Q2 2022 Mirati Therapeutics Inc Earnings Call

[music].

Operator: Good afternoon, and welcome to the Mirati Therapeutics second quarter 2022 earnings call.

Good afternoon, and welcome to the Marathi Therapeutics second quarter 2022 earnings call. My name is Daniel and I'll 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. If you would like to ask a question. During this time.

Operator: My name is Danielle, and I will be the operator for today's call.

Operator: All lines have been placed on mute to prevent any background noise.

Operator: After the conclusion of the speaker's prepared remarks, there will be a question and answer, session.

Operator: If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad.

Simply press Star followed by the number one on your telephone keypad. If you would like to withdraw your question press. The pound key it is now my pleasure to introduce right Ryan AC Vice President of corporate Affairs at Marathi Ryan. Please go ahead.

Operator: If you would like to withdraw your question,

Operator: press the pound key.

Operator: It is now my pleasure to introduce Ryan Acy, Vice President of Corporate

Thank you Danielle and welcome everyone to this afternoons call joining me on the call today are David <unk>, Chief Executive Officer, Dr. Chuck Baum, President founder and head of research and development Laurie Stelzer Chief.

Operator: Affairs at Mirati.

Ryan Acy: Ryan, please go ahead.

Chief Financial Officer, Dr. Jamey, Christiansen, Moroney scientific officer, and Ben Hickey brought as 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 involved with the U S Securities and Exchange Commission. This after.

We released financial results for the quarter ended June 32022, and recent corporate updates.

This press releases baseball in the investors section of our website at variety dot com with that David ill turn the call over to you.

Ryan Acy: Thank you, Danielle, and welcome everyone

Thank you, Brian and good afternoon, everyone on this afternoon'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 about aggressive this year, Chuck will share an update on our R&D programs.

Laurie our recently appointed CFO will summarize our financial results.

Ryan Acy: to this afternoon's call.

Then provide closing remarks before we open the line for questions. So let's get started.

Ryan Acy: Joining me on the call today are David Meek, Mirati's Chief Executive

Second quarter was a very productive and important one for variety and we've a lot to be excited about we made significant progress towards achieving a number of important milestones and strategic priorities in the second quarter.

Coding presenting our latest data are not aggressive, but <unk> and building out our commercial capabilities in advance of its launch.

Ryan Acy: Officer, Dr. Chuck Baum, Mirati's President, Founder, and Head of Research and Development,

At <unk>, we shared several significant out of basketball and Chuck will touch on the specifics.

Ryan Acy: and Lori Stelzer, Mirati's Chief Financial Officer.

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.

Ryan Acy: Dr. Jamie Christensen, Mirati's Chief

Ryan Acy: Scientific Officer, and Ben Hickey, Mirati's Chief Commercial Officer, are also with us and

<unk> CNS penetration and combinability about aggressive with concurrent number listen up.

Ryan Acy: will be available for the Q&A portion of the call.

Position us very well for both near and long term commercial success.

Our results give us confidence in our ability to secure a U S approval and execute a strong commercial launch Nevada granted in second line and beyond non small cell lung cancer, which is a key priority for the company.

We are very comfortable competing in the K Ras Jean Charles C inhibitor market, especially in the tablet formulation.

Our ongoing interactions with FDA are productive and we continue to collaborate closely and effectively to the review of the autographs a 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.

T. His voice no major safety issue to date or expectations for new studies prior to approval.

As such we are preparing for the approval of the NDA with the tablet formulation and are finalizing our commercial readiness plans.

Ryan Acy: 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 U.S. Securities and Exchange Commission.

Ryan Acy: This afternoon, we released financial results for the quarter, end of June 30, 2022, and recent corporate updates.

As a reminder, our <unk> date is December 14th, but we won't be ready to go if approval comes before then.

We recently hired the remainder of greater than 100 person customer facing U S. Field Force I believe we have the talent needed to drive a successful commercial launch. In addition, we built out our marketing market access patient support and medical affairs capabilities and now have in place all the components of this.

Ryan Acy: This press release is available on the

Accessible commercial organization necessary to execute our commercial strategies.

Our commercial team will be fully trained and launched for any of the U S. By the end of the third quarter.

Ryan Acy: investor section of our website at mirati.com.

Sounds like 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 a variety.

David Meek: With that, David, I'll turn the call over to you.

David Meek: Thank you, Ryan, and good afternoon, everyone.

David Meek: On this afternoon's call, I'll provide an update on key developments since our last earnings call, including steps we are taking to prepare for a potential commercial launch of Atagrassi this year.

Our commercial strategy is built on several pillars that we believe will enable us to be successful first at aggressive differentiating molecular profile and 24 hour half life have enabled us to generate meaningful clinical data and accordingly, the recently presented greater than 30% overall response rates and non.

Small cell lung cancer patients with active brain metastases and the longest median overall survival data to date of greater than 14 months and our pooled analysis.

Second we've been able to attract top talent across biotech pharma and health care 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 <unk> eligible patients and response, our field teams are working to assist and market development activities to improve both patient access and outcomes third we have purpose built our commercialization teams with a singular focus on that.

Aggressive.

We have built this team with an optimized design 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 probe.

Graham.

In summary, we're very excited about the potential launch and the opportunity to deliver out of grass, it and make a positive impact on patients living with cancer.

Beyond the U S. We completed the submission of that aggressive marketing authorization application for the treatment of patients with non small cell lung cancer harboring. The <unk> mutation, who have received at least one prior systemic therapy to the European Medicines agency.

Submission is an important step in bringing us closer to possibly expanding the availability about aggressive 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 <unk> as our CFO , bringing with her and a valuable skill set acquired over her 25 year career in the biopharmaceutical industry, including a wealth of finance expertise and strategic insight.

He has considerable experience navigating the needs of our company transitioning from a research and development stage to a commercial stage, which will be beneficial as we prepare for the commercial launch of that aggressive in the U S and finalize our strategy outside of the U S. We are very fortunate to bring Lori on at this pivotal time in our history.

And finally, we continue to be in a strong financial position, which enables us to execute on our strategy and provides us with the flexibility to prudently invest for success across our targeted oncology pipeline and prepare for a successful and aggressive launch pending FDA approval later this year.

David Meek: Chuck will share an update on our R&D programs, and Lori, our recently appointed CFO, will summarize our financial results.

That I will turn the call over to Chuck for a clinical update.

David Meek: I'll then provide closing remarks before we open the line for questions.

Thank you David I'll.

I'll begin with an aggressive.

David Meek: So let's get started.

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.

David Meek: The second quarter was a very productive and important one for Mirati, and we have 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 Atagrassi at ASCO and building out our commercial capabilities in advance of its launch.

We had a significant presence at wesco.

Where we shared positive at aggressive data in patients with <unk> mutations living with non small cell lung cancer across lines of therapy.

David Meek: At ASCO, we shared several significant Atagrassi updates, 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 CNS penetration and combinability of Atagrassi with concurrent pembrolizumab, and position us very well for both near and long-term commercial success.

These ESCO updates included.

Positive results from the registration, enabling phase II cohort of the Crystal one study evaluating <unk>.

David Meek: Our results give us confidence in our ability to secure U.S. approval and execute a strong commercial launch of Atagrassi in second line and beyond non-small cell lung cancer, which is a key priority for the company.

600 milligrams administered twice daily in patients with non small cell lung cancer harboring the <unk> mutation, who have received at least one prior systemic therapy.

David Meek: We are very comfortable competing in the KRES G12C inhibitor market, especially in the tablet formulation.

David Meek: Our ongoing interactions with FDA are productive, and we continue to collaborate closely and effectively through the review of the Atagrassi new drug application.

David Meek: 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.

David Meek: As such, we are preparing for the approval of the NDA with the tablet formulation and are finalizing our commercial readiness plan.

These positive results were also reported concurrently in the New England Journal of Medicine publication.

David Meek: As a reminder, our PDUFA date is December 14th, but we will be ready to go if approval comes before then. We recently hired the remainder of greater, than 100-person customer-facing U.S. field force and believe we have the talent needed to drive a successful commercial launch. In addition, we 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.

We also presented compelling results from a prospective analysis of the phase one b cohort of the Crystal one study demonstrating intracranial responses too aggressive in patients with <unk> mutated non small cell lung cancer with active and untreated.

Cerebral central nervous system metastasis.

<unk> is the first <unk> 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 that aggressive with <unk> and <unk>.

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 <unk> 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 a tablet formulation at a future medical meeting.

Feedback from key opinion leaders investigators and oncologists on the profile of that aggressive has been overwhelmingly positive.

Crystal 12, a randomized phase III confirmatory study in previously treated non small cell lung cancer patients with <unk> mutation.

<unk> to enroll well worldwide and is on track to complete enrollment in the first half of 2023.

Mario do you expect it to provide key updates in the second half of 2022 and 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 <unk> and SDK 11, co mutations as well as <unk> mutated patients with TPS score less than 1%.

We expect to share initial data from these subpopulations in 2023.

Our initial and most advanced and aggressive combination of bridge in first line non small cell lung cancer is the concurrent dosing of an aggressive tablets at 400 milligrams twice daily with full dose <unk>.

Our phase two crystal seven studies evaluating this combination is enrolling well, particularly following our initial update from this study at ESCO.

We plan to share more mature data with a larger number of patients in the fourth quarter of 2022.

We continue to evaluate.

To evaluate autographs and 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 advisors, which we all are aligned 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 <unk> mutations.

We expect to provide more mature data in late line colorectal cancer at the ESMO Congress conference in September .

We also expect to provide additional clarity on a possible pathway for accelerated approval of <unk> in late line colorectal cancer later this year.

Full approval will be based on our ongoing okay.

Crystal 10 randomized phase III registration study in second line <unk>.

The rectal cancer patients.

In addition, we are continuing to enroll patients with other solid tumors that carry the <unk> mutation, including pancreatic <unk>.

Cholangiocarcinoma non.

Non colorectal cancer gastrointestinal.

And other solid tumors based on our positive data presented earlier this year at the <unk> Gi conference.

At aggressive has the potential to treat multiple tumor types across a range of cancers and we believe this could be another important differentiating characteristic of our program.

Shifting to the center of that NIM.

<unk> is being studied in the Registrational phase III 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 interim analysis could be the basis of full approval in the U S and Europe with regulatory filings in both markets being submitted by the middle of next year.

<unk> has the potential to treat a large number of patients.

Since there are approximately 70000 patients with second or third line non squamous non small cell lung cancer in the U S and Europe .

Finally, I am pleased to announce that we've completed the submission of the investigational new drug application for <unk> <unk> 902.

<unk> is a selective <unk> inhibitor that shifts kers into its inactive state.

Enhancing the activity of that aggressive by addressing.

Feedback reactivation and intrinsic and acquired resistance to <unk> inhibitors.

This agent has the potential to complement other agents in the pipeline and <unk> and impact on K Ras mutant cancers across K Ras mutation types.

We expect to initiate clinical development with our <unk> 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 off to Laurie.

Thank you Chuck.

First let me begin by saying that I've now had 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.

From a financial management perspective, we will be vigilant and utilizing our capital in a disciplined manner to ensure we remain able to advance our pipeline invest in innovation and in fact and effectively launch products to drive sustainable long term growth.

Research and development expenses for the second quarter of 2022 or $128 3 million.

Compared to $134 6 million for the same period in 2021.

The decrease is primarily due to allografts and 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 head count to support our growing pipeline.

General and administrative expenses for the second quarter of 2022, or $54 2 million compared to $29 6 million for the same period in 2021.

The increase was primarily due to an increase in commercial readiness costs in preparation for a potential product lines and 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 cost to support the.

<unk>.

Net loss for the second quarter of 2022 was $176 4 million or.

Our $3 18 per share basic and diluted compared to a net loss of $166 4 million.

Our $3 23 per share basic and diluted for the same period in 2021.

We 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 2020, Q financial result, and with that David I'll hand, it back over to you.

Thank you Brian Chuck for your updates as you have heard today, we made considerable progress in the second quarter advanced our clinical pipeline and advancing our commercial efforts to be fully launch ready in the U S. 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.

David Meek: Our commercial team will be fully trained and launch ready, in the U.S. by the end of the third quarter.

David Meek: 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.

David Meek: Our commercial strategy is built on several pillars, that we believe will enable us to be successful.

David Meek: First, adegressive 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 meeting overall survival data to date of greater than 14 months in our pooled analysis.

David Meek: 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.

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 a tremendous value creation and meaningful operational and commercial synergies.

David Meek: There are opportunities to increase both testing, and identification of KRES G12C eligible patients. In response, our field teams are working to assist, in market development activities to improve both patient access and outcomes.

David Meek: Third, we have purpose-built our commercialization team, with a singular focus on adegressive. We have built this team with an optimized design and focus, on integration, digitization, and speed of execution across functions.

David Meek: 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.

David Meek: In summary, we're very excited about the potential launch, and the opportunity to deliver adegressive and make a positive impact on patients living with cancer.

David Meek: Beyond the U.S., we completed a submission, of adegressive marketing authorization application for the treatment of patients with non-small-cell lung cancer harboring the KRES G12C mutation who have received at least one prior systemic therapy to the European Medicines Agency.

We expect targeted oncology to play an important role in the fight against cancer, we have generated compelling clinical data showing <unk> inhibition has potential well beyond the second line setting in non small cell lung cancer is that proves out we will be able to help many people in need and create considerable value for the patients.

David Meek: This submission is an important step in bringing us closer, to possibly expanding the availability of adegressive to patients in the European Union.

David Meek: From a management team perspective, we made an important addition to our leadership team in the second quarter.

David Meek: Lori Stelzer joined Maradi as our CFO, 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. Lori 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 adegressive in the U.S. and finalize our strategy outside of the U.S. We are very fortunate to bring Lori, on at this pivotal time in our history.

David Meek: And finally, we continue to be in a strong financial position, which enables us to execute on our strategy and provides us with the flexibility to prudently invest for success across our target oncology pipeline and prepare for a successful ad aggressive launch, pending FDA approval later this year.

<unk> and other stakeholders that have supported a variety in that endeavor. It.

David Meek: With that, I'll turn the call over to Chuck

It is a privilege to lead a company whose team never loses sight of why we come to work each day.

Chuck Baum: for a clinical update.

And Danielle I'll turn it over to you we're ready to take questions.

Chuck Baum: Thank you, David.

Thank you I would like to remind everyone that if you'd like to ask a question. During this time simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question press the pound key.

Chuck Baum: I'll begin with ad aggressive.

Chuck Baum: 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.

Ask that you limit yourself to one question along with a related follow up.

And we will take our first question from the line of Michael Smith with Guggenheim. Please go ahead. Your line is now open hey, guys.

Chuck Baum: And we remain confident in the approval of the NDA this year.

Chuck Baum: We had a significant presence at ASCO, where we shared positive ad 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-enabling phase two cohort of the CRYSTAL1 study, evaluating ad aggressive 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.

Chuck Baum: We also presented compelling results, from a prospective analysis of the phase one B cohort of the CRYSTAL1 study, demonstrating intracranial responses to ad aggressive in patients with KRAS G12C mutated non-small-cell lung cancer with active and untreated cerebral central nervous system metastasis. Ad aggressive is the first KRAS G12C inhibitor, to demonstrate substantial clinical activity in this large and poorly served patient population.

Guys. Thanks for taking my questions I.

I had a question on your Keytruda combination study about a grass had where we've seen some very interesting early data at <unk>.

The median follow up at the time was the only two months.

Yes.

No questions about this.

Safety profile.

PD, one inhibitor combinations, but more follow up and I guess now that it's been.

Somewhat time since then and I was wondering whether your confidence level with respect to the Tolerability profile.

As more time has passed since the ESCO.

Data presentation.

So Michael it's David I'll turn it over to Chuck.

Chuck Baum: In addition, we showed encouraging early results, demonstrating the feasibility of combining ad aggressive with tumbrolizumab in first-line non-small-cell lung cancer patients.

The data we presented at <unk>, Yes. It was early data and the median time was two one months of timeline. The combination therapy. So we realize that at the time, we're continuing all of the trial.

Chuck Baum: These first-line results provide meaningful context, and clarity as we aggressively advance our first-line non-small-cell lung cancer strategy.

Chuck Baum: 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 the tablet formulation at a future medical meeting.

Chuck Baum: Feedback from key opinion leaders, investigators, and oncologists on the profile of ad aggressive has been overwhelmingly positive.

Chuck Baum: CRYSTAL-12, a randomized phase three confirmatory study, in previously treated non-small-cell lung cancer patients with a KRAS G12C mutation continues to enroll well worldwide and is on track to complete enrollment in the first half of 2023.

Chuck Baum: 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 multi-prong, development approach. This includes providing additional clarity on a possible regulatory pathway for accelerated approval as a single agent in patients harboring KRES-G12c and, STK11 co-mutations, as well as KRES-G12c mutated patients with PPS score of less than 1%.

Chuck Baum: We expect to share initial data from these subpopulations in 2023.

Chuck Baum: Our initial and most advanced adagressive combination approach in first line non-small, cell lung cancer is the concurrent dosing of adagressive tablets at 400 milligram twice daily with full dose Pembrolizumab.

Chuck Baum: Our phase two CRYSTAL7 study evaluating this combination is enrolling well, particularly following our initial update from this study at ASCO.

We feel though based on that trial as well as the earlier seven patients we have the wrong drug for more than a year at that point at <unk>.

Chuck Baum: We plan to share more mature data with a larger number of patients in the fourth quarter of 2022.

Chuck Baum: We continue to evaluate or have plans to evaluate adagressive in various other first line combinations, including targeted and chemotherapy based approaches.

We're building.

A nice database here of patients being on drug for a good amount of time that will give an update later this year on where we are with the crystal seven trial, but we're encouraged by what we saw and we're anxious to get an update later.

Chuck Baum: We are finalizing our first line non-small cell lung cancer strategy with our scientific advisors, which we'll align with the FDA and provide an update later this year.

Chuck Baum: Beyond lung cancer, we are advancing enrollment of, patients with a variety of cancers driven by KRES-G12c mutations.

Chuck Baum: We expect to provide more mature data in late line colorectal cancer at the ESMO conference, in September.

Yes.

Reinforce that by saying that.

Honestly in our previous experience with combinations of targeted agents.

And I owe that oftentimes the adverse events occur in the early cycle.

So that does give you some initial read at least on Tolerability of the combination.

Also.

As David said, we did have the seven patients that were treated for over a year, which gives you an idea of.

Chuck Baum: We also expect to provide additional clarity on a possible pathway for accelerated approval of adagressive in late line colorectal cancer later this year.

Chuck Baum: Full approval will be based on our ongoing CRYSTAL10 randomized phase three registration study in second line colorectal cancer patients. In addition, we are continuing to enroll patients with other solid tumors that carry the KRES-G12c mutation, including pancreatic, cholangiocarcinoma, non-colorectal cancer gastrointestinal, and other solid tumors based on our positive data presented earlier this year at the ESCO GI conference.

Chuck Baum: Adagressive 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.

Chuck Baum: Shifting to citrovapnin, which is being studied in a registrational phase three study called SAFIRE, 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 SAFIRE 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.

The tolerability of the combination as well over time and there were patients up to six months on treatment even in a.

Chuck Baum: If positive, this interim analysis could be the basis of full approval in the U.S. and Europe, with regulatory filings in both markets being submitted by the middle of next year.

Chuck Baum: Citratinib 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 U.S. and Europe.

Chuck Baum: Finally, I'm pleased to announce that we've completed the submission of the investigational new drug application for MRTx0902. 0902 is a selective SOX1 inhibitor that shifts KRAS into its inactive state. Potentially enhancing the activity of Adagrassiv by addressing KRAS feedback reactivation and intrinsic and acquired resistance to KRAS inhibitors. This agent has the potential to complement other agents in the Mirati pipeline and exert an impact on KRAS mutant cancers across KRAS mutation types.

Chuck Baum: 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.

Chuck Baum: We expect to initiate clinical development with our SOX1 program before year end.

And the data we presented the data updated for our case seven even though the median was two months so.

So far we're feeling confident in.

Looking forward to presenting more data later this year.

Chuck Baum: With that, I'll hand it off to Lori.

We will take our next question from Tyler Van Buren with Cowen. Please go ahead. Your line is open.

Lori Stelzer: Thank you, Chuck.

Lori Stelzer: First, let me begin by saying that I've now had 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.

Hey, guys. Good afternoon, congrats on the progress and thanks very much for taking the question Rick.

Lori Stelzer: 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.

Lori Stelzer: 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 adagrassive manufacturing costs incurred in Q2 2021 ahead of our NDA, which is partially offset by an increase in salaries and other employee-related expense, including share-based compensation expense associated with an increase in headcount to support our growing pipeline.

Lori Stelzer: 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.

Lori Stelzer: 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.

Regarding the ongoing autographs the regulatory review I appreciate the update.

Can you confirm that the final phase II data the CNS data and the tablet data have all been submitted them when they were submitted.

Related follow up.

<unk> will discuss voted yet or what are the outstanding items in the review.

So Tyler.

Yes, we can confirm deal with the <unk>.

This data was shared at <unk> that information all the clinical data has been shared with the agency.

It's important to do that so that data was shared with agency. They have everything that we have regard to the tablet formulation as well and that's why we've talked about we are preparing for an approval at our approval with it with a 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 is constructive, but it's active and ongoing with the agencies as we move along in the NDA process.

Okay.

Lori Stelzer: Please see our press release from earlier this afternoon for additional details about our, second quarter 2022 financial results.

We will take our next question from the line of Gena Wang with Barclays. Please go ahead. Your line is now open.

Lori Stelzer: And with that, David, I'll hand it back over to you.

David Meek: Thank you, Lorraine and Chuck, for your updates.

David Meek: 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 launch-ready in the U.S. by the end of the third quarter.

David Meek: I'll close our prepared remarks with a brief comment about the depth and breadth of the company and portfolio we are building.

David Meek: We have the products, capabilities, people, and capital needed to compete and succeed.

David Meek: Our pipeline spans numerous targets and tumor types and positions as well for tremendous value creation and meaningful operational and commercial synergies.

This is krisztina on for Gena, Thank you for taking our questions.

David Meek: We expect target oncology to play an important role in the fight against cancer.

David Meek: We have generated compelling clinical data showing KRES 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.

David Meek: It is a privilege to lead a company whose team never loses sight of why we come to work each day.

Our first question was on the K 12, plus.

Metairie trial for lung.

Remember correctly. The initial plan was to NGO 450 patients and I think the powering assumptions disclosed at <unk> last year.

The trial was sufficiently powered to detect a treatment effect of PFS and OS at an alpha of zero point Zero Fi.

But now that that and Goldman 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.

Operator: And, Danielle, I'll turn it over to you.

So yes.

Design of the trial was changed which is the reason for the change in numbers.

So that is the <unk>.

Primary endpoint was is now.

On PFS and so with PFS as the primary end point 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 has enhanced significantly enhances enrollment and when you do that.

It could potentially compromise the overall survival. So that's the rationale for the design but.

Operator: We're

In terms of the patient numbers.

We're still having similar power.

To detect the difference.

But that's going to be on PFS.

Okay, great. Thank you so much and the second question. We had quickly was on the tablet versus capture capsule formulation. We know you previously noted improvement with the tablet formulation, but I was wondering can you comment on how much improvement you saw for the Gi Tox.

Yes, we haven't gone into this specifics we will when we have more experience and have more patients I can say that the difference clinically and related from the ongoing trials by our investigators is in the gastrointestinal so things like that.

This.

Obviously vomiting.

Those are the primary.

Differences.

We don't have the exact quantitative at this time, but we will presented later when we have more data.

Operator: ready to take questions.

We will take our next question from Jonathan Miller with Evercore. Please go ahead. Your line is now open.

Operator: Thank you.

Operator: I'd like to remind everyone that if you'd like to ask a question during this time, simply press star followed by the number one on your telephone keypad.

Operator: If you'd like to withdraw your question, press the pound key.

Operator: We do ask that you limit yourself to one question along with a related follow-up.

Hi, guys. Thanks for taking the 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 potentially Registrational study at this point.

Operator: And we'll take our first question

Operator: from the line of Michael Smith with Guggenheim.

Michael Smith: Please go ahead.

Michael Smith: Your line is now open.

And I know you said you would give some clarity on what that path would be later this year, but.

What are we waiting for it to get that clarity at this point.

Okay.

As the trial matures.

Have more patient numbers longer time on the combination therapy.

It's important and then importantly, we want to have a conversation with the FDA as we as we craft together.

Registration trial, so thats, all going to take a little bit of time and as soon as we're ready for that will come we will let you guys know, but we expect that to be by the end of this year.

As the trial advances have a conversation with our scientific advisors as well as the agency of before rolling out of that trial.

But.

We're encouraged by it Chuck anything you'd like to add on.

Of course, the efficacy in terms of response rate and early reads on PFS will be part of the evaluation that triggering a phase III.

Randomized studies, so that takes a little bit longer as you know.

Uh huh.

Tolerability profile is really the first thing that you start to see and then looking at the efficacy is what we're doing.

As we get closer to later this year to getting ready to start a phase III program.

Yes. This is Jamie I think one thing I'd like to add is that the add up plus Pembroke combination will be our first foot forward just to note that we have additional activities ongoing we believe chemo immunotherapy may be an important combination and some first line settings, where we will be evaluating that.

Secondly, I think we have an increasing understanding of how <unk> signals and with some of the feedback pathways are and what might ultimately cause resistance. So a number of that targeted combination strategies are ongoing starting in the second line lung cancer space, but should they will compelling. There are there is an option to bring those up to earlier lines of therapy either as double.

That's our even in combination with immunotherapy so.

This is really a first foot forward with additional work ongoing.

We will take our next question from Savi <unk> Richter with Goldman Sachs. Please go ahead. Your line is now open.

Michael Smith: Hey, guys.

Michael Smith: Thanks for taking my questions.

Good afternoon. Thanks for taking the question is Andrea on for solving maybe a question.

Michael Smith: I had a question on your Keytruda combination study, of adagrassive where we've seen some very interesting early data at ASCO.

On the competitive landscape with Amgen, having their first keytruda combo data that at the end at World lung just curious what you'll be focused on to understand differentiation in your approach and then as a follow up to that can you just remind us on your thinking of sequential or concurrent common memorial approaches and Mechanistically is there reason to believe.

Approach might be more efficacious than the other.

So yes, it's David.

We're going to wait to see the data this weekend like everybody else. So we'll see what is released by Amgen at World lung and we'll take it from there, but I would say you know what we're looking for is for us to release that data as Chuck just mentioned you want to see immediate.

Michael Smith: And I think the median follow-up at the time was only two months. You know, there are some general questions about the safety profile of PD-1 inhibitor combinations with more follow-up.

Immediate tolerability tolerability over time with with any combination regimen. So that's what we're looking for then ultimately you want to add.

Efficacy and that 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 I think the only other thing I'd add is that we believe pretty strongly that the co administration of aggressive with <unk> is going to be the most.

Fueling to investigators and we think.

We will be the most successful way to combine the two so that's what we want and that's why we're focusing on that approach.

We will see what David said, what Amgen presents and that'll give us a better idea of where theyre going.

As we explore additional approaches as well.

And so that's why we're really careful to say and deliberate to say it's.

400 milligrams twice a day about aggressive plus full dose <unk> concurrently that.

That is where we think the greatest opportunity for activity is for the patients.

Michael Smith: And I guess now that it's been some more time since then, I was wondering, you know, where your confidence level is with respect to the tolerability profile as more time has passed now since the ASCO data presentation.

We will take our next question from Ben Burnett with Stifel. Please go ahead. Your line is now open.

David Meek: So, Michael, it's David.

David Meek: And I'll turn it over to Chuck.

Hey, Thank you very much I also wanted to ask a question about the competitive landscape I guess does does the outcome of Amgen is Lula Kras confirmatory study has any impact on how you guys are thinking about the regulatory path for four out of grasp whether whether that's a successful study or not.

David Meek: You know, 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 with the trial.

So for us with our Crystal 12 trial.

Look at our registration trial that was presented at <unk> as well as our confirmatory trial. It is.

David Meek: And, you know, we feel based on that trial as well as the earlier seven patients we have that, were on 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.

David Meek: And we'll give an update later this year on where we are with the CRISPR-7 trial.

David Meek: We're encouraged by what we saw.

Patient population remember 98, 3% of our patient population in the registration trial.

<unk> patients that had followed the keynote one airline regimen, if you will and Thats also our confirmatory trial.

We look at that we think of the pooled analysis. We've also shared at <unk>. So we're pretty confident with.

With our Crystal 12 trial design and the outcomes and the trial will finish enrollment next year and we'll see what happens.

David Meek: And we're anxious to give an update later.

Chuck Baum: Yeah, I just reinforce that by saying that, you know, honestly, in our previous experience with combinations of targeted agents and IO, that oftentimes the adverse events occur in the early cycles.

Chuck Baum: So, that does give you some initial read, at least on tolerability of the combination.

Yes, 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.

Okay.

Chuck Baum: Also, as David said, we did have the seven 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 will take our next question from Andrew Berens with SBB Securities. Please go ahead. Your line is now open.

Chuck Baum: We presented the data update for a K7, even though the median was two months.

Hi, Thanks for taking my questions a couple on the ongoing 400 milligram Bic's monotherapy cohort one can you give us an idea of when that cohort started enrolling how far along it is at this point.

Chuck Baum: So, you know, so far we're feeling confident and looking forward to presenting more data later this year.

Are the patients getting tablets or capsules.

As a cohort with the FDA specifically.

Ron.

So the trial started earlier this year regarding at it to get into the details I don't think we will get into the details of the trial is actively enrolling introducing the tablet formulation at this time the patients from the afforded a milligram twice a day of the tablet formulation.

The trials up and the FDA has of course aware of the trial as they are of all of our ongoing clinical trials in the second line plus non small cell lung cancer patient population the patients with <unk> mutation, so they're aware that trial.

We will not have data for that trial until next year.

Operator: We'll take our next question from Tyler Van Buren with COIN.

We'll take our next question from the line of Evan <unk> with BMO capital markets. Please go ahead. Your line is open.

Operator: Please go ahead.

Tyler Van Buren: Your line is open.

Tyler Van Buren: Hi, guys.

Hi, guys. Thank you so much for taking my question.

Tyler Van Buren: Good afternoon.

Tyler Van Buren: Congrats on the progress, and thanks very much for taking the question.

Just.

Thinking ahead still launch now that you are second to market I guess.

David Meek: Regarding the ongoing adagrassal regulatory review, I appreciate the update.

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 youll be able to secure approval ahead of your December to do far what indications have you gotten from regulators that that may be the case. Thank you.

David Meek: Can you confirm that the final Phase 2 data, the CNS MET data, and the tablet data have, all been submitted and when they were submitted?

So I will start and bill jump in too so.

David Meek: Do those are related follow-up, have label discussions started yet, or what are the outstanding, items in the review?

We are preparing and we are.

We are preparing for a launch as early as the end of Q3. There is no guarantee that the FDA will approve as early we wanted to certainly be prepared if we are fortunate enough to be approved early so I just wanted to be clear on that.

Part of the conversation the feedback, especially at <unk> and all of US were there. We spent a significant amount of time with the community based oncologists.

David Meek: So, Tyler, yes, we can't confirm, you know, the brain meds data that was shared at ASCO, that information.

David Meek: All the clinical data has been shared with the agency.

The investigators when overall the data that was shared at <unk> and the enthusiasm level is very high regarding the totality of the clinical data that's been.

Published four at aggressive in the second line setting.

Cohort eight data was we reviewed that the response rate. The overall survival data was very compelling to physicians as CNS brain Mets data for active in untreated. This is a real differentiator in the minds of physicians anything they can do to treat those patients and you'll even control brain mentioned is a good thing for patients. So the feedback was.

Great the feedback on the lifecycle management programs that we have in place such as a combination regimen with <unk> in the frontline setting colorectal cancer. The response rates across the board were very appealing, especially to the community based oncologists, where these most of these patients are treated so overall the feedback is good it's given us confidence in.

And for Us to go to the market and we're ready to compete in the marketplace and it's got a few more points to add.

David Meek: You know, that's important we do that, so that data was shared with the agency.

Sure.

David Meek: 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 our approval with the tablet formulation.

As you know we've been on there for a while also had a number of interactions with physicians, we've actually but I'll field force to date being able to actually interact with 90% of the top hundred plans across.

David Meek: 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 MTA process.

Operator: We'll take our next question from the line of Gina Wang with Barclays.

Operator: Please go ahead.

Across the country and have just very positive feedback.

It really is around some of the differentiation obviously that the molecule has been designed for 24 hour half life and that's enabled some of the the.

Response rates and up to 14 months of overall survival without pull dataset, so coupled with the CNS data in the active and untreated CNS Mets. We think we have a compelling story to bring to physicians working very hard out there.

And also ensuring that we will have unrestricted access. So we've also engaged on the payer front.

Ensure that we are actually bound to reach out to almost 90% of covered lives and had great deal of engagement with the payers to ensure that we can bring on aggressive and gain access to it in an affordable fashion as soon as possible and as soon as we're approved so yeah very positive today.

To add onto that Ben has done an outstanding job of bringing onboard a commercial organization as I mentioned, we're north of 100 people out there customer facing right now with sales and market access medical affairs, and so on and all of us around the table have been doing is doing this a lot.

Time, and it's a very impressive organization that we have that's out there interacting with customers and they know they know lung cancer. They know targeted oncology. They know these physicians well they know the clinics at the local level well. So the people I would say youre going to be the real secret sauce. In addition to the <unk>.

So far though that we have with that aggressive.

Operator: Your line is now open.

We will take our next question from the line of <unk> on <unk> with Citi. Please go ahead. Your line is now open.

Hrishita: This is Hrishita for Gina.

Hrishita: Thank you for taking our questions.

Hrishita: Our first question was on the K12-2L plus confirmatory trial for lung. If I remember correctly, the initial plan was to enroll 450 patients, and I think the, covering assumptions disclosed at ASCO last year.

Hrishita: 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?

Chuck Baum: And then I have a follow-up, if I may.

Hi, Thank you very much for taking the question I'm curious regarding your thoughts on differentiating properties for eight aggressive at the med chem level versus how it would behave differently from some tariffs from a tox perspective, when combined with <unk>, obviously, the molecule to have a lot of structural overlap, but there are also some important differences when you.

Chuck Baum: So, yeah, the design of the trial was changed, which is the reason for the change in numbers. So that if the primary endpoint was, is now PFS, and so with PFS as the primary endpoint, then it was possible to decrease the overall patient number without decreasing the power to detect the difference.

Chuck Baum: So that was the rationale, and partly that was based on the fact that we were allowing, crossover since that significantly enhances enrollment, and when you do that, that, you know, could potentially compromise the overall survival.

Sure the two thank you.

Jamie I'll take.

Chuck Baum: So that's the rationale for the design, but in terms of the patient numbers, we're still, having a similar power to detect the difference, but that's going to be on PFS.

This is Jamie.

Hrishita: Okay, great.

So I think when you look at <unk> and.

Since our SAB.

A few key differences, although they share part of the same core Cana hematite.

A lot of deep our surface area and other characteristics that are a bit different and.

The other difference is really and the reactivity of the molecules when you look at <unk>. So.

One difference for <unk> relative to solar asset as reactivity, and we've kind of tuned down the electric velocity of <unk>, which results in decreased binding other cysteine 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.

So <unk> has a high peak to trough ratio.

Administrated once a day and essentially it clears out and this is somewhat today. So the C. Max to see men is quite different and aggressive 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 C. Max to see men ratio may also allow us to avoid certain off targets that may be achieved at very high concentrations. So the drug really never hence the hiseq Max relative to the semen.

What might be different in terms of the toxicity from a target perspective, I think it's an unknown, but at least those two kind of theoretical is that necessary chemical property side could be a key difference.

We will take our next question from the line of Michael <unk> with Morgan Stanley . Please go ahead. Your line is now open.

Yeah, Hey, guys. Thanks for taking the question.

Hrishita: Thank you so much, and the second question we had quickly was on the tablet versus capsule, formulation.

Maybe a follow up.

Just on the AD aggressive formulation, so youre planning the launch with the tablet, but just curious how that might look in the label.

Hrishita: We know you previously noted improvement with the tablet formulation, but was wondering, Yeah, we haven't gone into the specifics.

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.

Alright.

I think it's a little early to be having that conversation about what will be in the label with the tablet formulation. So I think we will.

I'll punt on that one as we get a little bit closer.

To the <unk> date.

Hrishita: We will when we have more experience and have more patients.

Take our next question is from the line of Jason at Bank of America. Please go ahead. Your line is now open.

Hrishita: I can say that the difference clinically and it was related from the ongoing trials by, our investigators is in the gastrointestinal, 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.

Operator: Please go ahead.

Hi, good afternoon, good evening everyone.

Jonathan Miller: Your line is now open.

Jonathan Miller: Hi, guys.

Jonathan Miller: Thanks for taking the question.

Chi on for Jason.

Jonathan Miller: 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?

Question.

I'm curious.

You know when you play catch Canada are there clinical data, including bringing less data with the FDA.

Curious in what context do you think.

Bring metastasis.

Bringing the package with data might play a role in the anda or the label.

And.

In terms of what might ultimately make it to the label if I recall correctly.

Just one quick one and let's start with the standard of course out of all these intracranial blog. There was some crazy oncology drug. So I'm curious do you have set up the data the stimulus DNS data in resist one one how does that look compared to the data yet.

Send that previous high school. Thank you.

Jonathan Miller: 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?

So I'll start regarding the labeling.

David Meek: I think as the trial matures, you know, we have more patient numbers, longer time on, accommodation 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, you know, we'll let you guys know, but we expect that to be by the end of this year, as the trial advances, have a conversation with our scientific advisors as well as the agency before rolling out that trial.

Back to my previous reply to Mike, It's a little bit earlier talking about what's going to be in the label or not.

Brain metastasis data has been shared with the agency. So they have all of that.

The information we think in totality when we looked at the risk benefit profile that is certainly a benefit for the patients to have that.

Impact on the brain Mets patients. So that's a good thing so they haven't.

We'll see what happens over time as we move forward move closer to the approval ability I would say, it's not just having it in the label and ultimately we will get into the label at some point in time for sure.

So, let's see what happens with the approval, but also it's important for guidelines. So we'll work on the NCC guidelines companion listing and so on that's also very important along with the publication of the data.

David Meek: But we're, you know, we're encouraged by it.

Yes. This is Jamie added 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.

I think it should be recognized that with a drug on the market.

A first time presented activity in CNS matches 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.

So Carter question in there about resist one one or inter cranial resist and just to say we've looked at multiple ways of looking at the activity of <unk> by brain metastases in the IC resistance is very similar to the MRI outcomes. So we wouldn't expect a difference methodology for determining response.

David Meek: Chuck, anything you'd like to add on?

We will take our next question from Maury Raycroft with Jefferies. Please go ahead. Your line is now open.

Chuck Baum: Just that, you know, of course, the efficacy in terms of response rate and early reads, on PFS will be part of the evaluation in triggering a Phase III randomized study, so that takes a little bit longer, as you know.

Chuck Baum: The tolerability profile is 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 III program.

Hi, Thanks for taking my question.

You saw similar overall response rate for patients in our Registrational trial stratified by TPS score are you commenting on what the differences in duration of response or PFS were based on TPS and how are you currently thinking about combo versus mono therapy for <unk> patients.

Hi, This is Jamie so, yes, I think youre, referring to the data presented at <unk> in Atlanta Journal, where we'd look by the three TPS strata in response rate and would say that Theres a minor difference in response rate. We've also looked at outcomes by other measures PFS OS duration of response.

Chuck Baum: Yeah, this is Jamie.

James Christensen: I think one thing I'd like to add is that the adipose-pembro combination will be our, first foot forward, just to note that we have additional activities ongoing.

James Christensen: We believe in chemo-immunotherapy may be an important combination, and some first-line, settings will be evaluating that.

James Christensen: Secondly, I think we have an increasing understanding of how KRES 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.

James Christensen: 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.

I would say we have not presented that data yet, but I wouldn't expect large differences there based on our experience. Thus far we will be more replete and our characterization of outcomes by TPS strata in the future.

With regard to how we might develop that drug in different settings. One thing. We've talked about previously is the strong out of my medical need in the TPS and widen <unk> population inherits recognized that the outcomes and chemo immunotherapy.

Are fairly poor.

As noted in keynote 189% overall response rate was 32% in the TPS and the PFS and OS was a bit lower.

Lower bar is viewed.

Stinker cleaned by the regulatory agencies and that Theres, a chance to add aggressively work as a mono therapy in that setting to demonstrate response rate and durability are greater that Mike what might be anticipated for chemo immunotherapy. So we have a study ongoing in the TPS lesson one as a monotherapy and then secondly, the SDK 11.

Relation, where we've seen signs of clinical activity and again poor outcomes and chemo immunotherapy presented by Memorial Sloan Kettering, Dana Farber MD Anderson and became the response rates are really in the low twenties there.

And that's a place where we believe we can observe a higher response rate and that study is ongoing so we will be talking about it when the data is mature just to say that when we look across TPS straight out we're interested in Australia, and we believe we can devise a combination strategy. In addition to what I just mentioned for the monotherapy and 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 that for the program.

We will take our next question from Jay Olson with Oppenheimer. Please go ahead. Your line is now open.

Hey, Thank you for taking the question.

Is there any read across or other observations you'll be looking for in that data for the combination of Luna kras with Red mid ship too at World lung and then as it related follow up you indicated that at aggressive will be administered concurrently in combination with <unk>. So can you comment in the pros and cons.

The parallel versus sequential administration at aggressive combinations such as Pembroke.

Our ship to or any other combos. Thank you.

So it's one of the things we're looking at we've looked at preclinical data 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 ship too. We do have a study that's now unwilling but it's at early stage that we don't we haven't reported the data.

Same ship to combination with an aggressive so that data would come out sometime next year.

But we are interested in the mechanism, we believe that the shift to combination and certainly the preclinical data is supportive 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 I O combinations, we think that the <unk> Mab Co administration is the best way to go.

And is most consistent with standard of care and clinical practice, so that that's the best approach.

We don't have any reason to think that sequential would be superior to that so it just makes it more simple than.

Ben.

Any comment.

I would just say that the feedback has been.

The unanimous around that our medical affairs team has held numerous advisory boards around that and that's the way they treat today and that's the way they want to treat in the future. So that concurrent with Pembroke is a preferred approach to have a chemo sparing targeted agent.

We'll also be goods, so having a tad aggressive plus pembroke concurrently.

That's something that wouldn't be very keen on for patients with a <unk> mutation.

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 <unk> on antigen presentation. So the upregulation of MHC dependent antigen presentation. The second is a fairly acute effect on some enter tomorrow cytokines that resulted in the uptake.

T cells expansion of T cells reduction of immunosuppressive cells and you can see there we're having the K Ras inhibitor on board at a comparable time to the.

Immunotherapy agents would be desirable I think same starting with ship to ship two functions at least in part by shifting kers into its inactive state desirable to have those two drugs administered concurrently and Thats currently our focus for both of those areas.

This.

Today's question and answer session, David May I would like to turn the conference back over to you for any additional closing remarks.

James Christensen: So, this is really a first foot forward with additional work ongoing.

Thank you Danielle and thank you everybody for joining us. This afternoon. We appreciate your interest in <unk> and we look forward to sharing additional updates with you in the very near future.

Operator: We'll take our next question from Salveen Richter with Goldman Sachs.

Operator: Please go ahead.

Operator: Your line is now open.

Mike Alls: 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?

Andrea: Good afternoon.

David Meek: Thanks.

Andrea: Thanks for taking the question.

David Meek: Mike, I think it's a little early to be having that conversation about what would be in the, label, the tablet formulation.

Operator: This concludes today's question and answer session.

Andrea: This is Andrea.

Operator: So I think we'll punt on that one as we get a little bit closer to the PDUVA date.

David Meek: David Meek, I'd like to turn the conference back over to you for any additional closing remarks.

Andrea: I'm for Salveen.

Operator: We'll take our next question from the line of Jason Gerberi at Bank of America.

David Meek: Maybe a question on the competitive landscape with Amgen having their first contributive, combo data this weekend at World Lung.

Operator: Please go ahead.

David Meek: 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 combinatorial approaches, and mechanistically, is there reason to believe that one approach might be more efficacious than the other?

Operator: Your line is now open.

David Meek: So, yes, David, I would, you know, we're going to wait to see the data this weekend like everybody else.

Tian: Hi.

David Meek: Thank you, Danielle, and thank you, everybody, for joining us this afternoon.

David Meek: So, you know, we'll see what is released by Amgen at World Lung, and we'll take it from there.

Tian: Good afternoon.

David Meek: We appreciate your interest in Mirati, and we look forward to sharing additional updates with you in the very near future.

Operator: Thank you for your participation.

This concludes today's call. Thank you for your participation you may now disconnect.

David Meek: But I would say, you know, what we're looking for, you know, for us to release that data, as Chuck just mentioned, you want to see, you know, immediate tolerability, tolerability over time with any combination regimen.

Tian: Good evening, everyone.

Operator: This concludes today's call.

David Meek: So that's what we're looking for.

Tian: This is Tian for Jason.

You may now disconnect.

David Meek: Then, ultimately, you want efficacy in that.

Tian: Thanks for taking our question.

David Meek: So that's what we'd be looking for, I think, relative to the other combinations and so on.

Tian: I'm curious.

David Meek: I think Jamie just answered that a moment ago, other strategies we'd have.

Tian: You know, when you said you had shared all the clinical data, including the brain-web, data with the FDA, I'm curious in what context do you think the brain metastasis is going bring the data might play a role in the NDA or the label.

David Meek: So, Chuck?

Tian: And, you know, in terms of, you know, what might ultimately make it to the label, if I recall correctly, you know, resist 1.1 was sort of a standard for all these intracranial, including some of the target oncology drugs.

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Chuck Baum: I think the only other thing I'd add is that we believe pretty strongly that the co-administration of ad aggressive, with temporalizumab is going to be the most appealing to investigators, and we think will be the most successful kind of way to combine the two.

Tian: So I'm curious, you know, do you have sort of the data, the similar DNS data in resist 1.1?

Chuck Baum: So that's what we want.

Tian: How does that look compared to the data that you presented previously at Haskell?

Chuck Baum: That's why we're focusing on that approach.

Tian: Thank you.

Chuck Baum: 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: So I'll start regarding the labeling.

Chuck Baum: I'd say that's why we're really careful to say and deliberate to say.

David Meek: I go back to my previous reply to Mike.

Chuck Baum: It's 400 milligrams twice a day of ad aggressive plus full-dose Pembro concurrently.

David Meek: It's a little bit earlier.

Chuck Baum: That is where we think the greatest opportunity for activity is for the patients.

David Meek: He talked about what's going to be in the label or not.

Operator: We'll take our next question from Ben Burnett with Stifle.

David Meek: The brain metastasis data has been shared with the agency, so they have all of that information.

Operator: Please go ahead.

David Meek: We think in totality, when we look at the risk-benefit profile, it's certainly a benefit for the patients to have that, you know, that impact on the brain meds patients.

Ben Burnett: Your line is now open.

David Meek: So that's a good thing.

Ben Burnett: Hey, thank you very much.

David Meek: So they have it.

Ben Burnett: I also wanted to ask a question about the competitive landscape.

David Meek: We'll see what happens over time as we move forward, move closer to the approvability.

Yeah.

Ben Burnett: I guess does the outcome of Amgen's Lumocrast confirmatory study have any impact, in how you guys are thinking about the regulatory path for ad aggressive, whether that's a successful study or not?

David Meek: I would say it's not just having it in the label, and ultimately we'll get it in the label at some point in time for sure.

David Meek: So for us with our CRYSTAL-12 trial, when we look at our registration trial, it was presented at ASCO cohort A as well as our confirmatory trial. It's the same patient population.

David Meek: So let's see what happens with the approval, but also it's important for guidelines.

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David Meek: Remember, 98.3% of our patient population in the registration trial were patients, that had followed the Keno-189 regimen, if you will, and that's also our confirmatory trial.

David Meek: So we'll work on NCCN guidelines, compendia listing, and so on.

David Meek: We look at that.

David Meek: That's also very important along with the publications of the data.

David Meek: We think of the pool analysis.

David Meek: Yeah, this is Jamie.

David Meek: We've also shared at ASCO.

James Christensen: I had just two quick things to add.

David Meek: So we're pretty confident with our CRYSTAL-12 trial design and the outcomes.

James Christensen: So just following up on David's comment on risk-benefit profile, you know, this is part of a package that we've submitted that, you know, I think it should be recognized that with a drug on the market, you know, a first-time presented activity in CNS meds is unique to the class.

David Meek: And, you know, the trial will finish enrollment next year, and we'll see what happens.

James Christensen: 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.

David Meek: And 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.

James Christensen: I also caught a question in there about RESIST 1.1 or intracranial RESIST.

David Meek: But at this point, we don't see any reason to change our plan.

James Christensen: And just to say, we've looked at multiple ways of looking at the activity of adagrassive embryonic metastases, and the IC-RESIST is very similar to the emoryno outcome.

Operator: We'll take our next question from Andrew Behrens with SBB Securities.

James Christensen: So we wouldn't expect a difference via methodology for determining response.

Operator: Please go ahead.

Operator: We'll take our next question from Maury Raycross with Jefferies.

Operator: Your line is now open.

Operator: Please go ahead.

Andrew Behrens: Hi.

Maury Raycross: Your line is now open.

Andrew Behrens: Thanks for taking my questions.

Maury Raycross: Hi.

Andrew Behrens: A couple on the ongoing 400-milligram BID monotherapy cohort from CRYSTAL-1.

Maury Raycross: Thanks for taking my question.

Andrew Behrens: Can you give us an idea when that cohort started enrolling and how far along it is at this point?

Maury Raycross: You saw a similar overall response rate for patients in the registrational trial stratified by TPS score.

Andrew Behrens: Are the patients getting tablets or capsules?

Maury Raycross: Are you commenting on what the differences in duration of response or PFS were based on TPS?

Andrew Behrens: And is this a cohort that the FDA specifically needs to run?

Maury Raycross: And how are you currently thinking about combo versus monotherapy for TPS-low patients?

David Meek: So, the trial started earlier this year, regarding that, to get into details, I don't think we'll, get into the details.

James Christensen: Hi.

David Meek: The trial is actively enrolling, and it is in the tablet formulation at this time. The patients run the 400 milligram twice a day of the tablet formulation.

James Christensen: This is Jamie.

David Meek: And the trial's up, and the FDA is, of course, aware of the trial, as they are of all of, our ongoing clinical trials in the second line, plus non-small cell lung cancer patient population, the patients with KRES-G12 mutation, so they're aware of that trial.

James Christensen: Yes, I think you're referring to the data presented at ASCO in the journal where we've looked by the three TPS strata, and response rate and would say that there's a minor difference in response rate.

Yes.

David Meek: We will not have data for that trial until next year.

James Christensen: We've also looked at outcomes by other measures, PFS, OS, duration of response.

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Operator: We'll take our next question from the line of Evan Sigerman with BMO Capital Market.

James Christensen: I would say we have not presented that data yet, but I wouldn't expect large differences there based on our experience thus far.

Operator: Please go ahead.

James Christensen: We will be more replete in our characterization of outcomes by TPS strata in the future.

Operator: Your line is open.

James Christensen: With regard to how we might develop the drug in different settings, one thing we've talked about previously is the strong, medical need and the TPS less than 1 KRESG-12C population.

Evan Sigerman: Hi, guys.

James Christensen: Here it's recognized that the outcomes on chemoimmunotherapy are fairly poor.

Evan Sigerman: Thank you so much for taking my question.

James Christensen: Let's note in Keynote 189 that the overall response rate was 32% and the PFS and OS was a bit lower.

Evan Sigerman: You know, just thinking ahead to the launch, you know, now that you are second to market, I guess, you know, what feedback have you gotten from physicians and KWALs that you're interacting with as you build up the commercial course regarding differentiation?

James Christensen: We knew that lower bar is viewed distinctly by the regulatory agencies and that there's a chance that Adagast would work as a, monotherapy in that setting to demonstrate response rate and durability greater than what might be anticipated for chemoimmunotherapy.

Evan Sigerman: And then also, you know, you seem to be pretty optimistic that you'll be able to secure approval, ahead of your December PDUFA.

James Christensen: So we have a study ongoing in the TPS less than 1 as a monotherapy.

Evan Sigerman: You know, what indications have you gotten from regulators that that may be the case?

James Christensen: And then secondly, the STK-11 subpopulation where we've seen signs of clinical activity.

Evan Sigerman: Thank you.

James Christensen: 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.

David Meek: So I will start, and then I'll jump in, too.

James Christensen: And that's a place where we believe we can observe a higher response rate.

David Meek: So we're preparing, and we're preparing for a launch as early as the end of Q3.

James Christensen: And that study is ongoing, so we'll be talking about it when the data is mature.

David Meek: 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.

James Christensen: 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 the strata.

David Meek: So I just want to be clear on that part of the conversation.

James Christensen: And just to note here that slightly different study designs may be required for different strata.

David Meek: The feedback, especially at ASCO, 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 Atagrassi.

James Christensen: These are all part of our overall strategy for the...

David Meek: In the second-line setting, the COVID-A data was, you know, we reviewed that, the response, rates, the overall survival data was very compelling to physicians, the CNS brain match data for active and untreated.

Operator: We'll take our next question from Jay Olson with Oppenheimer.

David Meek: This is a real differentiator in the minds of the physicians, anything they can do to, treat those patients, and, you know, even control brain match is a good thing for patients.

Operator: Please go ahead.

David Meek: 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 front-line setting, colorectal cancer, the response rates across the board were very impealing, especially to the community-based oncologists where these patients are treated.

Jay Olson: Your line is now open.

David Meek: So overall, the feedback's been good, it's given us confidence for us to go to the market, and we're ready to compete in the marketplace.

Jay Olson: Oh, hey.

Benjamin Hickey: Ben's got a few more points to add. Sure.

Jay Olson: Thank you for taking the question.

Benjamin Hickey: As you know, we've been out there for a while, so we've had a number of interactions with, physicians.

Jay Olson: Is there any read-across or other observations you'll be looking for in the data for the combination of Lumicrast with RevMed SHP2 at World Lung?

Benjamin Hickey: We've actually, with our field force today, been able to actually interact with, you know, 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 molecule's been designed for a 24-hour half-life, and that's enabled some of the, you know, the response rates and up to 14 months of overall survival with our pooled data set.

Jay Olson: And then as a related follow-up, you indicated that Atagrassiv will be administered concurrently in combination with Pembro.

Benjamin Hickey: So coupled with the CNS data in the active and untreated CNS mets, we think we have a, compelling story to bring to physicians.

Jay Olson: So can you comment on the pros and cons of parallel versus sequential administration in Atagrassiv combinations such as Pembro or SHP2 or any other combos?

Benjamin Hickey: 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 ensured that we've actually been able to reach out to, you know, almost 90% of covered lives and had, you know, a great deal of engagement with the payers to ensure that we can bring AdAggressive and gain access to it in an affordable fashion as soon as possible and as soon as we're approved, so, yeah, very positive today.

Jay Olson: Thank you.

David Meek: And I would, you know, to add on to that, you know, Ben has done an outstanding job, of bringing on board a commercial organization.

Jay Olson: So it's one of the things we're looking at.

David Meek: 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 have 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 the 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 with AdAggressive.

Chuck Baum: We've looked at preclinically 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.

Operator: We'll take our next question from the line of Egle Nekomovitz with Citi.

Chuck Baum: To have a chemo-sparing targeted agent would also be good.

Operator: Please go ahead.

Chuck Baum: So having Atagrassiv plus Pembro concurrently is something that we'd be very keen on for patients with a KRAS-G12C mutation.

Operator: Your line is now open.

Chuck Baum: I think the same story with SHIP-2.

Egle Nekomovitz: Hi.

Chuck Baum: SHIP-2 functions, at least in part, by shifting KRAS into its inactive state, desirable to have those two drugs administered concurrently.

Egle Nekomovitz: Thank you very much for taking the question.

Chuck Baum: And that's currently our focus for both of those areas.

Egle Nekomovitz: I'm curious regarding your thoughts on differentiating properties for etagracib at the MedChem level, versus how it would behave differently from citaracib from a tox perspective when combined with Tembro.

Egle Nekomovitz: Obviously, the molecules have a lot of structural overlap, but there are also some important, differences when you compare the two.

James Christensen: Thank you.

James Christensen: Jamie Ulz.

James Christensen: Hi, Egle.

James Christensen: This is Jamie.

James Christensen: So I think when you look at etagracib and citaracib, you know, there are a few key differences. Although they share part of the same core chemotype, the log-D polar surface area and, other characteristics are a bit different.

James Christensen: And the other difference is really in the reactivity of the molecules when you look, at KI and KN-ACT.

James Christensen: So one difference for etagracib relative to citaracib is its reactivity.

James Christensen: You know, we've kind of tuned down the electrophilicity of etagracib, which results in decreased binding, to other cysteine-containing proteins and reduced propensity for off-target effect.

James Christensen: With regard to other physiochemical properties, you know, one might notice some of the differences, in pharmacokinetics.

James Christensen: For example, citaracib has a high peak-to-trough ratio when administered once a day, and essentially, it clears out of the system once a day. So the Cmax to Cmin is quite different.

James Christensen: Etagracib only changes 7% within the interval, and that's really related to the high tissue, distribution and, you know, kind of the physiochemical properties of the drug.

James Christensen: 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.

James Christensen: 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 Alls with Morgan Stanley.

Operator: Please go ahead.

Operator: Your line is now open.

Mike Alls: Yep.

Mike Alls: Hey, guys.

Mike Alls: Thanks for taking the question.

Mike Alls: Maybe a follow-up just on the Etagracib formulation.

Mike Alls: So, you know, you're planning to launch with the tablet, but just curious how that might, look in the label.