Q3 2023 Revolution Medicines Inc Earnings Call
Yeah.
Good day and thank you for standing by welcome to the Revolution Medicine's Q3, 2023 earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one one of your telephone and you will then hear an automated message.
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Draw. Your question. Please press Star one again, please be advised that today's conference is being recorded I would now like to hand, the conference over to your Speaker Erin Graves Senior director of corporate Communications and Investor Relations. Please go ahead.
Thank you and welcome everyone to the third quarter 2023 earnings call. Joining me on today's call our Doctor might Goldsmith Revolution medicines, Chairman and Chief Executive Officer, and Jack Anders Our Chief Financial Officer, Dr. Steve <unk>, our president of R&D will join us for the Q&A portion of <unk>.
Carl.
As we begin I would like to note that our presentation will include statements regarding our current beliefs of evolution medicines with respect to our business and the proposed acquisition of EQ Rx.
Including statements regarding our development plans and timelines for our portfolio and pipeline and the expected timing and benefits of the proposed acquisition all of which are intended to be covered by the safe Harbor provisions of the private Securities Litigation Reform Act of 1995 or forward looking statements.
These statements are subject to a number of assumptions risks and uncertainties actual results may differ materially from these statements and except as required by law. The company undertakes no obligation to revise or update any forward looking statements I encourage you to review the legal disclaimer slides of our corporate presentation, our earnings press release, and all of our filings with the SEC.
Concerning these and other matters with that I will turn the call over to Dr. Mark Goldsmith Revolution medicines, Chairman and Chief Executive Officer Mark.
Thank you for joining us.
I'd like to focus first on our remarkable headline investigational drug RMC 63, six and try to paint the picture we see based on a couple of important weeks of data updates and extensive dialogue with investigators and clinical experts.
First objectively and by hands on investigator experience treating over 131 patients so far.
63, six is well tolerated at clinically active doses, including 300 milligrams QD as reported to us by investigators.
These observations with the first ever Ras multi inhibitor in the clinic, our dogma braking and demonstrate clearly that this compound has a very sound therapeutic window.
Second this profile is enabling continuity of dosing, which we believe is critical in treating grass addicted cancers pace.
Patients receiving RMC 63 six.
Required few dose interruptions, and even fewer discontinuation for and Tolerability.
This differentiating feature of RMC 63, six as a core lever for evaluating meaningful clinical benefit.
Third despite the inter patient variability that is typical for oral anticancer agents.
<unk> 63, six showed dose dependent increase in exposure at every dose escalation tested up to and including 400 milligrams daily.
For RMC 63, six as shown objective antitumor activity.
Both by Radiographic imaging and Cte DNA quantitative.
Against three oncogenic, Ras Gina types for which no other targeted therapies available.
<unk> D <unk> and <unk> are.
<unk> alone account for more than half of all solid tumors and <unk> and <unk> mutations are the three most common RASK drivers of pancreatic ductal adenocarcinoma accounting for nearly 90%.
The results with each of these genotypes individually represent a first in class clinical validation for a direct rasp inhibitor.
And the breadth of activity is simply unique a true RASK multi inhibitor.
It is not possible to discern any obvious relationship between dose and objective response rate viruses at this stage of the study.
Due to small numbers at each dose level and the bias towards short follow up at the high dose levels.
With increased numbers of patients now enrolled in ongoing maturation of the data, we expect to be able to conduct a robust exposure efficacy analysis using several outcome measures.
The blended objective response rate in non small cell lung cancer is already solid at 38% and the data we shared in October.
Some patients are expected to develop a partial response after the first scan.
We anticipate this member settling out in the 40% to 50% range at recommended phase II dose.
And objective response rate in lung cancer generally correlates with progression free survival.
So we plan to select a candidate dose to discuss with the regulators and execute the foundational work to enable a pivotal phase III trial in second line Ras mutant non small cell lung cancer to begin in 2024, while we continue collecting durability data.
The blended objective response rate and pancreatic ductal adenocarcinoma and the data we shared in October was a respectable 20%, which may change as we gather more data at higher doses, followed patients on treatment longer and hone in on a go forward dose.
One relevant benchmark for comparison, we've highlighted is the objective response rate for cytotoxic chemotherapy that has been reported across many studies in second line pancreatic cancer, which hovers in the 7% to 11% range.
Notably most patients treated in the RMC $63 six studies so far.
Had two or more lines of treatment previously, making them third line or later by definition.
In the context of third line or later the reported objective response rate has been zero to 4%.
While the response rate for such patients in our study was as high or higher than the overall, 20% number.
For all of these reasons, our expert advisors and we believe that RMC 63, six is performing well by this standard for patients who are facing grim prospects with standard of care.
While these objective response rate observations are encouraging we continue to emphasize that objective response rate is not the key clinical endpoint for pancreatic ductal adenocarcinoma since rapid progression with short overall survival is the norm.
Even in those who respond initially to establish treatments.
We expect that doctors patients regulators and payers will be driven by durability of clinical benefit.
As indicated by progression free survival and overall survival.
Median progression free survival for standard second line pancreatic ductal adenocarcinoma treatment consistently has been reported to be approximately three months and may be shorter for patients beyond second line.
It's too early for us to project. These parameters for RMC six to three six and it will take some time into 2024 for us to be able to establish a true median PFS.
But here there are also encouraging signs.
The disease control rate, we shared in October was 87%.
Inefficiently higher than most reports for salvage chemotherapy in pancreatic cancer.
Many patients on study have already crossed the median PFS threshold mentioned above and remain on treatment, including as far out as 48 weeks.
This statement is true even for patients who have not yet shown an objective response.
20% of patients without a partial response.
Still on drug at 18 weeks with many of these 20% having reached 21 or more weeks, while continuing on drug well pass the short duration benchmark for second line pancreatic ductal adenocarcinoma.
Even the few patients with a partial response who progressed.
So at 18 weeks or later these.
These are highly encouraging findings.
Finally, we believe we have a proposed recommended phase II dose for lung cancer in hand, now and expansions are underway to develop a robust data set we think is needed to say.
<unk> project Optimists.
We have strong conviction about the potential clinical impact of RMC 63, 6% in serving the real unmet needs in lung cancer.
And with continuing consultation with advisors and engaging as appropriate with regulators in 2024, we expect to initiate a pivotal phase III monotherapy second line non small cell lung cancer trial.
<unk> on achieving full regulatory approval.
And with a potential accelerated approval opportunity built in via an interim analysis.
Investigators globally are highly interested in participating in this study.
Yes.
We are likewise excited about the potential for RMC 63, 6% in pancreatic cancer, where unmet needs are certainly profound.
Here.
Is the gating parameter for advancing into late stage development. Since overall is an unreliable predictor of durability.
We expect to establish RMC six to $3 six its durability profile.
Median PFS and identify a recommended phase II dose in 2024.
With that in hand, and continuing consultation with advisors and engaging as appropriate with regulators. We are designing a pivotal monotherapy trial in pancreatic cancer potentially to be initiated in 2024.
Our base plan currently has a phase III randomized trial for second line treatment.
But we are also evaluating options that could accelerate our reach into first line.
Investigators globally are highly interested in participating in this study or studies as well.
Next I'd like to comment on our exciting second investigational drug to show clinical activity RMC 60, 914, <unk> hundred 12, <unk> cancers and try to paint the picture, we see based on the recent update and extensive dialogue with investigators and clinical experts.
First objectively and by investigators who have treated more than 63 patients. So far RMC 69, one is well tolerated across a wide range of clinically active doses.
And so far investigators report that it is well tolerated.
Asymptomatic prolongation of GTC on electrocardiogram has been seen in some patients.
Only infrequently exceeding the 500 millisecond threshold.
Investigators broadly do not consider this laboratory finding a key limiter to clinical development of this compound.
Second good Tolerability enables continuity of treatment in patients receiving RMC 60, 91 have required few dose interruptions and even fewer discontinuation four and tolerability.
Third 69, one has shown objective antitumor activity, both by radiographic imaging and Cte DNA quantitative <unk> in both non small cell lung cancer and colorectal cancer.
Notably in lung cancer, the or are in the data. We shared in October was 50% in patients who had recently progressed on prior treatment with an approved <unk> inhibitor.
The only comparable reported data in similar patients using a <unk> inhibitor showed an objective response rate of 7%.
Similarly, the ore are for single agent RMC 69, one was 43% in colorectal cancer patients who had not yet experienced the rasp inhibitor similar.
Similar to reported data from <unk> the off inhibitors when used in combination with anti Egfr antibodies.
These results indicate two dimensions, a clinically meaningful differentiation from other <unk> inhibitors.
Differentiation is highly encouraging for the potential of RMC 69, one itself as a drug.
And it supports our preclinical prediction that inhibition of the Ras on state in a human tumor may be biologically differentiated relative to inhibition of the Ras off state.
Further we believe this paradigm likely applies across our portfolio of <unk> inhibitors boosting the probabilities of success across our entire deep pipeline.
Fourth based on these findings we believe that RMC 691 is an investigational drug with a profile that deserves to be evaluated in a late stage development program.
There remains several options to be considered and strategic decisions will need to be made among them based on further data we are collecting.
These include monotherapy approach is built directly upon the differentiated response profile described above.
And we are currently conducting monotherapy dose optimization with the goal of selecting the single agent recommended phase two dose with a project optimists data package that supports it.
We are also committed to evaluating several compelling combination options very soon and indeed have already begun recruiting for the exciting pairing of RMC 63, six plus RMC 69, one.
Just on compelling preclinical observations.
In aggregate. These findings are highly encouraging and points to large opportunities ahead for these first two compounds.
Just on this momentum we look forward to completing the acquisition of EQ Rx.
Let me summarize the status briefly.
We expect to acquire <unk> in an all stock transaction to gain an estimated $1 1 billion an additional net capital after estimated post closing <unk> wind down and transition costs.
A significant quantum of capital that can be deployed for revlimid programs and more than we had estimated conservatively when we signed the deal.
Our strengthened balance sheet is intended to enable the larger investments needed to support the parallel data driven late stage development for our rason inhibitor pipeline focused initially on RMC $63 669, one and $98 five.
Our shareholder meeting to vote on the transaction is scheduled for November eight 2023 at 11, a M. Eastern time and the deal is expected to close shortly following the shareholder vote subject to satisfaction of customary closing conditions.
The stock exchange ratio or determined and announced last week was as follows each common share of <unk> outstanding will be exchanged for one <unk> common shares of Revlimid.
We estimate we will be issuing approximately 55 million new shares to <unk> shareholders as part of this merger.
Thus acquiring approximately $20 and estimated net capital per share of common stock issued in connection with the merger.
<unk> on our updated net cash projection.
Revolution medicines, we will continue to focus on our mission to revolutionize treatment for patients with Ras addicted cancers through the discovery development and delivery of innovative targeted medicines.
Now, let's hear from Jack Anders our CFO regarding our Q3 financials Jack.
Thank you Mark.
Turning to our third quarter financials, we ended the quarter with $813 2 million in cash cash equivalents and investments.
Please note. This balance does not include any net proceeds from the anticipated acquisition of EQ Rx.
Which is expected to add approximately $1 1 billion in net cash proceeds should the transaction close.
Total operating expenses for the third quarter of 2023 or $123 2 million.
The increase in operating expenses over the prior year period was largely due to clinical trial and manufacturing expenses for RMC 63, 6% and RMC 69, one.
An increase in research expenses associated with our preclinical portfolio and an increase in personnel related expenses, resulting from additional head count.
GAAP net loss for the third quarter of 2023 was $108 4 million or <unk> 99 per share.
We are updating our financial guidance and expect full year 2023, GAAP net loss to be between 385 and $415 million, which includes estimated noncash stock based compensation expense of $45 million to $50 million.
The increase in GAAP net loss guidance is largely due to the anticipated acceleration of a portion of RMC 60, 236 manufacturing spend originally planned for 2024.
This spend was accelerated as a result of the progress in our RMC six to $3 six program.
We reiterate cash runway guidance into 2025 based on our current plan.
Please note that our current financial guidance excludes the impact of the proposed <unk> transaction.
And with that I'll now turn the call back over to Mark.
Thank you Jack.
We believe Revolution medicine has an unprecedented opportunity to deliver high impact benefit to patients through our pipeline and.
And toward that goal the deal with <unk> will markedly enhanced our ability to bring the most out of these exciting compounds.
We have heard broad and strong support for the <unk> portfolio approach and proposed transaction.
The board and management of Rev. Net encourage all of our shareholders to vote in favor of the EQM transaction.
The employees of Revolution medicines renew our deep commitment to outsmart cancer on behalf of patients and to build share value for our investors.
At this time, if you would like to ask a question. Please press star one.
One on your Touchtone telephone again for any questions. Please press star one one.
And one moment for our first question.
Our first question will come from Marc Frahm of TD Cowen Your line is open.
Hi, Thanks for taking my question.
I recognize it's not been a lot of time since the data cuts that were presented at ESMO.
ESMO in chemo, but there were a few patients who were unconfirmed but ongoing.
Partial responses at that time, I am not sure if youre able to update us some of those have been able to have subsequent scans and that can actually confirm.
And then maybe.
Bigger philosophical question.
Over those meetings. We also saw in the last few months, we've seen a handful of trials.
Take on Docetaxel in the second line setting in lung cancer.
Different settings within lung cancer.
Orphan drugs that look pretty promising has struggled a bit.
Or even failed to be Docetaxel, just philosophically since the.
Safety profile looks really good.
Why be aggressive intake just axon straight on instead of trying to combine with those taxes since that would seem to be a much easier hurdle on the efficacy side.
Thanks, a lot Mark I appreciate your questions.
Let me comment first on the question of confirmations, a number of those patients.
Really had just squeaked in.
In the <unk>.
Advanced period, we required in order to report them, which means that they just had one scan and it's only been a couple of weeks. Since then so I think for most patients. We just don't have any more information. So I can't really provide an update today.
The question of Docetaxel.
Yes.
A comparator.
Versus for a monotherapy trial versus.
Waiting for a combination well I think in part of the question and answers it felt a little bit, but maybe Steve Kelcey can give you a little bit more philosophy, a little bit.
I think mark.
The principal which we're trying to carry through.
The whole portfolio irrespective of lines of therapy, as we like to get chemotherapy. The equation, if we possibly can and so.
A good starting point would be.
The single agent study against Docetaxel to try and beat it really I think leaving leaving chemotherapy docetaxel in the.
So a therapeutic all in the entire area and for patients.
Suboptimal.
And I think that we would just rather.
Sure beats it hands tied on and relegate that those tax until later lines of therapy frankly.
I appreciate.
It is certainly an option to do top those types of both arms, but that's it.
Not really the philosophical basis of our portfolio.
Okay.
Okay. Thank you.
And one moment for our next question.
Our next question will be coming from Eric Joseph of Jpmorgan. Your line is open.
Hi, good evening, thanks for taking the question.
Just wanted to try and get a little bit a little more incremental color on.
The Tolerability profile that you are observing that the 400 milligram cohort and whether you see room to.
Further dose escalate and another 500 milligrams or something that you were contemplating and.
Just as we think about.
Your back filling.
Some of the.
Previous dose cohorts can you just kind of.
To elaborate a little bit on your sort of strategy there what cohorts you're prioritizing.
Perhaps whether you're opening the criteria for patients with <unk> mutation.
And perhaps also just sort of how.
Colorectal cancer patients might sort of fall.
Hi.
Within that scope is that a.
Histology year.
Keen on sort of revisiting here was in the phase one study. Thank you.
Thanks, a lot Eric.
I'll take the first question and Steve can comment on the second and the first about Tolerability, we don't really have any incremental information compared to what we just reported.
Two weeks ago.
And as you know once we have the information was submitted to.
The dose selection committee and they will determine where we are with it and whether or not.
It's a good dose whether or not we should advance the dose.
Those determinations will be made in the <unk>.
Right timeframe with the right data.
The second question I think.
The question really was how are we.
What are the what's the range of options that we're looking at combinations.
Over the next 12 months and how would you prioritize those.
Okay.
Yes.
Sort of there's actually more about.
As you are back filling some of the prior dose cohorts.
Taken to.
Yes.
Into consideration when thinking about or just selecting the.
<unk> II recommended dose.
I guess really it's a matter of what dose cohorts, which dose levels are you.
Perhaps operating more aggressively prioritizing.
Weather.
The patient mix going in is.
Peter perhaps being more concentrated to certain histology is or perhaps even being opened up.
Got it okay. So it's about monotherapy and dose selection.
Got it.
Okay.
Pragmatic reasons.
Eric which related to firstly, the number of patients queuing up to get on the study and secondly, the <unk>.
Relative paucity of guidance coming from the FDA about the specific requirements for.
To fulfill the project Optimus initiative.
Aggressively back filling most of the dose levels actually at 300 and below.
And it's a priority right now is to backfill them with patients who have non small cell lung cancer and pancreatic cancer because those are the ones that the FDA is going to be interested in the exposure response analysis that we submit to them for so when we recommend.
Go forward.
This into phase III.
There is.
<unk> Suisse.
Coach Sniping approved it's on clinical trials Dot Gov, which allows us to.
Expand.
Several different.
Histology is included in colorectal cancer.
In other tumor types and they're also include does include <unk> <unk> mutant tumors.
That's completely separate from the exercise to select the recommended phase II dose for both non small cell lung cancer pancreatic cancer.
The parallel activities at the Mt.
Okay, great very helpful. I appreciate that.
One moment for our next question.
Our next question will be coming from Jonathan Chang of Leerink partners. Your line is open.
Hi, guys. Thanks for taking my questions.
First question, how should investors be thinking about timelines for next data updates across our pipeline.
Yes, I don't have much specificity on that right now obviously, we've been asked that a lot over the last couple of weeks.
We just need to see how things play out.
I think it's pretty clear what we're trying to do.
In the near term, it's largely around dose selection.
And acquiring more durability data.
And to some degree.
Moreover, our data at higher doses so.
I don't think we're talking years out.
Can't give you specificity.
The most.
Sort of narrow question, we get asked is where we make a presentation at <unk> and I just don't know.
In order for us to do that we'd have to submit an abstract in February which means we have to know what it is we're going to presented in may to do so so we will just have to see but.
We'll try to provide more clarity.
Once we sort of get.
Get passed.
Next couple of months.
Give.
Some more specificity about expected milestones in the coming year.
Understood.
And second question, what do you see as the duration of disease control and PFS benchmarks in previously treated <unk> and what do you see a sufficiently good duration of disease control and PFS data relative to those benchmarks.
Yeah.
Yes, I think Steve can comment mostly on the first part of that question because thats objective information.
And then as to what we consider an improvement.
As.
It will be the subject of.
Ongoing conversation with experts in the FDA.
Yes, the benchmark right now is pretty universally sets at Orion three months.
There are a few series.
<unk> is two months on one or two where it's longer than that but the vast majority of studies that have been done in that second line salvage setting show three months PFS and frankly, that's when the scans.
It is a very dramatic drop off in freedom from progression of a point at which the second scan is done so.
I think thats the key that definitely debenture at your question about how good is good I mean, there are three constituencies that we have to satisfy here.
The regulators the prescribers in Enel <unk> and Enel.
Those exist in multiple geographic jurisdictions. So I think the consultations that are ongoing with those constituencies will also decide what is good enough and then we will be able to benchmark how actual data against that and decide if that's a meaningfully important improvement and the cycle, it's kind of a.
Somehow.
Understood. Thanks for taking my questions.
One moment for our next question.
Okay.
Okay.
And our next question will come from Chris Schott with Tani of Goldman Sachs. Your line is open.
Hi, everyone. This is Charlie on for Chris. Thank you so much for taking our questions just to start wondering if you could provide some clarity on the $63 six 691 combination trial that's enrolling.
Who are you actively recruiting in terms of <unk> experience versus naive patients in that study and then my second question is just regarding the potential for tissue agnostic approval, what does the TMC as the clinical bar to reach there in terms of <unk>. Thank you.
Just a clarification on your second question Charlie.
Were you asking about for the combination or for either of those compounds individually or just more generically I guess more generically.
Okay alright. Thanks.
Hey, <unk>.
Two to three six on long combination protocol right now is enrolling both lung cancer and colorectal cancer patients.
And.
The colorectal cancer cohort will prioritize patients with our <unk> inhibitor, the lung cancer cohort right now our lives either.
And we're not at a point, where we're biasing in any one direction or the other right now because we're still in the dose escalation dose finding dose exploration mode and it doesn't really matter frankly.
What disease or <unk> patients has flipped for them for that purpose.
So as soon as we've got our dose for that combo that I think will always be a little bit more selective.
The patients.
We want to encourage into the study and that was to some extent depend on what we've seen during the fiscal Asian area.
I think everybody knows.
Accelerated approval sharing.
Little bit hard glosses coming off at a little bit.
The bar moves around depending on the indication frankly Buck.
Accelerated approval traditionally have been given for single agents with response rates in the sort of 25% to 30% range and I don't expect it to be any different for <unk>.
<unk> inhibitor and <unk>.
Disease, particularly as the precedent that has essentially been set by the et cetera approvals of <unk> in the amount of our assets.
And even though he was asking specifically about.
Tissue agnostic tumor agnostic strategy, Yeah, I think but I think the.
In the core indicators indicate.
Zero tissue agnostic strategy theres going to be a couple of indications that we're going to do.
Almond.
We dominate that cohort and I think the.
The response rate.
And that sort of 30% range I think in order for anyone to take that seriously.
Clearly the point of the tissue agnostic strategy isn't going to be some indications, which are so uncommon, there's only going to be a handful of patients and you won't be able to compute a response rate with any any degree of certainty. So we're really talking about the.
Confidence central's around the overall response rate related indications within that.
Cohort.
Great. That's very helpful. Thank you both very much.
And we do have time for two more questions.
One moment for our next question.
It will be coming from Amit <unk> of Needham Your line is open.
Good evening, Thanks for taking my question.
Regards to the pivotal trial Youre planning in lung.
You believe that you need to generate data in <unk> patients.
Before you begin the trial.
And perhaps give us a sense off.
The number of patients you think youll need to enroll for this type of a market John at this time. Thank you.
Thanks, Amit I think Steve can comment.
On that.
Okay.
Didn't quite understand the first part of your question do we need to validate <unk> see in humans before including in a pivotal trial.
Okay.
Yes.
Validation.
Yeah.
Validation is a sort of a fairly hard baked wood.
I think we want some experience in those patients before included in Sigma.
A significant part of our pivotal trial.
But everything that we.
We have learned from that.
Clinical models.
Would lead us to expect the activity <unk> seen lung cancer to be very similar to the app to the changing <unk> 12.
Lung cancer for RMC.
$603 six.
And.
So I don't think it will validate.
We're going to we're going to try and get some some information that will help reassure us that what we've seen in the pre trough levels is also true in the clinic.
Im.
With regards to numbers.
Again, we're still refining the study design we have.
We obviously have to design a study you have to discuss with the.
With the regulators and.
We're still debating whether the GE 12 C mutation should be in the in the international They act and that is frankly so.
As soon as we have finalized that study design I think we'd be in a better position to excel.
Playing what it is and what we've done.
Why we've done that right now that are just a little too many moving parts to be able to be.
That's clear.
Yeah, and if I could if I could add to that on that last point.
With Steve's alluding to is sort of regardless of our confidence in the activity against <unk>. There is still our operational issues associated with having approved <unk> inhibitors available in.
Dozens of <unk> inhibitors.
Chelsea off inhibitors in.
Clinical studies and so there are risks associated with that cohort regardless of performance of 69, one and so managing that is part of what we're thinking through and that will probably have more impact on whether <unk> ends up in the core net store or on the periphery.
Because we want to make sure to protect.
The entirely unserved.
The population that is entirely unserved by targeted therapy today, which is the <unk> without C. But we're interested in both.
We will have to sort that out.
If I may just ask a quick follow up.
Maybe if you could sort of explain the concept of the mystic trial design.
We understood it.
You had power.
Right.
Now to be able to set up.
Okay. If you could just clarify.
Yes, the way. It works is the core nest gets evaluated statistically first so you enroll patients. However, they enroll it has nothing to do with the sequence of enrollment, but then statistically.
You test the core group that you pre designated as the core group.
If that.
Scores positively.
Then that permits you to go on to evaluating a larger group that still includes the core but also now includes additional patients and then you can keep I mean, you could do that 100 times. If you wanted you can keep great you can keep recycling the statistical power.
If at any point you have to make sure you do it in the right order because if at any point.
Don't see positivity and you no longer can go on and test even larger groups because it would be it would be futile to do so.
Got it that's very helpful. Thank you.
Okay.
One moment for our last question.
And our last question will come from Alex Stranahan of Bank of America and your line is open.
Hey, guys. Thanks for taking my questions for squeezing me in just a couple at a high level could you maybe talk about anticipated expense ramp to support multiple mid and late stage studies.
Planned for 63, six and the new candidates from the rats innovation engine I guess asked another way how do you continue to be judicious and you're spending despite having almost $2 billion in cash on the balance sheet, assuming the <unk> deal closed.
And just quickly to clarify for non small cell is it safe to assume that.
500 mix will not be pursued since you said that the pivotal monotherapy dose has been selected and if so is the reason just in terms of speed to start the Registrational studies or was there something in the clinical data that you think.
Next the 500 dose a nonstarter.
Thanks, Alex for your questions on the second question, let me just take care of that one and then come back to the expenses.
The comment that we believe we have a recommended phase two dose.
Candidate dose in hand, with specifically with regard to lung cancer, where we already have a response rate that's in the zone of where it needs to be and where that is generally better correlated with durability. So we can make we can make some good assumptions now continue planning and kind of pre execution in NOI.
The data to catch up with it.
In 2024.
<unk>.
The question about 500 milligrams and higher really where 400 milligrams and higher really has to do with pancreatic ductal adenocarcinoma, but we haven't really declare that we have.
A recommended phase II dose in hand in fact, we've made it pretty clear we want to see what happens not only at 300, but at 400 milligrams and then as we commented earlier, if we clear that dose level and dose selection committee wants to advance to 500 milligrams well then that's what we will do so just to separate.
Though the two statements they really they don't they don't.
Go together, they're on different concept.
Expense ramp Jack do you want to comment on it.
Yes.
We haven't necessarily given out any specifics on forward looking expense guidance outside of our 2023, GAAP net loss guidance, but it is fair.
To say that our expenses will increase from current levels.
We are going to be making investments in these programs.
We do need some more data in order to fully understand what those investments are.
And I think your question is.
Whether we're going to be judicious.
With our spend I mean, we obviously, we need to make investments that we're going to be we're going to be wise about the spend on a go forward basis, but we haven't given any specifics.
Yes, if I could just build on Jack's last comment there.
The whole point of the transaction just to give us the capital to make the investments in 'twenty four 'twenty five.
And beyond that we really need to make in order to maximize value creation by evaluating this.
These first two three compounds.
And in the right settings and to evaluate them aggressively in a competitive environment.
Taking into account also all the downstream commercial considerations and regulatory context, exclusivity and pricing and so on.
We will be increasing our spending there is no doubt about it.
I think it will increase our productivity and maximize value creation.
Our focus is not immediately on on boarding the capital, but at the same time, obviously, we'll make data driven decisions and we have lots of internal checks and balances to make sure that.
If we do so in that we do so in close alignment with a compelling strategy.
Yeah.
Thank you.
And I would now like to turn the conference back to Dr. Mark Goldsmith for closing remarks.
Thank you operator, thanks to everyone for participating today. We appreciate your continued support of Revolution medicines.
This.
Today's conference. Thank you for participating you may now disconnect.
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