Mirati Therapeutics, Inc. (NASDAQ:MRTX) Q2 2022 Earnings Conference Call August 3, 2022 4:30 PM ET
Company Participants
Ryan Asay – Vice President of Corporate Affairs
David Meek – Chief Executive Officer
Chuck Baum – President, Founder & Head of Research & Development
Laurie Stelzer – Chief Financial Officer
Jamie Christensen – Chief Scientific Officer
Ben Hickey – Chief Commercial Officer
Conference Call Participants
Michael Schmidt – Guggenheim
Tyler Van Buren – Cowen
Jonathan Miller – Evercore
Ben Burnett – Stifel
Andrew Berens – SVB Securities
Evan Seigerman – BMO Capital Markets
Yigal Nochomovitz – Citi
Mike Ulz – Morgan Stanley
Maury Raycroft – Jefferies
Jay Olson – Oppenheimer
Operator
Good afternoon, and welcome to the Mirati Therapeutics Second Quarter 2022 Earnings Call. My name is Danielle, 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 speakers prepared remarks. There will be a question-and-answer session. [Operator Instructions]
It is now my pleasure to introduce Ryan Asay, Vice President of Corporate Affairs at Mirati. Ryan, please go ahead.
Ryan Asay
Thank you, Danielle, and welcome everyone to this afternoon’s call. Joining me on the call today are David Meek, Mirati’s Chief Executive Officer; Dr. Chuck Baum, Mirati’s President Founder and Head of Research and Development; and Laurie Stelzer, Mirati’s Chief Financial Officer. Dr. Jamie Christensen, Mirati’s Chief Scientific Officer; and Ben Hickey, Maruti’s Chief Commercial Officer are also with us and will be available for the Q&A portion of the call.
Please note that, this conference call will include forward-looking statements. 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.
This afternoon, we released financial results for the quarter ended June 30, 2022 and recent corporate updates. This press release is available on the Investors section of our website at mirati.com.
With that, David I’ll turn the call over to you.
David Meek
Thank you, Ryan, and good afternoon, everyone. On this attorney’s call, I’ll provide an update on key developments, since our last earnings call, including steps we’re taking to prepare for a potential commercial launch of out aggressive this year. Chuck will share an update on our R&D programs. And Laurie, our recently appointed CFO, will summarize our financial results. I’ll then provide closing remarks, before we open the line for questions.
So let’s get started. The second quarter was a very productive and important one for Mirati, we a lot to be excited about. We made significant progress towards achieving a number of important milestones and strategic priorities in the second quarter, including presenting our latest data on that aggressive at ASCO, and building out our commercial capabilities in advance of its launch.
At ASCO, we shared several significant and adagrasib update and Chuck will touch on the specifics. I’d like to point out a few key takeaways that are worth noting as we believe there was a lot to be excited about with the data released.
At a high level, these results highlight important points of potential differentiation, including the CNS penetration, and combine ability of adagrasib with concurrent pembrolizumab and position us very well for both near and long-term commercial success.
Our results give us confidence in our ability to secure a US approval and execute a strong commercial launch of adagrasib and second line and beyond non-small cell lung cancer, which is a key priority for the company. We are very comfortable competing in the KRAS G12C inhibitor market, especially in the tablet formulation.
Our ongoing interactions with FDA are productive, and we continue to collaborate closely and effectively through the review of the adagrasib new drug application. We recently had our mid-cycle review and have added clarity that, there will be no advisory committee and no REMS program.
The FDA has voiced no major safety issues to date or expectations for new studies prior to approval. As such, we are preparing for the approval of the NDA with a tablet formulation and are finalizing our commercial readiness plans.
As a reminder, our PDUFA date is December 14, but we will be ready to go if approval comes before then. We recently hired the remainder of greater than 100 person customer-facing US field force, and believe we have the talent needed to drive a successful commercial launch.
In addition, we’ve built out our marketing, market access, patient support and medical affairs capabilities, and now have in place all the components of a successful commercial organization necessary to execute our commercial strategies.
Our commercial team will be fully trained and launch ready in the US by the end of the third quarter. Some of you know I have considerable commercial experience in pharma and biotech, and I can say without hesitation, I’m very impressed with the quality and caliber of the team we have been able to assemble at Mirati.
Our commercial strategy is built on several pillars that we believe will enable us to be successful. First, adagrasib differentiating molecular profile and 24-hour half-life have enabled us to generate meaningful clinical data, including the recently presented greater than 30% overall response rates in non-small cell lung cancer patients with active brain metastases, and the longest median overall survival data to date of greater than 14 months in our pooled analysis.
Second, we have been able to attract top talent across biotech, pharma and healthcare provider organizations giving us a team with extensive lung cancer experience and demonstrated success in launching top oncology products. There are opportunities to increase both testing and identification of KRAS G12C eligible patients. In response, our field teams are working to assist in market development activities to improve both patient access and outcomes.
Third we have purpose-built our commercialization team with a singular focus on adagrasib. We have built this team with an optimized design and focus on integration, digitization and speed of execution across functions.
Fourth, we have the capital necessary to invest for success both in terms of executing on the initial launch as well as investing in the long-term value optimization of this differentiated program.
In summary, we’re very excited about the potential launch and the opportunity to deliver out of grass and make a positive impact on patients living with cancer. Beyond the US, we completed the submission of adagrasib’s marketing authorization application for the treatment of patients with non-small cell lung cancer harboring the KRAS G12C mutation who have received at least one prior systemic therapy to the European Medicines Agency. This submission is an important step in bringing us closer to possibly expanding the availability of adagrasib to patients in the European Union.
From a management team perspective, we made an important addition to our leadership team in the second quarter. Laurie Stelzer joined Mirati, as our CFO and bringing with her an invaluable skill set acquired over her 25-year career in the biopharmaceutical industry, including a wealth of finance expertise and strategic insight.
Laurie has considerable experience navigating the needs of a company transitioning from a research and development stage to a commercial stage which will be beneficial as we prepare for the commercial launch of adagrasib in the U.S. and finalize our strategy outside of the US.
We are very fortunate to bring Laurie on at this pivotal front in our history. And finally we continue to be in a strong financial position which enables us to execute our strategy and provides us with the flexibility to prudently invest for success across our target oncology pipeline and prepare for a successful adagrasib launch pending FDA approval later this year.
With that I’ll turn the call over to Chuck for a clinical update.
Chuck Baum
Thank you, David. I’ll begin with adagrasib. It’s an exciting time for the company as we approach our first potential regulatory approval this year. Our breakthrough therapy designation and real-time oncology review status enable our ongoing engagement with the FDA during the review process and we remain confident in the approval of the NDA this year.
We had a significant presence at ASCO where we shared positive and aggressive data in patients with KRAS G12C mutations living with non-small cell lung cancer across lines of therapy. These ASCO updates included positive results from the registration and enabling Phase II cohort of the KRYSTAL-1 study evaluating adagrasib 600 milligrams, administered twice daily in patients with non-small cell lung cancer harboring the KRAS G12C mutation who have received at least one prior systemic therapy.
These positive results were also reported concurrently in the New England Journal of Medicine publication. We also presented compelling results from a prospective analysis of the Phase Ib cohort of the KRYSTAL I study. demonstrating intracranial responses of two adagrasib in patients with KRAS G12C mutated non-small cell lung cancer with active and untreated to rebuild central nervous system metastases.
Adagrasib is the first KRAS G12C inhibitor to demonstrate substantial clinical activity in this large and poorly served patient population. In addition we showed encouraging early results demonstrating the feasibility of combining adagrasib with pembrolizumab in first-line non-small cell lung cancer patients. These first-line results provide meaningful context and clarity as we aggressively advance our first-line non-small cell lung cancer strategy.
Finally, the results presented at ASCO were based on the capsule formulation. In agreement with the FDA, all of our trials have now switched to the tablet formulation and feedback from investigators has been positive regarding the tolerability. We expect the tablet to be our approved formulation for launch. We plan to present data from patients treated with tablet formulation at a future medical meeting.
Feedback from key opinion leaders, investigators and oncologists on the profile of Adagrasib has been overwhelmingly positive. KRYSTAL 12, our randomized Phase III confirmatory study in previously treated non-small cell lung cancer patients with a KRASG12C mutation continues to enroll well worldwide and is on track to complete enrollment in the first half of 2023.
Mirati expects to provide key updates in the second half of 2022 in the following areas: in first-line non-small cell lung cancer, we expect to share updates across our multipronged development approach. This includes providing additional clarity on a possible regulatory pathway for accelerated approval as a single agent in patients harboring KRAS G12C and STK11 co-mutations as well as KRAS G12C mutated patients with TPS score of less than 1%.
We expect to share initial data from these subpopulations in 2023. Our initial and most advanced and aggressive combination approach in first-line non-small cell lung cancer is the concurrent dosing of adagrasib tablets at 400-milligram twice daily with full dose pembrolizumab.
Our Phase II KRYSTAL 7 study evaluating this combination is enrolling well, particularly following our initial update from this study at ASCO. We plan to share more mature data with a larger number of patients in the fourth quarter of 2022.
We continue to evaluate or have plans to evaluate adagrasib in various other first-line combinations including targeted and chemotherapy-based approaches.
We are finalizing our first-line non-small cell lung cancer strategy with our scientific advisers which we will align with the FDA and provide an update later this year. Beyond lung cancer, we are advancing enrollment of patients with a variety of cancers driven by KRAS G12C mutations. We expect to provide more mature data in late-line colorectal cancer at the ESMO conference in September.
We also expect to provide additional clarity on a possible pathway for accelerated approval of adagrasib in late-line colorectal cancer later this year. Full approval will be based on our ongoing CRYSTAL 10 randomized Phase 3 registration study in second-line colorectal cancer patients.
In addition, we are continuing to enroll patients with other solid tumors that carry the KRAS G12C mutation, including pancreatic, cholangiocarcinoma, non-colorectal cancer gastrointestinal and other solid tumors based on our positive data presented earlier this year at the ASCO GI conference.
Adagrasib has the potential to treat multiple tumor types across a range of cancers and we believe this could be another important differentiated characteristic of our program. Shifting to sitravatinib, which is being studied in a registrational Phase 3 study called SAPPHIRE. This study enrolled patients with second or third-line non-small cell lung cancer, who derived prior clinical benefit following treatment with a checkpoint inhibitor.
The SAPPHIRE study is fully enrolled and is on track to reach the number of events needed to trigger an interim analysis for overall survival in the fourth quarter of 2022. If positive, this intra analysis could be the basis of full approval in the US and Europe with regulatory filings in both markets being submitted by the middle of next year.
Sitravatinib has the potential to treat a large number of patients, since there are approximately 70,000 patients with second or third-line non-squamous non-small cell lung cancer in the US and Europe.
Finally, I’m pleased to announce that we’ve completed the submission of the investigational New Drug Application for MRTX-0902. 0902 is a selective SOS1 inhibitor that shifts KRAS into its inactive state potentially enhancing the activity of adagrasib by addressing KRAS feedback reactivation and intrinsic and acquired resistance to KRAS inhibitors.
This agent has the potential to see complement other agents in the Mirati pipeline and exert an impact on KRAS mutant cancers across KRAS mutation types. We expect to initiate clinical development with our SOS1 program before year-end. We’re pleased with the significant progress we are making across the breadth of our R&D portfolio and look forward to a number of significant updates later this year.
With that, I’ll hand it back to Laurie.
Laurie Stelzer
Thank you, Chuck. First let me begin by saying that I now have more time to learn about the company, our technology, our team and our pipeline and it’s very clear why there is so much internal excitement about the future of Mirati.
From a financial management perspective, we will be vigilant in utilizing our capital in a disciplined manner to ensure we remain able to advance our pipeline, invest in innovation and effectively launch products to drive sustainable long-term growth.
Research and development expenses for the second quarter of 2022 were $128.3 million compared to $134.6 million for the same period in 2021. The decrease is primarily due to autograft in manufacturing costs incurred in Q2 2021 ahead of our NDA, which is partially offset by an increase in salaries and other employee-related expenses, including share-based compensation expense associated with an increase in headcount to support our growing pipeline.
General and administrative expenses for the second quarter of 2022 were $54.2 million, compared to $29.6 million for the same period in 2021. The increase is primarily due to an increase in commercial readiness costs in preparation for a potential product launch an increase in salaries and other employee-related expenses, including share-based compensation expense as we grow our sales, marketing and G&A staff and an increase in facilities and IT costs to support the organization.
Net loss for the second quarter of 2022 was $176.4 million, or $3.18 per share basic and diluted compared to a net loss of $166.4 million, or $3.23 per share basic and diluted for the same period in 2021. We’ve ended the second quarter with approximately $1.2 billion in cash, cash equivalents and short-term investments, which gives us a cash runway into 2024. Please see our press release from earlier this afternoon for additional details about our second quarter 2022 financial results.
And with that, David, I’ll hand it back over to you.
David Meek
Thank you Marie and Chuck for your updates. As you have heard today, we made considerable progress in the second quarter advancing our clinical pipeline and advancing our commercial efforts to be fully launched ready in the US by the end of the third quarter. I’ll close our prepared remarks with a brief comment about the depth and breadth of the company and portfolio we are building.
We have the products, capabilities, people and capital needed to compete and succeed. Our pipeline spans numerous targets and tumor types and positions us well for tremendous value creation and meaningful operational and commercial synergies. We expect target oncology to play an important role in the fight against cancer. We have generated compelling clinical data showing KRAS inhibition has potential well beyond the second-line setting in non-small cell lung cancer.
As that proves out, we will be able to help many people in need and create considerable value for the patients, physicians and other stakeholders that have supported Mirati in that endeavor. It is a privilege to lead a company his team never loses sight of why we come to work each day.
And Daniel, I’ll turn it over to you we’re ready to take questions.
Question-and-Answer Session
Operator
Thank you. [Operator Instructions] And we’ll take our first question from the line of Michael Schmidt with Guggenheim. Please go ahead. Your line is now open.
Michael Schmidt
Hey guys. Thanks for taking my question. I had a question on your KEYTRUDA combination study of adagrasib where we’ve seen some very interesting early data at ASCO. And I think the median follow-up at the time was only two months. There are some general questions about the safety profile of PD-1 inhibitor combinations with more follow-up. And I guess now that it’s been some more time since then. I was wondering where your confidence level is with respect to the tolerability profile as more time has passed now since the ASCO data presentation.
David Meek
Michael, it’s David, then I’ll turn it over to Chuck. The data we presented at ASCO, yes, it was early data and the median time was 2.1 months of time on the combination therapy. So we realized that at the time. We’re continuing on the trial. And we feel based on that trial as well as the earlier seven patients we have to run drug for more than a year at that point at ASCO that we’re building a nice database here of patients being on drug for a good amount of time. And we’ll give an update later this year on where we are with the CRYSTAL seven trial. We’re encouraged by what we saw and we’re anxious to give an update later.
Chuck Baum
Yes. I just to reinforce that by saying that, honestly in our previous experience with combinations of targeted agents and I/O, that oftentimes adverse events occur in the early cycles. So that does give you some initial read at least on tolerability of the combination. Also, as David said, we did have the semi patients that were treated for over a year, which gives you an idea of the tolerability of the combination as well over time. And there were patients up to six months on treatment even in the data we presented the data update for K7 even though the median was two months. So, far we’re feeling confident and looking forward to presenting more data later this year.
Operator
We’ll take our next question from Tyler Van Buren with Cowen. Please go ahead. Your line is open.
Tyler Van Buren
Hi guys. Good afternoon. Congrats on progress and thanks very much for taking the question. Regarding the ongoing the grass regulatory review I appreciate the update. Can you confirm that the final Phase II data the CNS MET data and the tablet data have all been submitted when they were submitted. And as a related follow-up have a discussion started yet, or what are the outstanding items in the review?
David Meek
So Tyler, yes, we can’t confirm the Brame data that was shared at ASCO that information all the clinical data has been shared with the agency that’s important to do that data we share with the agency. They have everything that we have regarding the tablet formulation as well and that’s why we’ve talked about, we’re preparing for an approval and approval with the tablet formulation regarding anything else with the ongoing and productive conversation with the agency. I think it’s premature to get into some of the details of the conversations. But as Chuck and I both said during the prepared remarks it’s constructive it’s active and ongoing with the agency as we move along in the FDA process.
Operator
We’ll take our next question from the line of Gena Wang with Barclays. Please go ahead. Your line is open.
Unidentified Analyst
This is Harshita on for Gena. Thank you for taking our questions s. Our first question was on the K122Lplus confirmatory trial for lung. If you remember correctly, the initial plan was to enroll 450 patients. And I think the powering assumptions disclosed at ASCO last year, the trial was sufficiently powered to detect the treatment effect of PFS and OS at an alpha of 0.05. But now that the enrollment has been decreased to 340 patients, can you remind us the rationale for decreasing the patient size and also comment on how this changes the powering assumptions? And then I have a follow-up if I may.
David Meek
So yes, the design of the trial was changed which is the reason for the change in numbers. So that the primary endpoint was — is now PFS. And so, with PFS as the primary endpoint that it was possible to decrease the overall patient number without decreasing the power to detect the difference. So that was the rationale.
And partly, that was based on the fact that we were allowing crossover, since that enhance — significantly enhances enrollment. And when you do that that could potentially compromise the overall survival. So that’s the rationale for the design, but in terms of the patient numbers, we’re still having similar power to detect the difference, but that’s going to be on PFS.
Unidentified Analyst
Okay, great. Thank you, so much. And the second question we had, quickly, was on the tablet versus capsule formulation. We know you previously noted improvement with the tablet formulation. But was wondering, can you comment on how much improvement you saw for the GI talks?
David Meek
Yes. We haven’t gone into the specifics. We will, when we have more experience and have more patients. I can say that the difference clinically and it was related from the ongoing trials by our investigators is in the gastrotestinal. So things like the nausea, vomiting. Those are the primary differences, but we don’t have the exact quantitation at this time, but we will present it later when we have more data.
Operator
We’ll take our next question from Jonathan Miller with Evercore. Please, go ahead. Your line is now open.
Jonathan Miller
Hi, guys. Thanks for taking my question. I’d love to ask, now that we’ve seen a little bit more data on the first-line combo and you’re feeling confident about the tolerability profile, what are the remaining gating factors on beginning a potentially registrational study at this point? And I know you said you’d give some clarity on what that path would be later this year, but what are we waiting for to get that clarity at this point?
David Meek
I think, as the trial matures, we have more patient numbers, longer time on the combination therapy, that’s important. And then, importantly, we want to have a conversation with the FDA, as we craft together a registration trial. So that’s all going to take a little bit of time.
And as soon as we’re ready for that, will come — well, we’ll let you guys know, but we expect that to be by the end of this year. As the trial advances has a conversation with our scientific advisers and as well as agency before rolling out that trial. But we’re encouraged by it. Chuck, anything you’d like to add on?
Chuck Baum
Just that, of course, the efficacy in terms of response rate and early reads on PFS will be part of the evaluation in triggering Phase 3 randomized study. So that takes a little bit longer. As you know, the tolerability profile was really the first thing that you start to see and then looking at the efficacy is what we’re doing, as we get closer later this year to getting ready to start a Phase 3 program.
Jamie Christensen
Yes, this is Jamie. I think one thing I’d like to add is that the ada plus pembro combination will be our first foot forward, just to note that we have additional activities ongoing. We believe chemoimmunotherapy may be an important combination in some first-line settings, we’ll be evaluating that.
Secondly, I think, we have an increasing understanding of how KRAS signals and what some of the feedback pathways are and what might ultimately cause resistance. So a number of the targeted combination strategies are ongoing starting in the second-line lung cancer space, but should they look compelling there. There’s an option to bring those up to earlier lines of therapy, either as doublets or even in combination with immunotherapy. So, this is really a first foot forward with additional work ongoing.
Operator
We’ll take our next question from Salveen Richter with Goldman Sachs. Please go ahead. Your line is now open.
Q – Unidentified Analyst
Thanks for taking my question This is Andrea [ph] on for Salveen. Maybe a question on the competitive landscape with Amgen having their first Keytruda combo data this weekend at [indiscernible]. Just curious what you’ll be focused on to understand differentiation, in your approaches? And then as a follow-up to that, can you just remind us on your thinking of sequential versus concurrent common atrial approaches. And mechanistically, is there reason to believe that one approach might be more efficacious than the other?
David Meek
So, yes, David. I would — we’re going to wait to see the data this weekend, like everybody else. So we’ll see what is released by Amgen, and World Lung and we’ll take it from there. But I would say, what we’re looking for is for us to release that data. As Chuck just mentioned, you want to see immediate tolerability, tolerability over time with any combination regimen. So that’s what we’re looking for. Then ultimately, you want efficacy. So that’s, what we’d be looking for. I think relative to the other combinations, and so on I think Jamie just answered that, a moment ago other strategies, we have. So, Chuck?
Chuck Baum
I think the only other thing, I’d add is that we believe strongly that the co-administration of an adagrasib with pembrolizumab is going to be the most appealing, to investigators and we think will be the most successful kind of way to combine the two. So that’s, what we want. That’s why we’re focusing on that approach. But we’ll see, what — as David said, what Amgen presents and that will give us a better idea of where they’re going, as we explore additional approaches as well.
David Meek
And that’s why we’re really careful to say and deliberate to say it’s 40 milligrams, twice a day of adagrasib, plus full dose pembro, concurrently. That is where we think the greatest opportunity for activity is for the patients.
Operator
We’ll take our next question from Ben Burnett with Stifel. Please go ahead. Your line is now open.
Ben Burnett
Hi. Thank you very much. I also wanted to ask a question about the competitive landscape. I guess, does the outcome of Amgen’s Lumakras confirmatory study have any impact on how you guys, are thinking about the regulatory path for adagrasib, whether that’s a successful study or not?
David Meek
So for us with our KRYSTAL-12 trial when we look at our registration trial that was presented at ASCO Cohort A as well as our confirmatory trial. It’s the same patient population. Remember, 98.3% of our patient population, in the registration trial, were patients that had followed the KEYNOTE-189 regimen, if you will and that’s also our confirmatory trial. We look at that. We think of a pooled analysis. We’ve also shared at ASCO. So we’re pretty confident, with our KRYSTAL-12 trial design and the outcomes and the trial will finish enrollment next year, and we’ll see what happens.
Chuck Baum
I think obviously, we’ll be watching to see what their results are once presented, to see if there’s anything there we can learn from. But at this point, we don’t see any reason to change our plan.
Operator
We’ll take our next question from Andrew Berens with SVB Securities. Please go ahead. Your line is now open.
Andrew Berens
Hi. Thanks for taking my question. A couple on the ongoing 400-milligram BID monotherapy cohort piston. Can you give us an idea when that cohort started enrolling how far along it is at this point? Are the patients getting tablets or capsules? And is this a cohort that the FDA specifically to run?
David Meek
So, the trial started earlier this year regarding that to get into the details. I don’t think we’ll get into the details. The trial is actively enrolling and it is in a tablet formulation. At this time the patients were on the 400-milligram twice a day of the tablet formulation.
And the trial is up in the FDA is of course aware of the trial as they are both our ongoing clinical trials in the second-line plus non-small cell lung cancer patient population the patients with KRAS G2C mutation. So, they’re where that trial, we will not have data for that trial until next year.
Operator
We’ll take our next question from the line of Evan Seigerman with BMO Capital Markets. Please go ahead, your line is open.
Evan Seigerman
Hi guys. Thank you so much for taking my question. Just thinking ahead to the launch now that you are second to market, I guess what feedback have you gotten from physicians and KOLs that you’re interacting with as you build up the commercial force regarding differentiation?
And then also you seem to be pretty optimistic that you’ll be able to secure approval ahead of your December PDUFA. What indications have you gotten from regulators that that may be the case? Thank you.
David Meek
So, I will start and Ben will jump in too. So, we’re preparing and we’re preparing for a launch as early as end of Q3. There’s no guarantee that the FDA will approve us early, we want to certainly be prepared if we are fortunate enough to be approved early. So, I just want to be clear on that part of the conversation.
The feedback, especially at ASO and all of us were there, we spent a significant amount of time with the community-based oncologists. The investigators went over all the data that was shared at ASCO and the enthusiasm level is very high regarding the totality of the clinical data that’s been published for adagrasib in the second-line setting.
The Cohort A data was we reviewed that the response rate the overall survival data was very compelling to position the CNS brain mets data for active and untreated. This is a real differentiator in the mind of the physicians anything they can do to treat those patients and even control brain mets is a good thing for patients.
So, the feedback was great. The feedback on the life cycle management programs that we have in place such as a combination regimen with pembro in the frontline setting, colorectal cancer, the response rates across the board were very impealing, especially to the community-based oncologists where these patients are treated.
So, overall, the feedback has got been good. It’s given us confidence and is for us to go to the market and we’re ready to compete in the marketplace Ben’s got a few more points to add.
Ben Hickey
Sure. As you know we’ve been out there for a while. So, we had a number of interactions with physicians. We’ve actually put our salesforce to-date been able to actually interact with 90% of the top 100 plans across the country and have just very positive feedback and it really is around some of the differentiation.
Obviously, the molecules being designed for a 24-hour half-life and that’s enabled some of the response rates and up to 14 months of overall survival with our core data set.
So, coupled with the CNS data in the active and untreated CNS mets, we think we have a compelling story to bring to physicians. We’re working very hard out there and also ensuring that we’ll have unrestricted access. So, we’ve also engaged on the payer front and ensure that we’ve actually been able to reach out to almost 90% of covered lives and had great build engagement with the payers to ensure that we can bring that aggressive gain access to it in an affordable fashion as soon as possible and as soon as we’re approved. So very positive today.
And I would add on to that Ben has done an outstanding job of bringing on board a commercial organization. As I mentioned we’re north of 100 people out there customer-facing right now with sales market access, medical affairs and so on.
And all of us around the table who’ve been doing this a long time and it’s a very impressive organization that we have that’s out there interacting with customers. And they know lung cancer, they know targeted oncology, they know these physicians well. They know the clinics at a local level well. So the people I would say are going to be the real secret sauce in addition to the profile that we have in that adagrasib.
Operator
We’ll take our next question from the line of Yigal Nochomovitz with Citi. Please go ahead. Your line is now open.
Yigal Nicomovitz
Hi. Thank you very much for taking my question. I’m curious regarding your thoughts on the differentiating properties for adagrasib at the MedChem level versus how it would behave differently from sotorasib from a tax perspective when combined with pembro. Obviously, the molecules of a lot of structural overlap, but there are also some important differences when you compare the two? Thank you.
David Meek
James, I would say this is a…
Jamie Christensen
Hi, Yigal. This is Jamie. So I think when you look at adagrasib and sotorasib — there are a few key differences. Although they share part of the same core chemotype, lot of the polar surface area and other characteristics are a bit different. And the other difference is really in the reactivity of the molecules when you look at KI and KNF. So one difference for adagrasib relative to sotorasib is it’s reactivity.
You know, we’ve kind of tuned down electric velocity of adagrasib which results in decreased binding to other system containing proteins and reduced propensity for off-target effect. With regard to other physiochemical properties, one might notice some of the differences in pharmacokinetics.
For example, sotorasib has a high peak to trough ratio when administered once a day and essentially it clears out of the system once a day. So that — seemed is quite different. And adagrasib only changes 7% within the interval. And that’s really related to the high tissue distribution and kind of physiochemical properties of the drug.
And this reduced Cmax to Cmin ratio may also allow us to avoid certain off targets that may be achieved at very high concentrations. So the drug really never hits a high Cmax relative to the Cmin. You know, what might be different in terms of the toxicity from a target perspective I think is an unknown but at least those two kind of theoreticals on the physiochemical property side could be a key difference.
Operator
We’ll take our next question from the line of Mike Ulz with Morgan Stanley. Please go ahead. Your line is open.
Mike Ulz
Hi, guys. Thanks for taking the question. Maybe a follow-up just on the adagrasib formulation. So you’re planning to launch with the tablet but just curious how that might look in the label. Do you expect to have any tablet data in the label like for example on safety, or is that something that might get adjusted at a later point in time? Thanks.
David Meek
Mike, I think, it’s a little early to be having that conversation about what will be in the label the tablet formulation. So I think we’ll punt on that one as we get a little bit closer to the PDUFA date.
Operator
We’ll take our next question from the line of Jason Gerberry at Bank of America. Please go ahead. Your line is now open.
Jason Gerberry
Hi, good afternoon, good evening, everyone. This was [indiscernible] on for Jason. Thanks for taking my question. Curious, when you share the other clinical data including the bringing the data with the FDA. I’m curious in what context do you think the bring the past data might play a role in the NDA or the label. And in terms of what might ultimately make it to the label, if I recall correctly RECIST 1.1 was sort of the standard for sort of all these intracranial owners including some of the other to oncology drugs. So I’m curious do you have sort of the state, the similar CNS data in RECIST 1.1 how does that look compared to the data you have presented previously at ASCO. Thank you.
David Meek
So I’ll start regarding the labeling. I feel back to my previous reply to Mike. It’s a little bit early to talk about what’s going to be in the label or not. The brain metastatic data has been shared with the agency. So they have all of that information. We think in totality when we look at the risk benefit profile it’s certainly a benefit for the patients to have that impact on the brain mets patients.
So we that’s a good thing. They have it. We’ll see what happens over time as we move closer to the approvability. I would say it’s not just having it in the label. And ultimately we’ll get in the label at some point in time for sure. So let’s do what happens with the approval. But also it’s important for guidelines. So we’ll work on NCCN guidelines company listing and so on. That’s also very important along with the publications of the data.
Jamie Christensen
Yes. This is Jamie. Just two quick things to add. So just following up on David’s comment on risk benefit profile. This is part of a package that we’ve submitted that I think it should be recognized that with a drug on the market, a first time presented activity in CNS mets is unique to the class. So it would be part of a favorable overall risk benefit picture, especially in consideration that this would be the second drug to the market.
I also caught a question and then they’re about RECIST 1.1 or intracranial resist. And just to say we’ve looked at multiple ways of looking at the activity of adagrasib in brain metastases and the IC resistance is very similar to the [indiscernible] outcome. So we wouldn’t expect a difference via methodology for determining response.
Operator
We’ll take our next question from Maury Raycroft with Jefferies. Please go ahead. Your line is now open.
Maury Raycroft
Hi. thanks for taking my question. You saw a similar overall response rate for patients in the registrational trial stratified by TPS score. Are you commenting on what the difference is in duration of response or PFS were based on TPS? And how are you currently thinking about combo versus monotherapy for TPS low patients?
Jamie Christensen
Hi. This is Jamie. So yes, I think you’re referring to the data presented at ASCO in [indiscernible] where we look by the three TPS strata and response rate, and would say that there’s a minor difference in response rate. We’ve also looked at outcomes by other measures PFS OS duration response, I would say we had not presented that data yet, but I wouldn’t expect large differences there based on our experience thus far. We will be more replete in our characterization of outcomes by TPS Strata in the future.
With regard to how we might develop the drug in different settings. One thing we’ve talked about previously is the strong unmet medical need and the TPS less than one KRAS G12C population. And here it’s recognized that the outcomes on chemoimmunotherapy are fairly poor.
Let’s note in KEYNOTE-189 of the overall response rate was 32% and the PFS and OS was a bit lower, mean that lower bar is viewed distinctly by the regulatory agencies and that there’s a chance that adagrasib would work as a monotherapy in that setting to demonstrate response rate and durability greater than what might be anticipated for chemoimmunotherapy. So we have a study ongoing in the TPS less than one is a model therapy.
And then secondly, the STK11 subpopulation where we’ve seen signs of clinical activity. And again, poor outcomes on chemoimmunotherapy presented by Memorial Sloan Kettering Dana-Farber, MD Anderson indicating the response rates are really in the low-20s there. And that’s a place where we believe we can observe a higher response rate and that study is ongoing. So we’ll be talking about it when the data is mature.
Just to say then when we look across TPS strata, we’re interested in all strata and we believe we can devise a combination strategy in addition to what I just mentioned for the monotherapy in the defined subset, the overall combination strategy would cover all of the strata. And just to note here that slightly different study designs may be required for a different strata. These are all part of our overall strategy for the program.
Operator
We’ll take our next question from Jay Olson with Oppenheimer. Please go ahead. Your line is now open.
Jay Olson
Hey. Thank you for taking the question. Is there any read across or other observations you’ll be looking for in the data for the combination of Lumicrast with Rev Med Ship 2 at World Lung. And then, as a related follow-up, you’ve indicated that adagrasib will be administered concurrently in combination with pembro. So, can you comment on the pros and cons of parallel versus sequential administration in adagrasib combinations such as pembro or SHP2 or any other combos? Thank you.
David Meek
So it’s one of the things we’re looking at. We’ve looked at pre-clinically as well in terms of the co-administration versus sequential. And so far at least there hasn’t been any clear advantage for sequential approaches versus co-administration.
I think you asked about SHP2. We do have a study that’s now ongoing, but it’s an early stage. So we don’t — we haven’t reported the data of the same SHP2 combination with adagrasib. So that data would come out sometime next year. But we are interested in the mechanism. We believe that the SHP2 combination and certainly the preclinical data is supported of doing that combination. So I think it’s just a matter of seeing how that clinical data develops.
And then in terms of the IO combinations we think that the pembrolizumab co-administration is the best way to go and is most consistent with standard of care in clinical practice so that that’s the best approach. And we don’t have any reason to think that sequential would be superior to that. So it just makes it more simple and Ben any comment on that.
Ben Hickey
I would just say, yes, the fee has been unanimous around that. Our medical affairs team has held numerous advisory boards around that and that’s the way they treat today and the way they’d like to treat in the future. So concurrent pembro, so approach.
David Meek
Chemo sparing targeted agent would also be good. So, having adagrasib plus pembro concurrently that’s something that would be very keen on for patients with a KRAS G12C mutation.
Jamie Christensen
And then maybe just to add one point from a scientific perspective. So, concurrent administration with immunotherapy, I think one thing we’ve been able to recognize through mechanistic studies both in preclinical and clinical studies is the impact of adagrasib on antigen presentation. So, the upper relation of MHC-dependent antigen presentation.
The second is a fairly acute effect on some intratumoral cytokines that result in the uptake of T cells expansion of T cells reduction of immunosuppressive cells. And you can see there we’re having the KRAS inhibitor on board at a comparable time to the immunotherapy agent would be desirable. I think same story will SHP2 functions at least in part by shifting KRAS into its inactive state desirable to have those two drugs administered concurrently and that’s currently our focus for both of those areas.
Operator
This concludes today’s question-and-answer session. David Meek, I’d like to turn the conference back over to you for any additional closing remarks.
David Meek
Thank you Daniel, and thank you everybody for joining us this afternoon. We appreciate your interest in Mirati, and we look forward to sharing additional updates with you in the very near future.
Operator
This concludes today’s call. Thank you for your participation. You may now disconnect.
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