inhibitor program. The opportunity is significant in this space, Andy. The patient population, the prevalence is about 2.5 times greater than the KRAS G12C space. All in all, it's about 180,000 patients in the U.S. and Europe. A significant patient population with a significant unmet need. There's also some overlap with the G12C patient population, such as colorectal cancer, pancreatic cancer, but also some other tumor types that have a significant prevalence of KRAS G12D mutation. We think we have the potentially first in-class, best in class G12D inhibitor. As we move forward, you know, it's a selective inhibitor. It's highly potent. A 50-hour human half-life, significant time on target. All in all, we're excited to move this into the clinic. We cleared the IND last month. You know, the phase I is, you know, around the corner. It is imminent. We'll start enrolling patients in the phase I program. You talk about the oral bioavailability. You know, we certainly have learned a lot. The team is now in the position that we've got an asset with eleven thirty-three, where the oral bioavailability is about 10 times greater than our previous, you know, lead formulation in a previous oral formulation. We think we're getting maximal time on target, which will mean maximal effect with a tumor. You know, we're, you know, pleased we got to this point, pleased the IND is across the line, and we look forward to enrolling the patients in the dose selection study for phase I. What's the reason that an oral, I mean, obviously there are a lot of convenience reasons that an oral regimen might be more commercially viable, but there are also, obviously a fair number of infusible agents. Is there any reason why, because of these tumor types that you feel it's important to have an oral agent versus an intravenous agent? Yeah. As you know, we were looking at an IV formulation as well, a liposomal formulation. We still have ongoing work there as well. We think at this point in time for us, having the oral formulation and the time on the tumor is really important for us. We think the oral formulation for us is a better path forward. Okay. Was this new formulation, you know, I remember that the G12D program was one of the former Array programs. Did they continue to refine it at Pfizer? Were they involved with this revisions to the formulation? This is all proprietary Mirati. Can you share with us what was done to improve the bioavailability? Yeah. It's fair question and one we're just not gonna get into right now and primarily for competitive reasons. You know, it is a competitive space. We're in pole position at this time, and we wanna maintain that pole position. At this time, we're not gonna get into that. Okay. detail on the formulation. Okay. In terms of levels that you might have to achieve, based on the preclinical models, any insights there, you know, where you might have to be, in the clinic? Yeah. I'd wait a little bit for us to talk about that if I were you, Andy. Okay. Is one of the attributes that you were looking for with this drug, would be that it can be combined with other agents, or do you feel like it's a monotherapy? We both. You know, we certainly learned a lot. As I mentioned earlier, you know, Mirati is a leader in KRAS discovery and development. We think with our KRAS G12D program, you know, we're certainly gonna get to the phase II, you know, program. We'll get through to do monotherapy and the dose selection there. At the same time, we'll move quickly into combinations. We think there's, you know, multiple rational combinations, in particular, we think of pancreatic cancer, colorectal cancer with an EGFR inhibitor like cetuximab. You know, we'll move it in that combination, as soon as we can, as soon as we get the dose for monotherapy. Okay. This is a question about the G12D program from an investor. At what point will you choose which agent to move forward? Because you have two candidates for G12D at this point. We're moving forward Eleven Thirty-Three, which is the oral formulation. Okay. Okay. Why don't we talk briefly about sitravatinib? Then we have about five minutes left, which you announced earlier or at the end of last year that the phase III SAPPHIRE trial was not stopped at the interim for efficacy or futility. Is there anything we should read into that, into the trial ultimately being successful? Sometimes companies will give us, you know, some idea of how much alpha they wanted to spend on the interim versus did not want to spend. So just like, I mean, should we, you know, what should we read into the interim not being stopped? I don't think you can read too much into it, apart from that we, you know, we expect to see the readout in Q2 of this year for the final analysis. It's powered for OS benefit, I think without giving the numbers, but we've described the alpha spend as very low in regards to the interim. We are cautiously optimistic. We've designed the study with a 12-week of required stable disease before enrolling in a specific to non-squamous histology. You know, if I go back and think about our phase II data, this is where we saw almost 15 months of overall survival, just shy of that at 14.9 months. We're hopeful, but the data will tell us, you know, we'll see the result in Q2. We obviously have, what I believe is a formidable, you know, lung cancer, you know, organization at this stage, and adding in sitravatinib would allow us to really maximize the potential of both adagrasib and potentially, sitravatinib. We're excited to see the results. Okay. Yeah, no, I think, I think everybody's excited to see the results. What about MRTX1719? Can you give us an overview of what you're doing with that program, and what we should expect with initial data set? Sure. You know, just quickly with the MRTX1719 for BRCA-deleted cancers, which are up to about 10% of patients with solid tumors, so significant potential there. Again, you know, hundreds of thousands of patients with BRCA-deleted cancer. We're in phase I right now. We are still in dose escalation. We will the second half of this year, we will disclose where we are with the randomized or phase II dose at that point in time. Certainly share PK and any other additional clinical data that we can publish second half of this year. We're pleased by what we're seeing so far in the phase I dose selection program. We think it's another big opportunity for targeted oncology and, you know, stay tuned for the data later this year. Okay. In terms of the competitive landscape, you know, a lot of your agents obviously are focused at lung cancer. There are a number of potentially game-changing trials reading out in lung cancer this year. One would be the Sharp Ion or one trial, which is AstraZeneca and Daiichi's ADC Dato-DXd. Well, what do you think, if that trial reads out successfully and let's say the hazard ratio is significantly better than Amgen showed in their phase II trial against docetaxel. So let's say it's, you know, 0.52 or 0.53, something like that, versus theirs at 0.65. Do you get a sense that the physicians are gonna, you know, that's gonna take some of the second line available to KRAZATI or maybe I guess even sitravatinib at some point? In our discussions with physicians, we don't think it'll be a significant competitor to the KRAS inhibitors and particularly KRAZATI, 'cause it's a different population. It's not studied prospectively in a KRAS population where we believe that outcomes can vary, particularly across a PD-1 continuum. I think it will be a legitimate competitor for sitravatinib as that comes and hopefully if that's a positive study, but less so for, you know, a KRAS G12C targeted agent such as KRAZATI. Okay. Interesting. Yeah, I don't know whether I mean, they're gonna probably enroll some KRAS patients. I don't know how many. What they'll reveal, will be interesting to see. Yeah, that's one that we're keeping an eye on obviously too, so. All right. Well, we're at the end of the half hour. Thank you for all the insights and for sharing... Thank you. the Mirati story with us. You guys have a lot of exciting things happening over the next six months to a year and even longer than that. I look forward to watching everything progress. Thank you, Andy. Thanks for the conversation. Yeah. Thanks for joining us, and thanks everyone for joining us. This concludes the webcast. You can disconnect now. Have a good day.