Good afternoon. Welcome to the Mirati Therapeutics webcast. My name is Jenny, and I will be the operator for today's call. All lines have been placed on mute to prevent any background noise. After the conclusion of the speaker's prepared remarks, there will be a Q&A question or session. If you would like to ask a question during this time, simply press star followed by 1 on your telephone keypad. If you would like to withdraw your question, press star followed by 2. It is my pleasure to introduce Ryan Assefi, Vice President of Corporate Affairs at Mirati. Ryan, you may begin the call. Thank you, welcome, everyone. Thank you for joining us on the call today. Joining me today are David Meek, our Chief Executive Officer, Dr. Chuck Baum, our President, Founder, and Head of Research and Development, Dr. Alan Sandler, our Chief Medical Officer, Dr. James Christensen, our Chief Medical Officer, Ben Hickey, our Chief Commercial Officer, and Laurie Stelzer, our Chief Financial Officer. Dr. Pasi Jänne from the Dana-Farber Cancer Institute, who earlier today presented data from the phase I-B KRYSTAL-1 and phase II KRYSTAL-7 studies in patients with first-line non-small cell lung cancer at the ESMO Immuno-Oncology Congress, is also joining us for the call. I'd like to remind you that certain statements we make during this call will be forward-looking. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the U.S. Securities and Exchange Commission. Slides supporting today's discussion are available on the webcast and also can be accessed on the investors section of our website at mirati.com. With that, I'll turn the call over to David. Thank you, Ryan, and thank you for joining us. Earlier today at ESMO, we presented updated data from the phase I-B KRYSTAL-1 and phase II KRYSTAL-7 studies evaluating the combination of adagrasib with pembrolizumab in patients with first-line advanced non-small cell lung cancer harboring a KRAS G12C mutation. On today's call, I'll begin by providing brief introductory remarks before turning the call over to Dr. Pasi Janne to summarize the data he presented earlier. Jamie will provide additional context regarding standard of care for first-line non-small cell lung cancer patients with a KRAS G12C mutation. Alan will outline our first-line clinical development strategy, and I'll provide closing comments before we open the line for questions. Slide five shows the significant potential of adagrasib, with multiple paths to long-term value optimization through both monotherapy and combination approaches. Adagrasib's differentiated molecular profile enables us to pursue a broad and aggressive development plan across multiple tumors, lines of therapy, and importantly, adagrasib also demonstrates strong penetration into the central nervous system, or CNS. We are relentlessly focused on developing best-in-class, first-in-class targeted oncology therapies and have a robust and sustainable pipeline across multiple targets that we are aggressively growing and advancing. On slide six, the focus of our call today is to discuss the significant opportunity for adagrasib in first-line treatment setting for non-small cell lung cancer and on the promising data of adagrasib in combination with pembrolizumab. Our case for adagrasib in first-line KRAS G12C non-small cell lung cancer includes the following key points as they will be presented today. The combination of adagrasib plus pembrolizumab, based upon adagrasib's activity and potential to enhance adaptive tumor immune response, has demonstrated the potential to improve efficacy and patient outcomes. The combination has also shown a manageable safety profile with no dose-limiting safety signals and a low rate of treatment-related adverse events leading to treatment discontinuation. The clinical efficacy data for the combination, although early, appears to be compelling and necessitates further exploration. Of note, chemo-immunotherapy outcomes for first-line KRAS G12C mutated non-small cell lung cancer patients with TPS scores of less than 50% have worse outcomes compared to the overall non-small cell lung cancer patient population. We have met with the FDA to discuss and align our approach for registration trials with the adagrasib plus pembrolizumab combination, and Alan will expand on our plans for our development program. As you'll see today, we're very excited about the preliminary data of this combination in the first-line setting. The efficacy and safety results are supportive of our expanded development program, and we're very confident in our approach in the first line. We have the potential to establish adagrasib as the first KRAS G12C inhibitor approved in the first line. We estimate that there are about 25,000 KRAS G12C positive lung cancer patients in the U.S. each year across all lines of therapy, with approximately 13,000 patients in the first-line setting. These patients tend to be in better health and have significantly longer duration of treatment compared with later lines of therapy. We believe this is a very significant market opportunity and a successful outcome in a phase III study would have a tremendously positive impact on Mirati and the patients we seek to help. I will now ask Dr. Pasi Jänne to summarize the clinical data presented earlier today. Dr. Janne? Thank you so much. We'll go through the clinical data today. The first slide here, slide eight, just shows kind of the rationale for combining pembrolizumab with adagrasib. These figures come from patients treated with the single-agent adagrasib, and the patients have a pre-treatment biopsy and an on-treatment biopsy eight days into treatment. What you can see in the on-treatment biopsy is that there's infiltration of T cells, and there's an increase in PD-L1 expression, and really indicative of an adaptive immune response that can be then further dealt with with PD-1 inhibition. The data presented today comes from really two cohorts: the KRYSTAL-1B cohort, which is an earlier cohort, of 7 patients, where here there's a much longer median follow-up of 19.3 months, and then the KRYSTAL-7 phase II cohort, that where there are patients with treated with either low PD-L1 or high PD-L1 scores. All these patients have advanced KRAS G12C mutant non-small cell lung cancer. They haven't had any prior systemic therapy for locally advanced or metastatic disease. Those with stable brain metastases are allowed and are all treated with adagrasib 400 milligrams twice daily with pembrolizumab 200 milligrams IV every 3 weeks. From the KRYSTAL-1B, KRYSTAL-1, the phase I-B portion, the data is shown here. These are the 7 patients. You can see the responses. All of them had some degree of tumor shrinkage with 57% or 4 of the 7 having an actual objective response. The waterfall plot is color-coded based on the PD-L1 status. All the 4 patients who responded had durable response of greater than 9 months, and 2 are still receiving treatment beyond 18 months, and you can appreciate that on the right-hand side in that, in this swimmer plot. The top 2 where the arrows are showing the treatment ongoing. There are a grade 3 treatment-related adverse events in 4 patients. There were no grade 4 or 5 treatment-related adverse events in this set. The KRYSTAL-7 study, this is a bigger study. There are sort of we've kind of broken down this kind of diagram to show how do we derive the different patient subsets. 75 patients were enrolled and received at least one dose of the combination regimen. Of those, 14 patients are on study for less than 6 weeks, so they're not evaluable due to non post baseline scan and 8 discontinued prior to the first scan. Hence there's 53 patients with at least one post baseline tumor assessment in this cohort. A smaller cohort of 25 patients that were enrolled greater than 6 months before the data cutoff, and because of that, there's longer follow-up in that patient population. Median follow-up of this entire group is 3.5 months, and median duration of treatment is 2.0 months. We're still early, but. Here are the patient characteristics of the 75 patients. Half female, mostly Caucasian. The PD-L1 status is sort of broken down as you would anticipate in advanced lung cancer patients. Most of the patients are current or former smokers, which is what you'd also expect for a KRAS G12C patient population. Patients had a spectrum of baseline metastases, including bone, CNS, adrenal and liver. These are the treatment-related adverse events of the combination. You can see here they're broken down by any grade and then grade one, two, three and four. There were no dose-limiting safety signals identified and no grade-five treatment-related adverse events were seen. LFT abnormalities, ALT and AST increases were seen in 21% of patients, and most of these are grade 1 and grade 2 toxicities. These tended to be early events. If patients had these, there was only 1 patient that had this as kind of a later event on treatment after 3 months of therapy. If patients are going to get it, this is gonna be relatively early on. Treatment-related adverse events that led to discontinuation of both drugs was occurred in 2 patients or 3%. TRAEs that led to discontinuation of pembrolizumab alone was only also in 2 patients or 3% of patients. Overall, if you look at this sort of, the, sort of the spectrum and the incidence of accumulated adverse events, it's very similar to single agent adagrasib and or single agent pembrolizumab. We're not really seeing anything new here that we haven't seen before with those two agents. This is efficacy data. The 53 patients are evaluable. The response rate is 49%. There's 47% of the patients had partial response, and 1 patient had complete response, 40 patients stable disease. The overall response rate includes both unconfirmed and confirmed responses. After the data cut off, 2 additional patients had a confirmed partial response, and 3 patients with an unconfirmed response remain unconfirmed, but those patients remain on actual study treatment. The responses occurred across the different PD-L1 levels, so 59% in the greater than 50%, 48% in the 1%-49%, and 30% in the less than 1% PD-L1 patients. This is the waterfall plot. Again, it's color-coded by the TPS status here, and there's a hash mark for treatment ongoing and an asterisk for patients who had a confirmed response. As I said, the response rate is 49% with a disease control rate of 89%. This is a swimmer's plot of those patients. You can see the arrows of a large majority of patients, 66% are the treatment's still ongoing, including 24 patients with a response. Median time to response was 1.4 months, and that time of response is shown in that open triangle. However, there are patients who achieved responses after prolonged treatment. Here 6 achieved the responses after greater than 2 months of treatment. It doesn't mean that if you're not going to respond early, you don't have a later response. It's just, you see both here. As I mentioned, there are 25 patients where there is a longer follow-up, 'cause they enrolled greater than 6 months before the data cut-off. This is the swimmer plot. For those individuals, again, on top you can see that the vast majority of those patients are still on therapy. The clinical activity of this longer cohort of patients of 25, n is 25, the overall response rate was 56%. All partial responses shown here are confirmed responses. On the right-hand side is a spider plot of the individual patients, and you can see that there is a fair bit of activity whereby there is more of an initial dip in the response and then stabilization. Again, this is color-coded by the different PD-L1 statuses. Okay, go to the next slide. Okay. I think that's all I have to present in terms of the data. All right. Thank you very much for the summary, Dr. Jänne. Hello, everyone. Let's advance to slide 20. As David mentioned earlier, there are three takeaways from adagrasib plus pembrolizumab combination experience to date. These include, first, the strong scientific rationale, including preclinical and clinical data, indicating that the combination enhances an adaptive immune response. Second, in the preliminary analysis of KRYSTAL-7 and KRYSTAL-1 data, the concurrent combination of adagrasib and pembrolizumab had a manageable safety profile with no dose limiting safety signals and a low rate of treatment-related adverse events that led to discontinuation. Third, early clinical activity for the combination to date is compelling. Looking ahead, our confidence in the development strategy for adagrasib in first-line non-small cell lung cancer is strengthened for several additional reasons, which I'll expand on in the upcoming slides. These include first-line G12C-mutated non-small cell lung cancer patients with TPS scores of less than 50% have poorer outcomes compared with the broader first-line non-small cell lung cancer patient population. This point is supported by collective evaluation of emerging experience at both major cancer centers as well as in real-world data presentations. Consistent with what has been observed for other targeted therapies in non-small cell lung cancer, our monotherapy experience with adagrasib suggests improved outcomes when moving from second-line to first-line non-small cell lung cancer. The adagrasib and pembrolizumab data set just presented is early, with a median follow-up of 3.5 months and median duration of treatment of 2 months, there are signals that maturing data will be supportive of improved response rates and durable clinical activity. These points taken together, along with the emerging data from KRYSTAL-7 and KRYSTAL-1, highlight the meaningful and potentially first-in-class opportunity we have with adagrasib in first-line non-small cell lung cancer. Alan will provide a bit more context for our registrational plans in a moment. Let's move on to slide 21. You'll see a summary of clinical outcomes for chemo-immunotherapy in first-line non-small cell lung cancer patients. In the table shown here, each row summarizes clinical outcomes by TPS stratification, as seen in the far left column. Three additional boxes from left to right highlight clinical outcomes for overall response rate, PFS, and OS respectively. Outcomes for KEYNOTE-189 and/or KEYNOTE-024 studies are summarized in the left column of each of these boxes, compared to collective data sets for KRAS-mutated patients or KRAS G12C-mutated patients in the right column of each box. Data for KRAS G12C-mutated patients is supported by multiple references summarized on the bottom of the slide and represents a collective evaluation comprised of over 400 patients, including both emerging experience at major cancer centers such as Dana-Farber or Memorial Sloan Kettering, as well as real world data sources such as Tempus. Together, these data indicate that chemo-immunotherapy outcomes in KRAS G12C-mutated non-small cell lung cancer are poorer in patients with TPS scores of less than 50% compared to what's observed for all non-small cell lung cancer patients. I would also like to point out two key conclusions from these data. As illustrated in the ORR, overall response box in the middle of the slide, the patients with KRAS G12C-mutated non-small cell lung cancer and TPS scores of less than 50%, response rates were significantly lower than seen in all non-squamous non-small cell lung cancer patients, irrespective of KRAS status, from the KEYNOTE-189 and KEYNOTE-024 clinical publications. The observation of poor outcomes for KRAS mutated patients with TPS scores of less than 50% also holds true for durability measures such as PFS and OS, as illustrated by the boxes on the right-hand side of the slide. If we move on to slide 22, we can expand on the data summarized on the previous slide with two important representative data sets summarizing chemo-immunotherapy outcomes in clinical practice for first-line non-small cell lung cancer patients with TPS scores of less than 50%. In our adagrasib monotherapy, the overall survival outcomes illustrated by the Kaplan-Meier curve on the left from the Tempus database highlight extensive real-world experience of KRAS G12C non-small cell lung cancer patients relative to KRAS G12C wild type patients. The overall survival outcomes illustrated by the Kaplan-Meier curve on the right highlight extensive institutional experience at Dana-Farber Cancer Institute and were kindly shared in advance of publication. Together, these data reinforce the conclusion that first-line KRAS G12C non-small cell lung cancer patients with TPS scores of less than 50% have poorer outcomes, including overall survival, again, compared with the broader first-line non-small cell lung cancer patient population. On slide 23, I'll switch gears a bit and discuss our expectations for adagrasib's clinical activity in the first-line patient population based both on historical precedent as well as our present experience. You may have noted from prior slides that the number of clinically evaluable patients in the PD-L1 less than 1% segment is fairly small in our ongoing KRYSTAL-7 study, as we are presently evaluating both adagrasib monotherapy and the combination with pembrolizumab in this PD-L1 expression segment. We want to provide a perspective on anticipated clinical activity and outcomes for these patients. In our adagrasib monotherapy experience in second-line and greater non-small cell lung cancer, we observed comparable response rates and overall survival across all TPS strata. The response rate was 47% in patients with PD-L1 TPS scores of less than 1%, which was comparable to the response rate for the full KRAS G12C mutated population. Similarly, we evaluated overall survival across all PD-L1 strata and did not observe a significant difference for PD-L1 negative or low patients compared with the full population. Just as a reminder, the overall survival for adagrasib monotherapy in the second-line setting was just over 14 months in a pooled data analysis of multiple cohorts from the KRYSTAL-1 study. The observation of comparable outcomes across PD-L1 expression segments is also consistent with experience across KRAS G12C inhibitors from our collaborators at major cancer centers. Thus, the second-line monotherapy results compare favorably to results observed from chemo-immunotherapy in first-line patients with TPS scores of less than 50%. Now on slide 24, targeted therapies approved in non-small cell lung cancer, including our own emerging adagrasib monotherapy experience in the first line, highlight the potential for improved outcomes in first-line compared with second-line non-small cell lung cancer. On the left panel of the slide, historical data for targeted therapy demonstrates enhanced efficacy in the first-line setting versus second-line. For example, capmatinib demonstrated a second-line response rate of 41% and overall survival of 13.6 months compared with a 68% response rate and nearly 21-month overall survival in the first-line setting. These trends for improved outcomes in first-line with response rate, PFS, and OS are all consistent for agents targeting RET, ALK, or EGFR, with key examples also provided here on the left-hand side of the slide. The waterfall plot and table on the middle and right panels of the slide show data from KRYSTAL-1 phase I-B cohort for first-line KRAS G12C non-small cell lung cancer evaluating adagrasib monotherapy at 600 milligrams twice daily. Although these data are early, we see encouraging signs of efficacy in the frontline setting with a 50% objective response rate and a progression-free survival of 15.2 months for the 12 evaluable patients in this cohort. Let's move to slide 25. Based on the preliminary nature of KRYSTAL-7 data, our PFS and OS data are not yet mature. We would like to provide perspective on how emerging response rates for our still maturing data set compares with experience using frontline chemotherapy at selected major cancer centers. As a reminder, a significant portion of our clinically evaluable data set of 53 patients have had only one on-study scan. We evaluated the subset of 25 patients that were enrolled at least six months prior to the data cutoff used for this study of August 30th. The review of these patients suggests that the majority of tumor responses continued to deepen between the first scan at 6 weeks and the second scan at 3 months, and also that approximately one-quarter of the responses occur at 3 months or later. Thus, we would expect clinical activity to improve with additional follow-up in a more mature data set. The objective response rate in this subset of 25 patients was 56% across PD-L1 levels, including 1 complete response and 13 partial responses. It's also worth noting that the majority of these patients remain on treatment beyond 6 months. As you can see, preliminary response rates are competitive with or exceed those anticipated for standard chemo-immunotherapy for KRAS G12C patients. Although we have limited experience with this analysis, with only 5 evaluable patients with PD-L1 TPS scores of less than 1% for the combination, we noted earlier that the response rate was 47% in second-line non-small cell lung cancer for adagrasib monotherapy, compared with the approximately 25% response rates reported for frontline chemoimmunotherapy reported in independent studies by Dana-Farber and Memorial Sloan Kettering. The response rates of patients with PD-L1 TPS scores of 1-49 was 50% in 10 evaluable patients, which exceeds the response rates reported for these institutional experience. In addition, the response rate in patients with PD-L1 TPS scores of greater than 50% was 80% in 10 evaluable patients, which again exceeds response rates based on the institutional experience. With that, I'd like to ask Dr. Jänne to offer any insights and perspective. Thanks, Jamie. Yeah, no. I mean, I think the data so far are encouraging and, what we're seeing with the combination and I think, you know, supports moving it further into the frontline setting. I think, you know, we're always, you know, looking for opportunities to treat patients with cancers that have genetic alterations like KRAS mutations with the targeted therapy either alone or in combination as the initial therapy as opposed to, you know, later on. I think this certainly supports moving that that forward and I'm excited to see how this is how this is gonna look. It's nice to be able to The other thing I would say that in the targeted therapy field, essentially no other targeted therapy has been combined with immune checkpoint inhibition. This is one of the first examples of that. I think that's an exciting development too, because I think that tells us that there are going to be instances where these combinations are feasible and again, also lead to a greater degree of activity than and more durable responses than the single agent. All right. Well, thanks again, Dr. Jänne. Let's advance to slide 28, where I will summarize our multi-pronged development plan for adagrasib in the frontline non-small cell lung cancer segment. The adagrasib plus pembrolizumab combination remains our most advanced and highest priority development approach. The initiation of a pivotal study evaluating the combination of adagrasib plus pembrolizumab in first-line KRAS G12C mutant non-small cell lung cancer in patients with TPS scores of less than 50% is ongoing, which is enabled in part by the conversion of KRYSTAL-7 into a phase III study. We expect that this approach will result in significant efficiencies in both time and resources. In parallel, a second pivotal study to evaluate adagrasib plus pembrolizumab in frontline KRAS G12C non-small cell lung cancer in patients with TPS scores of greater than 50% is also being planned. We continue to explore monotherapy approaches in first-line non-small cell lung cancer. Poorer outcomes for standard of care in KRAS G12C mutant non-small cell lung cancer patients with TPS scores of less than 1% provides the potential for an accelerated approval development path. We continue to enroll KRAS G12C-mutated first-line non-small cell lung cancer patients with TPS scores of less than 1% to continue to evaluate the adagrasib monotherapy approach in that setting. Our own preliminary data, along with historical improvements in objective response rates and durability for non-small cell lung cancer targeted therapies in first-line non-small cell lung cancer versus second-line, portend the possibility of further improved objective response rates for adagrasib in this setting. The tolerability profile we are seeing with adagrasib plus pembrolizumab provides us with a foundation to explore adagrasib in combination with chemoimmunotherapy. We are also evaluating or have plans to evaluate combinations with other targeted therapies which has the potential to inform additional first-line opportunities. Let's now move to slide 29, which summarizes our phase III study design for adagrasib plus pembrolizumab in the frontline setting. As stated earlier, we are initiating a phase III study for patients with TPS scores of less than 50% by converting the phase II KRYSTAL-7 study into a pivotal phase III trial. The design you see on the right side of the slide is consistent with recent FDA feedback, and the stratification of patients with TPS scores of less than 1% versus 1 to 49% will enable independent statistical analysis of each population within the phase III study. Collectively, these two subgroups represent approximately two-thirds of the frontline KRAS G12C mutant non-small cell lung cancer patients. Planning is also underway for a phase III study in patients with TPS scores of greater than or equal to 50%. Data from KRYSTAL-7 will continue to mature during our planning activities, we'll also have continued dialogue with the FDA to inform and optimize our study design. We expect that the comparator arm in the TPS greater than 50% study will be pembrolizumab monotherapy. I'll now turn the call back over to David. Thank you, Alan. I'd like to once again thank the team as well as Dr. Jänne for joining us and sharing his perspective today. I'll conclude by saying that these compelling data from KRYSTAL-1 and KRYSTAL-7, including the favorable tolerability profile and compelling early efficacy data, give us confidence in our ability to successfully execute on a phase III registrational plan evaluating the combination of adagrasib plus pembrolizumab in first-line non-small cell lung cancer. Adagrasib is a differentiated molecule, we are in a unique position to be the first targeted therapy to move into a phase III combination study with a checkpoint inhibitor in first line patients with a KRAS G12C mutation, which we view as a hugely meaningful opportunity for Mirati and patients. On behalf of all of us at Mirati, we thank you for your support and interest in the company. With that, Jenny, we're ready to open the call for questions. Thank you. For today's question and answer session, we ask that everyone limit their questions to one question per person. If you would like to ask a question, please signal by pressing star one on your telephone keypad. If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star one to ask a question. Our first question is going to come from Tyler Van Buren from Cowen. Great. Thanks, guys. That was a compelling presentation of historical data. As we think about the meta-analysis or the Arbor and Dana-Farber data, can you elaborate on the validity of it relative to some of these other studies, like the French and German study that people are pointing to, where they argue there isn't a difference in outcomes in mutant patients? Was this analysis discussed with the FDA? Sure. Yeah. Thanks, Tyler. This is Jamie. We haven't discussed this data particularly with the FDA for this purpose, so I'll answer that question first. Regarding the use of published or unpublished data sets, essentially what we're trying to do here is, first of all, look at every possible data set we can and then filter those for the highest quality data with the greatest numbers and the most, you know, kind of practical analysis for our purpose. You know, the reason we focused in on, you know, for example, Dana-Farber, Memorial Sloan Kettering, and Tempus, number one is, you know, in working with them, we are confident that that data is very high quality, that response rates are based on RECIST criteria and not just combing of medical records or otherwise. We do believe that data is solid. Then when we combine those data sets, we get appropriate numbers in the hundreds to start to draw conclusions. The second thing about the data sets we cited is they're broken down by PD-L1 status. As you know, there are practical considerations for the design of clinical trials in the frontline setting as they relate to PD-L1 status. You know, again, believe that these are the most informative data when we're looking at PD-L1 expression strata. For example, the comparison with, you know, the French and German study that you had mentioned earlier, you know, that data is also interesting, and we're of course, looking at it, but the challenge there is they're looking at first and second line patients. They're looking at multiple different types of therapy. You know, also the numbers are not super supportive with regard to PD-L1 expression strata. You know, that's the reason we've kind of highlighted the sets of data that we have in terms of drawing the conclusions we have. Next question, operator. Our next question is going to come from Michael Schmidt from Guggenheim. Yes, thanks for taking my questions. I was just wondering how we should think about the contribution of efficacy of the two agents in the first line setting, perhaps relative to that data on slide 24, showing a 50% monotherapy response rate for adagrasib. You know, is that data driven by the 600 mgs dose? How should we think about, you know, adagrasib's activity at the lower 400 mgs dose relative to the full, you know, dose? Michael, Jamie will take that question. Yeah, Michael, I'll answer that in two parts. I think, you know, part one is, you know, we do believe based on all of our preclinical and emerging clinical experience, that there's a strong mechanistic rationale to combine these agents. You know, for immunotherapy or chemoimmunotherapy in the frontline setting, you know, I think it's now well described that, you know, the lack of ability to stimulate a T-cell response or the presence of immunosuppressive cell populations, such as myeloid-derived suppressor cells or T-regulatory cells, can limit activity. What we're seeing preclinically and clinically is the ability of adagrasib to knock down immunosuppressive cell types and enhance an adaptive T-cell response. There's also a likely effect on the innate immune system, and together, you know, believe that the rationale for combining adagrasib and pembrolizumab is very strong. As you know, from our data set, it's maturing. You know, I think our hypothesis is starting to bear out in the data, but we will of course, continue to look at our data over time, and we're compelled by what we see so far, and we're also compelled, you know, really by the mechanism. With regard to your comment on dose, 400 versus 600. You know, we've done now an extensive analysis of all patients that we can evaluate at the 400 milligram dose. Note that, you know, I'll be fairly limited in my comments as this data is not yet published. You know, we know the exposures at 400 and 600. We've evaluated the exposures, as they relate to clinical outcome measures like response rate, PFS, and OS. So far in our analysis, there is not a major difference in monotherapy activity at the 400 and 600 doses, and this is something we will continue to evaluate. Bottom line is that we believe that the dose we're using in the pembrolizumab combination is a fully active or very active dose level, and we don't expect it to be rate-limiting in terms of the combination. Of course, this has been, you know, well-tolerated in combination with full dose pembrolizumab to date. Next question. Our next question comes from Gena Wang from Barclays. Thank you for taking my questions. I have one question regarding the 8 patient, who did not, receive the first scan. Just wondering, what are the ECOG status for these patients and also their PD-L1 status, the TPS status? I would say we haven't done a full evaluation of ECOG on those 8 patients. You know, that is something we can do. We've also looked at PD-L1 expression and would say we don't have, you know, complete data for these, but we've looked across all patients and would say that those 8 patients don't have any disproportional PD-L1 status relative to the rest of the population. Alan? Jamie, I'll just add that of those eight patients, five of the patients, as you saw, had separate deaths that were felt to be unrelated. One was lost to follow-up and another was an adverse event, also not related. The rationale for not including those, at least in the initial evaluation, is so that we can do a signal-seeking approach to evaluate the efficacy of the combination. Unlike using an ITT approach in a completed study where you know, the denominator includes everyone who's received some form of the therapy. Just to further add to that comment. Also, Gena, I guess the other comment to make is that we don't allow PS 2 patients on the KRYSTAL-7 protocol. Our next question comes from Eric Joseph. I'm sorry, Eric Joseph from JP Morgan. Hi. Thanks for taking the question. Is there a registration path forward, in your view, on the basis of non-inferiority versus Chemo IO in the first line setting? I guess, specifically in the TPS 1%-49% population. I guess related to that, I'd be interested to get Dr. Jänne's perspective on the meaningfulness of a chemo-free option for these patients if, you know, all efficacy outcomes were equal. Thanks. We'll start with Alan, then pass it to Dr. Yanni. Yeah. Thanks for the question. Non-inferiority is always a challenge because of the size of the requirements of the patient that are necessary to conduct such a study. But of foremost import is the fact and our confidence and belief in the efficacy of our combination in the setting. We believe very strongly in the data that we have to date, the data that we'll be continuing to, you'll continue to see as we look further, that we can actually have a superior result to the combination of chemo immunotherapy. That is our approach going forward. Dr. Jänne. Yeah. I mean, I think in general, we're looking for therapies that are superior to prior therapies or existing therapies. I think, I think that's a better approach in my mind than a non-inferiority approach. I think, you know, there's the data package so far looks compelling to move forward in that direction, and hopefully we'll show that. Next question. Next question comes from Eric Joseph from BMO. Hey, guys. Thanks for taking the question. You know, of the patients who've yet to respond but are still retrieving treatment, is there any skew in their TPS status one way or another? I'm just trying to get a sense as to, you know, if we're gonna see more benefit in, you know, the high or the mid patients. Thank you. Sorry, you broke up there for one second. Would you mind repeating that question? Sorry. Can you hear me now, guys? Yes. All right. Cool. Excellent. Of the patients who've yet to respond but are still receiving treatment, is there any skew in their TPS status one way or another? Just trying to get a sense as to, kind of how these subgroups could potentially perform. I think, you know, probably the best illustration is on the kind of swim lane and spider plot that we had shown in the presentation. Those are all color-coded by TPS status. I think at this point, due to the small number of PD-L1 TPS less than 1 patients, it's hard to draw any major conclusions as we're splitting those patients in the trial between monotherapy and combination therapy. Would say, for example, on that spider plot that we had a patient with a complete response in 1 lesion that later progressed due to a new lesion, it's, you know, kind of illustrates that there can be very deep responses and clinical activity in the PD-L1 segment, low segment or negative segment. You know, secondly, I think we drew your attention due to our small numbers, you know, due to our 2nd line experience with monotherapy. You know, in the PD-L1 segment, we can see very robust responses, including deep responses, with monotherapy experience. We have no reason to believe that that wouldn't extend to the combination. We just need to continue to enroll and evaluate patients. If you look at the 1 to 49 segment compared to the 50 segment, you know, you can see a good, you know, kind of deepening of response in most of those patients. The, you know, kind of the kinetics on depth of response seem to increase at scan 1 at around 6 weeks and continue to increase at scan 2 of around 3 months. We also get late occurring responses. As you might note from the spider plot, there are a number of patients in the 1 to 49 segment that are hovering right around 30%. You might expect if those responses were to further deepen, that the response rate would potentially increase. Just as a reminder, in the 1 to 49, we were 5 out of 10 for responses in that more mature data set of 25 patients, and then 8 out of 10 for the greater than 50. Next question. Yigal Nochomovitz from Citigroup, please go ahead. Hi, great. Thank you very much for taking the questions. It was obviously very good to see the efficacy come from G12C from some of the other data sets you showed. I was wondering, though, about KEYNOTE-042, which I didn't see in the slides. That one enrolled PPS greater than 1%, and in the G12C cohort in that pembro monotherapy study, it showed a 67% ORR, 15 months OS. Just curious if you could comment on that. With respect to the liver AEs, could you also comment on the treatment emergent AEs in addition to treatment-related? Thank you. On the KEYNOTE-042 comment, you know, yes, we have looked at that data. I think there, you know, we would point out that the number of patients is fairly small, and we're certainly factoring it into our large patient pool. When you get into the small number of patients and then also look at PD-L1 expression strata 1-49 versus greater than 50, I mean, I think it's hard to draw any major conclusions about the less than 50 where we've placed our investment so far. I think that's the answer to the 1st question. Treatment related versus treatment emergent adverse events. We've looked at both. I would say for, you know, generally when you're looking at laboratory abnormalities, you get a very strong overlap between emergent and related events. The numbers are very are, I think, identical. I think that. This is Alan. I think that's very consistent between the two. It's good to look at both, of course, given the single arm nature of the study. But we're, you know, confident that they're reflective of each other. Next question. Next question comes from Jason Gerberry, Bank of America. Hey, guys. Thanks for taking my questions. Just to confirm, when you guys talk about endpoint and superiority, it's still OS. I just wanted to get a sense of how you're thinking about, like, the 6-month landmark OS here, on an ITT basis for the ADA pembrolizumab combo on, like, the most like for like basis versus KEYNOTE-189. You know, what we see from KEYNOTE-189 is somewhere in, like, the mid 80% of patients on an ITT basis are alive, and we have about 12 deaths in what seemingly would be your ITT cohort. Just kind of, you know, how you look at this. I realize that a lot of what we're looking at today is small numbers, but I figured I'd throw that in the mix. I'll start with the first half of the question regarding the endpoints. We're looking for a dual endpoint of PFS, as well as OS in the study with the less than 50% and actually for the greater than 50% as well. These will be discussions that we've already had with the FDA on the less than 50%. We'll continue to have on the subsequent study of greater than 50%. Again, dual endpoint PFS we'll be looking at as well as OS. I think just to add, you know, you had mentioned a landmark ITT analysis. You know, I think as you know from our presentation, We don't have the data to do a 6-month landmark analysis yet. You know, that would be an obvious thing to look at as our data matures over time. What we have done is a 3-month landmark analysis for both patients that may have discontinued and then compared that to landmark PFS at 3 months for KEYNOTE-024, KEYNOTE-042, and KEYNOTE-189. We've done the same for overall survival as surrogate for patients that have died, you know, within 28 days of study and are reportable would say that for all 3 of those studies, our, you know, discontinuation rate, all causality, as well as patients that have died, all causality are better than what you see for KEYNOTE-042 and KEYNOTE-024, and they're comparable to what you see for KEYNOTE-189. I don't think we have so far a disproportionate number of patients dropping o f the trial or a disproportionate number of deaths compared to overall experience with standard of care in this setting. Next question, please. Our next question comes from Andrew Berens, SVB Securities. Hi, thanks. A couple of questions from me about the data that you presented at the meeting and then also the planned regulatory pathway that you just announced. I guess first, just were there any squamous patients in KRYSTAL-7? Can you give some color on the dose reductions and the interruptions that we're seeing in KRYSTAL-7? How large were these dose reductions generally for pembrolizumab and adagrasib, and how long were the interruptions? I just have a question on the planned regulatory pathway after these, please. Jamie will take the first couple, and Alan will talk about regulatory pathway. Okay. Just to get that first part of your question again, you were asking. Would you mind just kind of reasking that? I think you were asking about interruptions. Yeah. Well, I just wanted to know were there squamous patients in these cohorts from KRYSTAL-7 and then? Oh, yeah. Sorry. We do not have any documented squamous patients in KRYSTAL-7, so that's an easy one. The other piece. How large were they? Yeah, the dose interruptions. Yeah. I think what. I was just gonna say broad, the majority of the reductions were just a single dose reduction from the 600 twice daily to the 400. It was a minority of patients that had a second. I don't have the numbers with me, but I think we're capturing that right now. Yeah. I think, you know, what you were asking too about reductions, interruptions and otherwise, you know, the most common treatment-related adverse events that led to dose reduction were nausea and ALT increase at 7% and 5%, respectively. For dose interruption, were nausea, vomiting, and, you know, were the major interruptions. Just to note that we're calling anything greater than 1 day an interruption, or anything 1 day or greater as an interruption. Just to provide you that particular context. And that's just a reminder that there were a small number of treatment-related adverse events that led to treatment discontinuation. There was a question about the regulatory pathway. Yeah. I'm not sure what. Go ahead. If you could just clarify what precisely you're asking? Yeah. Which of these programs could potentially serve as an accelerated pathway? What happens to the 75 patients in KRYSTAL-7 that weren't randomized in part one? How do they fit into the overall trial scheme? The accelerated pathway approach would be with monotherapy, in the less than 1%. That study is ongoing. We're looking at that. In the other aspect for K-seven, those patients, we have about 100 patients or so on the study currently. They're being evaluated. When the study converts to a phase III, those patients will not be part of the phase III study. That will allow us to continue to evaluate those patients over time and be able to evaluate PFS and overall survival and provide us with guidance. They will not be part of the phase III study itself. Yeah. I think just to add to Alan's comment, you know, the conversion of KRYSTAL-7 from an exploratory phase II to a phase III is done through a protocol amendment. That amendment, as, you know, as most amendments do, will pace through sites differently. Sites that do not have the amendment approved will continue to evaluate patients or enroll patients in active cohorts for our study, including both the monotherapy and the TPS, you know, less than 1%. We would expect patients to continue to increase, whereas other sites will convert to the phase III earlier and will start essentially with the phase III portion of the study and discontinue the phase II portion. I'll build upon Jamie's comment again, that because of the fact that it's an amendment and the sites have been activated, this greatly increases the speed with which we're able to conduct that phase III study, as well as reducing resource requirements to conduct that study as well. Next question, please. Our next question is going to come from Benjamin Burnett from Stifel. Good morning. This is Neal Karnovsky on for Ben. On the adagrasib combination with chemoimmunotherapy, given the tolerability results you've seen for adagrasib plus pembrolizumab, can you explain how you're thinking about the dosing of each agent in a triplet combination? Right now, we have the studies where we're looking at the combination therapy. There is a study that we have, KRYSTAL-17, where we're looking at it in combination with chemotherapy, which actually would be a quadruplet study. We have what will be a 1B component, where we're looking at different approachesLooking at it in combination at the maintenance and it, which is with the single agent pemetrexed, they've tolerated, we'll be able to move that up into the beginning of the concurrent approach with the platinum pemetrexed, excuse me, and the adagrasib and pembrolizumab. We'll do it in a stepwise fashion, and should be able to initiate that with the doses of the 400 milligrams BID of the adagrasib and full dose of the pembrolizumab. We'll obviously be monitoring closely for safety. Our next question comes from I'm sorry, Maury Raycroft from Jefferies. Hi. Thanks for taking my question. Just wondering when you're gonna have the next data cut and update from the approximate 100 patients in KRYSTAL-7. For the phase III in the TPS greater than 50%, can you say anything additional about gating factors to getting the study started and how it's being informed by the maturing KRYSTAL-7 data? Yeah. the first part of your, question- Data cut. I'm sorry, the data cut. Yeah. That's something that we do have plans to look at that in the future, although as you know, it's this is event driven, and we'll be looking at it at an appropriate time when we have enough maturity to gain more information out of the study. No specific guidance yet, but we will be monitoring that closely. The next question related to the greater than 50% study, that is one that actually we are working on that in parallel with the less than 50%. What appears to be a difference in the pace of the study is really related to the less than 50% and the fact that it's an amendment from K-7, so we're able to go much, much faster with that. We are moving along. We have to write a new protocol with the greater than 50%, so the timeframe is a little bit different, but we're moving at a rapid pace going forward in that aspect. We'll continue to monitor the data that we have available as we go forward, but we're enthusiastic about what we've seen so far and are moving along with that phase III study in the greater than 50%. Just a reminder for the greater than 50%, the control, the comparator will be pembrolizumab mono. That's why we just can't do that amendment for KRYSTAL-7 just for that phase III trial. The comparator. Just to build on what David said was a great reminder. That's why, and I know, you know, why we're having two separate studies. When you're looking at populations or doing clinical trials, it's based upon the population itself and outcomes, as well as what the comparator arm will be. Really for the greater than 50%, those patients do very, very well. Also, this will be a pembrolizumab monotherapy as opposed to the chemo immunotherapy approach. Thanks, David, for that reminder. Sure. I think we have time for another question. Our next question comes from Michael Ulz from Morgan Stanley. Yep. Hey, guys. Thanks for taking the question. Can you just remind us, like, what% of patients in the KRYSTAL-7 study were on the tablet versus the capsule formulation? Were there any notable differences in terms of safety and/or efficacy? Thanks. Sure. you know, we had converted to the tablet earlier this year. I would say all patients at this point in time are on tablet, and the vast majority of what you saw for patients, any patient beyond six months of experience, you know, certainly was on tablet, and the vast majority of patients overall have been on tablet for at least part of their regimen. It's hard for us to compare capsule to tablet in the KRYSTAL-7 study, but what I can say is that we continue to look at all experience with adagrasib for tablet versus capsule. We're also looking at the effect of food. I'd say our overall conclusion is that the GI adverse events are, you know, pretty strongly decreased with regard to frequency. You may have noticed the GI adverse events overall, at the 400 mg tablet with pembrolizumab, appear lower to what we've reported previously at the 600 milligram dose, for capsule and, you know, for example, at ASCO this year. The grade of adverse events, nausea, vomiting, diarrhea, have generally been grade 1 in nature. I'd say so far we're very pleased with what we see with tablet, and we are pretty convinced that administration of adagrasib with food also has a very positive effect on GI tolerability. Just for clarity, all current trials, all patients are on tablets. The ongoing trials earlier in the year, those patients were converted to tablets. All new trials have patients on tablets. All of our clinical trial patients now have been on tablets, starting, you know, earlier this year. Also for registration, we expect a tablet formulation. With that, I do want to thank everybody for joining us today. Thank you for your interest in Mirati, and we look forward to updating you in the future with the exciting events we have with Mirati. Thank you and have a great day. This concludes today's call. You may disconnect.