Q2 2023 Mirati Therapeutics Inc Earnings Call
You're holding Frigging Marathi Therapeutics conference call. The conference is going to start in approximately one hour from now and.
You're welcome to continue to hold though if you like again the conference is going to probably start in roughly one hour and you're welcome to hold up until that time. Thank you.
[music].
[music].
[music].
[music].
[music].
[music].
[music].
[music].
[music].
[music].
[music].
[music].
Please stand by.
Good afternoon, and welcome to the Marathi therapeutic second quarter 2000 twenty-three earnings call. My name is Justin 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 remark.
There will be a question and answer session. If you would like to ask a question. During this time simply press the star followed by the number one on your telephone keypad. If you would like to withdraw your question press. The pound key it is my pleasure to introduce Ryan AC Vice.
President Corporate affairs at Marathi Bryant, you may be getting a call.
Thank you Justin and welcome everyone to this afternoon's call joining me on the call today I'd like to check off our president and founder.
Alexander for Chief Medical Officer, Doctor, Jamie Christiansen, our Chief Scientific Officer.
ER, Chief commercial officer, Laurie Stelzer, our Chief Financial Officer.
I'd like to I'd like to inform you that certain statements. We made during this call will be more looking because such statements deal with future events in our subject many risks and uncertainties actual results may differ materially from those.
Looking statements for a full discussion of these risks and uncertainties.
Review, our annual report on Form 10-K.
In our quarterly reports on Form 10-Q that are filed.
U S Securities and Exchange Commission.
Afternoon would be released financial results for the quarter ended June 30th 2023 recent corporate updates.
This press release accompanying second quarter earnings Slide presentation are available on the investors section of our website at <unk> Dot com. Additionally.
Additionally, this afternoon, we also announced the launch of a public offering this presentation shall not constitute an offer to sell or the solicitation of an offer to buy our securities Securities described are being offered pursuant to a shelf registration statement filed by us with the S E C.
[noise] came automatically effective upon filing we have filed a preliminary prospectus supplement and accompanying prospectus with the S. P. C related to be offering. These together with the final prospectus can be accessed on the SEC's website or the investment each of our website at <unk> Dot com.
Before we proceed you don't like to address an important leadership transition within our organization. This afternoon, we announced the departure of David meat and the appointment of Dr. Check borrowing interim CEO during the transition period, all our board leads to search for a permanent CEO with that and it's my pleasure to introduce Dr truck bomb, the president and or an interim CEO Albright.
Thank you Ryan.
Thank all of you for joining us on the call today.
Afternoons call I will provide initial remarks before turning the call over to Alan Jamie Ben and Lori to provide key updates.
Then provide some closing remarks before we open the lines for questions.
I'd like to start by thinking David and acknowledging the significant role he played in leading the company.
David guidance the past two years, we have continued to advanced a robust R. A D pipeline.
Made a lasting impact on people living with cancer during.
During this period, we received the F D a approval and launched Crisafi, becoming a commercial stage company.
I Express my and the company's gratitude Fort Davis contributions.
I have been appointed interim C E O of the company.
It is both an honor and a weighty responsibility to return to this role.
As founder President and C E O of morality for 10 years I am deeply committed to our mission.
And I will work tirelessly to advance a robust pipeline well pushing the boundaries of novels science and best in class capabilities.
As we navigate this transition our mission remains unchanged.
We will continue our relentless pursuit of scientific excellence and development of groundbreaking therapies and the improvement that's patient outcomes.
Our commitment to innovation and patience will remain at the core of everything we do.
I am confident in the strength of our team and the wealth of experience we possess.
Our focus is on building the capabilities needed to drive long term sustainable growth of our business.
We have a robust pipeline and innovative programs.
With one of the most productive drug discovery organizations in the industry.
Our focus is on the areas of cancer with large unmet needs and way of revolutionary treatments can have meaningful impact on the lives of patients.
Today, we will highlight several important updates, which we believe are very meaningful for a variety.
And the first line non small cell lung cancer Ellen will share in the updated dataset, which provides clear and compelling support for the rapid advancement of this combination into phase three development in patients with T. B S scores of greater than 50 per cent.
Earlier stage pipeline, Jamie will summarize the promising initial critical data for M. R. T X 17, 19, which is our potential best in class molecule and the emerging field of MTA Cooperative P. R. M T five inhibitors.
And second line non small cell lung cancer <unk>.
Describe how the differentiated profile pizatti, along with the World class commercial organization.
Led to a strong initial lunch and the promise.
Both.
Finally, lauria will share certain details regarding our recent announcement for provokes public offering along with a summary of our second quarter financial results.
I am very optimistic and very excited about the future of variety, we are well positioned to create significant value for shareholders. While also making a meaningful impact on the lives of people living with cancer.
With that.
Now turn the call over talent.
Thank you Jack Hello, everyone.
Let me get on slide six by discussing autographs it starting with the first by non small cell lung cancer.
My commentary will reflect outdated debit card as of February 28th of this year of course, what AIDS and two of Crystal seven phase two study evaluating at a grass it in combination with pepper lives Matt.
Patients, but non small cell lung cancer.
<unk> 212 C mutation.
Moving to slide southern patient.
Patient numbers and the median follow up nearly doubled since our prior updated as in Ohio in December 2022.
On slide eight.
We'll see what the baseline patient characteristics were generally consistent across Datacards and subgroups.
Let's now discuss the safety summary covered on slide nine.
Where all the autograph parallelism amp combination has been well tolerated with a manageable safety profile.
Most frequent treatment related adverse events of the combination are listed on the slide.
Importantly, most of these adverse events, where low grade and manageable, which led to acceptably low rates are dose reduction and dose interruption either added brass peverell isn't there.
Treatment related adverse events led to treatment discontinuation of either at a grass at Penn Brothers, and then I have an 18% of patients and both drugs and just 4% of patients.
This discontinuation rate is consistent with other regiments in the non small cell lung cancer treatment setting.
Let's now move to slide 10.
Combination of anagrams him with pedal isn't that demonstrated low rates of clinically meaningful liver toxicity.
I'm elevation was low is consistent with what was presented there that smell I.
Notably only two patients are 1.4%.
Tenured the combination to deliver treatment related adverse events.
I'll know summarize the interim efficacy results in patients with T. B S scores, a greater than 50 per cent.
On slide 12 ethics.
I bet cause see outcomes for the EDA grass and plus payment Elizabeth combination TPS greater than 50 per cent.
Highly encouraging and comfortably see the outcome September Elizabeth vinyl therapy.
Standard of care for these patients.
Okay confirmed objective response rate and the full analysis that was 63% again, comparing favourably to the benchmark, 39% in keyed out 42, and 45% and came out 24.
How about political activity evaluable patients defined as requiring at least one post baseline scan.
<unk> response rate was even higher at 71 per cent.
It's a dance the slide 13.
Medium progression free survival has not yet been reached but is tracking well about first line non small cell lung cancer standard of care thus far.
Similarly, Unsly 14.
Median duration of response is also not yet been reached.
[noise] again tracking well about the keynote 42 benchmark.
I will note that the median overall survival remains immature for analysis.
At the time to understand it cut.
Well, let's advance the slides the 15th.
Summary, crystal seven efficacy and safety data strongly support the advancement of the Outta grass.
Regiment into a pivotal phase three study in patients with T. B S scores, a greater than 50 per cent.
It's important to note that patients with T. P S greater than 50 per cent represent approximately 40% of the first line care asked to 12.
Non small cell lung cancer patient population.
And closer to 50% of the revenue opportunity when it counting for the longer treatment durations relative to patients with T. B S scores of less than 50 per cent.
That will advance the slides 16.
Let me summarize our phase three study design for autographs and plus Timbral isn't that compared to September Elizabeth mono therapy.
The conversion of approximately 150 crystal seven sites to the phase three study are underway, which we expect will help us move expeditiously.
We expect a primary endpoint of progression free survival, requiring approximately 500 patients we.
We plan to have additional discussion with the F D. A in the third quarter to finalize the phase three study design.
We expect to initiate patient enrollment in this phase III study by year end.
Allow discuss our clinical development approach and patience with T. B S scores of less than 50% summarized on slide 18.
Upon evaluating the updated data of Crystal seven.
Clear signals of political activity without a grand surplus Campbell is a map in the T. P S less than 50 per cent patient population.
However, these data suggest the doublet approach will not be sufficient to displace the existing standard of care for these patients which is the keynote 189 regiment of Carboplatin Pemetrexed Elizabeth.
However, safety and Tolerability profile, the autograph plus Kimberly Smith combination continues to be favorable which will potentially enable us to add add a grasp them to the peanuts 189 Regiment.
Phase two Crystal 17 study.
<unk> plus chemo immunotherapy combination is underway with the initial enrollment expected imminently to confirm the optimal phase three approach for patients with T. B S scores of less than 50 per cent.
We anticipate a decision regarding phase III registrational plans and the T. P S less than 50 per cent patient population in 2024.
Based on the safety and preliminary efficacy data pro Crystal 17.
Shifting gears and advancing a slide 20.
That'll briefly summarize at a grassroots potential first in class development plans for difficult to treat cancers beyond non small cell lung cancer.
A combination of an aggressive with Cetuximab had showed a compelling and differentiated profile in third line or later colorectal cancer.
And we are on track to submit a supplemental new drug application.
For accelerated approval in the fourth quarter of this year.
Our Crystal 10 phase III Registrational studying second line caller rectal cancer.
I'll be waiting the same combination of Madagascar, plus the types of that versus chemotherapy.
Track to complete enrollment this year.
Back to report the final analysis of progression free survival, an interim overall survival in 2024.
Plans for regulatory submission based on these results.
In addition.
Grasso demonstrated clinically meaningful activity and other previously treated K Ras G 12, C mutated solid tumors, including pancreatic cancer.
We are exploring potential accelerated regulatory approval pathways in these patient populations and we expect to gain clarity on our approach by the end of the year.
Finally, I'm pleased to report that we initiated a cohort within the phase one to study evaluating the combination and aggressive plus M. R. T X 0902 are a potential first in class sauce, one inhibitor.
I will now provide an update on the recent C. H M. P opinion related to edit grassroots conditional marketing authorization or CMA in Europe .
C H N pays states <unk>.
As a positive risk benefit profile, but that it does not fulfill certain requirements <unk>.
We firmly believe that at a grass roots should be granted a CIA based on its differentiated profile.
Re examination.
M P's opinion.
I'll turn the call over to Jamie for an update on our earlier stage in development pipeline.
Alan.
Today, a highlight promising initial clinical results from an emergency at 17 19.
Potentially best in class MTA cooperative five inhibitor.
Early proof of concept clinical data March exciting milestone for Friday.
Script characterizing our early experience was 17 19, including case studies from her face one study.
Has been accepted by cancer discovery and publish online this afternoon.
What was it that decided 22.
I will start by describing unique characteristics and the mechanism of action of 17 19.
You're empty five is essentials.
<unk> normal cells, including a number of bone marrow progenitor cell types.
Now select first generation purely five inhibitors.
<unk> five at both normal self injure myself.
That's generally resulted in a narrow therapeutic index dose lemonade email attic toxicities and low single digit response rate due to incomplete target coverage.
In contrast, how 'bout T X 17, 19 is a differentiated empty a cooperative seventy-five inhibitor.
Specifically target.
Tumor cells, while sparing bone marrow toxicities.
17, 19, Leverages unique sent that'd be Clifford Elling approach X twice a key difference.
Salvage pathway between normal cells in tumor cells harboring Ah Chi deletions.
Tumor cells illustrated in the last panel of the slide the intact protein tightly.
Regulates levels over the metabolite Mentos, Iowa darter scene or M T a.
And encapsulated tumor cells illustrated on the right hand side of the slide.
The <unk> protein results, an accumulation of M T a and up to 20 fold higher cellular concentrations compared to non tumor cells.
That's S X S. A M T a.
Two sides of the pure empty five protein rendering it in a partially inaccurate states.
This creates an Achilles heel that is uniquely present in MTF deleted tumor cells appear empty five empty a complex.
17, 19 exhibits at greater than 70 fold selectivity for inhibition up here P. Five dependent self survival and epitaph deleted versus normal cells, resulting in a significantly broader therapeutic index relative to not selective approaches.
In preclinical studies 17, 19 demonstrated regression and a variety of supermodels harboring an epitaph gene gene deletion.
With Maxwell antitumor activity expected to require near complete integration of the tarpon biomarker called S. T M a or symmetric dimethyl arginine.
17, 19 does not demonstrate a significant impact in bone marrow or other tissues and tummy trouble set completely inhibit S. D M a and M calculated tumor cells.
Now, let's move decided twenty-three.
Jean.
10% of all cancers across a broad range of tumors, including non small cell lung cancer and pancreatic adenocarcinoma with an estimated annual incidents in the U S and Europe upgraded that 250000 patients.
Additionally, the Kaplan Meier curb on the right.
Right that patients with two r's harboring an empty deletion.
Significantly poor prognosis compared to those without an Amtrak gene deletion across a composite of major solid tumors.
Now moving on to slide 24, I would I would describe are encouraging activity.
And clinical experience and how do we treat pre treated patients in our face one dose escalation studies.
I commentary will reflect a June 30th 2023 data card.
We dose escalation and 100 per cent increments from 30 to 800, Max one daily or Cutie.
There were 33 evaluable patients for safety across six to us levels and 21 patients so valuable for clinical response.
18 patients at therapeutic doses at or exceeding 100 Max.
800, Max has been defined as the maximum administrative jealous for acuity schedule and 600 makes Q D is currently under evaluation as a potett.
Recommended phase two dose.
The emerging preliminary PK results are favorable with a long half life support in Q D administration, and roughly proportional increases and exposure within the therapeutic range.
Average exposure at the 200, Meg Cutie dose exceeded the maximum preclinical target applications exposure.
Add a 400 milligram cutie dose exceeded target exposure by greater than five volt.
Addition, we evaluate the S D at many levels.
It's fine and a 21 post treatment tumor biopsies and three patients utilizing extra chemistry.
And all three biopsy pairs.
You may wish completely extinguished no treatment at a dose of 200 Max Cutie.
Early clinical proof of concept has been achieved was six personal responses, including five confirmed and one unconfirmed response as the 18 pages of valuable for response at therapeutic dose levels.
Sponsors were observed across multiple dose levels and super types, including non small cell lung cancer visa theory on my belly already tract tumors, belladonna and malignant peripheral nursery tumor.
And Fortunately, we observed deepening or sustained tumor regression and responding patients overtime, which suggests durable clinical benefit.
The unconfirmed response, I noted and malignant peripheral nursery tumor was observed shortly after data cut off and has subsequently confirmed.
The ongoing trial remains in the dose escalation phase and dose expansion is underway at several doses.
Variances early however, the observation of multiple objected responses across different tumor types. This encouraging.
Safety has also been encouraging.
17, 19 has been well tolerant and across dose levels to date with no great four or five treatment related adverse events observed.
The most frequently reported treatment related adverse events, where nausea, vomiting and fatigue.
<unk> majority of these were grade one or two.
Three treatment related adverse events were observed in only five at 33 patients or approximately 15%.
Finally, just let me make cytopenia, which were associated with natural active PRP five inhibitors have not been observed for 17 19 at any <unk>.
Taken together the apparent complete inhibition of S. D M a N patient tumors.
Favorable safety profile lack of dose lemonade cytopenia as an early evidence of clinical activity provide clear differentiation from NASA liked it first generation for your empty five inhibitors.
The state also highlight a significant opportunity to introduce a novel and meaningful therapeutic approach to the significant population of patients with anthrax related cancers in need of new treatment options.
The 70 fold selectivity and pharmaceutical properties of 17 19 also support as potential as both a first in class and best in class after Tiffany.
Finally, I will briefly summarize our potential development approach for 17 19.
First our goal is to identify a recommended phase two dose this year.
Development interest for phase two cards and beyond include pancreatic cancer.
Small cell lung cancer.
In addition, emerging signals from our ongoing phase one study and paste your basket.
Form additional indications for prioritization.
As we've already provided significant updates and other programs today I'll provide a very brief update on M. T. X 1133 are potent selective and potentially first in class or okay rescue <unk> inhibitor.
The face one to study continues to enroll while with <unk> with strong interest from both patients and investigators.
11, 33 has the potential to provide a transformative treatment options.
And underserved K rushed you 12 D patient population.
You remain excited about the future of the program and what sports are providing an update in the first half of 2024.
Overall, we are pleased with the significant progress we've made across our portfolio.
Now with that I'll turn the call over to that and for our commercial update.
Thank you Jamie well good afternoon, everyone.
The lines, it's a shared the very strong results we achieved during our second full cool to since the launch of <unk>.
The commercial performance and execution were very strong and we are thrilled with a positive impact, we're making more patience and native treatment.
We can send you to gain market share experts also expanding the size of the market.
Product launch continues to gain momentum witnessed robust demand for <unk> as we generated $13.4 million of net product revenue in the second quarter.
Included in this big it was 11.7 million a commercial for that the sales and $1.7 million a <unk> policy clinical studies.
The differentiation efficacy profile has resonated well with health care providers and patients alike.
We estimate that presents you achieved new to branch here within the mid 40 per cent range. Among second line patients not previously treated with a K rescue 12 C inhibitor.
I like seeing the rapid wrote adoption across both the academic community settings.
As of the end of the second quarter. We had reached the vast majority of target accounts, which constitute approximately 90 per cent of the market potential.
In addition, he has already been prescribed and 90% of the 1200 accounts.
We are targeting patients who are naive to a K rescue 12, <unk> inhibitor you originally progressed to the second line.
Patients constitute approximately 75% of our new to brand patience with the remainder coming from like the lines of therapy.
My reimbursement access and coverage perspective, we are place a rapid progress access and medical teams or a chain broad unrestricted coverage with minimum access barriers for patients.
Estimate over 90 per cent of patients are covered and pay feedback as being policies based on their clinical value.
Additionally, outpatient services have been well received with patients able to obtain drugs and an average of only four days of an oncologist prescription which is significantly ahead of analogues closer to two weeks.
Feedback from Oncologists office staff and importantly patients has also been extremely positive.
Importantly for those oncologist, who are familiar with <unk>, but have yet to describe intend to prescribe the approximately 80 per cent and those with experience of using presenting intend to continue to describe is similarly high.
A T messages centered around at 44% response rate 14.1 months, a median survival and low treatment related discontinuation rates are resonating well.
Additionally, data showing presents these activities impatience with central nervous system metastasis is being favorably received by physicians.
The research clinical oncology publication reflects the <unk> the only G 12 feet inhibitor to have proven efficacy and previously untreated see that Smith.
In addition, <unk>.
Is the only <unk> inhibitor added to the N C C and guidelines for patients with C N estimates.
Looking ahead, we believe that significant opportunity remains to grow up market share and a second line setting by increasing the depth of our prescribed the base and increasing depth of <unk>.
And expanding the addressable market.
I think it changed the focus on increasing both testing and identification of Terrace T 12 seat eligible patients, particularly in a community setting.
We now estimate the <unk> 12 C testing at time of lung cancer diagnosis is in the mid 70% range and we are working to further increase these testing rates.
There was also a meaningful opportunity to better identify patients with a K Rez G 12 C mutation at the local account level and the electronic medical Records system.
U S K rash detail C unit volume group, that's over 20 per cent on an annual basis. We expect this type of linear growth to continue with around 2023.
Conclusion.
Is well positioned to become the market, leading products and a growing <unk> 12 C market.
So in the cool of the lorry for financial update.
Thank you Dan.
A technician today, we launch the proposed underwritten public offering to sell $250 million of shares of our common stock and to certain investors that searches prefunded warrants to purchase shares of common stock. We also expect to grant to the underwriters at the offering a 30 day option to purchase up to an address.
<unk> $37.5 million six chairs at the public offering price lusby underwriting discounts and conditions.
Yeah, I'll bring this subject to market and other conditions and there can be no assurance as to whether or when the offering may be completed or as to the actual side or terms of the offering.
Alrighty cash and investments balance as of June 30th 2023 was approximately $780 million.
We now expect our 2023 net cash burn to annualize within a range of 562 $580 million.
Looking ahead, we are connected to evaluating ways to increase operational efficiencies across the organization and we intend to reduce our 2024 cash burn rate like can you extend that does it negatively impact our highest value drivers.
I will now walk through our income statement and catch on a few other key financial matrix.
Please see our press release from earlier this afternoon for additional details about our second quarter 2023 financial results.
Revenue for the second quarter of 2023 with $13.7 million, which was driven by $13.4 million as Chris <unk> $1.3 million of license in collaboration revenues.
This compares to revenue a $5.4 million for the second quarter is 20 twenty-two primarily due to a 5 million dollar milestone payment earn from zeinab for the first pivotal clinical trial and autographed it for the first indication in China.
The girls to that discount in the second quarter continued to be within our expected range of 20% to 25%.
Cost of product revenue for the second quarter at 2023 with $1 million a substantial portion of the inventory. So during the second quarter or manufactured prior to the F. D. A approval and therefore, we're extends to research and development prior to 2023.
Research and development expenses for the second quarter at 2023 for $124.2 million compared to $128.3 million for the same period in 2022.
The decrease was primarily during a buyer reduction in clinical development costs for <unk> and can be completed in Romania, Sapphire phase three clinical trial in the second quarter of 2022, and a decrease in sure based compensation.
Decreases partially offset by increases in our earlier stage clinical development program, such as M. I T X 1133, and an increase in salaries and employee related expenses to support the advancement of our portfolio.
Selling general and administrative expenses for the second quarter of 2023 $75.5 million compared to $54.2 million for the same period in 2022.
Increase was primarily due to an increase in headcount related costs, including sure based compensation and salaries and commercial related costs to supporting the marketing and sales.
<unk>.
Net loss for the second quarter of 2023 with $176.9 million or $3.04 per share basic and available.
Compared to a net loss of $176.4 million or $3, an 18 cents per share basic and deluded for the same period in 2022.
These results include non-cash expenses, including share based compensation, that's $39.4 million and depreciation and amortization of $1.1 million.
With that I'll turn the call back to check for closing remarks.
Thanks Lori.
Conclusion, I want to express my gratitude to our dedicated team for their relentless pursuit of scientific excellence and their commitment to improving the lives of people living with cancer.
I also want to extend my appreciation to our shareholders for their continued support which has been crucial to our success.
On behalf of all of US Marathi. Thank you all for joining us today and for your <unk>.
What are you, bringing support for our mission.
Very excited about the future of morality and.
To make a significant impact in the fight against cancer with that Justin we are ready to open the call for questions. Please proceed.
Thank you if you would like to signal with questions. Please press star one on your Touchtone telephone if your joints today use a speaker phone. Please make sure a new function is turned off to allow your signal to reach our equipment. If you would like to withdraw your question. Please press the pound key.
Please limit yourself to one question and one related follow up question again that is star one if you would like to signal.
And our first question comes from Michael Smith with Guggenheim.
Hey, guys. Thanks for taking my questions and check Uhm I guess, we'll come back in the C. O C at least for now.
Question on the lung cancer update the the plan phase three in the T. P. S. About 50 per cent of patients obviously makes a lot of sense to us.
I was wondering if you think there's an opportunity for accelerated approval with them or are entwined. Other projects von Braun out for this study and then the the follow up question would be.
The G P S less than 50 per cent patient population, obviously sauce like you're shifting towards a <unk> a combination strategy.
Perhaps help US understand you know if there were any learning something that uhm Crystal seven study in in that patient subset, what's that data <unk> October and how should you think about the <unk>.
Crystal 17 study you know in terms of the data that you want to see two tomato phase three dollar decision and that's patient population. Thanks, so much.
Yeah, Hi. This is this is Alexandra I'll answer that question and and so let's set will go bit by bit. The first one was the potential use of of an accelerated approval with the phase three study, but yeah <unk> versus pan-broil with an aggressive you know as you know.
The F. D. A is it started to talk some more about utilizing phase three studies as opportunities for accelerated approval. It's something we've considered but we it is a high bar number one but also the fact is that there's a certain time commitment that is involved in a study and increased complexity.
When conducting a study in that manner and this time, we're we're choosing to go towards the more traditional approach using a progression free survival, which will allow us we believe to get it to patients as quick as possible.
The other asked two questions related to the less than 50% of population and and yes, chrystal seven that did provide some learnings along the way they were clearer signal so clinical activity with a combination of that aggressive and <unk> in the setting but the data suggested that the doublet approach wouldn't be so.
<unk> to go head to head with the Triple a combination of chemotherapy and Pamela Lizabeth. We did however have some early correlate of analyses.
Your patience and T. P S, which may help to be informative for our subsequent an evaluation of a phase three study and the less than 50 population.
Which which also prompted us to believe that the addition of chemotherapy in the less than 50 per cent population will be important K 17 will help us address that by adding an aggressive chemotherapy and <unk> and will after valuating, both safety and early efficacy from.
K 17.
We should be able to have a decision perhaps in the first half next year regarding plans further plans and the less than 50 per cent population.
And our next question will come from Tyler Van Buren with T D Cowan.
Hey, guys. Good afternoon. Thanks wrote it this was a more exciting call that I think people were anticipating my question is an emergency 17 19 at first glance looking at the responses and the kids were discovery publication it looks like the depth of responses are around.
<unk> 50 per cent would you expect the depth of tumor reduction to continue to increase that consistently higher doses, one with longer follow up and ultimately do abuse 17, 19, as a mono therapy or a combination agent and a large indications like lung cancer.
Yeah. Thanks, Tyler this is Jamie I'll I'll take that question.
You know I think I think your question is is a very good one, but if something were parents paying very close to the attention to.
Yeah, I think you know something important to consider for this study is you know it's been ongoing for a bit over a year. We have some experience at the lower doses for a number of scans, but as we get up to 400 and higher doses most of those patients only have a single scan.
And I think you know in addition to that we kind of note that if we look at the 102 hundred Meg dose levels. These are where patients may have two or more scans first of all if the sixth responses. We've seen four of those have occurred as cycles to three or beyond.
And then secondly, Oh, a number of those responses or even stable diseases continue to deep red during that period of time.
And together that you don't really suggest that you know our data set may not be fully mature when it comes to response rate. So again, we will keep a close eye on that.
[laughter] forgotten. Your second question is could you repeat it for me. Please the combo vanilla, Okay, Oh, yeah combination.
<unk>.
<unk>. So I you know I think if you don't you will get our experiences and so far we have two out of three responses and <unk>. We have one out of two a non small cell lung cancer for many of the other indications we have an out of one. So we're you know we're still gathering that are.
Phase two approach will be initially mono therapy in the phase two setting and we have cohorts decide with clear first utility stopping rules and clear expansion rules and if we should hit response rates of 30% to 35 per cent plus with a six month duration of response or more we believe that accelerated.
Google as possible and indications like non small cell lung cancer pancreatic cancer, and <unk> and second line and beyond indication also you know we're using the opportunity to see responses in our study.
To prioritize further combination work so although we do believe that there is a possible accelerated path here, you know really not gonna hesitate to evaluate combinations as well.
And our next question will come from J Olson with Oppenheimer.
Oh, Hey, congrats on all the progress and we'll come back Chuck.
Uhm. Thank you for taking our questions. We had a question on the updated Crystal seven results.
Can you just help us understand why the data cough was in February and maybe qualitatively comment on any more recent results you may have seen and if we should expect additional updates from crystal seven this year and then I had to follow up if I could.
Sure again this is Alan up I'll take that so the February cut off was chosen because it was approximately six months. After the August which we felt would provide us with additional patients and additional duration of follow up which of course. It did Additionally, there are plans.
Consider additional data analysis and sufficient for.
Medical symptoms yet perhaps later this year, so there'll be another opportunity to update the data.
Okay, great. Thank you and then.
Grandson, the initial clinical advocacy for 17 19 can.
Can you talk about the duration of follow up that you've observed for patients in the therapeutic dose range is 800 milligrams the talk shows and.
And also can you just talk about how many prior lines of therapy, the patience failed and how many you had non small cell lung cancer.
Sure Yeah, there was a wide variety of different types of patients on the study.
And prior lies of therapy range between two and six immediate is over three for prior lines.
The.
Sorry could you repeat lung cancer of the lung cancer was one added to it.
So we're still building an experience there and duration duration of follow up. So you know I think this varies by Doe. So are you know first active dose level is 100, you know those patients that are stable disease or partial response remain on therapy and you know for those patients were over 30 week.
Six.
You know then for that 200 big dose level, we started of course a bit. After you know those patients have also not progressed unless they had an initial progressive disease. You know those places <unk> I'm over 20 weeks and then we have a more naissance experienced at 400 and you asked about eight.
Hundreds. So 800 was defined by protocol is the maximum administered dose.
We saw two great too intolerable adverse events vomiting, and a fatigue, so will not be going back to that dose of old, but we will be pursuing 600 and through the D. L T or to a swimming toxicity evaluation period, if we make it through that we will be looking at expanding that as a potential recommended phase two dose.
So bottom line is you know immediate follow up varies by dose level and this is something we'll have to let mature over time.
And our next question will come from <unk> Wang with Barclays.
Thank you for taking my questions also chat till I'll come back and looking forward to working with you at least in the meantime, one question regarding to fly 12.
Several clarification questions I know there are many different response, we hear 63 50 971 and also in the footnote you'll have a 74 per cent could you give us the denominator Alicia February 2023, uptake, 63%, 71% and also the 70.
Perfect.
Yeah, Hi, this is Alan I'll I'll be happy to to walk you through that so let's recall that the starting number of patients are 56 patients that is the full analysis that.
There were 35 responses overall, so that's your 63 per cent.
The political activity Evaluable patients that represents a 49 patients overall and again with that thirty-five responses had a response rate of 71% now how we got there, but 50 656 patients included three patients.
Who were an eligible to two one patient being a G 13 see another patients with atrial fibrillation and then another patient who suffered a stroke and anemia and all of those since they received therapy. They were included in the F. A yes. The full analysis set if you.
Remove those patients that's a response rate of 66 per cent on 53 patients.
And the political activity invaluable those are patients who had to have both received treatment and had a follow up scan for a valuation and that excluded five patients that did not have a scan and two of the three patients I mentioned that were ineligible the G.
13th see patient did go on to receive a scan and suffered progressive disease. So that 71% would actually be 73 per cent. If you included that in eligible G 13 see patient so I believe I.
<unk> your questions, let me know if.
That's true.
Yeah.
The response is there's 74 per cent.
It would be 73, not one more responds would be one pure in the denominator.
And our next question will come from solving Richter with Goldman Sachs.
Hey, this is that all for solving congrats on me afterwards.
What could we see more mature for your birth date for the T. P O screwed and 50% of the population and how confident are you guys will be meaningful and then could you just discuss the appropriate benchmark you're more broadly the particulars direct comparison to chemo 24 fine for all of them coins, including.
Including <unk> ongoing debate around this thank you.
Sure My Dad. This is Alan I'll I'll take those two questions. So the <unk> the next opportunity.
Will be coming later this year as I.
Mentioned and will have plans to to submit to a medical since I was young.
Later in the year, so there'll be a follow up and we are quite confident that we will be able to see that this progression free survival continues to to maintain we've done some internal scenarios, where are we verizon them with.
Various.
Six of how it may turn out to be with the with the Pff's moving forward with all those patients that are currently censored and again it seems to support very nicely that that P. F. S will be maintained with additional follow up now.
The second part of the <unk>.
Question related to the benchmark and so so number one the benchmark it is payment Iliza ma'am and there is a wealth of data single agent.
<unk> in the literature about 24 42, and then there's also real world evidence data when you look at subsets as well of the K Ras mutant patients. So there's a whole wide range of of opportunity to to establish what the standard of care <unk>.
We plan on taking the totality of the data and looking at that as the control in either way of looking at it whether you look at you know 24 42 or the real world evidence that suggests maybe the G 12 see patients do slightly better.
All of those scenarios. We are comfortably ahead of what that projected PFS to be we'll put that together and use that as our our standard of care in our benchmark moving forward for the phase three study.
And we have a question from Jonathan Miller with Evercore.
Hi, guys. Thanks specific question and <unk>.
I guess on the apparently five paper.
<unk> is this papers all we're gonna see this year from this early data are you planning on presenting this at a medical meeting and I asked specifically because I notice you didn't give a full safety table. For instance, then you didn't make mention of like L. F. Ts that caused <unk> discontinued I'm, just kind of get a sense for overall.
The ability for that and you'll see a full presentation at a medical meeting this year and then maybe just a housekeeping question can you give any color on the requirements for you Google that that weren't net what would they responding to something and trial designer or something beyond that.
Alright, I'll I'll take part one and you know I I think it's you know we've got at two a M. R. T X 17, 19 disclosure. This year you know we essentially consider this a high level topline disclosure and are not actively planning an additional disclosure until 2024. However, we continue to look at and T.
As we move forward and you know as soon as we have mature enough data to make a difference. We would you know have the opportunity data presented a medical meeting, but likely in the 24 time frame.
With regard to safety you know what generally say that this drug I spend well tolerated a dose levels up to 800 Max.
That you know a number of great three adverse events is only 15% on study no grade four or grade five of that the most common adverse events have bad fatigue, nausea, and diarrhea, you know most of those are great one or two and that's certainly the.
Nausea.
And diarrhea had that very well controlled with cold nights, when they need to be but generally the grades are well when they don't require cold Mad intervention. We have seen you know I think you mentioned a L. T. We've seen one patient with an E. L T and the great day range and that patient you know, especially you know I believe interrupted and stay.
That study so we.
You know are you know overall, Gary I'm encouraged by the the overall safety profile of dose intensity. You know in fact, we have very few dose interruptions or dose reductions at these dose levels up again update 800, so far.
This is but I don't think they'll see it shouldn't be question. So just as a reminder, osh empty conditional marketing approval was the finding was based upon a single arm study.
And the <unk> indicated that the available data showed that we had a positive benefit risk. However, we believe that negative opinion can be based on the fact that there is a <unk> and an existing conditionally approved <unk> inhibitor. In addition that was results from a competitor which showed essentially overwhelming pivotal results, which we believe could be.
Could it be part of the extrapolation there.
I'll stand point, we are very we we have fall for reexamination, we will have the results of that in the next four months. Additionally, the K 12 study is enrolling well and we look forward to the read out of that pivotal study in the first half of 2024 and that was always going to be the study that we would base of pricing.
And our launch plans both of those.
And we have a question from Jason <unk> with Bank of America.
Hey, guys. Thanks for taking my question I just wanted to follow up.
So it sounds like you're meeting with the F D. A to finalize your faith redesign for the C. P. S. Greater than 50, so I guess I'm, just curious sort of what what are going to be to keep talking points is this largely procedural are there elements of the design that you need buy in such as you know what your comparator is where the P. F. S. N points and then I guess my follow up to that.
Is a question of like commercial relevance if you'd go with a Katrina mono therapy comparator. It sounds like probably half the market. You know uses the keynote 189 regimen half uses could treat him out of therapy. So you just kind of wondering if your results are ultimately getting a benchmark against you don't want any nine in that segment of patient. Thanks.
The greatest this this is Alan I'll take the first half of the question the meeting with the F. D. A so I I think it's probably a combination of Ah Ah Ah <unk>.
Procedural and also just an open dialogue with the F. D. A there were some early discussions when we were there for one another topic, where they had stated that <unk> Elizabeth would be inappropriate standard of care control arm, but what we'd like to do is meet with them again had that for him.
The lies the discussions regarding the the control <unk> Ma'am also PFS as the primary endpoint.
As well and where we're confident that we should have a very fruitful discussion with them in agreement on both on both key points and I'll have ben's going to discuss the commercial.
Commercial standpoint, there's been a care in the greater than 50 population is payment Elizabeth monotherapy concentrates over 60 per cent of the current use.
From an attractive, but the standpoint attractiveness standpoint, chemo free regimen is hardly so fast that by both physicians and patients. So we believe actually the the target too.
<unk> approach with the the long tail and I owe a combination will be very attractive to the market and we hopefully look forward to a successful studying and bring it to the market.
And we have a question from bin Burnett with Stifel.
Alright. Thank you for taking your question just one on on Crystal seven and the results. Congrats on the improved F. T proof all you're seeing indeed, you on high patients.
I wanted to just ask about there was a slight did mentioned liver related adverse events that led to discontinuation as it looked pretty low but I was wondering if you maybe give just a little color on what adverse events led to the dose reductions described on slide nine I believe and I guess was there any trend in dose reduction by P. D O one status or is that.
Pretty much cut abroad.
Alright. So this is Alan again, so first.
Last question first there was no difference based on levels of P. D. L. One expression as far as the the discontinuation rates.
<unk> no one particular T R. A stood out there's a number.
That there were a few different events such as perhaps the G. I with you diarrhea, or vomiting, and there were a wide range of lines that had low levels of discount associated with it no. Other one that really stood out.
And we have a question from Mikey holes with Morgan Stanley .
Hey, guys. Thanks for taking the question, maybe just to follow up on the phase three frontline long studying.
Patients with T P S greater than 50.
You're proposing roughly 500 patients. They're just curious you know based on your estimates how long it might take to enroll that number of patience. Thanks.
Yeah. This is now and again, we we think that enrollment probably will be in the range of about two and a half to three years.
And yeah that will be expedited, we we'd like that as a result of the transfer of it pays to to the phase III being able to activate sites uhm quickly.
And our next question comes from Egal Gotcha moments with Citigroup.
Yeah, Hi, thanks for taking the questions and great to see back then let's see your role temper at least temporarily talk with regard to the greater than 50 per cent cut of the market for the frontline trial.
Just wondering a few things can you just talk about how you're getting confidence on the PSS is a primary unplanned.
F D. A has been on record, saying they want a C O S for for I O therapies, and then obviously, there's a big data point coming in the competitive landscape with Roche's Die one trial for <unk> when the P. D O one grid and 50 per cent, what what type of flexibility might you have to adapt the trial was that hits in the standard.
<unk> <unk>.
Frontline or where to rapidly change. Thank you.
Alright, so two two questions. The first one will talk about PSA US again, we're certainly confident that PFS that we're seeing will be maintained over all as I mentioned a little bit earlier.
The the comment about whether or not the F. D. A will require.
Of course, there's going to be somebody that we'll be talking with him speaking with them. This quarter I will say that it is your call in the second line study PFS was accepted as a primary endpoint.
And primarily because of that the note entity of crossover in second line therapy. Although there is not necessarily for little crossover. This study and frontline patients the opportunity since I live so much longer the opportunity for subsequent lives of therapy can certainly impact the overall survival.
Detecting a difference between survival, so that will be a discussion with the F. D. A uhm based on that we will of course look at overall survival in this study as well.
Second part of your question related to the impact of other potential agents that may have positive studies down the road such as say ticket.
Basically we in essence that that impact is not does not actually occur with a positive study it only the impact only happens when there's been a formal approval not even accelerated approval, but a full approval of an agent we believe but once our study has.
Started and we've agreed with the F. D. A has agreed in principle that should be able to go as is and not have to be changed midstream.
And we'll take a question from Evan secret menu with female.
Hi, guys. Thank you so much for taking my question. Thank you for all the data.
Data on the call a favorite picture question from my perspective, you talk about.
And your investments maybe relief the cash burn.
A little more granular and help us understand how you prioritize what's important.
Maybe you would like to thank you.
Yeah, Hi. This is Laurie we you know we're continuing continuing to evaluate our extend face looking for ways to be more efficient with our capital will continue to do so we're committed to reducing the fairness we go into 2024.
I am so we will be looking across the organization that you know.
With a focus on ensuring that we do not you know we do not apply to extend since as it relates to that most value driving programs and and parts of the organization. So you know I I can't go into more detail today.
Alright. Thank you. Thanks every thanks, everyone for joining us on the call today, we appreciate your interest and variety and look forward to sharing additional updates with you in the future. Thank you.
Well. Thank you that does conclude today's conference with you. Thank you for your participation have an excellent day.
Mmm.
[music].