Q1 2023 Mirati Therapeutics Inc Earnings Call
Yeah.
Please standby.
Good afternoon, and welcome to the Marathi Therapeutics first quarter 2023 earnings call. My name is Justin and I'll be the operator for today's call. All lines have been placed on mute to prevent any background noise. After the conclusion of the Speakers' prepared remarks, there will.
A question and answer session.
If you would like to ask a question. During this time simply press star followed by number one telephone keypad. If you would like to withdraw your question Press Star two.
My pleasure to introduce Brian AC Vice President of corporate Affairs at Marathi Ryan you may begin the call.
Thank you Jasmine and welcome everyone to this afternoons call joining me on the call today are David <unk>, Our Chief Executive Officer, Chuck Baum, President founder and head of research and development, Dr. Alan Sandler Chief Medical Officer, Dr. Jamey Christiansen, our Chief Scientific Officer and hit your Chief Commercial Officer, Laurie Stelzer, our Chief Financial Officer before.
Let me begin I would 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 are filed with the U S Securities.
And Exchange Commission.
This afternoon, we released financial results for the quarter ended March 31, 2023, and recent corporate updates. This press release is available on the investors section of our website at <unk> Dot com with that I'll turn the call over to you.
Thank you Ryan and thank you all for joining us on the call today on this afternoons call I will provide additional remarks before turning the call over to Ben I'll, let Jamie and Lori to provide updates I'll then provide some closing remarks before we open the line for questions.
Pleased to report that 2023 is off to a great start.
Other key highlights for the first quarter, starting with of course at the launch performance. We are delighted to see the rapid acceptance of course, Aussie, which is driven by <unk> differentiated profile and our highly experienced lung cancer commercial team. We also began enrolling patients in a clinical study for M. A R. T X 11 33 are highly used.
Selective and potent oral <unk> inhibitor.
Our MTA cooperative PRT, five inhibitor and our K Ras enabling sauce, one inhibitor continues to move in a positive direction.
In addition, we expect to communicate the top line outcome of the phase III Sapphire study this quarter.
Positive result would be a transformational milestone for Marathi.
Furthermore, and this quarter, we continued to employ a data driven approach to capital deployment and remaining fiscally vigilant and continue to explore ex U S partnerships as a source of capital and risk sharing and as a means of further strengthening our balance sheet.
We continue to be optimistic and very excited about the future of Marathi the full potential of <unk> combined with our innovative pipeline represents an opportunity to help hundreds of thousands of people in need and create substantial value in the process.
I'll now turn the call over to Beth who will provide an update on our crews at the launch event.
Thank you David and good afternoon, everyone.
We are very pleased with the strong launch performance of <unk> in the first quarter following FDA approval in mid December .
Our prelaunch preparations are clearly paying off in our first quarter full quarter of launch Chris actually generated $6 3 million of net revenue.
Our experienced loan focused field force achieve strong access to prescribers in both the academic and community setting we estimate the crews that we achieved approximately one third share of U K rescue 12 C patients highlighting the rapid and broad adoption across both the academic and community settings.
As of the end of the first quarter, we had reached over 90% of all target accounts, which constitutes approximately 95% of the market potential.
In addition presents he is already being prescribed in 80% of the top 50 accounts. The first quarter sales included a modest bolus of patients early in the quarter, some of whom had transitioned from treatment on another K rescue inhibits it and some more heavily pretreated late line patients the majority about patients with <unk>.
Patients who are naive to treatment in the K rescue 12 C class.
From a reimbursement access and coverage perspective, we are pleased with our rapid progress. The access team has achieved broad unrestricted coverage with minimal access barriers for patients.
That's a physician feedback payer feedback has been positive based on the clinical value of Chris' asking.
Additionally, our patient services have been well received with patients able to obtain drug and less than one week of an oncologist prescription. When she is significantly ahead of analogs closer to two weeks.
Or is that ticket was also included in the National comprehensive sensor network or N. C. C. N guidelines within one week of approval aiding coverage reimbursement decisions, particularly with Medicare patients.
Back from Oncologists office staff, and importantly patients has been extremely positive imports.
Importantly, there was oncologists, who are familiar with crews that they intend to prescribe is approximately 90%.
Looking ahead, we believe that significant opportunity remains to grow our market share in the second line setting by increasing the breadth of prescribing base, increasing depth of use and expanding the addressable market.
We will accomplish this by focusing on the attributes that differentiate presented by accelerated market development.
Key messages centered around a 44% response rate 14 months of median overall survival and low treatment related discontinuation rates are resonating well.
Additionally, data showing presents its activity in patients with central nervous system metastases has been favorably received by physicians, who recognize the importance to the approximately 40% of patients known to have CNS metastases.
Or is it actually was recently added to the NCC guidelines for patients with CNS Mets, the only <unk> inhibitor, which received this designation.
The highlights in the differentiated profile of <unk>.
From a market development perspective, we believe there was a significant opportunities to expand the second line <unk> non small cell lung cancer market.
<unk> continues to focus on increasing both testing and identification of <unk> eligible patients, particularly in the community setting.
We now estimate that the K raised 12 C testing right at time of lung cancer diagnosis is approximately 70%.
Testing rates for other targeted therapies, such as Egfr and alpha mutations, but closer to 85%. So there is a significant opportunity to grow the market and meaningful opportunities to better identify patients with a K rescue mutation at the local account level, where we've established partnerships with community oncology providers.
We expect the D C market to grow at a robust rate into 2023.
In summary, we believe that the important differentiating clinical characteristics as Chris ft, combined with an experienced and focused commercialization organization position presenting to ultimately become the market leader in K rescue to oxy inhibits it announced.
I'll now turn the call over to Allen for an update on our clinical activities Hello.
Thank you Ben and Hello, everyone.
By discussing at aggressive starting with first line non small cell lung cancer, where we expect to share key updates across our multi pronged development approach in the second half of this year.
Our most advanced and aggressive combination approach in first line non small cell lung cancer is the concurrent dosing of Angra asset with Pembroke isn't that in our phase two crystal seven study.
Our update in the second half of 2023 will include a first look at durability measures such as duration of response and landmark PFS analysis stratified TPS score.
In the meantime, we are preparing for phase III studies by laying the administrative groundwork and this will enable us to quickly begin enrollment of patients. This year. If the data are supported.
Given the Tolerability profile of the doublet combination Nevada grass.
Kimberly this map, we initiated a phase III study called Crystal 17, evaluating grass it in combination with the keynote 189 regimen.
Arbor, Platen, Pemetrexed and timber Elizabeth.
This whole focus of this study is on the safety and Tolerability of this combination.
I'll now touch on the autograph with in second line non small cell lung cancer.
With the European Medicines agency are advancing well in their review of <unk> marketing authorization application.
We anticipate potential approval in the third quarter.
It was about 12, a confirmatory phase III study is enrolling well, we expect to share progression free survival data in 2024, which will be the basis of a regulatory filing for full approval.
In colorectal cancer several important upcoming milestones.
Our assets in combination with Cetuximab, they showed a compelling and differentiated profile and a registrational strategy represents a fast to market opportunity.
Based on dialogue with the FDA, we are pursuing an accelerated approval pathway for this combination in third line or later colorectal cancer.
We are on track to submit a supplemental new drug application in the fourth quarter of this year.
Our Crystal 10 phase III Registrational study in second line colorectal cancer patients evaluating the same combination of allografts that plus rituxan versus chemotherapy continues to enroll well, especially following the recent new England Journal of Medicine publication and breakthrough therapy designation.
<unk> granted in December of last year.
We expect to achieve full enrollment of Crystal 10 by year end 2023, and we anticipate reporting the final analysis of progression free survival and interim overall survival in 2024 with plans for regulatory submission based on these results.
We believe the allografts, plus rituxan combination and potentially offer a substantial improvement compared to the current standard of care in the second line setting.
Real World and retrospective data in patients with <unk> mutated colorectal cancer in the second line, we estimate that the medium progression free survival is less than five months and median overall survival is less than 10 months on the current standard of care in this setting.
In addition, we presented compelling updated data in the largest phase two datasets evaluating K Ras G 12 tumors beyond non small cell lung cancer and colorectal cancer at the <unk> virtual plenary series in April of this year.
In this study at a grass have demonstrated clinically meaningful activity in a variety of K, Ras <unk> mutated solid tumors, including pancreatic cancer for which no standard of care treatment options currently exist.
Based on these compelling results allografts. It was added to NCC and guidelines last week for K, Ras <unk> mutation positive pancreatic cancer patients.
This is in addition to the inclusion that was previously granted for patients with second line non small cell lung cancer with CNS metastases.
We'll continue to explore potential accelerated regulatory approval pathways in these patient sub populations and we expect to gain clarity on our approach later this year.
Finally, I'll briefly touch on central or afternoon, which is being studied in a registrational phase III study called Sapphire.
Sapphire is on track for a top line final analysis for overall survival. This quarter, while we remain blinded to the ongoing study. We believe it was sufficiently powered to demonstrate statistically significant and clinically meaningful outcomes.
I'll turn the call over to Jamie for an update on our earlier stage development pipeline.
Thank you Alan today I'll cover cover progress on our early clinical development pipeline.
<unk> 317, 19, and all that.
Two.
I'll begin with Emirates, CX 103, our potent selective and potentially first in class oral G D inhibitor, which targets both the active and inactive states are picking <unk> mutant protein.
Can you talk to your mutation is predominantly associated with poor outcomes and standard of care therapy and several types of cancer. We estimate that there is an annual incidence of approximately 125000 patients across lines of therapy with pay rescue <unk> mutations in the U S and Europe .
I was gonna attributes of 11, 33 nanometer potency them to yourselves high plasma free fraction long target residence time in a long plasma half life.
These attributes are consistent with a low target plasma threshold for maximal target inhibition for the full duration of the dose interval and have increased our confidence in a successful development path for 11 33.
As David mentioned, we initiated the phase one two study, which is designed to evaluate the safety PK PD and anti tumor activity of 11, 33 and patients with advanced solid tumors that harbor and congrats to you talk to your mutation.
The study began enrolling patients in March overall, 133 has the potential to provide a transformative treatment option with a large and underserved K Ras G <unk> patient population.
Moving onto our TX 17 19.
Our potentially best in class MTA cooperative or <unk> inhibitor.
17, 19 is enrolling in a phase one two clinical study for patients with tumors harboring and tap Jim deletion.
Touching the leases occurred in approximately 10% of all human cancers.
We estimate that there is an annual incidence of greater than 200000 patients across lines of therapy in the U S and Europe .
The potential to make a significant difference in treatment outcomes for these patients with high unmet medical needs may enable a rapid development path.
17, 19 selectively binds to the guarantee five MTA complex, which is uniquely present only in tumors harboring tap gene deletions.
This results in extensive selectivity for <unk> deleted tumors house compared with normal normal cells.
Why therapeutic index and the lead to see if we achieve near complete target inhibition with 17 19.
Clearly differentiated therapeutic modality compared with non flagship your empty five inhibitors.
We're limited by mechanism based bone marrow and systemic toxicities.
Finally, the greater than 70 fold selectivity of 17 19 as potentially the highest selectivity ratio for amtech to lead itself relative to other reported peer MP five MTA complex inhibitors.
Our early clinical experience in the phase III study has been encouraging.
17, 19 continues in dose escalation.
Current does help us are achieving consistent PK properties and plasma exposures, which now alexey levels predicted to demonstrate durable and near complete inhibition of <unk> five mm tap deleted tumors.
Based on our preclinical modeling.
At the present dose what wasn't predicted therapeutic plasma exposures. We are now observing we are not observing any dose limiting toxicities.
Any mechanism based dose limiting toxicity is consistently reported from that selective <unk> inhibitors. We look forward to sharing initial clinical data in the second half of this year, including safety and potential early signals of clinical activity.
Finally, our phase one study for <unk> a potential first in class ask one inhibitor continues to enroll well.
This agent has the potential to be synergistic with <unk> you can talk to you in Egfr inhibitors.
Is an excellent example of our strategy to maximize the value of our Prs portfolio by pursuing a broad range of kers targeting strategies and indications.
We're on track to initiate dose escalation cohorts, combining <unk> and <unk> in our ongoing phase <unk> clinical study and.
In the second half of this year.
Overall, we're pleased with the significant progress we've made across our portfolio this quarter and look forward to providing additional updates in the near future.
With that I'll turn the call over to Laurie for our financial update.
Thank you Jamie.
I will begin by walking through our income statement and touching on a few other key financial metrics.
Please see our press release from earlier this afternoon for additional details about our first quarter 2023 financial results.
Revenue for the first quarter of 2023, with seven $2 million, which was driven by $6 3 million or <unk>.
<unk> sales and $9 million of license and collaboration revenues.
This compares to revenue of $7 million for the first quarter of 2022, which consisted solely of license and collaboration revenues.
The gross to net discount in the first quarter was in line with other similar small molecule oncology therapies and are expected steady state rate moving forward in the range of 20% to 25%. However.
However, this may fluctuate from quarter to court.
Cost of product revenues for the first quarter of 2023 with point $6 million.
A substantial portion at the end of the toy sold during the first quarter were manufactured prior to the FDA approval and therefore were expense to research and development prior to 2023.
Research and development expenses for the first quarter of 'twenty, 'twenty, three or $126 $7 million compared to $131 million for the same period in 2022.
The decrease was primarily driven by a reduction in clinical development costs for sinter gotten yet as we completed enrollment in the Sapphire phase III clinical trial in the second quarter at 2022 and forward clinical manufacturing costs to support ongoing clinical trials for Atlassian.
These decreases were partially offset by increases in our earlier stage clinical development programs, such as our T X.
<unk> 33.
And an increase in salaries and other employee related expenses to support the advancement of our portfolio.
Selling general and administrative expenses for the first quarter of 2023 were $73 $5 million compared to $54 million for the same period in 2022.
The increase was primarily due to an increase in headcount related costs, including share based compensation and salaries and commercial related costs to support the marketing and sales Chris Auty.
Net loss for the first quarter of 2023 with $184 $6 million or $3 18 per share basic and diluted.
Parents of a net loss of $188 4 million or $3 40 per share basic and diluted for the same period in 2022.
We ended the first quarter with approximately $900 million in cash cash equivalents and short term investments.
Net cash burn was 181 $5 million in the first quarter and the first quarter will be our highest cash flow quarter of the year.
Drivers of the higher net cash burn in the first quarter included the 2022 bonus payment.
Milestone payment to Pfizer and timing of vendor payments associated with the crude expenses.
We recognize that a disciplined data driven approach to capital deployment is critical as we advance our pipeline invest in innovation and effectively launched products to drive sustainable long term growth we.
We have focused our investments on our highest priority opportunities those that have the greatest potential to benefit patients create value and drive shareholder return.
We expect our 2023 net cash burn to annualized within a range of $525 million to $580 million, our current cash runway into 2025.
And with that I'll turn the call back to David for closing remarks. Thank you Lori as you've heard there is an abundance of positive activity and opportunity from variety in the near term and beyond.
Much of our confidence centers around our belief that <unk> is the best in class <unk> inhibitor and has the potential to address a $1 billion plus market opportunity across multiple lines of therapy and tumor types, although as a mono therapy and in combinations.
We're also proud of the quality of the commercial organization, we have assembled it gives us confidence that resulting in any paint your products will be well represented in the marketplace. We also continue to make meaningful progress advancing our broad and differentiated pipeline of targeted oncology programs.
Closing I won't reiterate an important point I made earlier, our clinical pipeline is deep and has the potential to address unmet medical need for hundreds of thousands of people living with cancer and that motivates us to succeed each and everyday.
On behalf of all of US at Marathi, we thank you for your continued support and interest in the company.
With that Justin we're 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.
Joining us today using a speaker phone. Please make sure mute function is turned off to buy your signal to reach our equipment.
Please limit yourself to one question and one related follow up question again that is star one if you would like to signals question Star one.
The first will come from Michael Schmidt with Guggenheim.
Hey, guys. Thanks for taking my questions.
I had one perhaps for Jamie on the updated Crystal seven data that we'll get in the second half of this year on the.
First line lung cancer combination study and just help us understand how potential outcomes here will influence your phase III plans is it simply a a powering question are there any other considerations as to how the data might inform next steps and then the the other question was really on you know where you are.
Or with any potential pursue itself mono therapy.
The first line non small cell lung cancer is that still on the table at this point. Thanks, so much.
Sure. Thanks, Michael I know you directed that question to me, but how long, it's gonna be handling that aggressive related questions today.
Great. Thank you for the question so.
The data again, we will be looking at the data and having that data available in the second half of this year. The data, we'll be able to help guide us toward a data driven approach in frontline, which as you know.
There's different types of patients the greater than 50% of less than 15%, which is also divided into the less than one in 1% to 49%. So evaluating all that data in case, seven which is predominantly the doublet combination of an aggressive bid pemble isn't that will provide us with information.
Information to guide that.
And also there is a mono therapy group for that mono therapy had a core asset that we're looking at in the less than 1% and we will have updates on that as well in the second half of the year. So all of that will help guide us towards an informed decision making process and at that time.
And our next question will come from Salvino, Victor with Goldman Sachs.
Hey, Thanks. This is Matt on for <unk>, just a few on the croissant launch.
First what kind of share do you think is likely by the end of the year.
And do you know what was driving the switches from Lou Mcgrath.
And then finally, just given the stronger than expected quarter are you still expecting a linear trajectory for sales. Thank you.
Sure, we will have or will have been addressed those questions.
Sure so.
As we said in my prepared remarks, we saw about a third of new patients starting on Chris' asking and keep in mind that that's new patients, which only constitutes about 10% of patients at any one time, but is really the mark for what you could expect to see in the future. So we're very excited about the growth to date there in regards to <unk>.
The switches, which came from <unk> the two.
The most common reasons around that where where physicians had seen some toxicity and we're looking to switch as well as we had some reports of physicians moving patients again from the other <unk> inhibitors, where there was a CNS Mets prisons.
Again, we estimate that at around 20% of our Q1 volume, but were still getting up to put a hold on that as we move forward and then in regards to growth moving forward. Yes, we have kind of guided to that linear type of adoption, we think that because the test. They rate is still beginning to increase we are still increasing as well as patient identification.
<unk> is increasing too, but we do think more of a linear adoption for the patients in plate will occur and ultimately we believe we will be the market, leading K rents were not directing at which particular time, but we're confident that we'll get there.
Okay.
And our next question will come from Tyler Van Buren with TD Cowen.
Yeah.
Hey, guys. Thanks for taking the question and congratulations on all the progress encouraging comments on the <unk> launch I wanted to ask on.
Hey, Russ did you talk D or <unk> 11 33.
Can you tell us what the early bioavailability or and pharmacokinetic data in the early patients being treated is looking as expected based upon what was anticipated from the preclinical data.
Tyler will Jamie I'll take that obviously sure Tyler, Yes, I think so far there has spent a lot of enthusiasm among investigators to open the trial. So the patients have been readily available and quite interested in this study is enrolling well.
So far our experience has been good but it is our plan to really provide a fulsome update at a later time likely in 2024 to cover all of the PK Tolerability and early signs of clinical activity.
In context, so that's our that's our plan currently.
Okay, and just for a follow up for that update in the first half of 'twenty four.
Is the plan to hopefully reach a recommended phase II dose by then.
Yeah, It would be our goal to have a recommended phase II dose.
You know at some point this year and that would be able to present data related to the recommended phase two dose in the 'twenty 'twenty four time frame.
And our next question will come from Gena Wang with Barclays.
I have two questions. The first one just wanted to confirm when you said, 20% wanted to make sure that patient.
Out of all of the patients treated equally.
Patients are naive.
And also experienced patients and then my second question is also regarding the <unk> 12.
I'm just wondering how many dose levels have you explored.
500 milligrams is still a good estimate for optimal therapeutic window and also what kind of cancer types.
Quickest.
So Gina will have been first and then Jamie I'll take the <unk> question.
So thanks for the question Jami.
Characterization of approximately 20% was inclusive of both late line patients as well as those with CNS Mets. So it's kind of a composite across those.
Again, we'll get better color in the next couple of months, but maybe an update towards the middle of the year, but 20% is kind of more of a all encompassing of those different sources.
Sure Yeah on the <unk> question. It's early days in the trial, we are in dose escalation, we haven't guided to what escalation cohort currently and but again the study is making good progress.
PK predictions, we've done for $11 33, and do believe a modest dose level.
At or below 500 milligrams on a daily basis could be approaching the level of.
Therapeutic exposure.
So we continue to monitor the study it's an open label study and again you know as soon as the data looks like we have a reasonably sized data package, we would be updating likely in the 2024 timeframe.
And our next question will come from Jonathan Miller with Evercore ISI.
Hi, guys. Thanks, so much for taking my question I'd also like to follow up on <unk> B.
Is that a.
First half next year update I, just want to get a sense that we will have a meaningful amount of data at that RPT D.
Would you expect to be able to give reasonable estimates of or are at that point for instance.
And secondly on formulation I know originally this was expected to be IV could you give a little bit of color on how this has evolved and what's giving you confidence that you're going to get the PD you need from and an oral formulation.
Yes, Jonathan It's David then I'll pass on to Jamie the second and I appreciate all the questions coming at around <unk> 12.
The enthusiasm is there and we're very enthusiastic about the Brooklyn as well, but just just wanted liberty no. We're not going to do piecemeal data with <unk>, we're going to come out with the fulsome data package.
Go to the Phase one program and we think that's the most appropriate way to release data. So as things play out certainly will go as fast as we can and we are doing that but we'll give the full data package.
It's ready I'll pass along Jamie, though and I think just to build on David's comment of course. It is our goal to reach a recommended phase $2.
Want to make sure we get it right. So we will be exploring dose schedule at formulation in our in our clinical trial.
So that is I think the first part of the question. The second part is related to a formulation. So we.
Have been developing multiple formulations in the preclinical setting we.
We have identified a formulation that we believe well achieve that therapeutic exposure and has given us a lot of confidence in the ability to reach those therapeutic exposures via oral administration in the preclinical setting we have identified formulations that.
<unk> increased the AUC or oral exposure by up to 10 fold or greater we have seen evidence of bioavailability in preclinical studies.
At or exceeding 10% and when you couple that with the low threshold to hit the target with regard to systemic exposure and concentration has really given us the confidence that we can reach the goal.
With this particular oral formulation of course, we will be continuing to manage this program throughout its lifecycle and we will be exploring.
<unk> ways to administer the drug including continued work with the IV, but here, we would like to assure the oral has full full opportunity and may be important with regard to maximizing target coverage for the full dose interval, which we believe is important for K Ras inhibitors.
And moving on to Michael's with Morgan Stanley .
Okay.
Hey, guys. Thanks for taking the question maybe just another one on <unk>.
And that's in place as well so it's still significant upside in this marketplace.
Got it thanks.
And our next question will come from then Burnett with Stifel.
Okay, great. Thank you I actually had a question, but the the basket study about a grasp that you spoke about earlier it looks like you're seeing results across a variety of tumor types is there a a tumor ignostic regulatory path for autographs or with the F. D. A or do you see a path for the various treatment guidelines to recognize that a grasp in addition to that the pink.
Out of cancer update that you mentioned.
Sure Uhm Allen is gonna take that.
What kind of question. So it's an important one and one that we are in communication with with the FDA and we'll be discussing that with this year. There as you mentioned there actually.
Two different approaches that can be taken with.
We're looking toward that tumor agnostic approach and will have discussions with that and they're also is that backup plan as you mention of having individual potential individual indications with as a pancreatic cancer and potentially you'll probably need your personal but two of the diseases that had a higher risk.
<unk> right.
So we should be able to give you an update on that later this year.
On the regulatory okay over there.
Okay, that's great and if I could also to ask just a follow up question on the purity five program M. R. T X 17 19.
I believe you you mentioned that you're not seeing D. L. Ts at this point I was just wondering just maybe give us a sense of where you are in that dose escalation schema relative to where you would expect to see activity based on on preclinical work.
Yeah, I'll I'll I'll put that over to Jamie a second I'll caveat that with what we said about our G. Both the program as well.
We're excited about 17, 19, where we're not gonna release piecemeal data, we will have a full sum of data date. The plan is for later this year. They have this update on 17 19 and with that I'll pass it on to Jamie sure. Yeah, I think we've been able to make very nice progress in the program.
You know again the investigators I think are an increasingly enthusiastic and are looking for these patients and we've been able to enroll rapidly through the dose escalation cohorts an hour several dose escalation court and uhm as mentioned just limiting toxicities.
Limited our ability to continue to escalate at this time. So now there are you know kind of key questions about.
Looking at early signs of clinical activity and tumor pharmacodynamics as a way to guide our selection of dose and having said that you know we are at a point when we have taken our preclinical data looked at what the target therapeutic exposures would be and do believe that we are now at dose levels that well cover though.
It was targets so I'd say good progress to date, and we'll look forward to being able to talk about down there this year.
And we have a question from Jason with Bank of America.
Oh, Hey, guys. This is chia for Jason Thanks for taking our questions. I'm wondering if you can quantify the number of patients that were treated <unk> and I think you just have one I think we're starting at one side of the new shares authentication share your competitor I used to like.
Provide some level of numbers on set up your patient numbers I'm, hoping if you can't quantify that product that'll be helpful. Thank you.
<unk>.
Yeah.
We'd send it as a guy right at this stage around the accounts because we think that's a more robust data set we see that within some of the patient physician <unk> volatile, particularly in the launch window, so could consider that in the future.
But we have to be really happy about it has been the field teams execution and again being able to actually access and promote to 90 per cent of key accounts and then actually be adopted in Britain and 80 per cent of the top 50, So again very happy with where we are today and great execution not counting from a sales sales standpoint, but very strong access as well.
We can consider it kind of opening up and talking about additional data matches in the future.
Really please with the momentum and the other one third.
<unk>, new patient starts of the cave rescue Tolsey inhibitor class already.
[noise] and moving onto Mori Raycroft with Jeffries.
I congrats on the update thanks for taking my question I was just wondering if you can share additional perspective on <unk> being prescribed in relation to prior anti P. D. One use including timing between the prior Pembroke treatment and for those patients that switched from luma crass with Apatow tags or.
Or the patients with C. N S maps, how are they doing <unk> any perspective from real world observation Sir.
Absolutely.
Yeah. So thanks for the question, we have seen and heard anecdotally, but one of the benefits of <unk> is the ability to <unk> in close sequence to the <unk> therapy.
Because we have not seen as we've displayed with some of our first line combination data we've seen a very tolerable profile from Manhattan toxicity standpoint, So that has something that is something that's come up multiple times, particularly in the academic setting and as a reminder, acting without Oh 12 study, we've actually nope requiring actually that.
A wash that period there because we think we have advantages for my profile standpoint in relation to the patience, which are being switched <unk>, you'll see in a Smith, it's just a little bit too early to get a strong sense of that we will be following up with physicians, who have these anecdotal case studies and be considering that.
Publication purposes in the future, but very early for Miss them. So from this standpoint.
Once you're ready.
<unk> and how they're doing.
And we have a question from Silvana entertain with J M P Securities.
Yeah. Thank you congrats on the update and thank you for taking my question I'm, just regarding the update and frontline non small cell lung cancer that we are anticipating for the second half of the year could you tell us a little bit about I understand how we have the tablets and the three P. P. P. S scores patient populations here, but with without.
Having.
Data with the chemo pemble with this so the trip triplet how can we make a decision in the frontline. If you could just talk a little bit about the options that you've seen here. Thank you very much.
Yep and thanks for the question. So yes, K seven of course, we'll have the update moving forward, which is predominantly with the doublet, which is impatience across all all of the cohort the greater than 50 in less than 50 as well it will be a waiting for the data update on that although you.
Well, we'll call we did have some encouraging data in the greater than 50% I do have some ohio.
In addition, what we're doing is we have a study that has started that has activate it.
And is ongoing now she's 17, which essentially it looks to add add a grass head to the keynote 189 regimen. So that's the Fort Bragg regimen, we're looking at that as well as an opportunity and the less than 50% I'm trying to <unk> review of the data for case seven in the second half of this year.
Here and then also some of the data that is emerges with K 17. The latter part of this year, which is predominantly in a safety evaluation will be able to look at the totality of the data and be able to make.
And informed decision as to what direction to move forward and which cohort.
Why isn't the best approach.
And we have a question from Eric Joseph with J P. Morgan.
Hello, Good evening, Thanks for taking my question so.
Thanks for all the color on the watch so far I'm wondering if any there's any inventory bill that's contributing to the first quarter print and and you also laid out <unk> expectations in the range of 20 to 25 per cent I guess, how should we be thinking about the function nation sequentially here and in the second quarter.
And then 17 19, if I could.
I guess, just given the breath of addressable tumor types with this mechanism any particular bias or concentration tomorrow histology, so far the dose escalation phase of Patricia <unk>. Thanks.
Loyal take the first part the Jamie old things a second yeah.
Yeah. So for inventory you know, we we have seen the out of the 6.3 million in sales just a modest amount of inventory based on our model our specialty distributor in pharmacy model. We don't see you know, we don't expect large inventory Donald I'm, a discount rate, 20% to 25% that's in my.
Line with our expectations I as we move through the year, we will see fluctuations corner to corner, especially given you know kind of that early days of lunch, but that that that range is is kind of where we expect it to be as in line with other oral oncology products.
You know, we expect that the hold for the year.
Yeah, and I think on the 17 19 Friday you know first your question about the different types of tumors and we've seen a broad spectrum of different tumors.
<unk> on our phase one escalation.
<unk>. So I think we have a lot of different representative tumor types with that tap gene deletions I will say that you know a number of our sites should be have thoracic oncologist. For example is the P. I and in other cases, we put a moment for G. I units or otherwise. So you don't need to believe based on both are preclinical data in terms.
Seeing responses and the preclinical models as well as the frequency of epitaph gene deletion of different tumor types. There may be certain settings like non small cell lung cancer, both adenocarcinoma and squamous cell pancreatic adenocarcinoma, a smaller indications like <unk> on my way or we wouldn't expect both strong.
<unk> mono therapy activity as well as a reasonable frequency of these mutations that if we see the requisite response rate is possibly could develop this drug as a motto therapy and somewhat of an accelerated setting using response as a primary endpoint.
That's driven the design of our clinical trial as well as a selection of our investigators.
And we'll take a question from <unk>.
With city.
Hi, Thanks for taking your questions in just a few more for you on the launch could you comment on the split between the academic and community uptake <unk> and then I think he made a comment regarding the 10th prescribing, 90% could you comment on the conversion rate for the intent to prescribed there and then third with respect.
To the discontinuation rate, how is that comparing and the commercials setting versus what you'd seen in the clinical experience. Thank you.
Sure.
Start with the academic community split, it's actually been a bit more weight to the academic it's about 60 40 in the first quarter, which is encouraging because obviously you have you thought leaders in the academic setting. So it's great that we've seen such strong adoption across the academia, we do expect the community too.
All of them and that's been a big focus of our Salesforce efforts. So overtime expect that to constitute closer to 70 to 80 per cent of the mix a longer term in relation to intend to prescribe yeah. That's part of a survey that we conducted in in the first quarter and he's in relation to those physicians who were familiar with the profile.
And may or May not have written <unk> and for those but stated that they their intent so right the product in the future is around 90%. So that's just a very positive indicates every every intent I don't have the exact conversion rate of what that looks like but again my survey standpoint, a very a very strong indicator of intent.
There the the <unk>.
Part of the question was <unk> Oh, yes on the discontinuation right, we're not saying anything unusual here, it's very early.
So really comment more broadly than that but no surprises here is we're beginning to see refill rights come through again, obviously the first quarter.
A R. A pharmacy is very we only launched the product in late December mid to late December so very early to comment on that but we're not saying anything out of that'll be.
<unk> from that standpoint.
And we'll take a question from sugerman with BMO capital markets.
Hi, guys, just knock them off and on for Evan.
We wanted to ask how do you think about the second line and third line colorectal market's run across it and <unk> size to the non small cell lung and are there any synergies you would be able to leverage with the non small cell sale teams when entering those markets.
Yeah well.
Then I'll take that.
Sure could colorectal innovations of pancreas cancer really important indications for us because it really shows the breadth of the efficacy.
That's possible with <unk>.
Particularly important in the community where the vast majority prescribed as they are actually writing a cross therapeutic.
Therapeutic areas and across the human tops when she's very important in regards to the numbers is about 3000 patients with the CRC from second line and beyond saying, we have an opportunity. There and then in addition is you know a couple of thousand in relation to pancreas and other indications as well so.
Not only the numbers and our ability to help these patients who really are in dire how 'bout die unmet need, but we think it's really supportive of the overall profile of of <unk> and from a <unk> standpoint, we will build the infrastructure, we need we don't need to add to that and we've got a super experienced <unk> and they would be able.
Cover of those colorectal targets as well so yeah excited about the opportunity there and more to come on.
And we have a question from Calvin with be Riley Securities.
Good afternoon. This is Andy pleasure on for to help it and thank you for taking the question a couple from us regarding the potential timelines for publication first you presented some unpublished clinical outcomes and frontline non small cell lung cancer from the Dana Farber Cancer Institute in December .
When should we expect these data to be published and how many centers in patients with the data are we expecting.
And second are there any timelines surrounding when we could see a preclinical publication showing data with the oral formulation of the G called the inhibitor that you discuss a bit earlier.
Okay sure Yeah, I think regarding the clinical outcomes on frontline some of that data has been published.
A manuscript uhm from Dana Farber is is out there. There's another manuscript that is going to follow from memorial Sloan Kettering M. N M. D. Anderson is working on this as well so we do.
You know anticipate additional color being out there in the public domain. In addition to the academics at our institutional experience, which often covers both clinical trials and patients that enroll on a given regiment, but then the institution.
Working with large providers like Tempus, where you know <unk>.
Additional data is has been put together and we do plan on on disclosing that in collaboration with that organization at some point and you know just as a reminder, I think overall.
Overall, when you look at the outcomes and the less than 50 per cent population <unk> subset.
There is likely.
<unk> medical need air.
Regarding the G 12 D. You know I think are forward looking publication strategy.
Likely be linked to I, you know tying any preclinical data and with clinical data.
So you know I think you know again will be looking at the updates for 11 33 likely being in the 2024 timeframe.
And our next question will come from J Olson with Oppenheimer.
[noise] Oh, congrats on all the progress and thank you for taking our questions.
There've been a few <unk> data presentations on emerging <unk> inhibitor is that okay.
T. R. Another conferences can you talk about the key points of differentiation across the G. P. L C landscape.
And how do you expect to feel <unk> and then I have a follow up on your anti fine. Thank you.
Sure Yeah.
Yeah, I think I'm Gonna <unk> <unk> of course, we monitor that space closely and are looking at the competitors.
I think there are a number of points for EDA grass at where we we do believe that.
That there are some positive attributes that we can leverage.
One of those is kind of a long half life and a b I T schedule, where we have very little peak to trough variation and I think that comes in in two places one is the ability to really hit the target hard.
For the vast majority if not the fall Center Hall.
And then to avoid hyping concentrations the second place where that particular aspect comes in is if we can avoid concentrations.
I do believe that the <unk> toxicity observed has been associated with facilitating an immune response due to off target immunogenic captains and the ability to have a fairly flat profile may help us have a cleaner profile when it comes to this patent toxicity remain related toxicity issue.
Ooh.
Another attribute of anagrams that also helps.
Therapeutic index, especially when it relates to immune related eighties.
Is the fact that this drug has a favorable <unk> ratio. It has good <unk> noncovalent binding or any and we've been able to dial the reactivity down to the point, where I don't think we're gonna run into targeted China cabinet incessant driver of therapeutic index Uhm. We do believe that we may be have a best in class.
File with regard to break in a trance.
Ben had covered that in his presentation. When we do believe that this is another area, we can leverage four and grass. So we continue to monitor the space, but we do think we have a number of advantages here and one of those advantages I think is emerging and that is the ability to combine with immunotherapy and leverage that gain.
Presence in the frontline setting that.
Yeah, Jamie. Thank you very much I just add onto that you know what we've been able to.
Presents and various conferences are approval numbers at the response rates or overall survival data CNS activity the.
Goodbye to bill with with other agents such as immuno oncology B.
Egfr inhibitors is also nice advantage, we have in the marketplace and then across multiple tumor types, we've shown that too and I'd say finally as word word years ahead of folk too. So we feel that is a K O S. T tolsey inhibitor, a market leader or well on our way.
Great. Thank you so much that's super helpful. And then for the M. T. A cooperative P. R T five and you can.
Can you just talk about what we should expect from the initial data later this year and is there any read across from the Tango Therapeutics program.
Yeah, I think I'll mention a few things there. So our data. This year you know we are a dose escalating phase one study we hope shortly to be in the face one b expansion, where we can enroll additional patients perhaps at two different dose levels and that would expand our patient pool, but I think to setup.
Expectations, we are a dose escalation and you know we're escalating with cohorts of three to four patients in peace. So you know that should provide color towards the number of patients that we would have I think the second point here is that our call would be 2% a P. K P D tolerability.
In any early signs of clinical activity.
Uhm one advantage we thank our program does have its the 70 to 80 fold.
Ratio of being able to target M tab deleted tumor cells relative to sell us that don't Harper this deletion and I think the important to take home here is that we believe we need to be at a pharmacodynamic inhibition level four P. M T five and perky five dependent S. TMA that seems about an icy 99, and if we're able to.
Achieve an icy 99, and then epitaph deleted tumor cell that will allow us to avoid the levels that have historically been associated with off target mindless suppression neutropenia, thrombocytopenia and other issues and I think that that's.
I just needed preclinically to see two of our responses and we do believe that this is a potential feature of differentiation for 17 19 relative to some of the other programs out there and we will be able to give them then fulsome update the second half of this year.
And we'll take a question from harmony.
Hi, good afternoon, Thanks for making my questions first on M. I T X My monthly three.
Could you give us some color on the size of the data that you will be presenting sounds like.
You want to wait to achieve D. A recommended fees to those and then 10% or more wholesome data that you can give us some color on the.
The size of goodness <unk> that <unk>.
<unk> to be able to cover by that time.
And then what would be.
Okay benchmark that you should keep in mind as we get some of that data.
Thank you.
611 33.
Just a reminder, we just started the the base one dose escalation trial in March of this year. So it's early days with the program is mentioned by Jamie Yeah, We will present, the fulsome update in the first half of 2024. So so it is early days might be a little bit premature to talk about how many numbers will have at that point in time.
Yeah, David I agree I, you know, it's hard to provide a lot of color other than to say this is a dose escalating face one what the opportunity to have face wouldn't be dose expansions and really the size of the dataset depends on how many dose levels. It takes to get up to a reasonable.
And Ah recommended phase two dose and how much additional optimization is ongoing in that study.
I think you are limited to a second question is what to expect so you know I think are learning opportunity Israeli with added grass at the energy 12 C space, where we do know that there are single agent development opportunities based on response rate.
Literally in the long setting.
We had mentioned earlier in the pancreatic adenocarcinoma and Billy already track setting, where we're seeing mono therapy response rates and durability associated with being able to develop the drug as a mono therapy potentially in a single arm accelerated past there.
And finally to note that 12% of.
Colon cancer also has a K rescue 12 D mutation, we do think fees to talk some app combination strategy. There it looks very good preclinically and what the likely apply clinically. So really I think that provides a clear development path shut the drugged you when it's supposed to do and that was your particular settings. So we're moving as far.
<unk>. We can this is a significant opportunity. The patient population is is Jamie mentioned the incidents over 120000 patients a year in the U S and Europe , but we've got an opportunity for first in class. So it's all hands on deck. Your body for <unk> 11, 33 investigators are very enthusiastic about.
So we're moving as fast as we can.
And that does conclude the question and answer session I'll now turn the conference back over to you for any additional or closing remarks.
Well. Thank you everyone for joining us. This afternoon. We certainly appreciate your interested in Marathi and we look forward to sharing additional updates with you throughout the year.
Thank you that does conclude today's conference would you. Thank you for your participation have an excellent day.
Mmm.
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