Good morning, welcome to the Mirati Therapeutics update call. My name is Katie, and I will be your 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 question-and-answer session. If you'd like to ask a question during this time, simply press the star followed by one on your telephone keypad. If you'd like to withdraw your question, press star, then two. In the interest of time, we ask you limit yourself to one question. It is my pleasure to introduce Ryan Asay, Vice President of Corporate Affairs at Mirati. Ryan, you may begin the call. Thank you, Katie. Welcome everyone to this morning's call, where we are very pleased to discuss the US Food and Drug Administration's approval of KRAZATI, the trade name for adagrasib. 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, and Ben Hickey, our Chief Commercial Officer. Dr. Alex Spira from Virginia Cancer Specialists Research Institute, who is the lead adagrasib investigator, is also with us. Laurie Stelzer, our Chief Financial Officer, will also be available for the Q&A portion of the call. I'd like to remind you that certain statements we make during the 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 US Securities and Exchange Commission. Slides supporting today's discussion are available on the webcast and can also be accessed on the investor section of our website at mirati.com. I'll turn the call over to David. Thank you, Ryan, and thank you for joining us on the call today. The US FDA granting accelerated approval of KRAZATI or adagrasib as a treatment for patients with KRAS G12C mutated non-small cell lung cancer who have received at least one prior systemic therapy marks an incredibly exciting milestone for patients and for Mirati. First and foremost, I want to thank everyone who has helped us get here today, especially the patients and their families who were willing to participate in the clinical trials that ultimately led to KRAZATI's approval. I want to thank the clinical investigators along with their nurses, site coordinators, and support staff for their contribution to this study. I would also like to thank and congratulate the members of the Mirati team, past and present, who worked tirelessly on KRAZATI's discovery and development and now approval. This is an important day for patients, and it would not have been possible without the assistance and support of all those I just mentioned. At Mirati, our mission is to discover, develop, and deliver breakthrough therapies to transform the lives of people with cancer. This includes a deep commitment to addressing cancers with high unmet needs. It is in the spirit of that mission that I'm excited to introduce KRAZATI. The KRAS mutation is one of the most common cancer-causing mutations, and for over 40 years have been difficult to target. With the advancement of our understanding of the KRAS G12C mutation and emergence of new options, patients and oncologists now have encouraging therapies tailored for KRAS G12C mutated cancers. KRAS G12C mutated non-small cell lung cancer remains an aggressive form of cancer with significant unmet medical need. We believe, based on the available data, KRAZATI may represent a best-in-class targeted therapy to help in this fight. As we celebrate KRAZATI's approval, I am more confident and enthusiastic than ever for the future of Mirati. We are making an important transition to a commercial stage enterprise. We're incredibly proud to have the opportunity to enhance the way cancer is treated by delivering this important therapeutic option to patients. I will now turn it over to Chuck to summarize the key clinical data supporting the KRAZATI approval. Chuck. Thank you, David. Hello everyone. I echo David's sentiments regarding the sense of pride and gratitude amongst all of us here at Mirati for the privilege of bringing this innovative therapy to patients. I'd like to thank the patients and their families and the investigators, as well as the Mirati team, who made KRAZATI development and approval possible. We are pleased that patients and physicians now have a compelling new treatment option. As you can see on slide seven, the approval of KRAZATI is based on data from cohort A of the phase II KRYSTAL-1 study, evaluating KRAZATI 600 milligrams taken daily, twice daily in 112 patients with previously treated non-small cell lung cancer harboring a KRAS G12C mutation. I'll briefly summarize the results and touch on the key study findings shown on slide eight. The major efficacy outcome measures were confirmed objective response and duration of response as evaluated by blinded independent central review. In cohort A of phase II KRYSTAL-1 study, KRAZATI demonstrated an objective response rate of 43% and 80% of patients achieving stable disease or better. The median duration of response was 8.5 months, and median overall survival was 12.6 months. Beyond the data included in the label, we also conducted a pooled analysis in a total of 132 non-small cell lung cancer patients evaluable by blinded independent central review. Which includes the phase II and phase I, 1B non-small cell lung cancer cohorts from KRYSTAL-1. The baseline characteristics of patients across both cohorts were similar. The pooled analysis showed an objective response rate of 44% and duration of response of 12.5 months, as well as a median overall survival of 14.1 months. In retrospective analysis from the phase 1B cohort of the KRYSTAL-1 study in patients with KRAS G12C mutated non-small cell lung cancer was stable, adequately treated central nervous system or CNS metastasis, showed that approximately one-third of those patients had an intracranial response. CNS metastasis are a common complication of patients with KRAS G12C mutated non-small cell lung cancer, with up to 40% of patients developing CNS metastasis over the course of their disease. These patients represent a poorly served patient population associated with increased mortality and morbidity. adagrasib is also the first and only KRAS G12C inhibitor to demonstrate substantial clinical activity in patients with active, untreated CNS metastasis in a clinical study. We also recently published data or presented data showing that the combination of adagrasib plus pembrolizumab is combinable with a favorable safety and tolerability profile and promising early clinical results. This information provides another important element of differentiation in the second line and beyond setting, where physicians are often making decisions about how and when to start patients on a KRAS G12C inhibitor immediately following progression on a checkpoint inhibitor-based regimen. On slide nine, disease control in cohort A was broad, with tumor shrinkage of any magnitude observed in 80% of patients. Importantly, the responses were deep, with 75% of patients experiencing tumor reduction of greater than 50%. Overall, the clinical data and approval reflect the favorable benefit-risk profile for KRAZATI in this patient population. I believe we have an opportunity to improve treatment for people with KRAS G12C mutated non-small cell lung cancer. I'll wrap up my prepared remarks by mentioning the two companion diagnostics that have been approved in conjunction with KRAZATI. We've been happy to partner with Agilent on a liquid biopsy kit and QIAGEN on their therascreen PCR assay. Both are FDA-approved companion diagnostic tests to identify non-small cell lung cancer patients with KRAS G12C mutations who may benefit from KRAZATI. Let me pass the call to Alan to review the FDA-approved label. Thank you, Chuck. Hello, everyone. On slide 10, you'll see a summary of the KRAZATI label. KRAZATI, under accelerated approval, is now indicated for the treatment of adult patients with KRAS G12C mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy. KRAZATI is approved with a recommended starting dose of 600 milligrams twice daily with no fasting requirement in a tablet formulation. Let's discuss the safety summary, which is covered on slide 11. Overall, KRAZATI is well-tolerated with a manageable adverse events profile. Adverse Reactions occurring in greater than or equal to 25% of KRAZATI-treated patients in the trial are listed on the slide. Importantly, most of these adverse events were low-grade and manageable. Dose interruptions due to an adverse reaction occurred in 77% of patients, and permanent discontinuation of KRAZATI due to an adverse reaction occurred in 13% of patients. 11% of patients were characterized as having a Grade five adverse reaction. Prior to entering industry as an academic medical oncologist for approximately 18 years, specializing in lung cancer, my opinion that KRAZATI is an exciting and very compelling option for patients. KRAZATI's labeling information and other important details are also available on the new KRAZATI website at www.krazati.com. Let's now move to slide 12, which shows the schema for KRYSTAL-12, our randomized phase III confirmatory study, which is enrolling well worldwide. Consistent with the accelerated approval regulatory guidelines, full approval for this indication may be contingent on ratification of clinical benefit. Based on the potential to further differentiate KRAZATI and with FDA's input, we are shifting the KRYSTAL-12 trial to have dual primary endpoints of overall survival and progression-free survival. As a result, the trial will be larger. We anticipate this change will have a meaningful positive impact on the potential strength of the full approval label. I'll conclude by saying that the approval of KRAZATI adds a new treatment to oncologists' arsenal and provides patients with an important option for their treatment journey. With that, I'll ask Dr. Alex Spira, who has graciously joined on the call this morning, if he would like to share a brief perspective of his experience. Dr. Spira is a key opinion leader at the forefront of lung cancer research and an investigator on many lung cancer clinical trials, including lead investigator for adagrasib studies. Dr. Spira. Thank you, Alan. This approval confirms the strong evidence of KRAZATI's favorable properties, including long half-life, dose-dependent pharmacokinetics, and CNS penetration. The efficacy profile for KRAZATI is compelling, with a strong response rate, good durability, robust intracranial activity, and demonstrated activity in other lines of therapy and across a broad range of tumors. From a safety and tolerability perspective, the majority of adverse events are low grade in severity, start early in treatment, resolve quickly after occurrence, and are manageable with concomitant medications or dose modifications. I have significant experience with KRAZATI in my clinic and have been very pleased with the results my patients have experienced. I'm grateful to have another option to treat patients and believe that KRAZATI's unique profile has the potential to benefit a large number of patients with advanced non-small cell lung cancer harboring a KRAS G12C mutation. With that, I'll pass it back to my colleagues at Mirati. Thank you, Dr. Spira. Let me start by saying that this is an incredible time for our organization, and we've spent over two years building up to this moment to ensure we can execute a successful launch of KRAZATI in the U.S. We're ready to go. Our market research indicates that KRAZATI's differentiated profile and unique CNS penetration are very compelling to physicians. We are excited to bring this therapy to market, which has the potential to improve the lives of people living with cancer. We've built a highly qualified and deeply experienced commercial team. They are fully trained and fluent on our messages and data. The KRAZATI launch is starting now. The team at Mirati is extremely energized, and we'll be putting everything we can into ensuring that patients who are eligible for KRAZATI are able to access it. I'm going to spend the next few minutes discussing several important aspects of our commercial plans. Let's move to slide 15. Our commercial launch strategy is focused on establishing KRAZATI as a leader in second-line or beyond non-small cell lung cancer in patients harboring a G12C mutation. This strategy includes the following three strategic imperatives, and I will expand on each one. First, we aim to generate unrestricted and affordable patient access across government and commercial payers, which we have been working on over the past year. Providing value to patients, oncologists, and the healthcare system at large is a priority for us. We believe that having KRAZATI available at the U.S. list price of $19,750 for a one-month supply appropriately reflects the clinical benefit and innovation KRAZATI provides and the value it delivers. From a coverage perspective, we are confident that payers recognize the significance of KRAZATI, and we are committed to working with them to ensure patient access. Our commercialization team has interacted with health plans covering over 90% of covered lives and have received encouraging feedback on the unique profile of KRAZATI. As a result, we expect to generate broad coverage within the first few months of launch. In addition, we've established strong partnerships with community oncology networks and distributors to ensure we can efficiently deliver KRAZATI to the patients who need it, regardless of location within the U.S. We also have a dedicated patient-centric support program called Mirati & Me, designed to provide assistance with insurance coverage, financial support, and additional resources. A fundamental component of our mission is a dedication to improving access and outcomes for all eligible patients. Our second strategic imperative is to drive trial and adoption of KRAZATI. This includes the important work of educating the greater than 7,000 of our target oncologists about KRAZATI's unique clinical profile, including robust objective response rates, progression-free survival, and overall survival. In addition, we will continue to educate physicians around the unmet need for approximately 40% of non-small cell lung cancer patients with a KRAS G12C mutation who develop CNS mets-metastases. Based on the data we shared at ASCO, KRAZATI has the potential to make a big impact on these patients' lives, and we believe physicians see the intracranial response rates as an important characteristic and important differentiation for KRAZATI. We will also deploy a proprietary customer model engagement platform with coordinated in-person and digital content, industry-leading service programs, and field expertise to support the complete account. Our third strategic imperative is to expand the eligible second-line KRAS G12C non-small cell lung cancer patient population. Our team continues to work on market development opportunities, such as increasing both testing and identification of KRAS G12C-eligible patients to improve patient access and outcomes. While the testing rate is rising, we estimate that only two-thirds of patients have been tested for their KRAS G12C mutation status at the time of diagnosis. With the growing awareness of actionability of the KRAS G12C mutation, we are confident the testing rate will continue to steadily rise. Most non-small cell lung cancer patients are treated in a community oncology setting. We can leverage our strength and experience in the community setting where approximately 40% of the patients in our pivotal study were enrolled. Armed with physician-level data, we are focused at the account level to ensure that patients have testing availability in their ordering system at the point of clinical care and that patient testing records are readily available at the time of disease progression. We believe the real available second-line patient population being presented to the oncologist is currently well below its full potential. We will continue to generate real-world evidence to further elucidate gaps in testing and highlight the unique benefits of KRAZATI in the real-world setting. Let's move to slide 16, describing the epidemiology of lung cancer in the United States and how we view the market opportunity. KRAS G12C mutations occur in approximately 14% of adenocarcinomas and about 2%-4% of squamous cell carcinoma patients. That translates to about 25,000 KRAS G12C positive lung cancer patients in the U.S. each year across all lines of therapy, with approximately 12,000-13,000 progressing to second or later lines of therapy for whom KRAZATI could be a therapeutic option based on the current label. Within this figure, we estimate that the second line will account for approximately 7,000 KRAS G12C positive cases in the U.S. each year, and these patients who are new to second-line treatment are likely to constitute the majority of the expected demand for KRAZATI. In advance of our anticipated launch, our teams have been actively engaging in market research with physicians and executing on an awareness campaign supplemented with medically led publications and data presentations. We track progress and measured our success with several metrics, including whether physicians have a high level of familiarity about adagrasib, awareness of Mirati, and an understanding of the importance of CNS metastases. We've exceeded our target benchmarks in all of these areas. Importantly, we also measured awareness of adagrasib among LUMAKRAS prescribers, which was approximately 85%. We believe awareness and physician enthusiasm for KRAZATI is high, and this will position us to compete effectively out of the gate. On slide 17, I will now shift my focus to our sales and access teams. The average oncology experience on our team is approximately 19 years from top-tier oncology companies. Our field force has extensive experience in lung cancer, spanning both pharma and biotech, with existing relationships across our target accounts, which we believe will facilitate more immediate access to key target physicians. Our field team has been involved in launches of many of the most successful oncology drugs across the industry and will be exclusively dedicated to KRAZATI for the launch period. We believe this laser focus can provide a competitive advantage. Beyond our sales force, our broader commercialization team includes an integrated team of marketing, analytics, patient support, and medical affairs, which will facilitate a seamless and efficient interactions with physicians and their staff. We are highly confident that we have assembled a best-in-class commercialization organization which can successfully deliver on our commercial goals. We believe that the compelling characteristics of KRAZATI's profile, combined with an experienced and focused commercialization organization, positions well for market leadership within the KRAS G12C space over the long term. I'll turn the call back over to David. Thank you, Ben. Let me reiterate our belief that the FDA approval of KRAZATI is an important advancement for people with KRAS G12C mutant non-small cell lung cancer and to physicians who treat them. This approval marks a major step in Mirati's mission to bring forward therapies that address areas of high unmet medical need and provide more tailored options for people living with cancer. Let me advance to slide 19 to touch on the significant potential of KRAZATI beyond this initial approval, which we believe is just the beginning of our journey with KRAZATI. Our strategy provides multiple paths to long-term value optimization through both monotherapy and various combination approaches. KRAZATI's differentiating molecular profile enables us to pursue a broad and data-driven development plan in lung cancer and across multiple tumors, including colorectal cancer, pancreatic cancer, and others, and across lines of therapy. Uniquely important, adagrasib has also demonstrated strong penetration in the CNS to treat brain metastases. These attributes position us well to optimize the potential value of KRAZATI. On slide 20, I'll remind you of the significant strength and breadth of Mirati's broader portfolio and capabilities. We are far more than a one-drug company. I'm very proud of the company we are building and the momentum we have established. We have built a world-class team at Mirati. I'm incredibly proud of the team and the work we have done to execute on our mission and the progress we've made. The depth of experience, passion and commitment is second to none. We are relentlessly focused on developing best-in-class target oncology therapies and have a robust and sustainable pipeline across multiple targets that are aggressively growing and advancing. We see significant long-term value in the operational and commercial synergies across our portfolio, particularly in lung cancer. In addition, an important priority is to enhance and accelerate our progress through selective partnerships to maximize KRAZATI's full potential. We also have sufficient capital to appropriately invest in our portfolio and capabilities. We recently completed our annual budgeting process, and based on our current financial projections, we expect to end 2022 with a cash runway that extends beyond two years into 2025. We are focusing our spending on our highest priority opportunities, which have the greatest potential to drive value. This includes the initiation of phase III registrational activities with adagrasib in combination with pembrolizumab in first-line non-small cell lung cancer. We will take a data-driven approach as we invest in the advancement of our pipeline, including with our first-line lung cancer studies, to appropriately manage risk and ensure we are maximizing return on investment. In 2023, we have multiple catalysts, including the maturation of our adagrasib first-line lung cancer data, the sitravatinib final analysis readout, which, if positive, would result in an NDA filing and is highly synergistic with KRAZATI. Initial clinical data for MRTX1719, our MTA-cooperative PRMT5 inhibitor, and MRTX1133, our KRAS G12D program, is also expected to enter the clinic. In addition, we expect strong progress across the rest of our innovative pipeline. As we transition to a commercial stage company, our team is laser-focused on execution. We remain steadfast in our commitment to ensuring that our business is as strong as our science. We are appropriately stacked, trained, and energized to make the KRAZATI launch successful. I'll conclude by once again saying thanks to everyone for making today possible. On behalf of all of us at Mirati, we thank you for your support and interest in the company. With that, we're ready to open the call for questions. Thank you. If you would like to ask a question, you may signal by pressing star one on your telephone keypad. Once again, we ask that you ask one question. We'll take our first question from Michael Schmidt with Guggenheim. Yes, good morning and congrats on the slightly early approval. I noticed the data in the label, especially the adverse event tables, were presumably derived from, you know, the study that was done with the capsule formulation. You have the tablet approved. I was wondering if there's a way to, you know, update the label in the future with additional data from the tablet formulation. Your competitor obviously was asked to do additional post-marketing studies. Could you please comment on any, you know, post-marketing requirements that the FDA has asked you to complete? Sure. It's David. Regarding the capsule formulation, the data that's in the label is the capsule formulation. All of our current clinical studies, including our confirmatory trial, KRYSTAL-12, are in the tablet formulation. That will be the first randomized trial that will read out the data versus the tablet formulation. We'll see the data in that with the tablet formulation. I would also go on to say with the tablet formulation, we have anecdotal experience from physicians that are very pleased with the tablet formulation, those physicians that have experience with the tablet and the capsule formulation, and we think there will be an improved GI profile with the tablet formulation. Alan will add a few comments. Yes, I would also add that, you know, the FDA had access to data from ongoing trials, which helped to support the approval for the tablet in this setting. In addition- Thank you. Yeah, no, that's fine. Please go ahead. Thank you. We'll take our next question from Tyler Van Buren with Cowen. Hey, guys. Good morning, and congratulations on the approval. As expected, the CNS met data is not in the label, but can you speak to your ability to educate physicians through the appropriate medical channels? Should we expect future publications or updates regarding CNS activity? Sure, Tyler. It's Ben Hickey. Thanks for the question. Yes, in the future, we are expecting to be able to publish the active and untreated portion of our data set, so we look forward to that being published. I'm pretty excited about what we've seen on that front. In relation to promotion strategy, we will be promoting within cohort A, where there was the previously treated or radiated population, where, as was mentioned in the prepared remarks, we've seen approximately a 33% response rate. We will be able to talk to that. We believe that's consistent with the final label. In the medical domain, again, we look forward to be able to publish and talk to the untreated CNS Mets portion as well, where we've seen response rates which should really mirror our systemic response rates. We're, you know, very excited about that data. It's Alex. Just one additional comment. You know, the word on the street, you know, given the data that it's already out there, is that the CNS activity is already well-described and well-known and is already being talked about in the oncologic community as both a differentiating factor and an important aspect of the use of the drug. I have no doubt that this will get out there, either via KOLs, knowledge leaders, second opinions, et cetera. Thank you. We'll take our next question from Geena Wang with Barclays. Thank you for taking my questions. Also congrats on the approval. What is your protocol on dose reduction for the doctors? you know, also regarding the target occupancy, could you remind us the target occupancy for 400 milligram BID and also 600 milligram QD? Quickly, if I hear correctly, did you say the phase 3 confirmatory trial will be upsized? Just wondering if upsized, what size you will change to. When I checked clinicaltrials.gov, it's still 340 patients. Yes. Thanks, Geena. This is Alan. Let's see, two questions in there. The first one, dose reduction, the protocol and the standard is to go from the 600 milligrams orally twice daily to 400 milligrams orally twice daily. If needed, a subsequent dose reduction is to that 600 milligrams once daily, as you mentioned. For the KRYSTAL-12 study, the confirmatory phase III study, as you point out, this is we are enlarging the study. It will go to approximately 600 patients so that we'll be able to have that dual endpoint that I mentioned, which will be the PFS, the original endpoint, and also an opportunity to show significance in overall survival. This is something that we think is very important. It's something we've discussed with the FDA. This will be another key opportunity to differentiate ourselves as the first KRAS G12C agent to show a survival advantage. Just the other point of the question, Geena, was the coverage. We're quite confident that the 400 milligram BID dose, we have a fair amount of data there now, both from the dose reduction patients and from new patients that are starting at that dose in various studies. We're confident that we can cover the target and that the durability of responses is another thing we've looked at. Even in those patients where there's been dose reductions, the durability of the response looks similar. We feel that we have sufficient drug coverage. Thank you. We'll take our next question from Jonathan Miller with Evercore ISI. Hi, guys. Congrats on the approval, thanks for taking the question. Maybe I'll focus on commercialization. Is there anything you can do differently to your competitor to drive identification of patients in the second line? Is this the sort of situation where you have to wait for first line testing to increase and flow through? Is there something you can do in the second line that your competitor hasn't been doing to develop this market? Sure. I can take the question, Jonathan. There are a couple of things. First of all, as a reminder, we'll be launching with both a tumor-driven CDX as well as a liquid biopsy, when we think that can actually be helpful in regards to testing in second line. The other thing we've done, we've spent a lot of time at the account level and really understanding which counts are testing at what type of rate. We actually have some unique and actually confidential partnerships we're putting into place which help identify these patients as they are flowing through and progressing from first line. We think we are doing some things which can create some unique advantages. Lastly, I would say that just having a laser focus and having an organization that, you know, basically all day, every day is really focused on KRAZATI and ensuring that we're identifying patients and presenting KRAZATI as a potential option for them, we think that focus and dedication of our field teams, will help bring a great deal more promotional activity and help with physicians and healthcare systems in identifying those patients. Thank you. We'll take our next question from Salveen Richter with Goldman Sachs. Good morning and congratulations. Could you just speak to how you're going to educate doctors regarding the capsule tablet for the capsule data versus the tablet data? Help guide us here as you look towards the launch, how doctors and patients will decide between the two options on the market and how you're thinking of the trajectory moving forward. Sure. Again, it's Ben, I'll take that. In regards to the tablet formulation, that is the formulation we'll be launching with, and I think that will be very clear to physician. It's part of the label and will be part of our education. We will over time be presenting and putting public domain some of the data around the tablet. That will just take a little bit of time as we get experience from our ongoing studies. But I think we're in a unique position where we'll actually be launching a drug where we think the experience will actually be enhanced potentially versus the label. We're quite excited about the real world, you know, experience that we had in the study, that we can actually bring forth with the tablet. In regards to differentiation and drivers of prescribing, the number one driver of prescriber in targeted oncology is really around overall survival. As was mentioned earlier on the call, with the pool data representing over 14 months of survival, we have our strong PFS data and then leading, you know, mid-40s on the overall response rate. You couple that with then CNS penetration, we think we have a pretty compelling rationale. As a reminder, unfortunately, up to 40% of patients at some time in their journey will present with CNS metastases, we think that's an important differentiator. That coupled with a tolerable profile, we think, you know, we think we have a unique differentiated profile, and we have a field force that really believes in the differentiation of the product and can't wait to get out there and educate physicians. Thank you. We'll take our next question from Evan Seigerman with BMO. Hi, guys. Thank you so much for taking my question. just one on kind of the Grade five AE rate. You know, it's 11% in your label, a little lower in your competitive label. How are you gonna detail against that? Thank you. Sure. It's Ben again. We'll obviously go through the label with our physicians and the efficacy as well as the differentiated profile and OS PFS as well as then the safety profile. As a reminder, we'll also be able to use the New England Journal of Medicine, where we actually saw the rate of ARs was about 1.7%, where we actually had two fatalities. When it is. And that's based upon physician association. That's how we're planning on educating around it, and maybe I'll let either Alan or maybe Dr. Spira on the call can give any further comments on that. Yeah, thanks, Ben. I'll go, and then Dr. Spira can follow afterwards. A couple of key points that I'd like to address building upon the New England Journal of Medicine. Again, you know, causality in a single arm study can be challenging. The FDA tends to take that conservative approach with that. That's why we think the data from the New England Journal of Medicine papers is important. That said, based on the FDA approval, the agency clearly has ascribed a positive benefit risk ratio to KRAZATI. Another key point is that the randomized study KRYSTAL-12 will also continue to provide important insights in this randomized setting to help us fully understand the risk profile associated with KRAZATI. Dr. Spira, any additional comments? Yeah. I mean, little to add to Alan. I think the major thing is we as physicians, when we think about it, we think about it in the context of these patients. We all know these patients are very well, very heavily pretreated. Again, in context of the New England Journal article, which really points to the tolerability and the much lower rates seen there, we all realize in the FDA label they take a very conservative approach, as you both eloquently described, for obvious reasons. I don't think that's gonna weigh on physicians, if any. Thank you. We'll take our next question from Maury Raycroft with Jefferies. Hi. Congrats on the update, thanks for taking my question. I was gonna ask about the phase III endpoint switch. Was that encouraged by FDA, or is it primarily for competitive advantage purposes? What are your expectations on overall survival, and how exactly are they informed by Amgen's data, given both studies include crossover? It's David, you know. Thanks, Maury. We're actually, you know, really encouraged by this change with our KRYSTAL-12 trial having the dual endpoint of PFS and OS because we do think over time it is a differentiator. If we can be the only G12C inhibitor on the market here, when that confirmatory trial reads out with a survival advantage, we think it's a competitive advantage. You know, watching the data, you know, being released early this year gave us a chance to step back, look at our data, look at the competitive landscape, and make the appropriate adjustment. Alan can talk about our conversations with the FDA to make that adjustment. Yeah. Thanks for the question. This was a discussion that was in conjunction with the FDA. This is something that we were very interested in doing, as David had mentioned. The question that you raise is the concern about crossover. In our discussions with the FDA, we've come up with an approach that will allow for crossover, but not until the primary endpoint of PFS has been met. That should diminish the impact of crossover in this particular study and setting. Again, we're very encouraged about the design of the study and excited about it and look forward to being the first KRAS G12C agent to show an improvement in overall survival. Thank you. We'll go next to Eric Joseph with J.P. Morgan. Hi. Good morning. Congrats on the approval. Thanks for taking the question. I, maybe just a commercial one. It's likely too early to talk about guidance at this point, but can you just describe how you're gonna be talking about commercial metrics as they relate to the launch as it matures, you know, new prescriptions, unique and repeat prescribers? I would be curious to know whether the KRAZATI prescription data will be available, accessible via third-party vendors. Thanks. Thanks for the question, Eric. It's Ben. I think in regards to third-party availability of data, you just gotta keep in mind that based upon the different distribution strategies of different companies, that shows up in the data in different ways. I think sometimes the trends are a little bit understated from some of the third parties, so I think you'll have to wait for the full kind of sales readout from us on our quarterly updates to get a real sense of the adoption. In addition to that, we'll be providing color as we think about the early experience of physicians. We actually think that that is very important. The qualitative experience that physicians have with treating KRAZATI is one area we'll provide updates. We'll also be talking about the coverage in regards to the access, and broader coverage and payer adoption is another metric we'll be talking about that. Those are a couple of the things. Obviously, we'll do, again, a fair bit on the qualitative side until we have sufficient data to be able to talk about more concrete quantitative metrics. Thank you. We'll take our next question from Andrew Berens with SVB Securities. Hi. Congrats on the approval, guys. Sorry about another question on the confirmatory trial change. I just wanna clarify. This is a co-primary endpoint. It's not a multiple primary endpoint. To obtain approval, you do need to demonstrate a stat sig benefit in both OS and PFS. What happens if you only demonstrate a PFS benefit but no OS benefit? Can you share the statistical assumptions for the powering of the OS benefit of this trial? Where do you think this leaves your competitor in regards to their confirmatory trial results? Yeah, thanks. Thanks again for the question. To go over the design, it's a dual endpoint. We actually believe we have an opportunity with either of those endpoints to secure full approval. The study was increased from approximately 340 patients to approximately 600 patients to allow for increased power for the overall survival. I think that, you know, this would differentiate ourselves by being, again, the first KRAS G12C agent to be able to show a survival advantage moving forward. Okay. Where do you think it leaves LUMAKRAS with the data that they have for their confirmatory trial results? I think you'll have to ask Amgen that question, so. We'll take our next question from Michael with Morgan Stanley. Hey, guys. Thanks for taking the question. Congrats on the approval as well. Maybe just a follow-up in terms of patient identification. You mentioned about two-thirds of patients are tested at diagnosis. Just curious if that% is higher, as patients move from front line to second line treatment. Thanks. Thanks. I'll take that. The data is that we see about 2/3 of patients being tested at diagnosis, as you correctly state. What happens, unfortunately, is that because these patients are on therapy for quite a long time in front line, which is great, when they progress, sometimes that record is lost in the system, and the actual pathology report is not always uploaded to the EHR system. What we're very much focused on is helping the physician to identify that as they actually come through and progress in the system. While about 2/3 of them are being tested, there's still a lot of patients, unfortunately, which are lost in the system there. We only see about half of the patient population coming through in second line. That's why we think there's such a big opportunity to grow the market, and it really is an immature market at currently. It's Alex Spira. I'll just chime in from the physician perspective. There's been obviously every month and every day that goes on, there's increasing numbers of patients tested. You know, the number of patients that get liquid biopsies are continue to increase and will continue to increase. In the second line setting, it's a little easier sometimes because you know that you need to test them. You know, initially with patients, there's a quick rush to get patients on, lack of tissue at that point, and that's why they're not getting treated. There is data that shows that the further you go, the more likely you are to test those patients in the second line setting, which obviously is important because that's currently in the label for adagrasib. I think over time, there will you know, there'll be a continuing increase day by day and week by week of more and more patients tested by any means possible. We'll take our next question from Yigal Nochomovitz with Citigroup. Hi. Great. Thank you. Congrats on the approval of KRAZATI. I just have one commercial and then one for Dr. Spira. Just regarding the price, LUMAKRAS obviously is $18,990 a month, and you're pricing it $19,750. Can you just comment quickly on the slight difference? Is that essentially preprogrammed given you're expecting Amgen to take a low to mid-single% price increase in early 2023? For Dr. Spira, we've heard from some of our channel checks that on LUMAKRAS some patients are starting at a slightly reduced dose, not the full dose. Just curious if you would expect a similar adoption pattern for KRAZATI. Would you basically expect patients to start on KRAZATI that are new to therapy, or would you also consider switching patients off LUMAKRAS, especially the ones that have CNS disease? Thanks. I'll start with the pricing question. As you note, from a small premium to LUMAKRAS, which we think represents the innovation that we're bringing to market. I won't comment on competitors' pricing strategy in the future, but we think what we are bringing to the market is accurately reflected in the innovation, given the profile of the drug. Maybe I'll kick it to Dr. Spira in a second, but I would just say that what we've seen to date in our experience that all of our patients obviously are starting on the 600 milligram, and then those that transition over time have done well on the 400 milligram. The data set that we'll be promoting and the data set that we have is really around starting with the 600 milligram upfront. Dr. Spira? Yeah. In terms of... Again, you know, I don't wanna speak for every physician in the world, and certainly, for Amgen's sotorasib. I think that, you know, there's been a lot of talk, obviously with Project Optimus, talking about how to best dose patients, and, you know, obviously everybody knows, you know, the study comparing 240 versus 960. There's a few select physicians, I wouldn't say they're community physicians, but I would say that they're vocal academicians, that strongly believe that starting people at 240 is probably just as good, and that's why they're doing that. That is not the general rule. I think in terms of specifically, regarding KRAZATI, I think most people are gonna follow the label and start at the current approved dose and then dose down as needed. I think one of the big differentiating factors, if you look at the clinical studies, KRYSTAL-1 was really a community-based study, and those are patients that I think reflect real world patients probably a little bit more than did the CodeBreaK studies with sotorasib. I think what you're seeing in terms of, you know, the tolerability in the study published in the New England Journal is going to be a very real world demonstration, where, yes, there's some dose reductions, but I think the general take is start at the FDA-approved dose and then have a low threshold to dose down. At least that's what I'm gonna tell my colleagues when they ask, and it's also the word on the street. With no additional questions in queue, I'd like to turn the call back over to our speakers for any additional or closing remarks. Well, thank you very much for joining us this morning, and we greatly appreciate your interest in Mirati and look forward to sharing additional updates with you. Thank you. That will conclude today's call. We appreciate your participation.