Q1 2022 Mirati Therapeutics Inc Earnings Call

Operator: Good afternoon and welcome to the Mirati Therapeutics First Quarter 2022 Earnings Call. My name is Kevin and I will be the operator for today's call. All lines have been placed on mute to prevent any background noise.

Operator: After the conclusion of the speaker's preparatory remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star followed by the number 2.

Good afternoon, and welcome to the Meraki Therapeutics first quarter 2022 earnings call.

My name is Kevin and I will be the operator for today's call.

Operator: It is my pleasure to introduce Ryan A.C., Vice President of Corporate Affairs at Mirati. Ryan, you may begin the call. Thank you, Kevin.

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

Ryan A.C.: Welcome everyone to this afternoon's call. Joining me on the call today from a couple of different locations are David Meek, Mirati's Chief Executive Officer, Dr. Chuck Baum, Mirati's President, Founder, and Head of Research and Development, Dr. Jamie Christensen, Mirati's Chief Scientific Officer, and Vicki Reed, Mirati's Chief Accounting Officer. Ben Hickey, Mirati's Chief Commercial Officer, is 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.

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 simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question Press Star followed by the number to.

It is my pleasure to introduce Ryan <unk>, Vice President of corporate Affairs of Karachi, Ryan you may begin the call.

Thank you, Kevin and welcome everyone to this afternoons call joining me on the call today from a couple of different locations or David Meek, Chief Executive Officer, Patrick shortfall, <unk>, President founder and head of research and development, Dr. Jamey Christiansen, Brian as Chief Scientific Officer, and Vickie Reed varieties, Chief Accounting Officer.

Ben Hickey <unk> Chief commercial officer is also with us and will be available for the Q&A portion of the call.

Note that this conference call will include forward looking statements.

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 A.C.: 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. This afternoon, we released financial results for the quarter ended March 31st, 2022 and recent corporate updates. This press release is available on the investor's section of our website at mirati.com. With that, David, I'll turn the call over to you. Thank you, Ryan. Good afternoon and thank you for joining us today.

David Meek: On this afternoon's call, I will provide initial remarks before attorneys at Chuck to share an update on our clinical development program, to Jamie to comment on our preclinical portfolio, and Vicky to summarize our first quarter financial results. I will then provide a few concluding remarks before taking your questions. 2022 is a critical and transformational year for Mirati, and in the first quarter, we made significant progress on the ambitious goals we established for ourselves.

This afternoon, we released financial results for the quarter ended March 31, 2022, and recent corporate updates. This press release is available on the investors section of our website at <unk> Dot com with that David ill turn the call over to you.

Thank you Ryan good afternoon, and thank you for joining us today on this afternoons call I will provide initial remarks before turning to Chuck to share an update on our clinical development programs.

David Meek: We continue to execute well across our portfolio and there continues to be significant enthusiasm across all areas of the company for the work we are doing, the progress we are making and the life-changing impact we are having on patients living with cancer. We are pleased that our first new drug application is under review with the FDA. The FDA is reviewing our NDA for adagrassive as a treatment for patients with previously treated non-small cell lung cancer who harbor a KRAS G12C mutation for accelerated approval under the FDA's real-time oncology review pilot program. We remain confident in the approvability of the NBA and will be fully launch ready in the third quarter.

Jamie to comment on our preclinical portfolio and Vicki to summarize our first quarter financial results. I will then provide a few concluding remarks before taking your questions.

2022 is a critical and transformational year for Marathi and in the first quarter, we made significant progress on the ambitious goals, we established for ourselves.

We continue to execute well across our portfolio and there continues to be significant enthusiasm across all areas of the company for the work. We are doing the progress we are making in the life changing impact we are having on patients living with cancer.

We are pleased that our first new drug application is under review with the FDA.

He is reviewing our NDA for an aggressive as a treatment for patients with previously treated non small cell lung cancer, who harbor a <unk> mutation for accelerated approval under the Fda's real time oncology review pilot program.

David Meek: Securing a U.S. approval and executing a commercial launch of Atagrassis in the second-line, non-small cell, lung cancer setting is a key priority for the company. But it is also just the beginning of the full potential of where we believe this investigational product can help patients. With that aggressive, we're advancing a broad development plan beyond previously treated non-small cell lung cancer is both a single agent and in combination with other therapies, including in earlier lines of therapy and across a number of solid tumors.

We remain confident in the approve ability of the NDA and will be fully launch ready in the third quarter.

Securing a U S approval and executing a commercial launch of <unk> aggressive in the second line non small cell lung cancer setting is a key priority for the company.

David Meek: This includes the work we are doing in first-line non-small cell lung cancer in combination with pembrolizumab and in a broad range of other tumors such as colorectal and pancreatic cancers where we have previously presented compelling early results. In addition to adagrassive, we continue to advance and expand our broad targeted oncology pipeline. We recently completed enrollment in the Phase 3 SAFIRE registration trial and expect to reach the number of events needed to trigger an interim analysis for overall survival in the fourth quarter of 2022. If positive, Citravacinib would be a highly synergistic commercial opportunity without a grasshopper.

But it is also just the beginning of the full potential of where we believe this investigational product can help patients.

With that aggressive we are advancing a broad development plan beyond previously treated non small cell lung cancer as both a single agent and in combination with other therapies, including in earlier lines of therapy and across a number of solid tumors.

This includes the work we are doing in first line non small cell lung cancer in combination with <unk> and in a broad range of other tumors, such as colorectal and pancreatic cancers, where we have previously presented compelling early results.

In addition to autograph said, we continued to advance and expand our broad targeted oncology pipeline.

For <unk>, we recently completed enrollment in the phase III Sapphire registration trial and expect to reach the number of events needed to trigger an interim analysis for overall survival in the fourth quarter of 2022.

David Meek: As a reminder, in the U.S. and Europe, there are over 100,000 patients with second or third line non-small cell lung cancer who derive prior clinical benefit following treatment with a checkpoint inhibitor, and approximately 70,000 of these patients are of the non-squamous histology. MRTx1719, our MTA cooperative PRMT-5 program, is enrolling patients in an ongoing Phase I, II clinical trial with proof of concept clinical data expected next year. Our earlier stage target oncology pipeline, including MRTX1133, our KRES-G12 inhibitor, and MRTX0902, our SOS-1 inhibitor, continue to advance toward investigational new drug applications in the second half of 2022.

If positive Citron Citron <unk> would be a highly synergistic commercial opportunity without aggressive as a reminder, in the U S and Europe . There are over 100000 patients with second or third line non small cell lung cancer, who derive prior clinical benefit following treatment with a checkpoint inhibitor.

EBITA and approximately 70000 of these patients are on the non squamous squamous histology.

<unk>, TX 17, 19, our MTA cooperative <unk> five program is enrolling patients in an ongoing phase one two clinical trial with proof of concept clinical data expected next year.

David Meek: We have a tremendously productive in-house discovery capability that continues to discover and advance novel mechanisms and put us in a position to have as many as five unique yet synergistic programs in terms of the clinical execution and future commercial call points in clinical development in the next 12 months. We continue to be in a strong financial position to execute on our strategy, which provides us with the flexibility to invest for success across our target ecology pipeline and in preparation for a successful and aggressive launch, pending potential FDA approval later this year. As we grow and advance our pipeline, we are continuing to strengthen our capabilities to better enable us to achieve our objectives. With that, I'll turn the call over to Chuck.

Our earlier stage target oncology pipeline, including <unk>, 11, 33, or <unk> inhibitor and <unk>. Our sauce, one inhibitor continued to advance towards investigational new drug applications in the second half of 2022.

We have a tremendously productive in house discovery capability that continues to discover and advance novel mechanisms and put us in a position to have as many as five unique yet synergistic programs in terms of the clinical execution and future commercial call points and clinical development in the next 12 months.

We continue to be in a strong financial position to execute on our strategy, which provides us with a flexibility to invest for success across our targeted oncology pipeline and in preparation for a successful and aggressive launch pending potential FDA approval later this year.

Chuck Baum: Thank you, David. I'll begin with an ad aggressive update. We continue to work with the FDA as they review our new drug application based on our real-time oncology review and breakthrough therapy designation. We continue to work closely with the FDA to complete the review as quickly as possible. We are pleased with how the review is progressing and remain confident in an accelerated approval in the United States this year, outside the United States.

As we grow and advance our pipeline, we are continuing to strengthen our capabilities to better enable us to achieve our objectives.

With that I'll turn the call over to Chuck.

Thank you David.

I'll begin with then out aggressive update.

We continue to work with the FDA as they review our new drug application based on a real time oncology review and breakthrough therapy designation.

Chuck Baum: We are making progress and expect to complete the submission and validation of our marketing authorization application to the European Medicines Agency in the second quarter of 2022. In 2022, we will report a number of significant clinical updates for the adagressive program. Beginning with ASCO.

We continue to work closely with the FDA to complete the review as quickly as possible.

We are pleased with how the review is progressing and remain confident in an accelerated approval in the United States. This year.

Outside the United States, we are making progress and expect to complete the submission and validation of our marketing authorization application to the European Medicines agency in the second quarter of 2022.

Chuck Baum: We are pleased to have two abstracts accepted by ASCO for oral presentation. The first presentation is for the results of the registration-enabling phase two cohort of the CRSTL1 study evaluating adagressive inpatients with previously treated non-small cell lung cancer whose tumors harbor the KRAS G12C mutation. In addition, the presentation will include data across several important patient subgroups. Based on PD-L1 status, genomically defined patient populations, including co-occurring mutations like STK11, as well as patients with previously treated stable central nervous system, or CNS, metastases.

In 2022, we will report a number of significant clinical updates for the AD aggressive program.

Beginning with <unk>.

We are pleased to have two abstracts accepted by US go for oral presentation.

The first presentation as further results of the registration, enabling phase II cohort of the Crystal one study evaluating <unk> in patients with previously treated non small cell lung cancer, whose tumors harbor.

<unk> G <unk> mutation.

In addition, the presentation will include data across several important patient subgroups based on PD lone status.

Chuck Baum: The second presentation will highlight the activity of adigrassive in patients with G12c mutated non-small cell lung cancer tumors with untreated CNS metastases. This presentation will be the first clinical data with a KRAS inhibitor showing activity in patients with active and untreated. IAN MATEA.

<unk> defined patient populations, including co occurring mutations like SDK 11, as well as patients with previously treated stable central nervous system or CNS metastases.

The second presentation will highlight the activity of that aggressive in patients with <unk> mutated non small cell lung cancer tumors with untreated CNS metastases.

Chuck Baum: CNS activity is an important attribute because up to approximately 40% of KRAS G12C patients with non-small cell lung cancer present with CNS metastases. And the frequency of these mutations increases over time with the current standard of care. Together, these presentations reinforce Adagrassive's unique molecular profile and underscore our commitment to advancing Adagrassive's full development program as a single agent and in combination, where we are pursuing a broad development approach, including combinations with Pembrolizumab, Cetuximab, SHIP-2, SOS-1, TDK4-6, and a MecGraf dual pathway inhibitor.

This presentation will be the first clinical data with a <unk> inhibitor showing activity in patients with active and untreated.

Metastasis.

CNS activity is an important attribute because up to approximately 40% of <unk> patients with non small cell lung cancer present with CNS metastases.

And the frequency of these mutations increases over time with the current standard of care.

Together these presentations reinforce at aggressive unique molecular profile and underscore our commitment to advancing <unk> full development program as a single agent.

Chuck Baum: We are actively enrolling patients worldwide in adagressive clinical studies that are generating additional data in patients with a wide range of cancer. Our Phase 3 confirmatory study in previously treated non-small cell lung cancer patients with a KRES-G12C mutation, known as CRYSTAL-12, in which patients are randomized to adegrassib or docetaxel continues to enroll well worldwide. In first-line non-small-cell lung cancer, we continue to explore adagressive monotherapy in certain underserved subpopulations, including patients harboring KRAS G12C and SDK11 comutations, as well as KRAS G12C-mutated patients with TPS scores of less than 1%.

And in combination, where we are pursuing a broad development approach, including combinations with <unk>.

Tuxtla ma'am.

Two <unk> one <unk>.

CDK four six and a met graph dual pathway inhibitor.

We are actively enrolling patients worldwide and Ed aggressive clinical studies that are generating additional data in patients with a wide range of cancers.

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

In which patients are randomized to <unk> or docetaxel continues to enroll well worldwide.

Chuck Baum: We expect to provide additional clarity on a potential regulatory pathway for accelerated approval in these subpopulations this year, as well as sharing initial data from these cohorts in 2023. Also in first line, non-small cell lung cancer patients. We are aggressively exploring adagressive in combination trials with a focus on the combination with temporalism. This Adagrassiv plus Pembrolizumab combination, which is using 400 milligram BID dose of Adagrassiv with full dose Pembrolizumab, in the Phase 2 crystal 7 study is enrolling well with strong interest from both patients and physicians.

In first line non small cell lung cancer, we continue to explore at aggressive monotherapy in certain underserved sub populations, including patients harboring <unk> and SDK 11, co mutations as well as <unk> 12, <unk> mutated patients with TPS score.

<unk> of less than 1%.

We expect to provide additional clarity on our potential regulatory pathway for accelerated approval in the sub populations. This year as well as sharing initial data from these cohorts in 2023.

Also in first line non small cell lung cancer patients, we are aggressively exploring <unk> in combination trials.

With a focus on the combination with <unk>.

Chuck Baum: We plan to share an update from this combination study this year, which will include an analysis of patients stratified by TPS score. Based on the results from CRYSTAL-7, we plan to initiate a Phase 3 trial evaluating the combination of Atagrassiv and Pembrolizumab in first-line non-small-cell lung cancer patients, later this year. Beyond lung cancer, we are advancing enrollment, in patients with colorectal cancer, both in late-line and in the second-line setting. The ongoing Phase 3 registration-enabling study, in combination with cetuximab and second-line colorectal cancer, continues to enroll well and potentially provides us with an opportunity to be the first to market in this patient population.

This at aggressive plus <unk> combination, which is using 400 milligram.

Dose at aggressive with full dose <unk>.

In the phase two Kate Crystal <unk> study is enrolling well with strong interest from both patients and physicians.

We plan to share an update from this combination study this year, which will include an analysis of patients stratified by TPS score.

Based on the results from Crystal seven we plan to initiate a phase III trial evaluating the combination of <unk> in first line non small cell lung cancer patients.

Later this year.

Beyond lung cancer, we are advancing enrollment in.

In patients with colorectal cancer, both in late line and then the second line settings.

Chuck Baum: We continue to enroll patients with G12C mutations in other solid tumors, including pancreatic, Pilary cancer, gastrointestinal, and others, and will continue to explore potential accelerated regulatory approval pathways in these patient subpopulations. We expect to provide additional clarity on a potential pathway for accelerated approval of adegrassive and late-line CRC, as well as sharing next steps in other solid tumors later this year. Now to move on to citravadmin.

The ongoing phase III registration, enabling study in combination with Cetuximab in second line colorectal cancer.

<unk> to enroll well and potentially provides us with an opportunity to be the first to market in this patient population.

We continue to enroll patients with <unk> mutations in other solid tumors, including pancreatic.

Ciliary cancer.

Gastrointestinal and others and we will continue to explore potential accelerated regulatory approval pathways in these patient sub populations.

Chuck Baum: As David mentioned, we recently completed enrollment in the Phase III SAFIRE trial, which is being conducted in patients with second or third line non-small cell lung cancer who have derived prior clinical benefit following treatment with a checkpoint inhibitor. We are 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, the interim analysis could be the basis for full approval in the U.S. and Europe, with regulatory filings in both markets being submitted by the middle of next year. For MRTX.

We expect to provide additional clarity on a potential pathway for accelerated approval of <unk> they've been late line CRC.

As well as sharing next steps and other solid tumors later this year.

Now to move on to sit from that.

As David mentioned, we recently completed enrollment in the phase III Sapphire trial, which is being conducted in patients with second or third line non small cell lung cancer, who have derived prior clinical benefit following treatment with a checkpoint inhibitor.

We are on track to reach the number of events needed to trigger an interim analysis for overall survival in the fourth quarter of 2022.

Chuck Baum: 17-19, our MTA Cooperative PRMT-5 program. We are enrolling a Phase I dose escalation and dose expansion study in patients whose tumors harbor MTAP deletion, which make up up to 10% of solid tumor patients. We will explore MRTX1719 as a single agent and through rational combination strategies identified in non-clinical translational studies across several tumor types, including mesothelioma, pancreatic, lung, malignant peripheral nerve sheath tumor, and a basket cohort of other MTAP-deleted tumor types.

If positive.

The interim analysis could be the basis for full approval in the U S and Europe with regulatory filings in both markets being submitted by the middle of next year.

For <unk>, TX 17, 19, our MTA cooperative Prs <unk> five program, we are enrolling a phase one dose escalation and dose expansion study in patients, whose tumors harbor <unk> deletion.

Which makes up to 10% of solid tumor patients.

We will explore <unk>, TX 17, 19, as a single agent and through rational combination strategies identified in non clinical translational studies across several tumor types, including mesothelioma.

Jamie Christensen: We expect to share the initial clinical data for this program in 2023 after we have selected a dose and generated sufficient data to demonstrate clinical proof of concept. With that... Let me hand it off to Jamie to discuss our preclinical program. Thanks, Chuck.

<unk> lung malignant <unk>.

Throw nerve sheath tumor.

And a basket cohort of other tap deleted tumor types.

Jamie Christensen: I'll briefly touch on our pipeline of preclinical programs, including our SOS-1 inhibitor, MRTX0902, our selective KRAS-T12D inhibitor, MRTX1133, and our next-generation spectrum-selective platform to target additional KRAS mutations. We recently presented preclinical data for 0902 and 1133 at the American Association for Cancer Research Annual Meeting, also known as AACR. O902 is a selective SOS1 inhibitor which shifts KRAS into its inactivated state and enhances inactivation by KRAS, of KRAS by adegrassi. This combination is anticipated to address feedback reactivation of KRAS and to address intrinsic and acquired resistance to KRAS inhibitors. At AACR, we disclose the chemical structure and profile of O902, along with its broad anti-tumor activity in KRAS G12C preclinical models in combination with Atagrass.

We expect to share the initial clinical data for this program in 2023. After we have selected a dose and generated sufficient data to demonstrate clinical proof of concept.

With that.

Let me hand, it off to Jamie to discuss our preclinical programs.

Thanks Chuck.

We touch on our pipeline of preclinical programs.

Including our SaaS one inhibitor <unk>.

Our selective <unk> inhibitor <unk>.

And our next generation spectrum selective platform to target additional K Ras mutations.

We recently presented preclinical data for <unk> 902, and 133 at the American Association for Cancer Research annual meeting also known as ACR.

<unk> is a selective <unk> one inhibitor with <unk> into its inactivated stayed and enhances and activation by K Ras <unk> by <unk>.

Jamie Christensen: O902 is also anticipated to complement additional agents in the Mirati pipeline and exert an impact on KRAS mutated cancers, irrespective of the KRAS mutation type. O902 also has the potential to target additional mutations within the MAP kinase pathway. These include the opportunity to combine with other MAP kinase pathway inhibitors. This agent is currently in IND-enabling studies and we are on track to complete the IND filing in 2022. 1133 is a potent and selective non-covalent KRAS G12D inhibitor that binds the switch to pocket with high affinity in either the active or inactive state of KRAS G12D.

This combination is anticipated to address feedback reactivation of K, Ras and to address intrinsic and acquired resistance to <unk> inhibitors.

<unk>, we disclose the chemical structure and profile of our 902, along with its broad anti tumor activity in <unk> preclinical models and combination with <unk>.

102 is also anticipated to complement additional agents in a variety of pipeline and a certain impact on K Ras mutated cancers irrespective of the K Ras mutation type.

<unk> also has the potential to target additional mutations within the map kinase pathway. These include the opportunity to combine with other map kinase pathway inhibitors.

Jamie Christensen: At AACR, we shared additional preclinical data reinforcing the broad antitumor activity of 1133, including marker regression in the majority of pancreatic cancer models. This presentation also provided insight towards combinatorial strategies to augment the activity of 1130. We continue to pursue IND-TRAC development of 1133 with focus on long-acting injectable formulation strategies, including stealth liposomal strategies, and continue to focus on filing the IND in 2022. Additionally, we continue to pursue targeting of additional mutant variants of KRAS through our spectrum-selective KRAS inhibitor program. This is a potential platform approach which could yield multiple development candidates targeting various KRAS mutations with differing mutation selectivity profiles and ratios of potency for targeting KRAS wild type versus these selected mutations.

This agent is currently in IND, enabling studies and we are on track to complete the filing in 2022.

133 is a potent and selective non covalent <unk> inhibitor that binds the switch to pocket with high affinity and either the active or inactive state of <unk> at ACR, we shared additional preclinical data reinforcing the broad antitumor activity of 133 and coding market rigs.

And the majority of pancreatic cancer models.

This presentation also provided insight towards combinatorial strategies to augment the activity of 133.

We continue to pursue <unk> development of 183 with focus on the long acting injectable formulation strategies, including stealth life is almost strategies and continue to focus on filing the IND in 2022.

Additionally, we continue to pursue targeting of additional meat and variance of <unk> to our spectrum selective K Ras inhibitor program. This is a potential platform approach, which could yield multiple development candidates targeting various K Ras mutations with differing mutation selectivity profiles and ratios of potency.

Jamie Christensen: We have a goal of identifying potential development candidates for this program in 2022. With that, I will turn it over to the. Thank you, Jamie. We ended the first quarter with approximately $1.3 billion in cash, cash equivalents, and short-term investments.

Vicki Reed: Research and development expenses for the first quarter of 2022 were $131 million compared to $104.1 million for the same period in 2021. The increase in research and development expenses is primarily due to costs associated with the ongoing advancement of our Adagrassi and Citravatna clinical programs, preclinical and early discovery activities, employee-related expenses, including an increase in salaries and share-based compensation, as well as professional services, facilities, and IT expense. General and administrative expenses for the first quarter of 2022 were $54 million compared to $28.4 million for the same period in 2021.

Our targeted K Ras wild type versus these selected mutations.

We have a goal of identifying potential development candidates for this program in 2022.

With that I will turn it over to Nicky.

Thank you Jamie.

We ended the first quarter with approximately $1 $38 million in cash cash equivalents and short term announcements.

Research and development expenses for the first quarter of 2022.

131 million compared to $104 1 million at the same period in 2021.

The increase in research and development expenses is primarily due to costs associated with the ongoing advancement of our <unk> clinical program preclinical and early discovery activity employee related expenses, including an increase in salaries and share based compensation as well as <unk>.

Professional services facilities and Ikea.

Vicki Reed: The increase is due to growth in employee-related expenses, including salaries and share-based compensation, and costs related to the growth of our business as we continue to prepare for commercialization. Net loss for the first quarter of 2022 was $188.4 million, or $3.40 per share, basic and diluted, compared to a net loss of $135.7 million, or $2.67 per share, basic and diluted, for the same period in 2021. Please see our press release from earlier this afternoon for additional details about our first quarter of 2022 financial results.

General and administrative expenses for the first quarter of 2022 were $54 million compared to $28 4 million for the same period and 21 <unk>.

The increase is due to growth in employee related expenses, including salaries and share based compensation and costs related to the growth of our business as we continue to prepare to prepare for commercialization.

Net loss for the first quarter of 2022, with $188 4 million or $3 <unk> per share basic and diluted compared to a net loss of 137.

Vicki Reed: David, I'll hand it back over to you. Thank you, Vicki. As you can hear from the team, there is a lot happening at Verati. We're excited about the progress we've made and about both the short and long-term potential of the opportunity that lies before us. We have the products, capabilities, people, and capital we need to not only execute the short-term, but also to drive long-term sustainable growth.

$7 million or $2 67 per share basic and diluted for the same period in 2021.

Please see our press release earlier this afternoon for additional details about our first quarter 2002.

Financial results, David I'll hand, it back over to you.

David Meek: Our targeted oncology pipeline is broad, spanning multiple targets and tumors and gives us a strong platform to support tremendous value creation and significant operational and commercial synergies across the portfolio. As Vicky indicated, we have the financial resources to enable us to continue to appropriately and prudently invest in the advancement and expansion of our clinical and preclinical portfolio, and also in preparing to become a commercial stage company. We have continued to advance our commercial preparations and execute on our commercial strategy as we prepare for a successful ad aggressive launch subject to FDA approval.

Thank you Vicky and you can hear from the team there is a lot happening at Marathi we're.

Cited about the progress we've made and about both the short and long term potential of the opportunity that lies before us we have the products capabilities people and capital we need to not only execute in the short term, but also to drive long term sustainable growth.

<unk> targeted oncology pipeline is broad spanning multiple targets and tumors and gives us a strong platform to support tremendous value creation and significant operational and commercial synergies across the portfolio.

As Vicki indicated we have the financial resources to enable us to continue to appropriately and prudently invest in the advancement and expansion of our clinical and preclinical portfolio and also in preparing to become a commercial stage company.

David Meek: Our objective to launch and further develop a market-leading KRAS G12C inhibitor, optimizing the full and tremendous potential of this important product, remains the critical priority, while we also invest to drive sustainable growth with the other exciting and innovative target oncology assets in our portfolio. I continue to be grateful and impressed by the talented, committed, and passionate team we have at Mirati. We're asking a lot of every member of our team.

We have continued to advance our commercial preparations and execute on our commercial strategy as we prepare for a successful and aggressive launch subject to FDA approval.

Our objective to launch and further develop our market, leading <unk> inhibitor optimizing the full and tremendous potential of this important product remains the critical priority. While we also invest to drive sustainable growth with the other exciting and innovative targeted oncology assets in our portfolio.

David Meek: They continue to not only meet but exceed expectations as we strive to improve the lives of patients. With that, we're ready to take questions. I would like to remind everyone that if you would 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 star followed by the number two.

I continue to be grateful and impressed by the talented committed and passionate team we have a variety we're asking a lot of every member of our team. They continue to not only meet but exceed expectations as we strive to improve the lives of patients.

Operator: To ensure all participants have the opportunity to ask a question, we ask you please limit yourself to one question and one follow-up. Please hold for a moment while we poll for questions. And the first question comes from Salveen Richter of Goldman Sachs. Hi, thanks for taking our question. This is Tommy on for Salveen.

With that we're ready to take questions.

Okay.

I would like to remind everyone that if you would 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 Star followed by the number too.

Benjamin Hickey: And our question is about how Amgen has talked about how many KRAS patients are being diagnosed, but that the KRAS status isn't necessarily showing up in the patient files, like as they progress to later in line. So, what steps or actions can you take to facilitate patient identification and ensure that patients are being treated with a KRAS inhibitor? Thanks so much.

To ensure all participants have the opportunity to ask a question. We ask you. Please limit yourself to one question and one follow up please hold for a moment, while we poll for questions.

And the first question comes from <unk> Richter of Goldman Sachs.

Hi, Thanks for taking my question. This is Tommy on for solving.

Benjamin Hickey: Great question, Tony. Thanks, Bob. We've got Ben here, our Chief Commercial Officer, so he's been looking at this closely with his team, so I'll turn it over to Ben. Yeah, thanks for the question. I would say, first of all, that it is a real issue in regards to the patient identification. And a number of these lung cancer patients are being treated in the community. So we've spent a lot of time, first of all, ensuring that our study actually included lung cancer patients from the community is one.

Our question is about how Amgen has talked about how many patients are being diagnosed with that the.

Necessarily showing up in the patient files like as they progress to later line. So what steps are actions can you take to facilitate patient identification and ensure that patients are being treated with the kiosks.

Thanks, so much.

Great question. Thanks, Bob we've got that here, our chief commercial officer so.

He's been looking at this closely with his team so I'll turn it over to Ben.

Benjamin Hickey: And then, secondarily, ensuring that as we get commercially ready, we're spending a lot of time, particularly with community networks, and understand their patient flow, how they're recording patients within the EMR, how they're flagging that patient, the G12C patient. And we really believe that the market will mature over time. And over time, as they become tested in the front line, more of those patients will become available in second line. But I would say the market is still immature and is taking some time to fully present itself. Our next question comes from Tyler Van Buren of Cohen. Hey guys. Good afternoon.

Yes.

Thanks for the question I would say first of all that it is a real issue in regards to the patient identification and a number of these lung cancer patients have been treated in the community.

We've spent a lot of time.

First of all including ensuring that our study actually included lung cancer patients from the community as one.

And then secondarily, ensuring that as we get commercially ready, we spending a lot of competition.

Community networks and understand that patient flow kind of recording patients within the EMR habit flagging that patient is a <unk> patient.

And we really believe that the market will mature over time.

Chuck Baum: Congrats on the progress and thanks for taking the questions. I want to ask you about the Phase 2 presentation on Friday at ASCO. Should the bar for medium-duration response be the prior Satorisib world-long dataset or the more recent AACR dataset?

And overtime as they become tested in frontline more of those patients will become available in second line, but I would say the market is still immature and he's taking some time to fully presents itself.

Chuck Baum: And do you think Adagrassiv could improve upon it? Or how should we think about the potential to treat CNS-Mets and its ability to impact DOR and PFS when comparing to Satorisib? Yeah, Tyler.

Our next question comes from Tyler Van.

<unk> of Cowen.

Hey, guys. Good afternoon, congrats on the progress and thanks for taking the questions I wanted to ask about the phase two presentation on Friday at <unk> should the bar for medium duration of response with the price of tourist world lung dataset or the more.

Chuck Baum: Hi. First of all, regarding the data that's going to be released at ASCO, I think it's best that we reserve that conversation until we see the data. We're certainly excited to share all the data that's going to be presented at ASCO, so I think we can have that conversation at ASCO. Okay, understood. The next question comes from Ben Burnett of Stiefel. Good afternoon. This is Neal Carnahan on for Ben.

Our dataset and do you think out aggressive could improve upon it or how should we think about the potential to treat CNS Mets and its ability to impact <unk> and PFS when comparing to tourists.

Yes, Tyler Hi.

First of all regarding the data that's going to be released at <unk> I think it's best that.

We reserve that conversation until we see the data we're certainly excited to share all the data we're seeing that's going to be presented at <unk>.

Chuck Baum: On the Pembrolizumab combo, are you now able to characterize the safety profile for the 600 milligram BID dose? And then could you also say if you evaluated any doses? Any adagressive doses below the 400 milligram BID that you're pulling forward? Thank you. Sure. Yeah, we'll have Chuck answer that question for the team.

I think we can have that conversation at <unk>.

Sure.

Yes.

Okay understood.

The next question comes from Ben Burnett of Stifel.

Good afternoon. This is Neil Carnahan on for Ben.

On the <unk> <unk> combo.

Chuck Baum: Okay. So, yeah, we're going to have, in the second half of the year, we were planning to present the data fully for those patients with an emphasis on the 400 milligrams, because that's our, as we've indicated, that's our go-forward dose. But the doses that we've looked at were, the study started with 600 milligrams VID in full dose pembrolizumab. And then we, as we had talked about previously, that the tolerability there was not as good.

We're now able to characterize the safety profile for the 600 milligram dose and then could you also say if you evaluated any doses any at aggressive doses below the 400 milligram PID that youre pulling forward. Thank you.

Sure, Yes, we will have Chuck answer to answer that question for the team.

Okay. So yes, we're going to have.

In the second half of the year, we were planning to present the data.

Fully for those patients.

Chuck Baum: So, we switched to the 400 milligram VID. And that's the patient population we're enrolling now. So, we'll have a substantial number of patients treated at 400 milligram VID in full dose pembro in the second half of this year. And that'll put us in a position to make the go-no-go decision on the phase three, which we intend to make by the end of the year. So, so far, things are looking good at the 400 milligrams. So, we talked about seven of those patients last year.

With an emphasis on the 400 milligram because that's our.

We've indicated that's our go forward dose.

At the doses that we've looked at where the study started with 600 milligram B I D.

Full dose <unk>.

And then as.

As we had.

About previously.

Tolerability there was not as good so we switched to the 400 milligram Tid and that's the that's the patient population we're enrolling now.

So we will have a substantial number of patients treated at 400 milligram tid and full dose <unk>.

Chuck Baum: And we continue to follow those, as well as all the new patients. And we're pleased with the results thus far. But as I said, in the second half, we'll present the data in a more fulsome way. Our next question comes from Gina Wang from Barclays. Thank you.

In the second half of this year and that will put us in a position to make the go no go decision on the phase III, which we intend to make by the end of the year.

So far things are looking good at the 400 milligram. So we talked about seven of those patients last year.

Chuck Baum: I'll just follow up regarding also the PEMBRO combo first-line data, safety data. So, Chuck, you know, based on the data you've seen so far, do you think that, you know, 400 milligram BID plus PEMBRO dosing is the path forward, or do you think, you know, the liver tox, do you agree that liver tox is a drug class effect, or you think it's a specific, unique to specific compound? And then another question is regarding the ASCO update. For CRYSTAL1 full data, do you expect to show definitive differentiation versus the LumaCRUST, i.e., you know, one to two months better PFS or DOI?

And we continue to follow those as well as all the new patients.

And we're pleased with the results, thus far but as I said within the second half, we'll present that data in a more fulsome way.

Okay.

Our next question comes from Gena Wang from Barclays.

Thank you I just follow up regarding also the PEMCO combo first line.

Data safety data. So Chuck you know based on the data you've seen so far.

I think that 400 milligram PID plus.

<unk> dosing is the path forward or do you think the liver Tox you agree the liver tox.

He's a drug class effect or you think it's a specific unique to specific compounds.

Chuck Baum: So for the first question, we are going forward with the 400 milligram BID dose. We're happy with that dose at this time. We're accruing a lot of patients, and we'll have patients at all the entire TPS range, which will give us a good sense of what the next step should be and what the design of the phase three trial should be. So all of that continues as planned and is enrolling quite well, so we're encouraged by that.

Then another question is regarding to ask will update for Christa one full data do you expect to show definitive differentiation versus the luma crossed I E. One to two months better PFS or do you want.

So for the first question.

Going forward with the 400 milligram dose were happy with that dose at this time, we're accruing that lot of patients.

Chuck Baum: In terms of liver toxicity, I think that that can be sort of compound specific, not necessarily class specific. But part of the challenge is that we really haven't seen the full data from competitors. So we've heard about it, but we haven't really seen it.

We will have patients at all the entire TPS range, which will give us a good sense of what the next steps should be and what the design of the phase III trials should be so all of that continues as planned.

And it's been growing quite well so we're encouraged by that.

Chuck Baum: So I'm hoping that as we present more data and they present more data this year, that we'll have more clarity around what the nature of those results is. But I would say at this point, we're not, for our program, that is not a high level of concern in terms of liver toxicity. Yeah, I might just add a few comments to Chuck's here.

In terms of liver toxicity I think.

That can be sort of compound specific.

Not necessarily class specific.

But the part of the challenges that we really haven't seen the full data from competitors. So we've heard about it but we haven't really seen it so I'm hoping that.

As we present more data they present more data this year that we will have more clarity around what the nature of those results is.

Chuck Baum: I think, first of all, from the, you know, new chemical entity perspective that, you know, adagrassive and psoriasis are distinct small molecules with different physiochemical properties, different tissue penetration, different peak to trough ratios at steady state with regard to the PK properties. So, although they share the mechanism being able to irreversibly modify KRAS-GTOF-C, they are distinct small molecules. I think it's also fair to note that in the field today, you know, looking at TKIs, for example, the split kinase or VEGFR TKIs, when you, you know, kind of look at their ability to combine with immune checkpoint inhibitors, for whatever reason, you know, these molecules have the same set of shared targets.

But I would say at this point we're not.

Our program.

That is not a high level of concern in terms of liver tox.

Yeah, Mike.

Mike just add a few comments to Chuck's here I think first of all from that.

New chemical entity perspective that.

Chuck Baum: But Pembrolizumab and Sinitinib, for example, were deemed to be non-combinable, as was Crizotinib, with immune checkpoint inhibitors. And in contrast, our own Citravatinib, other drugs like Cabazatinib, were quite combinable and effective in combination. So there's, I think, a couple examples historically of different drugs within a target class that differentiate with regard to their tolerability. I think the last point to make is just what we've seen so far with regard to liver function and anything that might be deemed as a pedotoxicity. So, as a monotherapy, we have seen, you know, grade one and grade two liver function test elevations. We've seen a small fraction of those being grade three.

And aggressive in silver asset by our distinct small molecules with different physiochemical properties different tissue penetration different peak to trough ratio is at steady state with regard to the PK properties. So although they share the mechanism being able unable to irreversibly modifying <unk> they arent.

Six small molecules.

I think it's also fair to note that in the field to date.

Looking at <unk> for example split kinase or <unk>.

You kind of look at their ability to combined with immune checkpoint inhibitors for whatever reason. These molecules have the same set of share targets, but <unk> and Sunitinib. For example were deemed to be non combinable as was croissant nib.

Chuck Baum: We have not seen patients discontinue due to liver function tests, abnormalities, or hepatotoxicity. We've seen no high log cases with respect to hepatotoxicity to monotherapy. In combination, as Chuck mentioned, we're fairly happy with what we've seen so far at the 400 mg BID dose level. But I think one thing to add to that is that we do not see a signal with respect to one underlying toxicity, including hepatotoxicity, to be dose limiting with respect to dose intensity or patient discontinuation. So I think all of our signals to date look, you know, fairly positive with respect to the Pembrolizumab combination. Okay. And I think there was another one. Jonathan Miller from Evercore.

With immune checkpoint inhibitors, and then contrast, our own <unk> other drugs like Cabozantinib look quite combinable and effective in combination. So there is I think a couple of examples historically of <unk>.

Drugs within a target class that differentiate with regard to their tolerability.

Think last point to make is just what we've seen so far with regard to.

Liver function and anything that might be deemed as a pilot toxicity. So as a monotherapy we have seen grade one and grade two Oliver function test elevations, we've seen a small fraction of those being grade three we have not seen patients discontinued due to liver function test abnormalities.

Or hepatic toxicity, we have seen no highs law cases with respect to pay the taxes to monotherapy and combination as Chuck mentioned, we're fairly happy with what we've seen so far is that 400 Meg.

At dose level, but I think one thing to add to that is that we do not see a signal with respect to one underlying toxicity, including hepatic toxicity to be dose limiting with respect to dose intensity of patient discontinuation. So I think all of our signals to date look fairly positive with respect to the pepper Elysium have combination.

David Meek: Hey guys, thanks so much for taking the question. I guess following up on that PD-1 combo question, obviously everybody's looking forward to data later this year, but I also want to ask how rapidly you could move to larger Phase 3s. It does seem like you're getting a little bit more comfortable with the strategy here and the safety profile in combination here, so what are the gating factors at this point on pivotal trial starts? I'll jump on that. Good work, everybody. Yeah, Chuck, I was going to say, let me start and jump over to you.

Okay.

Yeah.

And I think.

Request.

Jonathan Miller from Evercore.

Hey, guys. Thanks, so much for taking the question I guess following up on that PD. One combo question I'd be looking forward to data later this year, but I also wanted to ask how rapidly you could move to larger phase threes. It does seem like youre getting a little bit more comfortable with the strategy here and the safety profile in combination here. So what are the gating factors at this <unk>.

David Meek: Yeah, folks, we're at a couple different locations as a team. You know, I think we're getting, we're advancing the program. We haven't discussed what those gating points are. I think as the year evolves, as we share the data, we'll certainly discuss what some of those gating items are. But as we did say, we're preparing for a phase 3 start later this year. And we can go to Evan Siegerman of BMO Capital Markets. Hi, guys.

On pivotal trial start.

And when should we expect that.

So the work anyway.

Yes, Chuck I would just say new.

Start and then jump over to you folks had just a couple of different locations of the team.

I think we're getting.

We're advancing the program we haven't discussed what those gating points are I think as the year evolves as we share the data, we'll certainly discuss with some of the gating getting on Saar.

Chuck Baum: Thank you so much for taking the question. Looking ahead to the ASCO data, can you just talk about, I know you discussed the brain penetrability of the drug, but what are your thoughts on whether or not the drug actually can stick around in the brain? I've heard some reports where we're seeing, or I've heard theoretically that the drug may be expelled and not actually kind of giving the target engagement you want.

But as we did say we're preparing for a phase III start later this year.

And we can go to Evan <unk> of BMO capital markets.

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

And ahead to the Afterdeck talk about I know you discussed the brain penetrant <unk> of the drug but.

Chuck Baum: Any thoughts on that would be super helpful. And any color on the enrollment of the phase three confirmatory. Sure, yeah, I would say with regard to the CNS penetrance of Edegrassep, we've looked at this both preclinically and clinically and would say that Edegrassep actually has a unique mechanism to enter the CNS relative to other drugs. Point number one is it has favorable physiochemical properties with regard to tissue distribution, you know, appropriate Log D, lipophilicity, and polar surface area to get into tissue.

What are your thoughts on whether or not the drug actually can pick around in the Brian I've heard some reports, where we're seeing or I've heard theoretically that the drug may be expelled and not actually kind of giving the target engagement you want.

Any thoughts on that would be helpful and any color on the enrollment of the phase III confirmatory.

Okay.

Sure, Yes, I would say with regard to the CNS penetrance of Madagascar.

Chuck Baum: And that is, I think, the first principle of any drug that would have brain penetrance. The second is that you brought it up, related to efflux. So, it's true that adagrassive is a PGP, peak glycoprotein, or efflux substrate. But what's unique is that at concentrations that we achieve clinically, we also are a PGP inhibitor. And thus, the drug actually inhibits its own efflux out of the CNS.

We've looked at this both pre clinically and clinically and let's say the Ed aggressive actually has a unique mechanism to enter the CNS relative to other drugs.

Number one is it has favorable physiochemical properties with regard to tissue distribution.

Appropriate body, lippo, felicitate and polar surface area to get into tissue and.

And that is I think the first principle of any drug that would have brain penetrant.

Chuck Baum: And when we've looked preclinically at dose levels that are associated with achieving the clinical dose levels, you know, let's say translation of mouse to human, we see a KPU, or a partition coefficient, in CNS tissue relative to the free fraction plasma, that is between .4 and 1.0. So, meaning we get in extensively into the CNS at the dose levels we achieve clinically. When we've measured that in patients with a 600 BID dose level, we see a KPU of .47. Again, meaning we're getting extensive tissue distribution. Asmertinib is an example of a drug that has CNS activity. It's measured KPU is generally lower than adagrassive, around .3 to .4, depending on which study is cited.

The second is that you bought it up related to Eplex. So it's true that <unk> is a PGP P glycoprotein or eplex substrate, but what's unique is that at concentrations that we achieved clinically.

We also are a PGP inhibitor and thus the drug actually inhibits its own eplex side of the CNS and when we've looked pre clinically at dose levels that are associated with achieving the clinical dose levels, let's say translation of mouse to human we see a TPU or a partition coefficient and CNS.

Tissue relative to the free fraction plasma that is between four and one now so meaning we get in extensively into the CNS at at the dose levels, we achieved clinically when we measure that in patients with the 600 B I D dose level, we see a <unk> of <unk>.

Chuck Baum: Electinib and lorlatinib are additional examples of elk inhibitors with CNS penetrants. It would just say that their systemic response rates and their intracranial response rates are comparable. Our evidence of seeing uptake into the CSF are consistent with what we've seen there. So, I think that's point one.

Seven again, meaning we're getting extensive tissue distribution.

<unk> is an example of a drug that has CNS activity. It's measured <unk> is generally lower than and aggressive.

Around three to four depending on which study are sited.

Chuck Baum: Point two, you know, you mentioned the ebb and flow and efflux out of the CNS. You know, just to remind you here that, you know, our drug has about a 24-hour half-life. We're administering BID. The effective half-life at steady state is around 60 hours and the peak to trough variation of adagrassive at steady state is only around 10 to 20%.

<unk> and <unk>.

And <unk> are additional examples of Elk inhibitors with CNS penetrance and would just say that they're systemic response rates and Theyre intracranial response rates are comparable.

Our evidence of seeing uptake into the CSF are consistent with what we've seen there. So I think that's 0.1 0.2, you mentioned the ebb and flow in Eplex out of the CNS.

Chuck Baum: And we never drop below concentrations that are associated with being able to inhibit the target. We believe that that's relevant for both for peripheral disease as well as the metastases. So, so far, so good there.

Just to remind you here that I know.

Our drug has about a 24 hour half life for administering.

The effective half life at steady state is around <unk> 60 hours and the peak to trough variation of it.

Chuck Baum: And, of course, we'll be talking about the actual intracranial response here upcoming at ASCO. The second question, I believe, was the Pivotal Study, and I think David is going to take it. I'll answer that quickly.

<unk> at steady state is only around 10% to 20% and we never dropped below concentrations that are associated with being able to inhibit the target. We believe that that's relevant for both for our peripheral.

David Meek: Regarding our Phase 3 Confirmatory, this is the CRYSTAL-12 Study, you know, we're pleased with the enrollment. As you know, we're enrolling in the U.S. and Europe. Also, Xi, our partner in China, will also help drive enrollment.

Peripheral disease as.

As well as.

As well as the metastases. So so far so good there and of course, we'll be talking about the actual intracranial response here upcoming at <unk>.

David Meek: So we're pleased with the rate of enrollment we're seeing at this time, and the study should be fully enrolled in the first half of 2023. The next question comes from Michael Schmidt of Guggenheim. Good afternoon, this is Paul Long from iQOLA.

The second question I believe was the pivotal study and I think David is going to take don't answer that quickly regarding of our phase III confirmatory. This the crystal 12 study.

Pleased with the enrollment as you know we're enrolling in the U S and Europe also <unk> our partner in China will also help drive enrollment. So we're pleased with the rate of enrollment we are seeing at this time in the study should be fully enrolled in the first half of 2023.

Chuck Baum: Thanks for taking our questions. Just another quick one on the upcoming adagrassive data at ASCO in patients with brain... Sort of based on your conversations with physicians, is there a CNS response rate that you expect physicians to find clinically meaningful? And then secondly, just any color on how many patients we could see in the Adagasta plus Pembro combo data later this year. Thank you.

Yeah.

The next question comes from Michael Schmidt of Guggenheim.

Hey, good afternoon, Paul on for Michael Thanks for taking my question just another quick one on the upcoming <unk> data at <unk> in patients with brain Mets.

Chuck Baum: So let's talk first about CNS, what the physicians expect. You know, we think it's in that 20% to 25% range that C activity would be well accepted. That's the research and the conversations we've had with physicians in the community as well as academic centers. Yeah, I would say, you know, we'll continue to build on the program.

Based on your conversations with physicians because there are CNS response rate that you expect conditions define clinically meaningful and then secondly, just any color on how many patients we could see.

<unk> got that plus <unk> combo data.

Chuck Baum: You know, I think that that is what we anticipate with respect to monotherapy. We know, you know, a lot of our combination strategy evolves around combining antaggressive with additional targeted or immunotherapies. You know, the ability to enhance response rate and combination should apply to our drug being able to get into the CNS as well. So we'd expect our ability to augment the intracranial response rate as we advance in the program. And the next question comes from Mike Ulz of Morgan Stanley. Hey guys, thanks for taking a question. Maybe just another one, go up.

This year. Thank you.

So let's talk first about the CNS, what the physicians expect we think it's in that 20% 25% range.

To see activity would be well accepted thats the research and the conversations we've had with physicians in the community as well as academic centers.

I would say we will continue to build on the program I think that that is what we anticipate with respect to mono therapy, we know a lot of our combination strategy evolves around combining and aggressive.

Additional targeted or Immunotherapies.

The ability to enhance response rate in combination should apply to our drug being able to get into the CNS as well. So we would expect our ability to augment and a cranial response rate as we advance in the program.

Chuck Baum: You mentioned some subgroup analysis from the K1 study and in particular based on, status. Can you maybe clarify that? And is it specifically in TPS less than? Sure, we will be presenting data at ASCO on Covert A that goes into molecular subtypes, so that includes both PD-L1 status. And would say that, you know, this data set that we will present will have a significant number of patients to be able to draw conclusions about whether different TPS strata categorically or continuously are related to their response to adagressive. Secondly, we'll be looking by mutation subtype. That includes things we've talked about before, like STK11, but also common mutations like TP53 and CDKN2A.

The next question comes from Michael <unk> of Morgan Stanley .

Hey, guys. Thanks for taking the question maybe just another one on some of the ESCO updates will get.

Yes.

In a month or so here you mentioned some subgroup analysis from the <unk> study and in particular based on PD one status could you maybe clarify that.

Is it specifically in TPS less than one patients.

Yeah, sure we will be presenting data at <unk> on cohort a.

That goes into molecular subtypes, so the adequate bolt.

One status and would say that this dataset that we'll present will have a significant number of patients to be able to draw conclusions about whether a different TPS strata categorically or continuously.

Chuck Baum: So we will be able to provide perspective on all those. I think, as you also know, you know, we are pursuing strategies in the first line, non-small cell lung cancer related to molecular subtype. TPS less than one, for example, and STK11, for example.

It's a response to <unk>.

Secondly, we will be looking by mutation subtype that includes things we've talked about before like SDK 11, but also common mutations with <unk> 53, and CDK and two way. So we will be able to provide perspective on all of those I think as you also know we are pursuing strategies in the first line non small cell lung cancer related to <unk>.

Chuck Baum: You know, just to remind you all that, you know, those are two particular subtypes when they're seen with KRAS mutation. They're particularly non-responsive to chemoimmunotherapy, thus creating an opportunity for potential accelerated path development in that setting. And would just say, in general, that we continue to be pleased by what we see in those particular subpopulations and are continuing the enrollment of those first-line studies. But bottom line is, you know, we will be presenting that data as part of the ASCLE. Maybe just a follow-up there.

Acura subtype TPS less than one for example, an SDK 11 for example.

Just to remind you all that those are two particular subtypes, when they're seeing with K Ras mutation, there, particularly nonresponsive to chemo immunotherapy, thus, creating an opportunity for a potential accelerated path development in that setting.

Chuck Baum: What do you think, or what's the bar for adagressive monotherapy based on... You know, I would just say, you know, knowing what's out there, we do not anticipate that TPS less than one would have, a TPS score would have a major impact on the response to KRAS inhibitors. But we do know, based on, you know, subset analysis of Keno 189, work out of major medical institutions or otherwise that, you know, those same patients have a poor response to chemoimmunotherapy.

And would just say in general that we continue to be pleased by what we see in those particular subpopulations and are continuing the enrollment.

Those first line studies, but bottom line is we will be presenting that data as part of the ESCO presentation.

Got you that's helpful. Maybe just a follow up there.

What do you think or what's the bar for an aggressive monotherapy based on.

TPS.

Vacation less than one.

Greater than one.

I would just say knowing what's out there.

Chuck Baum: Notably here with PD-L1 less than one, if you do the, if you look at the Keno 189 subset analysis, the response rate was around 30% for that particular subset. If you look at the STK 11, you know, again, either in Keno 189 or at major medical institutions, the response rate is 25%. Note here that these are treatment naive patients, so they have never seen chemoimmunotherapy, and this is their response to chemoimmunotherapy.

We do not anticipate.

That TPS less than one would have in.

TPS score would have a major impact on our response to K Ras inhibitors, but we do know based center subset analysis of keynote 189, we're kind of major medical institutions or otherwise that those same patients have a poor response to chemo immunotherapy, notably here with PDL one lesson. One if you do if you look at the <unk>.

Chuck Baum: So in a way, that creates a bar for us to shoot for, and if our data continues to hold up for KRAS inhibitor or adagrassive even as a monotherapy, reason to believe that we should be able to exceed the response rates seen in those unmet medical need populations. And we can go to the Eagle now, can't we? Bob Sittie.

189 subset analysis, the response rate was around 38% for.

For that particular subset if you look at the SDK 11 again, either in keynote 189 or at major medical institutions. The response rate is 25% note here that these are treatment naive patients. So they have never seen chemo immunotherapy and this is a response to chemo immunotherapy. So in a way that creates a bar for us to shoot.

Chuck Baum: Hi, this is Carly on FreyaGal. Thank you for taking our question. Just to follow up on some of the prior questions on the combo with PEMBRO, can you share any preliminary thoughts on how you're thinking of designing a potential phase three? I know it'll depend on the data from CRYSTAL-7 later this year, but any early thoughts on the different options on the table would be helpful. And then we did notice on clinicaltrials.gov that the adagressive combo study with Boeringer-Ingelheim and SOS-1 inhibitors stopped recruiting, so if you could give any more color on the reason for that, that would be helpful. Sure, I'll start.

Four and our data continues to hold up four K, Ras inhibitor or <unk>, even as a monotherapy.

To believe that we should be able to exceed the response rates seen in those unmet medical need populations.

We can go to <unk>.

Sandy.

Hi, This is Carly on for Yigal. Thank you for taking our question.

Follow up on some of the prior questions on the combo with <unk> can you share any preliminary thoughts on how youre thinking of designing a potential phase three I know it will depend on the data from Crystal seven later this year, but any early thoughts on the different options on the table would be helpful and then.

Chuck Baum: I'll turn it over to Chuck regarding the combination study, CRYSTAL-7, and then what could evolve into a Phase III trial. Just a reminder, we'll share more data in the second half of this year, but we'll give you maybe some really high-level, at this point, where we're thinking of for a registration trial, but it's preliminary. Chuck.

I did notice on clinical trials that.

The <unk> combo study with Boehringer Ingelheim sauce, one inhibitor stopped recruiting so if you could give any more color on the <unk>.

And for that that would be helpful. As well. Thank you.

Sure I'll start and I'll turn it over to Chuck regarding the combination study Crystal <unk>.

Chuck Baum: Yeah, it's still early, obviously, but I think we might have had a conversation previously where we're thinking that the optimal opportunity for us initially would be in those patients with a TPS score of less than 50% versus the 189 regimen. So that's the thoughts right now. It's not solidified yet, but we're working on that. We're not ignoring the greater than 50% population. We continue to study that, and we'll have more data there, but that would be a larger and longer trial.

And then what would could evolve into will evolve into a phase III trial.

Just a reminder, we will share more data in the second half of this year.

But we'll give you maybe some really high level at this point, where we're thinking for a registration trial, but its preliminary Chuck.

Yes, yes.

Early obviously, but I think we might have had a conversation previously where we're thinking that.

The.

Optimal opportunity for us initially.

Would be in those patients with TPS score.

Less than 50%.

Chuck Baum: So in terms of sort of first priority, doing the trial that's more doable and could get us to a first-line approval faster, we think would be in the less than 50% TPS score. And then you mentioned the BI study. Yeah, we did discontinue.

Versus the 189 regiment. So that's the thoughts right now it's not solidified yet.

But we're working on that we're also we're not ignoring the greater than 50% population will continue to study that and we'll have more data there.

Chuck Baum: As you probably also noted, we have a SOS-1 of our own that's going to enter the clinic in the second half of this year. And we think that it has potentially favorable properties. And so that's where we're going to focus our efforts going forward.

But that would be a larger and longer trials. So in terms of sort of first priority doing the trial.

It's more doable and could get us to a first line approval faster.

Think would be less than 50%.

TPS score and.

Then you mentioned the <unk> study, yes, we did discontinue as you probably also noted we have a thoughts one of our own that's going to enter the clinic in the second half of this year.

Chuck Baum: I think just one thing to add to Chuck's comment as well is, you know, the basis for stopping that study was not related to any antagressive-related toxicities or adverse events. And as Chuck mentioned, we remain quite enthusiastic about our own program, which we hope to start enrolling patients by the end of this year after we file the IEP. The next question comes from Andrew Behrens of SVD Security.

And we think that it has potentially favorable property.

And so that's where we're going to focus our efforts going forward.

I think just one thing to add to Chuck's comment as well as the basis for stopping that study was not related to any added grasp related toxicities or adverse events.

David Meek: Thanks for taking my question. I assume you had some additional dialogue with the FDA. Since there's still some concern about the reason you didn't get a priority review despite having breakthrough designation, I was wondering if you could give us some more color on what you think happened. I know you may be reluctant. I do think it would help investors feel more comfortable with the outcome of the review process, does seem to be a lingering concern that I continue to get questions about. Spoilers.

And as Chuck mentioned, we remain quite enthusiastic about our own program, which we hope to.

Start up only patients by the end of this year after we filed the <unk>.

The next question comes from Andrew Burns of SPD Securities.

Thanks for taking my question.

You had some additional dialogue with the FDA.

David Meek: You know, as Chuck and I both mentioned in our opening comments, we remained very confident in the approvability of the new drug application, Prada-Aggressive. You know, we're working with the FDA, leveraging our breakthrough therapy designation in the real-time oncology review pilot program we have. There's good, active dialogue, productive, and we think it's progressing well.

And since there's still some concern about the reason you didn't get a priority review despite having breakthrough designation I was wondering if you could give us some more color on what you think happened, but I know you may be reluctant.

I do think it would help investors feel more comfortable with the outcome of the review process. Since it does seem to be a lingering concern that I continue to get questions about.

Soil.

David Meek: And while we do have a standard review, there's many examples where drugs have been approved before the PDUPA date, and we're going to be fully launch-ready in Q3. So that's where we are with the NDA review. It's progressing, and we remain optimistic. And the next question comes from J. Olsen of Oppenheimer. Oh, hey.

Chuck and I, both mentioned in her opening comments, we remain very confident in the approve ability.

The new drug application fraud aggressive we're working with the FDA leveraging our breakthrough therapy designation and the real time oncology review pilot program. We have there is good active dialogue productive and with its progressing well and while we do have a standard review, there's many examples where drugs have been approved before the <unk>.

Jamie Christensen: Thanks for taking the question. I appreciate it. Can you talk about what is required for a tumor agnostic path forward for adigrassib and non-long and non-colorectal tumor types? And then maybe just a big picture question, what are some of the lessons learned from adigrassib that you can apply to the development of 1133? And do you plan to have the first FDA-approved KRAS G12D inhibitor? Thank you. Sure, we'll start with Jamie on that.

<unk> date, and we're going to be fully launch ready in Q3, So thats, where we are with the NDA review is progressing and we remain optimistic.

The next question comes from Jay Olson of Oppenheimer.

Oh, Hey, thanks for taking the question I appreciate it.

Can you talk about what is required for a tumor agnostic path forward for <unk> and <unk>.

Jamie Christensen: Sure, yeah. Regarding the agnostic path, I think you are familiar with what we've shown in pancreatic cancers and then also other GI solid tumors. And we've seen what I would call as response rates that were compelling with early signs of the type of durability that would be associated with a tumor agnostic approval. We know the regulatory precedent here with immune checkpoint inhibitors looking at patients with MSI high. We also know of this with respect to NTRK inhibitors as well as BRAP inhibitors.

Non long and non colorectal tumor types.

Then maybe just a big picture question what are some of the lessons learned from <unk>.

You can apply to the development of $11 33, and do you plan to have the first FDA approved <unk> inhibitor. Thank you.

Sure I will start with Jamie on that sure yes regarding the agnostic path I think youre familiar with what we've shown in pancreatic cancers, and then also other Gi solid tumors and we've seen what I would call as response rates that were compelling with early signs of the type of durability that would be it.

Jamie Christensen: So do believe that there's a path there, both based on the activity that we've seen with the drug so far, as well as having a regulatory precedent. Due to the infrequency of the KRAS T12C mutation in tumors other than lung and colon, we wouldn't anticipate that it would take a large number of patients to get a tumor agnostic approval. But we do anticipate that it would be valuable for us to have as many different tumor types enrolled on the trial so that we can show the diversity of tumors that would respond to the drug. So I think we remain optimistic that that's going to be a path for us. Regarding the G12D read-through from G12C.

Associated with that tumor agnostic approval.

We know the regulatory precedent here with immune checkpoint inhibitors looking at patients with MSI High. We also know of this with respect to and track inhibitors as well as BRAF inhibitors. So do you believe that there is a path they're both based on the activity that we've seen with the drug so far as well.

<unk> is having a regulatory precedent due to the infrequency of the <unk> mutation in tumors other than lung and colon, we wouldnt anticipate that it would take a large number of patients to get a tumor agnostic approval, but we do anticipate that it would be valuable for us to have as many different tumor types.

Jamie Christensen: So, you know, we have been evaluating our G12D inhibitor and models of colon and pancreatic cancer. And the read-through from anagrassiv is, you know, that we have been able to see activity, particularly in combination with cituximab in patients with third line plus, you know, heavily pretreated colon cancer and the response rates and durability hold up with response rates over 40%. And then, you know, we will be talking about the duration of response and activity in the colon cancer setting later this year.

Enrolled on the trial, so that we can show the diversity of tumors that would respond.

So the drug so I think we remain optimistic that thats going to be a path for us regarding the <unk> read through from <unk>. So.

We have been evaluating our <unk> inhibitor in models of colon and pancreatic cancer.

And the read through from <unk>.

Jamie Christensen: But just suffice to say that we are, you know, encouraged by what we see there so far. On the pancreatic side, you know, the response rate of around 50% with the durability that we've seen so far, you know, seems supportive of monotherapy and KRAS being a driver in the pancreatic cancer setting. What we've seen preclinically with the 1133 compound is very consistent with that. With a monotherapy, 1133, we see about a 20% response rate in the colon cancer models.

That we have been able to see activity, particularly in combination with cetuximab in patients with third line plus heavily pre treated colon cancer and the response rates and durability holdup with response rates over 40%.

And then we will be talking about the duration of response in activity in the colon cancer setting later this year, but just suffice to say that we are.

Encouraged by what we see there so far on the pancreatic side that the response rate of around 50% with the durability that we've seen so far seems supportive of monotherapy <unk> being a driver in the pancreatic cancer setting what we've seen pre clinically with the 133 compound is very consistent with that with.

Jamie Christensen: When we combine with cituximab, that response rate starts to go up in the models to around 40 to 50%, just like what we're seeing clinically with G12C. And then, regarding pancreatic cancer models, we've seen 8 out of 11 responses. So, you know, response rates over 50%, probably consistent with what we've seen with adegressive monotherapy. We also know that combining with EGFR inhibitors or monoclonal antibodies in the pancreatic setting seems to be a promising approach based on our preclinical data.

With a monotherapy 133, we see about a 20% response rate in the colon cancer models. When we combined with Cetuximab that response rate starts to go up and the models.

To around $40 to 50% just like what we are seeing clinically with E C.

Jamie Christensen: So, we do believe that if we are able to advance 1133 into the clinic at a dose level that, you know, really covers the target, that we would be confident that KRAS is a driver and that we can come up with therapeutic strategies to advance the molecule forward. I am blanking on your last question. I think you've pretty much hit it.

And then regarding pancreatic cancer models, we've seen eight out of 11 responses.

So response rates over 50%, probably consistent with what we've seen with an aggressive monotherapy. We also know that combining with Egfr inhibitors are monoclonal antibodies in the pancreatic setting seems to be a promising approach based on our preclinical data. So we do believe that if we are able to advance 133 into the clinic.

David Meek: I would add, you know, just elaborate a little bit more, is the lessons learned from, you know, adegressive into, you know, 1133, you know, what's very comforting for us is the team that, you know, transitioned the program from, you know, discovery through development. That team is here in Maradi and certainly there's lessons learned from the adegressive program that we can apply to the G12D program. So, we think that'll help. Some of the synergies we talked about earlier, there's significant synergies we have in the development organization as well as the portfolio expands with the tumor types and, you know, academic center, study sites, and so on.

At a dose level that really covers the target that we would be confident that K. Ras is a driver in that we can come up with therapeutic strategies.

To advance the molecule forward.

I am blanking on your last question I think you've pretty much hit it.

Ed.

Elaborate a little bit more is the lessons learned from autographs had been to 133.

What's very comforting for US is the team that deal transition the program for them.

Discovery through development that that team is here a variety and certainly there is lessons learned from the from the <unk> asset program. So that we can apply.

David Meek: So, we're excited about that. Yeah, I guess just to hit on your last question, competitive state, so. You know, probably can't answer that question directly, whether we would be the first G12D inhibitor approved. We would certainly hope and aspire to that.

Two the <unk> program. So we think that will help some of the synergies we talked about earlier there are significant synergies we have the development organization as well as the portfolio expands with a tumor types and academic center study sites.

Jamie Christensen: But just to say, you know, we've been following the patent literature and publications. And, you know, we haven't really seen much out there that would indicate that the entry of another G12D inhibitor into the clinic is imminent, and of course, we'll continue to keep a pulse on that as we advance our program. The next question comes from Sylvain Twerken of JMP Security.

So we're excited about that yes.

On your last question competitive state so.

Probably can't answer that question directly or whether we would be the first <unk> inhibitor approved we would certainly hope and aspire to that.

But just to say we've been following the patent literature publications.

Jamie Christensen: Thank you very much for taking my question and congrats on the progress in the quarter. In my opinion, I've seen at AUCR where obviously much earlier stage KRAS-on inhibitors and also the potential emergence of pan-KRAS inhibitors. Could you just tell us about how they would compare or contrast?

And we haven't really seen much out there that would indicate that the entry of another <unk> inhibitor into the clinic is imminent.

And of course, we'll continue to keep a pulse on that as we advance our program.

The next question comes from Silvan <unk> of JMP Securities.

Jamie Christensen: direct KRAS neighbors such as yours that are already in the clinic. Thank you. Sure.

Thank you very much for taking my question and congrats on the progress on the quarter.

Jamie Christensen: I think first to note that, you know, we remain interested in that space as well. We have our own spectrum selective KRAS inhibitor program. We've learned in that program, as well as our G-12D program, that there are legitimate ways to target the active state, so we continue to look at that with respect to our programs. With regard to the, you know, kind of read-through for G12C, so, you know, G12C is among the most rapidly cycling mutations for KRAS, meaning that it shifts significantly between its GTP and GDEP-bound state.

In my opinion, a theme at ACR, where obviously much earlier stage <unk> inhibitors and also the potential emergence of pad kiosks in April could you just tell us about how they would compare or contrast to direct kiosks neighborhoods, such as yours, but already in the clinic.

Thank you.

Sure.

I think first to note that we remain interested in that space as well.

We have our own spectrum selective <unk> inhibitor program.

We've learned in that program as well as our <unk> program that there are legitimate ways to target the active state.

Jamie Christensen: And as you know, idegressive does bind in the inactive confirmation of KRAS G12C. One advantage we think adagressive has with that respect is that although it binds irreversibly in the inactive state, we remain above target plasma concentrations for the full dose interval. So even though active state inhibitors may be able to bind effectively to the active state, due to the kinetics by which that G12C cycles, we still believe that we are, at least with G12C, able to achieve the level of inhibition, regardless of whether the active state or inactive state is present.

So we continue to look at that with respect to our programs.

With regard to the kind of read through for <unk>. So <unk>.

<unk> is among the most rapidly cycling.

Mutations for <unk>, meaning that it shifts.

Significantly between its GDP and GDP bound state and as you know at aggressive does binding the inactive confirmation of <unk>.

One advantage, we think at aggressive has with that respect is that although it binds irreversibly and the inactive state we remain above targeted plasma concentrations for the full dose interval. So even now.

Jamie Christensen: You know, also to note that, you know, with regard to, targeting the active state, there are other mutations like G12R or some of the Q61 mutations that actually predominate then in the active state. And to go after those mutations, it probably is desirable to target the active state.

Active state inhibitors may be able to buy and effectively to the active state due to the kinetics by which that GLC cycles. We still believe that we are at least would <unk> be able to achieve.

The level of inhibition, regardless of whether the active state or inactive state is present.

Also to note that with regard to.

Jamie Christensen: And we do believe that that is something we're able to accomplish with our pipeline. And finally, I think you kind of asked about competition there. So for the pan-K-res setting, really all we're aware of right now is kind of the Boringer-Ingelheim and Revolution Medicines Program. And we know that Boringer-Ingelheim has talked a lot about pro-tac based strategies and that RevMed has talked a lot about strategies to kind of engage the cyclophilin machinery. What we're looking at is to stick from that.

Okay.

The targeting the active state there are other mutations.

Like 12 hour or.

Some of the Q 61 mutations that actually predominate than in the active state and to go after those mutations.

Currently is desirable to target the active state and we do believe that that is something we're able to accomplish with our pipeline.

And finally, I think you just kind of ask about competition. There. So for the <unk> setting really all were aware of right now is kind of the Boehringer Ingelheim and Revolution medicines program.

And we know that Boehringer Ingelheim has talked a lot about protect based strategies and that rather that has talked a lot about strategies too.

Chuck Baum: So bottom line is we think we can target the active state with a differentiated mechanism of action. The next question comes from Mauree Raycroft of Jefferies. Hi, thanks for taking my question. I was wondering, for the docetaxel arm in your adagrassive phase 3, what kind of PFS are you expecting in these patients, and is there anything to suggest that KRAS G12C patients could do better or worse than the general patient population on docetaxel? And then lastly, can you remind what proportion of patients in the confirmatory are coming from China? Sure, I can take that.

Engage.

<unk> engaged the cyclical and machinery, what we're looking at is distinct from that so bottom line is we think we can target the active state with a differentiated mechanism of action.

The next question is from Maury Raycroft of Jefferies.

Hi, Thanks for taking my question.

Chuck Baum: So we've done a meta-analysis, or a meta-like analysis, of all the published data for dose-to-taxol controlled studies where KRAS was looked at as a subset. And generally, our conclusions from those studies is that the PFS falls around 2.8 months if you look at the conglomerate. So a little bit worse than what you would expect from the overall population.

I was wondering for the Docetaxel arm in your <unk> phase III, what kind of PFS are you expecting in these patients and is there anything to suggest that <unk> patients could do better or worse than the general patient population on Docetaxel and then lastly can you remind what proportion of patients in the confirmatory are coming from China.

Sure I can take that.

So we've done a meta analysis or a metal like analysis of all the published data for Docetaxel controlled studies, where <unk> was looked at as a subset.

Chuck Baum: When we look at overall survival, generally the numbers are landing at around 8% based, again, on historical data. So again, the data suggests a little bit less than the overall population. I think one caveat to note is that immunotherapy and chemo immunotherapy are present, and those studies are older. But the preponderance of the evidence suggests that KRAS is a poor player in that KRAS mutated subpopulation. Regarding the China question, I think David is going to take that. Regarding the CRISPR-12 trial, the confirmatory trial, the trial is currently enrolling in the US and Europe. China's not yet come online. It will come online later this year.

And generally our conclusions.

From those studies is that the PFS falls around two eight months. If you look at the conglomerate so a little bit worse than what you would expect from the overall population.

When we look at overall survival generally the numbers are landing at around 8% based again on historical data. So again, the data suggests a little bit less than the overall population.

Sure.

I think one caveat to note is that immunotherapy and chemo immunotherapy President and those studies are older.

David Meek: So by the study finishing in the first half of next year, China will be a relatively small amount of patients that are contributed to the total enrollment, primarily Europe and the US. And our next question comes from Jason Gerberi of Bank of America. Oh, hey, this is Chiang for Jason.

Preponderance of the evidence suggests that K Ras in the port player and that K Ras mutated sub population.

Regarding the China question, I think David is going to take the share regarding the clinical trial, a confirmatory trial. The trial is currently enrolling in the U S and Europe , China has not yet come online. It will come on later online later this year. So by the study finishing in the first half of next year, China will be a relatively small amount of patients that have contributed to the total.

Chuck Baum: Thanks for taking our questions. Two from me, one on monotherapy and one on SHIP-2 combination. So, on monotherapy, I'm curious, have you explored the 400 milligram BID dose with monotherapy in saccline lung patients, specifically looking at sort of how the response rate and safety profile compared to the 600 milligram BID? It looks like from the combination with Pembro, you're getting better therapeutics window with the 400 milligram combined with PD-1. So, and then secondarily, on the same question, based on your understanding of Project Optimist, do you think the body of work of pedagogy of motor therapy is the kind of non-status quo that we require?

Roland.

Primarily Europe and the us.

Our next question comes from Jason <unk> of Bank of America.

Okay.

Oh, Hey, this is chi on for Jason Thanks for taking my questions. Two from me, one monotherapy and one not ship to your combination.

So on monotherapy I'm curious have you explored the 400 milligram tid Telus with monotherapy in second line lung patients specifically looking at sort of how the response rate and safety profile compared to the six central Connecticut PID. It looks like from the combination with Pembroke Youre getting better therapeutics window.

Chuck Baum: And then on shift to combination, you know, I think there was initially quite a bit of excitement because of the mechanistic rationale and also preliminary clinical data by the number of patients. But we haven't quite seen a lot of data since then and there are some timeline push from players across the industry. So, but lately, Novartis indicated they are starting a phase 3 with a ship 2 combination. Obviously, you cannot speak to what other companies rationale, but from Mirati perspective.

With the 400 <unk>.

Combined with PD one.

So.

And then secondarily on the thing.

A question based on your understanding about project Optimus do you think a body of work of <unk> monotherapy in second line non satisfy that requirement.

And then on a ship to combination I think that was initially quite a bit of excitement because of the mechanistic rationale and also.

Clothing machinery clinical data outbound into the number of patients, but we haven't quite seen a lot of beta cells and there are some timelines push from players across the industry.

Chuck Baum: Where are you at right now regarding the opportunity with the shift to combination? Thank you. So, yeah, I would say a few things. You know, number one is... We're highly confident in the approvability of the 600 milligram BID dose as part of our submission package. And you had mentioned Project Optimist.

But lately novartis and indicate that they are starting a phase III with a shift to a combination obviously you cannot speak to what other companys rationale from variety of puts that task.

Chuck Baum: So, you know, the agency, you know, does continue to, you know, reinforce the importance of Project Optimist. And as part of the collaboration with the agency, we're looking at the 400 milligram BID doses of monotherapy. We do anticipate that this is, you know, kind of a post-approval commitment, and we're going to continue to work with the agency on that front. And then noting your question about 400 mgs BID. So, several things to note.

Where are you at right now we're getting the opportunity with the ship to a combination.

Okay.

So, yes, I would say a few things number one as well.

We're highly confident in the approve ability of the 600 milligram.

Dose as part of our submission package.

And you had mentioned project optimists so.

The agency.

It does continue to reinforce the importance of project Optimus and.

Chuck Baum: One is that it covers our target plasma concentration of 1.5 micrograms per mil. And that is a concentration derived both from preclinical models, suggesting if we remain above that target for the full dose interval, that we are near completely inhibiting KRAS. And the 400 dose appears to accomplish that. That data is also derived from our ability to look at PKPD and repeat biopsies in the clinic. Again, at the 600 milligram dose, I think we have data suggesting that we are near completely inhibiting KRAS and modifying KRAS as a target.

As part of the collaboration with the agency, we're looking at the 400 milligram B I D dose as a monotherapy.

We do anticipate that this is kind of a post approval commitment and we're going to continue to work with the agency on that front and then noting your question about 400 Megs PID. So several things to note. One is that it covers our target plasma concentration of one five micrograms per mil and that is it.

Our concentration derived both from preclinical models, suggesting flea Raymond remain above that target for the full dose interval that we're near completely inhibiting K Ras in the 400 dose.

Chuck Baum: We, of course, continue to look at our own data clinically. And we're confident that the 400 mg dose level is covering the target based on exposure response analysis. In short, that is looking at the concentrations that would be anticipated at the 400 mg dose level, and looking at the response rates, and noting that those response rates are fairly consistent across the various, you know, kind of quartiles of exposure observed.

Appears to accomplish that.

That data is also derived from our ability to look at PK PD and repeat biopsies in the clinic again at the 600 milligram dose I think we have data, suggesting that we are near completely inhibiting K Ras.

And modifying K Ras as a target.

We of course continue to look at our own data clinically and we're confident that the 400 Meg dose level is covering the target based on exposure response analysis and short that is looking at the concentrations that would be anticipated that the 400, Meg dose level and looking at the response rates and noting.

Chuck Baum: So, we're confident in the 400 dose in general, especially, you know, in combination as we see increased dose intensity in combination with febrilezumab. And then, I think your last question was related to SHIP-2. You know, we do have plans to continue in our exploration of adegrassib in combination with SHIP-2 inhibitors as part of our overall development program. Ladies and gentlemen, that concludes the question and answer session for today's conference. I'd now like to hand over to David Meek for any additional or closing remarks.

That those response rates are fairly consistent across the various.

Kind of core titles of exposure observed so we're confident in our 400 dose in general, especially in combination as we see increased dose intensity.

In combination with <unk>.

Chuck Baum: Well, thanks for joining us this afternoon. In closing, I'll reinforce the relentless focus we have at Mirati on translating novel science into innovative therapies to bring health to patients. We're excited about the path we're blazing, and we're confident in our ability to successfully execute. And we look forward to speaking with many of you, sharing additional updates in the coming weeks and months, and see you at ASCO. Take care, everybody. That concludes today's call, you may now disconnect.

And then I think your last question was related to ship to.

We do have plans to continue in our exploration.

<unk> had been combination with ship two inhibitors as part of our overall development program.

Sure.

Ladies and gentlemen that concludes the question and answer session for today's conference I would like to hand over to David <unk> for any additional or closing remarks.

Well, thanks for joining us this afternoon and closing all reinforced the relentless focus we have a variety of translating novel science and innovative therapies. The brake ulcer patients. We're excited about the path, we're blazing and we're confident in our ability to successfully execute.

Look forward to speaking with many of you view sharing additional updates in the coming weeks and months and so you would ask so thank you everybody.

That concludes today's call you may now disconnect.

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