Q3 2022 Mirati Therapeutics Inc Earnings Call
Good afternoon, and welcome to the Marathi Therapeutics third quarter 2022 earnings call. My name is Jenny and I will be the operator for today's call. All lines have been placed on mute to prevent any background noise. After the conclusion of the 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.
Ask that you please limit yourself to one question and one related follow up if you'd like to withdraw. Your question. Please press star followed by the number two key it is my pleasure to introduce Ryan Asay.
Vice President of corporate Affairs Marathi.
Brian you may begin the call.
Thank you Jenny and welcome everyone to this afternoons call joining me on the call today are David <unk>, Our Chief Executive Officer Dr.
Dr. Chuck Baum, our president founder and head of research and development Dr. Jamey Christiansen, our Chief Scientific Officer, Ben Hickey, our Chief commercial officer, and Laurie Stelzer, Our Chief Financial Officer. We're also joined by our recently appointed Chief Medical Officer, Dr Al and Sandler.
Before we begin I'd like to inform you that certain statements. We make during this call will be forward looking because such statements deal with future events and are subject to many risks and uncertainties actual results may differ materially from those in the forward looking statements for a full discussion of these risks and uncertainties. Please review our annual report on Form 10-K, and our quarterly reports on Form 10-Q that.
Filed with U S Securities and Exchange Commission.
Afternoon, We released financial results for the quarter ended September 32022, and recent corporate updates. This press release is available on the investors section of our website at variety Dot com.
David I'll turn the call over to you. Thanks, Brian and thank you for joining us on the call today. The third quarter was another productive one for broady is it team made important progress advancing our strategic initiatives.
As a result, we are in the break of realizing what could be transformative catalyst over the next several months first our paducah date for autographs at its December 14th and we're excited by the prospect that people living with non small cell lung cancer could soon have the opportunity to receive out of grass. It.
We believe we've made a thorough and compelling application for U S approval in our interactions with the agency continue to be very constructive.
Second in first line non small cell lung cancer, we expect to share updates indirect in the cross our multipronged development approach this quarter.
This will include more data on the concurrent dosing, Nevada grass. It at 400 milligrams twice daily with full dose parallelism, App, which is our most advanced AD aggressive combination approach in the first line setting.
Third we're on track to topline the interim readout of the <unk> phase III Sapphire study by the end of the year for.
Fourth we made significant progress advancing M. R. T X 11, 33 R. K Ras G 12, D inhibitor and plan to file an IND later this quarter.
Jamie will say more about 11 33 program in his commentary.
With that I'll turn the call over to Ben to provide an update on our launch readiness and commercial organization.
Thank you David and good afternoon, everyone.
I'm pleased to report that we have now launched ready we have a greater than 100 person customer facing U S field force and our commercial.
<unk> seems a fully trained.
I'll take a few minutes to explain why we are highly confident that we have assembled an effective commercialization organization, which can successfully deliver on our commercial goals.
First our U S commercialization team has specific and extensive experience in lung cancer supporting multiple launches and includes a fully integrated team market access sales and medical affairs supported by unique digital platform.
Second.
Leasing team has a singular and unrelenting focus delivering at aggressive today oncologists hcp's and people living with cancer that we serve.
But from a payer perspective, our team has interacted with nearly all of the top clients across the country receiving positive feedback on the unique profile of that aggressive we expect to generate broad coverage within the first few months of launch.
Well it seems to continue to work on market development opportunities such as increasing about testing and identification of <unk> eligible patients, particularly in the community setting where over 40% of our pivotal study was enrolled.
We have also designed a distribution and patient assistance program in partnership with community Oncologists and we believe this program is best in class.
Importantly, we are also coming to market from a position of strength due to aggressive compelling clinical profile.
We believe the key attributes of allografts it will dry prescribe is to utilize it in that treatment decisions.
These attributes include at aggressive strong activity, including a 44% response rate and a 14 one months median overall survival as demonstrated in the pooled analysis, we presented at ESCO.
And low treatment related discontinuation rates. Additionally.
Additionally, the data we presented at <unk> demonstrated at aggressive had significant activity in patients with central nervous system metastases, including those with active and untreated CNS metastases, which is estimated to occur in approximately 40% of K rescue 12 C patients.
We are also seeing compelling clinical data in people with multiple non lung tumor types, which we believe is important in the minds of physicians.
In summary, we believe that these important differentiating characteristics combined with an experienced and focused commercialization organization position us well for market leadership within the K rescue 12 space over the long term, including future opportunities beyond the initial second line setting David I'll turn it back to you. Thanks Ben.
Before we provide an update on our pipeline I'd like to take a few moments to discuss the leadership transition we announced today Dr.
Dr. Chuck Baum has made the decision to retire next year. After 30 years of service to the biopharmaceutical industry and more than 10 years they'd Marathi.
Where audio is a great debt of gratitude to Chuck who founded and led the organization as CEO for nine years.
We would not be in position today to receive approval product grass, it and have a broad and innovative pipeline without chuck's dedication and vision Chuck is a pioneer and his life's work has positively impacted people living with cancer.
It's been a very generous partner and colleague to US all we thank him for his leadership, which has established Marathi at the forefront of targeted oncology.
I'm pleased that we will continue to benefit from chucks guidance as he transitions in the second quarter of 2023 and will provide ongoing strategic leadership as a member of the board of directors.
Chuck will continue to operate as president and head of R&D into the second quarter of 2023. This will enable Chuck to oversee several important milestones in the fourth quarter and support a smooth transition of the development organization to Doctor outlet family, who has joined Marathi as our Chief Medical Officer.
We're very delighted to bring Doctor Sandler to the company with 30 years of oncology drug development experience, including as the global head of oncology product development inside lab.
And late stage oncology development and Genentech.
Alan It's extremely qualified to continue the progress we've made in our pipeline and explore additional opportunities for autographs it including our first line combination strategy.
Now, let's step the medical knowledge, including approximately 18 years as a practicing academic medical oncologist, a key opinion leader and an investigator during his academic career paired with his experience and proven track record as a clinical leader.
Makes him an ideal successor to Chuck.
Alan has extensive experience managing complex R&D programs and I fully expect that his leadership and industry knowledge will benefit patients employees and our shareholders I'll turn the call over to Alan to share his initial thoughts.
Thank you David Good afternoon, everyone I want to start by saying that it's an absolute privilege to work at a company with such a relentless focus on science and deep commitment to improving the lives of people need.
Sure that same passion.
Ideas rapidly ascending to leadership and targeted oncology I'm thrilled to be joined with the exceptionally talented team at Roddy at such a pivotal time.
I have a long personal and professional relationship with Chuck and I appreciate his support and encouragement as I joined variety it will be an honor to work alongside him over the next several months as we navigate through a number of important clinical events, which could prove to be significant catalyst for variety.
Looking ahead I'm excited to assume the role of Chief Medical Officer Marathi.
Prior experience I'm intimately familiar with an aggressive and believe it is a best in class dry, but the potential to make a significant impact on people living with cancer.
I look forward to applying my decades of experience towards advancing our robust pipeline of compelling clinical programs, which I believe show great promise.
Chuck I'll turn the call over to you for an update on our clinical activities. Thank you Allen.
Let me begin by expressing my sincere gratitude to all my dedicated colleagues who have worked with me at Marathi over the last 10 years.
The opportunity to lead Marathi and bringing forward several potentially best in class treatment options for people with cancer has been the highlight of my career.
Proud of the organization's accomplishments and extremely optimistic about our future.
With David at the helm, Alan onboard and just a few corridors needed to complete the work I would like to finish.
It's a perfect time for my transition.
I will be moving on from them daily operational responsibilities during the second quarter of 2023, but I will continue to be a part of the company's strategic leadership as a member of the board of directors to support influence and celebrate our future success.
I want to extend a warm welcome to Alan and I expressed how thrilled I am that he has joined our my personal and professional interaction with Alan over the last 20 years lead me to believe that we are fortunate to have him leading our development organization through the next phase of growth.
In fact, Alan and I have been working closely together for the last two years.
He knows that aggressive well and has worked extremely well with the Marathi team I look forward to working with Alan.
As we advance the pipeline together.
With that.
I'll switch gears and begin with discussing at aggressive.
Let's begin with ESMO.
Where are we shared positive results from Krystal one.
<unk>, that's a monotherapy and in combination with Cetuximab in people with previously treated K Ras G 12, C mutated metastatic colorectal cancer or CRC and the third or later lines of therapy.
Feedback from Kols investigators and oncologists on our CRC data have been overwhelmingly positive.
As we expected the combination with Cetuximab should it put together, particularly compelling and differentiated efficacy profile.
No.
Our primary approach in CRC moving forward the.
The combination demonstrated a response rate of 46% and median progression free survival of six nine months.
Notably these results suggest that potential.
Substantial improvement compared with the current standard of care and are part of the differentiation story for autographs.
The combination data has strengthened our confidence in the potential for accelerated approval in late line CRC and we expect to finalize discussions with the FDA about the viability of utilizing this pathway soon.
We are actively enrolling additional late line CRC patients and the combination of at aggressive plus the types of matters.
In a phase two cohort of the Crystal one study, which we expect to be part of our supplementary NDA filings seeking approval for this indication.
We also have the phase III Registrational study ongoing in second line colorectal cancer patients called Krystal Ted.
Which is comparing the efficacy of that aggressive in combination with cetuximab versus standard of care chemotherapy.
The study continues to enroll well with strong interest from patients and physicians and we expect krystal tend to be the basis for all approval in second line and beyond colorectal cancer patients.
As we see from these CRC data at aggressive has the potential to treat people living with multiple tumor types.
And we believe this is an important differentiating characteristic for our program.
Moving to lung cancer.
We have several important upcoming catalysts.
We have an active and ongoing.
Dialogue with the FDA as we approach our December 14th and infinite.
As David mentioned, our interactions with the agency continues to be constructed.
Beyond the U S. We are continuing to advance discussions with European medicines agency on their review of that aggressive marketing authorization application. We continue to make progress toward our goal to expand the availability of that aggressive to patients in the European Union.
In first line non small cell lung cancer, we expect to share updates across our multi pronged development approach as.
As a reminder, our initial and most advanced at aggressive combination approach in first line non small cell lung cancer.
Concurrent dosing of autograph set at 400 milligrams twice daily with full dose umbrella is a mountain.
The initial data we shared at <unk>.
Give us confidence in the path forward.
The combination in the first line setting.
Our phase II Krystal seven study evaluating this combination is enrolling well and we are targeting targeting ESMO immuno oncology conference in December to share more mature data with a larger number of patients.
With these data we expect to have enough follow up on a sufficient number of patients to have a better understanding of the safety and tolerability of the combination.
These data along with feedback from scientific advisers and from the FDA will help inform our registrational plans in the first line non small cell lung cancer setting.
We are finalizing our first line strategy and we will provide an update on our next steps at ESMO Io.
I'll now discuss Krystal 12, a randomized phase three confirmatory study in previously treated non small cell lung cancer patients with a K Ras G 12 seat mutation, which is enrolling well worldwide.
As a reminder, <unk> phase III Registrational study cohort day was conducted in a heavily pre treated patient population with 98% of patients having received both prior chemotherapy and checkpoint inhibitor therapy.
The same patient population being evaluated in Crystal 12, and we would therefore expect our performance and Krystal 12 to be consistent with our cohort a results.
Additionally.
It's possible that with the introduction of the tablet formulation, we may see improve tolerability.
Based on the clinical data will be shared to date and our expectation for Crystal 12, we believe that aggressive we'll have a strongly differentiated profile in lung cancer.
With best in class objective response rates overall survival and penetration of the central nervous system or CNS.
<unk> is the first <unk> inhibitor to demonstrate substantial clinical activity and people with active untreated CNS metastases, which is a large and poorly served patient population.
Let's shift to sit to that which is being studied in a registrational phase III study called Sapphire.
This study enrolled patients.
With the second or third line.
Non squamous non small cell lung cancer, who derived prior clinical benefit following treatment with a checkpoint inhibitor and chemotherapy.
The Sapphire study is on track to top line interim results for overall survival this quarter.
We believe the study was well designed and sufficiently powered to demonstrate a positive outcome.
We intend to share the top line results in the form of a press release by the end of the year, depending on the outcome, we expect to disclose the data at a medical meeting in 2023.
If positive this 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 2023.
<unk> has the potential to treat a large number of people.
With approximately 70000 patients with second or third line non squamous non small cell lung cancer in the U S and Europe .
With that.
I'll turn the call over to Jamie for an update on our earlier stage development pipeline.
Thanks Chuck.
Ill begin by briefly touching on that my T X 133, which is a potent and selective <unk> inhibitor that targets, both the active and inactive states of the K Ras protein.
In the past we've highlighted our research emphasizing the importance of maintaining Maxwell Hey, Rusty 12, do you target inhibition for the full duration of the human dose administration cycles, which has historically been a challenge.
In response to these observations we have emphasized the development of formulation strategies designed to enhance oral absorption and increased durable systemic drug exposure.
We've made progress and significantly increased our confidence in the ability to achieve sufficient drug concentrations and maximal target coverage and human clinical trials with oral administration.
As a result, we're prioritizing the IMD for the oral formulation of 133, which we expect to submit by the Covid This year.
We remain very excited about 133, and the transformational potential that this compound could have in a large and underserved patient population, which he 12 T mutated cancers.
As a reminder, the kers G 12 D mutated cancer patient population is approximately three times larger than the <unk> 12 C. Patient population. In addition, <unk> mutations are highly prevalent and people with pancreatic cancer and colorectal cancer.
Now moving onto Emirates, TX 17, 19, our MTA cooperative P. R M. A C five inhibitor.
17, 19 isn't rolling in ongoing phase one two clinical trial in patients, whose tumors harbor an M tap gene deletion.
This gene deletion represents up to 10% of cancer patients with solid tumors.
Encouraged by our early clinical experience with shows that the pharmacokinetics and systemic exposure are consistent with expectations to achieve therapeutically meaningful drug concentrations based on our preclinical defined targets.
We're also pleased to report that we were granted fast track designation for 17 19 in the third quarter.
Which reflects the strength of our preclinical data and the potential for 17 19 to address unmet medical needs.
Looking ahead, we expect to share initial clinical data for this program in 2023. After we've selected a dose and generated sufficient data to demonstrate clinical proof of concept.
In addition, our investigational new drug application for <unk> 902, our sauce, one inhibitor was accepted by the FDA and we've recently initiated phase one clinical trial.
We believe that Orlando two has the potential to be used in combination to enhance the activity of EDA grass. It and it's another example of our strategy to maximize the value of a head of grass it by pursuing a broad range of <unk> targeting strategies and indications.
We also recognized the potential value of sauce, one inhibition independent of K, Ras mutations, including Egfr mutated non small cell lung cancer as well as malignancies harboring other non G <unk> family mutations.
Also we recently announced two clinical collaborations which continue to be an important part part of an aggressive strategy.
First we entered into a clinical collaboration with Audi Bioscience to evaluate the combination of EDA grass it with Nab Sirolimus and people with advanced non small cell lung cancer and other solid tumors harboring at K rash CTO of <unk> mutation.
Preclinical models have shown compelling evidence supporting the combination of K ration M Tor inhibitors, and K Ras mutated cancers.
Combination is directed at achieving a deeper and more durable inhibition of the <unk> dependent signaling pathway and also addressing resistance pathways that may bypass K, Ras dependent and selected tumors we.
We anticipate that this will result in improved patient outcomes compared to either single agent.
Secondly, we entered into a clinical supply agreement with insight to evaluate the combination of a grass it with their oral small one small molecule PD L. One inhibitor.
Both clinical collaborations demonstrate varieties focused on pursuing the grass it and combination therapies to benefit people living with difficult to treat cancers.
Overall, we're pleased with the significant progress, we're making across the portfolio.
I am Archie X 133 will be our third I N D. In the last 12 months.
This illustrates the productivity and efficiency of varieties internal discovery engine, we look forward to providing additional updates in the near future with that I will hand, it off to Laurie.
Jamie.
Let me begin by saying that from a financial management perspective, we continue to utilize our capital and a disciplined manner to ensure we advance our pipeline invest in innovation and effectively launched products to drive sustainable long term growth now.
Now I will walk through our income statement and touch on a few other key financial metrics.
Revenue for the third quarter 2022 like $5 $4 million, which was driven by the recognition of a $5 million milestone payment from design that that was contingent on starting a pivotal clinical study for autographs that in a second indication and design that designated territories.
This compares to revenue of $71.8 million in third quarter of 2021, where we recognized $66 $6 million of revenue associated with the transfer of the license and know how in Madagascar. It's part of our agreement, we sign them and a $5 million milestone payment from Beijing associated with the start.
The first pivotal center back in a clinical study and the Beijing designated territories.
Research and development expenses for the third quarter of 'twenty, 'twenty, two or $131.1 million compared to $116 $1 million for the same period in 2021.
The increase is primarily due to an increase in salaries and other employee related expenses, including share based compensation expense associated with an increase in head count to support our growing pipeline.
General and administrative expenses for the third quarter of 2022 were $68 million compared to $35 $2 million in the same period in 2021.
The increase is primarily due to an increase in commercial readiness costs in preparation for a potential product launch an increase in salaries and other employee related expenses, including share based compensation expense as we grow our sales marketing and G&A staff.
And an increase in facilities costs to support the organization.
Net loss for the third quarter of 2022 with $173.6 million or $3 90 per share basic and diluted compared to a net loss of $81 million or $1.55 per share basic and diluted for the same period in 2021.
The net loss for the third quarter 2022 included $9 5 million dollar gain recorded upon the dissolution of metal gene, which leads Marathi Canadian subsidiary.
We ended the third quarter with approximately $1 $2 billion in cash cash equivalents and short term investments, which gives us a cash runway well into 2024.
During the third quarter, we sold approximately one 9 million shares of common stock under our ATM facility, which generated net proceeds of $155 million.
Please see our press release from earlier this afternoon for additional details about our third quarter 2022 financial result.
David I'll hand, it back over to you.
Thank you Laurie.
We're opening the call for questions. Let me conclude by saying how pleased I am with the considerable progress our team has made this quarter.
Continued to advance our diversified clinical pipeline and prepare for the potential launch about a grass had been in the U S. As.
As we closed out the remainder of this year and look to 2023, we're very excited about the prospect of Marathi, helping people with cancer and creating value for the stakeholders will enable that to happen.
Thanks to those stakeholders, we are well capitalized which gives us the ability to further investigate hosted promising clinical opportunities.
We remain optimistic that we will be granted approval to launch out of glass in the coming weeks and I can assure you that we will do so with vigor.
Fortunately, we benefited from watching and analyzing the kers G 12 C market evolved in the last 18 months as it has been built from the ground up we've engaged extensively with key accounts and community oncologist, which helped us to formulate what we believe will be a very effective launch strategy.
As you've heard today, we are making solid progress on our key pipeline initiatives and we are very optimistic and excited about our future.
I'll close by thanking the <unk> team for their individual and collective efforts this quarter I'm truly proud and grateful to lead such a dedicated and accomplished organization.
On behalf of all of US are Marathi, we thank you for your support and interest in the company.
With that Jenny we're ready to open the call for questions.
Thank you.
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. We ask that you. Please limit yourself to one question and one related follow up if you'd like to withdraw. Your question. Please press star followed by the number two key.
Please hold for a moment, while we poll for questions.
And your first question comes from solving Richter with Goldman Sachs.
Good afternoon. Thanks for taking my question just with regard to the partnership with insight on their oral PDL. One could you just share what led you to this collaboration and what aspects of the early data that gives you confidence here and your thoughts about where this may fit in longer term.
Absolutely, yeah, but Jamie I'll take that sure. Yes, I think first of all we remain very confident in our strategy to combine with <unk> in the frontline setting and as Chuck mentioned, we'll be talking about that at ESMO I O.
Essentially with the insight collaboration they.
They approached us theyre very interested in augmenting their PDL, one oral inhibitor program with a variety of combination strategies and I think it was easy for us to have a very robust discussion with them about clinical trial design and essentially it's an opportunity for the further development of EDA grasp.
But in that setting, but essentially driven by insight.
Thank you.
And we'll go next to Tyler Van Buren with Cowen.
Hey, guys. Thanks, very much Chuck I would just like to say a heartfelt congratulations on the many impressive accomplishments you've achieved during your tenure of variety in your career.
He made a mark your mark on the chaos in the broader targeted oncology space and I've enjoyed working with you and you'll be missed.
Thank you.
With that I'd, just like to ask about the impending Krystal seven out aggressive Pembroke combo data at ESMO I O. What do you guys believe is the upper bound of the acceptable limit of grade three plus <unk> and on the efficacy side. What response rate do you think would be compelling as we think about the potential to beat Pembroke chemo in a pivotal trial.
Yeah.
Sure Tyler.
Yeah I'll take that.
First of all thanks for your kind words about Chuck just to let you know that he's not going anywhere tomorrow.
So you'll see him again Trust me.
Regarding okay, seven and what we expect to see upper balances. So on let's let's have a conversation about four weeks, we're gonna be at ESMO Io with four weeks as Chuck mentioned it will lay out everything to you. Our overall strategy for the frontline setting with that and we'll get into all those details. So it is Mario.
Fair enough. Thank you.
And well move to our next question from Gena Wang with Barclays.
Okay.
I also wanted to add Chuck you you'll be missed.
It has been great working with you in the past many years.
Also Allen of we look you know will come on board, we look forward to working with you. So I also have just one question regarding Krystal seven Arsenal Io will you be aiming for regular abstract all late breaker abstract and also you know since last update June all the patients were from.
The cohort that peaking capsules what percentage of patient from this update will be unpopular.
Sure Al.
Jump in to that and I'll throw it over to Chuck to talk about some of the specifics of that.
We're shooting for a late breaker abstract at ESMO oil and as soon as that's up.
What we know more details we'll share that with you Gina but stay tuned over the next couple of weeks Chuckle answered the question about perhaps a caps, yes. So as you know all of the recently enrolled patients since our last discussion where on the tablet and.
Don't have the exact percentage for you, but it's the vast majority of the patients that will report it.
ESMO Io will be will have been dosed on the tablet.
Okay, great. Thank you.
And moving on we will go to a question from Jonathan Miller with Evercore ISI.
Thanks for taking my question and congrats from me as well Jack.
Why don't I ask about a second line launch actually since we've since we've had a bunch of questions on the Crystal seven data.
I'd love to get your sense on testing adoption in the second line and what proportion of patients you expect in the second line.
No they're K Ras status is that still going to be a major limitation on the rate of our launch in the second line setting.
Yeah Yeah.
Yes, Jonathan we looked at this very closely we continue to look at it closely enough then I'll share some of the details with you sure. So.
As you know testing predominantly because at diagnosis. So we think that testing rate today is just over two thirds or so with the market. So still some room to grow there.
And to your point as they transition. Unfortunately, some of these patients progressing second line, we're seeing over 50% of those patients have been identified so we do think that over half of the market is available today and we expect it to continue to grow almost on a linear basis as both the testing rate has room to grow as well as that patient identification issue.
And second line. So again, we think it will be a continued to grow and I think we'll be launching into a market with the momentum, but it will take a little while to fully mature.
Thanks, very much and how about reimbursement in that setting a do you expect that to be a relatively easy to accomplish given.
Hey, Ross is already active in the space.
We spent the last six to 12 months engaging with all of the top payers across the country and they understand our profile very well and understand our efficacy profile in particular, so we do expect it to get broad coverage the rate of adoption.
It will take a couple of months, but we'll do that very quickly.
Pretty broad coverage, we don't see significant issues on that front.
Thank you very much.
Yeah.
And we'll go next to Michael Schmidt with Guggenheim.
Oh, Hey, guys. Thanks for taking my question.
Yeah, maybe another commercial question.
The <unk> date approaching here in December how should we think about the potential launch trajectory of that aggressive next year, perhaps relative to the Amgen experience.
Centering the clinically differentiated profile of the drug.
Is there perhaps.
You know an opportunity to switch patients from from other care us inhibitors or are we thinking more about.
No industry addressing on newly diagnosed patients. Thanks, so much.
I'll start and then I'll add a couple of things.
Let's not forget we're 18 months after the launch of little across we are the second to market being the first to market you do have a bolus of patients that are quickly available to you our patients. So we're on the early access program.
For the launch of a liberal kras, you'll immediately move to commercial drug. So that certainly helps the first mover that patient population will not be available to us some of the second and third line patients that a deal where available at launch will not be available to us.
Rapid reimbursement will happen as Ben mentioned, so we expect reimbursement in the first in the early months of approval, but that's going to take a few months. So that the launch trajectory will be slightly different as a second asset to the market, but over time, we certainly see.
You'll uptake of <unk>.
So that aggressive goal and over time, we clearly see market leadership over time, but the launch reactor will be a little bit different than one does see what's the Democrats.
Yeah, I'll just I'll just add in the no we wouldn't expect to see a great deal of switching from existing so we're really playing in that you. Just second line patient population, which is where we will be sourcing patients from so as David mentioned, we don't expect to see the significant bolus that first to market assets.
But more of this linear incremental approach over time.
With the you know the benefits being realized by the patients and physicians overtime.
And we'll go next to Michael <unk> with Morgan Stanley .
Hey, guys. Thanks for taking the question, maybe just a follow up on the case of data that we're expecting as Hawaii, Oh here in a couple of weeks or months here.
I know you mentioned, having sort of sufficient data to get a good read on efficacy and safety, but wondering if you could maybe give us a rough idea of the patient numbers and maybe also the level of follow up we should expect.
Hey, Mike.
What we're going to share in it as four weeks from now we'll certainly share all the details there it will be more patients that we.
Sure that ESCO it will be longer durations of therapy that will be shared at <unk>, we're definitely need to have and it will be early data, let's let's not forget that but it is to look at safety and Tolerability. The combination of an early look at the efficacy in this case it would be more response rates, but over time, we're looking at PFS and OS and those pay.
Population will have all those details in four weeks.
Yep.
Thanks.
Yes.
And we'll go next to Jason <unk> with Bank of America.
Hey, guys. Thanks for taking my questions.
My question just curious.
Curious on the insight press release, there was some commentary about mitigating.
Mitigating immune related adverse events. So I'm, just curious sort of what you potentially see as sort of the unmet need of going to an oral PD one may solve for or maybe that's just language that anti chose to use when you don't agree with and then also.
Just the rationale it seems like you started a new phase III study looking at <unk> monotherapy sequentially, followed by K Ras PD, one in the TPS greater than 1% patient. So just curious to what extent that may have been driven by anything that was seen with the Amgen study data at world lung.
Sure Yeah. This is Jeremy again.
So regarding your first question on the commentary and the insight press release.
I'd just say that this is a way that insight is really positioning their molecule are they really believed that the flexibility around an oral and the shorter half life as a way to kind of.
You know mitigate potential immune related aes, but I think if you look at all of insights press releases and positioning around this molecule. They abuse consistent language throughout and then I'll take this especially applies to add a grass it.
In any way.
So I think that's the first answer I think on the second question regarding sequential administration.
K Ras inhibitors with Pembina as a mab.
You know I think or other immune checkpoint inhibitors.
Our focus remains concurrent administration, we do believe that there is a clear path forward with concurrent administration. We do believe that there is a mechanism based interaction between K Ras and its ability to essentially.
Some of the cells in the microenvironment and the ability to co administer with that drug effects.
Checkpoints is in our mind, a clear advantage and this remains our strategy moving forward.
As mentioned a couple of times on the call you'll get a good picture of that at ESMO Io This year.
And well go to our next question from Maury Raycroft with Jefferies.
Hi, Thanks for taking my question.
You talked about the potential to get the AD a graduate of approval before December 14th can you provide more specifics on where you're at with discussions with FDA I guess, particularly do you have a draft label in place and does it include any specifics on CNS activity and have you had a late cycle review meeting.
Sure.
What I would say is we remain very confident in the approved the ability of the NDA.
We don't think it's appropriate to get into the D.
Or disclose the details of the conversations of the recent interactions we're having with the agency.
The conversations are productive, they're constructive and more details will come out.
As soon as we have them.
We remain optimistic about the approve ability.
Got it and as far as the label goes is there anything do you have the CNS data in the label can you comment on that.
Yeah, we're not going to get it to the Congress the specifics of the deal the.
The FDA interactions at this time.
And we will move on to my question from Eric Joseph with JP Morgan.
Hi, good evening, thanks for taking my questions.
I'm, just wondering whether I guess, given the co break 200 update with Luna Cross at ESMO.
Where data sort of underperform that safety performance I'm wondering if there are any read throughs in your view to your phase.
Phase III Krystal 12 study, but I'm also curious to know whether you've had any feedback from physicians on sort of the.
Evolving efficacy profile of Bloomberg crossing whether that kind of represents an opportunity for differentiation with the launch about aggressive. Thanks.
Yeah. So.
I think importantly, we pointed out during the call.
At our patient population from cohort, a and K 12, Krystal 12 were identical.
And just to point out that if you look at the patient population for co break 100.
Just look at those patients that had I O plus chemotherapy.
The response rate there and the PFS looked very similar to what was seen it could break 200. So we do think actually that the data from 100 was predictive of what would happen in 200 is just that the patient population was different.
So we don't expect in our case for there to be any difference between those patient populations that we're studying all patients in our studies were administered both chemotherapy and Io checkpoint inhibitor therapy before coming on to our trial.
And regarding the physician reaction.
We're at aggressive will fit in the in the.
Terry will physicians when they do need a K rest of Utah <unk> inhibitor.
It's been a really good third quarter for us as we roll it out more data actually began at <unk> and then the data that we've shared the competitive landscape.
The more of the profile of the physicians that see with that aggressive as Ben has mentioned with the response rate CNS activity median overall survival data that we shared at the house go.
Colorectal cancer data that was shared a desk. The totality of this data has been very encouraging feedback all of US. It's been a lot of time with customers and the feedback has been very positive for us. So physicians are anxious to have another product to be able to treat their patients. So we're excited about the.
Coming opportunity to present that to physicians.
And we'll go next to Ben Burnett with Stifel.
Alright, Thank you very much I.
I wanted to ask a question just on the ongoing NDA review.
The the change about a grasp of the formulation change from from capsule to tablet did you have you disclosed how many patients or what level of patient data with the tablet that you submitted to the FDA that's being reviewed as part of this NDA.
But we have not we've not disclosed that information.
Regarding the tablet formulation, but what I can say is the the tablet formulation is in the NDA and that's the formulation we expect to have approved.
And we will move on to Andrew Berens with SBB Securities.
Hi, Thanks for the questions and my congrats to the Chuck for reaching a milestone.
Guess another on the commercial lumen Crafts, you mentioned in the prepared comments that you've learned a lot on the <unk> launch, which I think most agree has been more sluggish than many had anticipated wondering if you could give us some color on what you think was going on and what you plan to do differently and then I just have a follow up question too.
After that.
Sure Ben I'll take that first question sure I'll just start with the we very intentionally built an organization around the customers in the micro markets that we see so that's coming across access medical and our sales representatives. So we really think that we've hired that are best in class team.
<unk> differentiated team secondly, we really do believe we've got a differentiated product and then specifically as it pertains to the account dynamics, we've been out there for a while and we spent a lot of time keep in mind that our study over 40% of the patients were actually enrolled from the community. So we've spent a lot of time in the community centers.
Really understanding the patient flow and where the genetic marker occurs in the electronic health system or if it doesn't and who in the office is responsible for that role. So there really is some operational challenges that we've spent a lot of time with.
But we think that we can help try and effect.
And keep in mind that with our over 100 person field team, we really kind of doubling the noise and promotion in the space and bringing K resonates well see even more to the top of mind. So we think with those additional efforts will continue to see the market opportunity grow overtime.
And hopefully, we really think that that aggressive as a really competitive agent in that market.
Okay.
And then just a question on the ongoing.
400 milligram B I D second line cohort I'm, just wondering how far along that ends in enrollment.
Just wanted to confirmation you still think that's going to be a phase four commitment at this point.
So regarding the enrollment we ever disclose where we are with enrolment with that specific trial.
Regarding a pull.
Post approval commitments.
I don't think we're prepared to have that conversation at this time as well I think you ought upon approval, assuming any post marketing requirements, we'll share those details.
And we will go next to yourself.
With Citigroup.
Alright, great. Thank you very much for taking the questions I just had a question on Krystal 12, and then an unrelated follow up on the RMT five so on Krystal 12, I think Chuck said your you said, it's enrolling well worldwide I'm wondering if you could say specifically what the percent enrollment was in Crystal 12 at the time, when we submitted the NDA for <unk>.
And the reason I ask is I'm sure you guys saw that earlier today another company ADC therapeutics indicated that for the.
The FDA would consider celebrated approval pathways that they want to see that the confirmatory phase III is well underway and ideally fully enrolled at the time of the filing.
Yeah.
Yeah, I'll take that question that that's.
Pretty clear one.
What I can say is our trial Krystal 12 was underway prior to our NDA being submitted.
<unk> well underway on our NDA was accepted the FDA is very aware of where Krystal 12 is an enrollment and we met the bar of substantially.
Enrolled.
So we do not see that as an issue for a proof of ability for at aggressive Krystal 12.
Okay got it and then this one's probably for Jamie.
Amy So with respect to 17 19, P&C five inhibitor can you comment on the how its different potentially from the Amgen drug AMG 193.
Biochemicals perspective, as well as how youre planning to develop the drug differently versus Amgen strategy. Thank you.
Sure, Yes, it's a little bit hard to read through to Amgen is they have not disclosed the chemical structure of their molecule to my knowledge.
We have been following the patent literature and otherwise.
I would just say with regard to 17 19.
We are very comfortable with the degree of selectivity.
For <unk> deleted tumors cells versus non <unk> that includes normal cells. So we have a 70 fold class ratio of selectivity and when we model that out with regard to the clinical pharmacokinetics and peak to trough ratio. We believe that it's very likely we would be spared.
<unk> <unk> five in normal cells I think as you know one of the key issues for first generation <unk> inhibitors that don't discriminate for the MTA binding and PMT five that there are mechanism based toxicities or lot of myeloid suppression neutropenia thrombocytopenia anemia.
And other issues that are encountered and we do not anticipate too.
Are those for that reason and finally.
As you noted.
You know the development path for the drive vs Amgen and I would just suffice to say that we are interested in a lot of key I'm tap deleted cancers, where the deletion is common and where genomic testing is available that includes non small cell lung cancer pancreatic cancer and a number of small.
There are indications, where we believe there might be a fast to market strategy. If the response rate should hold up our preclinical data has suggested that this can't be a mechanism of action, where you do see tumor response or set a reductive activity, we would like to leverage that certainly during our development program.
And we will go next to Silvan <unk> with JMP Securities.
Yeah. Thank you very much for taking my question.
I have a question regarding kind of comments made by Amgen.
So far.
Democrats, that's been prescribed for 3700 patients and they estimate that roughly 7000 in the second line non small cell lung cancer available. So in my eye I view the penetration fairly good so how how would.
Would you say going forward now you could influence or kind of tip, the hand, and the new patients that come in.
You know telling doctors to pick.
Other gossip Christmas Lowe crossing in these new patients.
Giving that that's already a fairly high penetration and then the second line non small cell lung cancer patients. Thank you.
Sure Ben is that question sure.
Just on definite it's important to get definitions correct. Here. So there are seven line 7000 patients who are new to second line. When you look at the entire second line plus market. That's 12 to 13000 patients. So that's the market that Amgen launched into was the 12 to 13000 now over time that.
Market gets closer to really the 7000, those patients get treated and they will likely only get treated once with a K Ras inhibitors. So well they had launched into that in a 3700 really comes from that larger pool.
The majority of the opportunity moving forward will be in that 7000.
But again that coal that 3700 was being pulled from a much larger market.
We will go next to Evan Sacramento with BMO.
Hi, guys. This is knocking Hoffman on for Adam and thanks for taking our question.
So you had mentioned on call our focus in that aggressive on the opportunity in the <unk> setting.
How are you thinking about the community versus academic setting and we are just wondering what youre seeing in the market or hearing from physicians and what this means for potential market segmentation.
Sure, we're going to the community the academic setting where we're actually focused on bolt.
So it's important that the academic centers, that's where you'll have a lot of clinical trials are conducted it's where a lot of the key opinion leaders are in the community setting you have that plus you have a lot more of the patients that are in the community setting in second line non small cell lung cancer. The majority of the patients who are in the community setting. So we are focused on bolt at this time as Ben mentioned.
And in his comments, 40% of our patients in the cohort a trial to registration for all or from the community setting. So it's good that the community physicians with a number of them already have clinical experience that we have other ongoing clinical trials within the community setting as well because thats, where the patients are so.
We've got that deal surround sound approach. If you will it's not just the academic setting. It's also the heavy reliance on the community setting because that's where the patients are then thats a comment to me too yeah. I think the only thing I'd add to that is in the community are also treating across tumor types as well as we think about the data that Chuck.
As I've mentioned now that we presented in CFC in pancreatic and <unk>.
Human data, we continue to see differentiated efficacy there.
So we think that is a very robust part of our differentiation story.
Moving forward, both in monotherapy as well as a combination so across James.
Good point, because the community center for the community setting physicians they treat all tumor types not theyre not as specialized as the academic centers.
Okay.
And we will go next to Jay Olson with Oppenheimer.
Oh hi.
Thanks for taking the question and I'll add my congrats and well wishes to Chuck.
I'm curious about any thoughts you could share on the accommodation is looming crash plus ship two inhibitor and how that may impact your expectations for <unk> plus ship to.
And when we might expect to see data from that study.
I had one follow up if I could.
Sure. It's David here I would say, we've got the ongoing study with a ship to with Novartis that trials underway Novartis is leading the way with that program.
We'll look forward to share the data when it becomes available some time, yeah. It would be sometime next year.
I'm, sorry, I said novartis in this therapy.
Okay great.
I guess can you also comment on the.
The potential for added gradually plus chemotherapy in first line non small cell lung cancer.
And whether or not that could be a registrational approach.
We will get to that next month at ESMO Io, we talked about the holistic frontline strategy, who will talk.
But our multi pronged approach to the frontline setting.
So four weeks from now.
And we will go next to swap note Malakar with Piper Sandler.
Hey, Thank you for taking my question, although alluded to in the past given the importance of the combination approach also I talked about some <unk> in the frontline setting.
Just wondering if there is any specific data that has been generated to see that the talks that are associated with low market ups and Pembroke is not a class effect of <unk> inhibition in the buyback of absolute differentiator.
Jamie I'll take that yeah, Hi, this is Jamie.
First of all I think we do not believe this is a class effect again, we're moving forward with the combination and we'll be talking about that more.
In the future and I'd say there are a few reasons to believe that this not a class effect. One is if you look at historical combinations with.
Immune checkpoint inhibitors and tyrosine kinase inhibitors, it's very clear that there are some agents that are readily combinable.
Our own central that nib.
And.
Cabozantinib and and others are readily combinable same drugs and class <unk> sunitinib drugs like Chris. Unfortunately, not so I think it's hard to say that the Teekay is a class effect when you see that.
No particular observation I.
I think point number two is we could point to that differentiated physiochemical properties of drugs like <unk> and some of the competitors and one thing to note about <unk> is the kind of <unk> ratio is probably a best in class that means an aggressive as low intrinsic reactivity and a lot of its binding affinity is through non covalent.
That means we're likely to avoid off target issues. The second Physiochemical properties I think notice the peak to trough ratio in terms of pharmacokinetics, we don't see a large variation.
And C. Max exposure to <unk> exposure, so its likely we don't see high levels of drug in tissue.
That are disproportional over the dose interval, we do think that that's another way we might be able to avoid any.
For example, hepatic toxicity.
So yes bottom line.
I don't think this is a class effect I think there are several reasons to believe both based on historical development of drugs as well as the Physiochemical properties of data.
Thank you Jamie we have time for one more question Jenny.
And well go to our cabinet Patel with B Riley Securities.
Yeah, Hey, good.
Good afternoon, thanks for taking the question.
Maybe first just to be clear on one of the previous questions that was asked.
Can you can you confirm that based on any recent communication.
With the FDA that the agency is not requiring you to fully enroll krystal seven before potentially granting approval by the particular Friday.
Yeah first somebody said I think give me Krystal 12, which is our confirmatory trial Krystal.
So yes, we can confirm that.
Okay, Okay and then.
Today, I think that's a different situation I can't speak for that company I can just speak for us.
Okay Fair enough and then I think previously there was some talk about.
Maybe a potentially.
Accelerated approval path in certain sub populations in the frontline setting.
Particularly the SDK 11 called mutation patients maybe how is that plan shaping up is that still on the table or are you leaning towards.
For a complete phase III trial instead.
We really look forward to having that conversation in four weeks at ESMO Io because it's all that's certainly part of our multipronged approach to.
Investigated in the frontline setting, where we see a tremendous opportunity and potential for autographs and so we'll get into those details at ESMO Io and then hopefully you all can join us in Geneva for that conversation.
So thanks for joining us this afternoon to everybody. We really appreciate your interest in Marathi and when you look forward to sharing additional updates with you here in the coming weeks.
And so.
Today's call.
Thank you for your participation you may now disconnect.
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