Q2 2024 Revolution Medicines Inc Earnings Call
Good day and thank you for standing by.
Operator: Welcome to Revolution Medicine's Q2 2024 Earnings Conference Call. At this time, our participants are in listen-only mode.
Speaker Change: Welcome to the Revolution Medicine's Q2 2024 Earnings Conference Call. At this time, our participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you need to press star 1 1 on your telephone. You will then hear an automated message advising that your hand is raised.
Speaker Change: To ask a question during this session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised.
Operator: To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Ryan Asay, Senior Vice President of Corporate Affairs.
Speaker Change: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Ryan Acey, Senior Vice President of Corporate Affairs. Please go ahead.
Ryan Asay: Please go ahead. Thank you and welcome everyone to the second quarter 2024 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer, and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of R&D, and Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call. I'll note 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, and as a result, 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 report on Form 10-Q, which are filed with the U.S. Securities and Exchange Commission.
Speaker Change: Thank you and welcome everyone to the second quarter 2024 earnings call. Joining me on today's call are Dr. Marc Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer.
Speaker Change: and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of R&D, and Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call.
Speaker Change: I'll note 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 as a result may differ materially from those in the forward-looking statements.
Speaker Change: For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly report on Form 10-Q that are filed with the U.S. Securities and Exchange Commission.
Ryan Asay: This afternoon, we released financial results for the quarter ended June 30, 2024, and recent corporate updates. This press release is available in the investor section of our website at resmed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicines Chairman and CEO. Thanks, Ryan. It's good to be with you this afternoon.
Mark Goldsmith: This afternoon, we released financial results for the quarter ended June 30, 2024, and recent corporate updates. This press release is available on the investor section of our website at resmed.com. With that, I'll turn the call over to Dr. Marc Goldsmith, Revolution Medicines Chairman and CEO . Marc.
Mark Goldsmith: Thanks, Ryan. It's good to be with you this afternoon.
Mark Goldsmith: Given our recent webcast in which we provided an update on our clinical progress in pancreatic cancer, we will keep our remarks relatively brief today. I'll share a quick summary of the data we presented last month, highlight recent progress we've made across the rest of our pipeline, and discuss several corporate updates. I'll then turn the call over to Jack, who will provide highlights of our financial results before we open the line for questions.
Speaker Change: Given our recent webcast in which we provided an update on our clinical progress in pancreatic cancer, we will keep our remarks relatively brief today.
Mark Goldsmith: I'll share a quick summary of the data we presented last month, highlight recent progress we've made across the rest of our pipeline, and discuss several corporate updates. I'll then turn the call over to Jack, who will provide highlights of our financial results before we open the line for questions.
Mark Goldsmith: We've made meaningful progress with our pioneering RAS-on inhibitor pipeline, notably preparing RMC6236, our RAS-on multiselective inhibitor, to move into its first pivotal monotherapy studies in common, difficult-to-treat cancers driven by oncogenic RAS variants. We kicked off the second half of the year with an important clinical milestone for RMC6236. We disclosed recent data from the RMC6236-001 trial showing compelling preliminary progression-free survival and overall survival for patients with metastatic pancreatic cancer receiving RMC6236 monotherapy.
Jack: We've made meaningful progress with our pioneering RASON inhibitor pipeline, notably preparing RMC6236, our RASON multi-selective inhibitor, to move into its first pivotal monotherapy studies in common difficult-to-treat cancers driven by oncogenic RAS variants.
Mark Goldsmith: These data have increased our confidence in the promise of this program and reinforced our commitment to initiate our first registrational study this year. I'll take a few minutes to walk through some of the key findings from the pancreatic cancer results we shared last month. The full details of these results can be found in the investor section of our website at redmed.com. The data, with a May 11, 2024 cutoff date, reflect patients with previously treated pancreatic cancer across the RMC6236 160 milligram to 300 milligram daily dose cohort.
Jack: We kicked off the second half of the year with an important clinical milestone for RMC 6236.
Jack: We disclosed recent data from the RMC6236-001 trial, showing compelling preliminary progression-free survival and overall survival for patients with metastatic pancreatic cancer receiving RMC6236 monotherapy.
Jack: These data have increased our confidence in the promise of this program and reinforced our commitment to initiate our first registrational study this year.
Jack: I'll take a few minutes to walk through some of the key findings from the pancreatic cancer results we shared last month. The full detail of these results can be found on the investor section of our website at RevMed.com.
Jack: The data, with a May 11, 2024 cutoff date, reflect patients with previously treated pancreatic cancer across the RMC6236 160mg to 300mg daily dose cohorts.
Mark Goldsmith: The safety findings were promising. The most common adverse events are believed to be on target and associated with the inhibition of wild-type RAFs in normal tissue. Most adverse events were low-grade, with approximately 22% of patients experiencing a grade 3 or higher treatment-related adverse event. The most common treatment-related adverse events observed were rash and gastrointestinal-related toxicity.
Jack: The safety findings were promising.
Jack: The most common adverse events are believed to be on target and associated with the inhibition of wild-type RAS in normal tissue.
Jack: Most adverse events were low grade with approximately 22% of patients experiencing a grade 3 or higher treatment related adverse events.
Jack: The most common treatment-related adverse events observed were rash and gastrointestinal-related toxicities.
Mark Goldsmith: There were no discontinuations due to treatment-related adverse events, and those modifications of any kind occurred in only 28% of patients; the anti-tumor durability data were quite compelling as well. Historical progression-free survival benchmarks in pancreatic cancer are poor overall and deteriorate with advancing lines of therapy. In a progression-free survival analysis of second-line patients, which is consistent with the patient population we plan to evaluate in our phase 3 study, we observed an initial median progression-free survival of 8.1 months in patients with KRAS G12X tumors and 7.6 months in patients with RAS-mutated tumors broadly.
Jack: There were no discontinuations due to treatment-related adverse events, and those modifications of any kind occurred in only 28% of patients.
Jack: The anti-tumor durability data were quite compelling as well.
Jack: Historical progression-free survival benchmarks in pancreatic cancer are poor overall and deteriorate with advancing lines of therapy.
Jack: In a progression-free survival analysis of second-line patients, which is consistent with the patient population we plan to evaluate in our phase 3 study,
Jack: We observed an initial median progression-free survival of 8.1 months in patients with KRAS G12X tumors.
Jack: and 7.6 months in patients with RAS-mutated tumors broadly.
Mark Goldsmith: While these data continue to mature with longer patient follow-up, these preliminary findings compare favorably to standard of care in this patient population. We also showed an early interim look at overall survival in these patients. As of the cutoff date, the median overall survival had not been reached for patients with either KRAS G12X mutations or other RAS mutations. And importantly, the lower bound of the 95% confidence interval for the median overall survival estimate is above the standard of care benchmark for median overall survival in second-line metastatic pancreatic cancer.
Jack: While these data continue to mature with longer patient follow-up, these preliminary findings compare favorably to standard of care in this patient population.
Jack: We also showed an early interim look at overall survival in these patients. As of the cutoff date, the median overall survival had not been reached.
Jack: for patients with either KRAS G12X mutations or other RAS mutations, and importantly, the lower bound of the 95% confidence interval for the median overall survival estimate is above the standard of care benchmark for median overall survival in second-line metastatic pancreatic cancer.
Mark Goldsmith: As we noted in July, while early overall survival estimates represent a relatively immature data set, in the context of the strong progression-free survival data, we believe these observations provide a meaningful complement to the overall efficacy story of RMC6236 in metastatic pancreatic cancer. We anticipate that these two measures, progression-free survival and overall survival, will be dual primary endpoints in our planned Phase 3 study. Additional metrics and more detail regarding these data can be found on our website.
Jack: As we noted in July , while early overall survival estimates represent a relatively immature dataset,
Jack: In the context of the strong progression-free survival data, we believe these observations provide a meaningful complement to the overall efficacy story of RMC6236 in metastatic pancreatic cancer.
Jack: We anticipate that these two measures, progression-free survival and overall survival, will be dual primary endpoints in our planned Phase 3 study. Additional metrics and more detail regarding these data can be found on our website.
Mark Goldsmith: Given the strength of these data, and based on initial feedback from the Food and Drug Administration, including alignment around high-level study design and the selection of 300 milligrams as our go-forward dose for pancreatic cancer, we plan to initiate our first global, registrational Phase III study this year. This phase 3 study, called RAS-ELUTE-302, will evaluate RMC6236 as a second-line therapy for patients with metastatic pancreatic cancer Of course, while we are excited to initiate this study shortly on behalf of patients, our ambitions for RMC6236 go well beyond second-line pancreatic cancer as we explore or plan to explore other tumor types and earlier lines of therapy. Data from the non-small cell lung cancer portion of the RMC6236 monotherapy study continue to mature.
Jack: Given the strength of these data and based on initial feedback from the Food and Drug Administration, including alignment around high-level study design and the selection of 300 milligrams as our go-forward dose for pancreatic cancer, we plan to initiate our first global registrational phase 3 study this year.
Jack: This Phase III study, called RAS-ELUTE-302, will evaluate RMC6236 as a second-line therapy for patients with metastatic pancreatic cancer.
Speaker Change: Of course, while we are excited to initiate this study shortly on behalf of patients, our ambitions for RMC6236 go well beyond second-line pancreatic cancer as we explore or plan to explore other tumor types and earlier lines of therapy.
Speaker Change: Data from the non-small cell lung cancer portion of the RMC6236 monotherapy study continue to mature.
Mark Goldsmith: In the fourth quarter, we expect to provide updated safety and antitumor activity data, including durability data, and to initiate a second registrational study evaluating RMC6236 monotherapy for patients with previously treated non-small cell lung cancer. The strength of the data we've presented also enhances our commitment to expand the reach of RMC6236 into earlier lines of therapy, including first-line metastatic, locally-advanced unresectable, Exploratory studies evaluating RMC6236 in combination with current standard of care chemotherapy in first-line pancreatic cancer and colorectal cancer are currently enrolling and will yield important insights that should inform dosing paradigms for potential first-line registrational pathways.
Speaker Change: In the fourth quarter, we expect to provide updated safety and anti-tumor activity, including durability data, and to initiate a second registrational study evaluating RMC6236 monotherapy for patients with previously treated non-small cell lung cancer.
Speaker Change: The strength of the data we've presented also enhances our commitment to expand the reach of RMC6236 into earlier lines of therapy, including first-line metastatic, locally advanced unresectable, and resectable disease.
Speaker Change: Exploratory Studies Evaluating RMC6236 in Combination with Current Standard of Care Chemotherapy in First-Line Pancreatic Cancer
Speaker Change: and colorectal cancer.
Speaker Change: are currently enrolling and will yield important insights.
Speaker Change: that should inform dosing paradigms for potential first-line registrational paths.
Mark Goldsmith: This area remains a significant focus for RevMed. Another important combination study in progress is evaluating RMC6236 with pembrolizumab, with or without chemotherapy, in patients with advanced RAS-mutated non-small cell lung cancer. We expect to report initial data for this combination in the fourth quarter of 2024. While there is substantial focus and investment in RMC6236 as our most advanced RAS-on inhibitor in the clinic, we also continue to prioritize investment in qualifying our first two RASON mutant-selective inhibitors, RMC6291, our G12C-selective inhibitor, and RMC9805, our G12D-selective inhibitor, for late-stage development.
Speaker Change: this area remains a significant focus for redmint
Speaker Change: Another important combination study in progress is evaluating RMC6236 with pembrolizumab, with or without chemotherapy, in patients with advanced RAS-mutated non-small cell lung cancer.
Speaker Change: We expect to report initial data for this combination in the fourth quarter of 2024.
Speaker Change: While there is substantial focus and investment in RMC6236 as our most advanced RAS-on inhibitor in the clinic,
Speaker Change: We also continue to prioritize investment in qualifying our first two RAS-on mutant-selective inhibitors—RMC6291, our G12C-selective inhibitor, and RMC9805, our G12D-selective inhibitor—for late-stage development.
Mark Goldsmith: First, we continue to make progress in our combination studies with the goal of moving RMC6291 into early lines of therapy for patients with RAS G12C tumors. The RAS-on inhibitor doublet of RMC6291 in combination with RMC6236 in patients with KRAS G12C solid tumors, primarily non-small cell lung cancer, is a vanguard study of this sort of combination regimen. This study is ongoing, and we expect to share initial data in the fourth quarter of this year. Another combination approach with KRAS G12C non-small cell lung cancer is RMC6291 with pembrolizumab with or without chemotherapy.
Speaker Change: First, we continue to make progress in our combination studies with the goal of moving RMC6291 into early lines of therapy for patients with RAS G12C tumors.
Speaker Change: The RAS-on inhibitor doublet of RMC6291 in combination with RMC6236 in patients with KRAS G12C solid tumors, primarily non-small cell lung cancer, is a vanguard study of this sort of combination regimen.
Speaker Change: This study is ongoing and we expect to share initial data in the fourth quarter of this year.
Speaker Change: Another combination approach with KRAS G12C non-small cell lung cancer is RMC 6291 with pembrolizumab with or without chemotherapy.
Mark Goldsmith: A study of this combination is ongoing, and we anticipate disclosing initial data for RMC6291 with Pemberlizumab in the first half of 2025. Second, the first in human monotherapy study of RMC9805, a Ras-on-G12 deselective inhibitor, continues to enroll well. Dose optimization is ongoing, and we are on track to share initial safety, tolerability, and anti-tumor activity data in the fourth quarter. Overall, we have a busy and exciting road ahead with the anticipated initiation of two RMC6236 monotherapy registrational studies, a number of important exploratory combination study data updates, and additional data maturation that may validate the potential to advance two clinical-stage RASOM mutant-selective inhibitor In addition to advancing our studies, we are also preparing the organization for the next phase of growth. We are pleased to announce that we have appointed Frank Clyburn to our board of directors.
Speaker Change: A study of this combination is ongoing, and we anticipate disclosing initial data for RMC6291 with Pembrolizumab in the first half of 2025.
Speaker Change: Second, the first in human monotherapy study of RMC9805, a RAS on G12 deselective inhibitor, continues to enroll well.
Speaker Change: Dose optimization is ongoing, and we are on track to share initial safety, tolerability, and anti-tumor activity in the fourth quarter.
Speaker Change: Overall, we have a busy and exciting road ahead with the anticipated initiation of two RMC6236 monotherapy registrational studies.
Speaker Change: a number of important exploratory combination study data updates and additional data maturation that may validate the potential to advance two clinical stage ras on utton selective inhibitors into late stage development
Speaker Change: In addition to advancing our studies, we are also preparing the organization for the next phase of growth. We are pleased to announce that we have appointed Frank Clyburn to our Board of Directors.
Mark Goldsmith: Frank is a distinguished commercial pharmaceutical leader who brings a wealth of experience to help Revolution Medicines advance toward late-stage clinical development and prelaunch commercial readiness. Notably, he was instrumental in building Merck's modern oncology business, leading the successful global launch and commercialization of Merck's Keytruda to create the dominant immuno-oncology franchise. These insights and experience will be invaluable as we move forward. We've also made several strategic leadership hires across medical affairs, research and development, program management, and corporate affairs to help scale our organization as we move closer to becoming a fully integrated commercial organization.
Speaker Change: Frank is a distinguished commercial pharmaceutical leader who brings a wealth of experience to help Revolution Medicines advance toward late stage clinical development and pre-launch commercial readiness.
Speaker Change: Notably, he was instrumental in building Merck's modern oncology business.
Speaker Change: Leading the successful global launch.
Speaker Change: and commercialization of Merck's Keytruda to create the dominant immuno-oncology franchise.
Speaker Change: His insights and experience will be invaluable as we move forward.
Speaker Change: We've also made several strategic leadership hires across medical affairs, research and development, program management, and corporate affairs to help scale our organization as we move closer to becoming a fully integrated commercial organization.
Mark Goldsmith: In particular, I'd like to highlight two individuals who have joined RevMed's senior leadership team. First, Ryan Asay, who is hosting today's call, brings extensive business experience in the biopharmaceutical industry to his new role as our Senior Vice President for Corporate Affairs. Second, Dr. Mary Pinder Shank has joined the organization as our senior vice president and head of medical.
Speaker Change: In particular, I'd like to highlight two individuals who have joined RevMed's senior leadership team.
Speaker Change: First, Ryan Acey, who is hosting today's call, brings extensive business experience in the biopharmaceutical industry to his new role as our Senior Vice President for Corporate Affairs.
Mark Goldsmith: In addition to being a well-respected board-certified medical oncologist, Dr. Pinder-Shank brings extensive U.S. and global medical affairs leadership experience to Rev. I'm highly confident in the strength of our team and the collective depth and breadth of experience we can apply to this transformative stage of the company. We continue to build the capabilities needed to drive the long-term sustainable growth of our business.
Speaker Change: Second, Dr. Mary Pinder-Shank has joined the organization as our Senior Vice President and Head of Medical Affairs.
Speaker Change: In addition to being a well-respected board-certified medical oncologist, Dr. Pinder-Shank brings extensive U.S. and global medical affairs leadership experience to RevMed.
Speaker Change: I'm highly confident in the strength of our team and the collective depth and breadth of experience we can apply to this transformative stage of the company.
Speaker Change: We continue to build the capabilities needed to drive the long-term, sustainable growth of our business.
Jack Anders: This team, along with our robust pipeline of innovative programs and one of the most productive drug discovery organizations in the industry, positions us well for what lies ahead. Now, I'd like to turn the call over to Jack Anders, our Chief Financial Officer, to provide a financial update. Thank you, Marc. We ended the second quarter of 2024 with $1.59 billion in cash and investments. This compares to $1.7 billion at the end of Q1. The decrease in cash investments during the second quarter was primarily due to a net loss for the quarter.
Speaker Change: This team, along with our robust pipeline of innovative programs and one of the most productive drug discovery organizations in the industry, position us well for what lies ahead.
Jack Anders: Turning to expenses, R&D expenses for the second quarter of 2024 were $134.9 million compared to $98.0 million for the second quarter of 2023. The increase in R&D expenses was primarily due to increases in clinical trial expenses for our first wave of Rasson inhibitors, preclinical portfolio expenses, personnel-related expenses associated with additional headcount, and stock-based compensation. BNA expenses for the second quarter of 2024 were $21.7 million compared to $14.6 million for the second quarter of 2023. The increase in G&A expenses was primarily due to increases in personnel-related expenses associated with additional headcount.
Speaker Change: Now, I'd like to turn the call over to Jack Anders, our Chief Financial Officer, to provide a financial update.
Jack Anders: Commercial Preparation Activities, and stock-based compensation expense. The net loss for the second quarter of 2024 was $133.2 million compared to $98.3 million for the second quarter of 2023. As previously disclosed on July 15th, we have updated our 2024 financial guidance and expect full year 2024 gap net loss to be between $560 million and $600 million, which includes estimated non-cash stock-based compensation expense of between $70 million and $80 million. That concludes the financial update. I'll now turn the call back over to Marc. Thank you, Jack.
Jack Anders: Thank you, Mark.
Jack Anders: When did the second quarter of 2024, with $1.59 billion in cash and investments?
Jack Anders: This compares to $1.7 billion at the end of Q1. The decrease in cash investments during the second quarter was primarily due to net loss for the quarter.
Speaker Change: Turning to expenses, R&D expenses for the second quarter of 2024 were $134.9 million compared to $98.0 million for the second quarter of 2023.
Speaker Change: The increase in R&D expenses was primarily due to increases in clinical trial expenses for our first wave of Rathon inhibitors, preclinical portfolio expenses.
Jack Anders: personnel-related expenses associated with additional headcount, and stock-based compensation expense.
Jack Anders: BNA expenses for the second quarter of 2024 were $21.7 million compared to $14.6 million for the second quarter of 2023.
Jack Anders: The increase in G&A expenses was primarily due to increases in personnel related expenses associated with additional headcount, commercial preparation activities, and stock-based compensation expense.
Speaker Change: Net loss for the second quarter of 2024 was $133.2 million compared to $98.3 million for the second quarter of 2023.
Speaker Change: As previously disclosed on July 15th, we have updated our 2024 financial guidance and expect full year 2024 gap net loss to be between $560 million and $600 million.
Speaker Change: which includes estimated non-cash stock-based compensation expense of between $70 million and $80 million.
Speaker Change: That concludes the financial update. I'll now turn the call back over to Marc.
Mark Goldsmith: Revolution Medicines entered the second half of the year by fulfilling one of many important clinical milestones for our organization. We are well-capitalized and remain focused on delivering key data and actions to advance RMC6236 into its first registrational studies, while evaluating several opportunities to move into earlier lines of treatment for patients living with RAS-addicted cancer. We are also laying the groundwork to move our first two RASOM mutant-selective inhibitors into late-stage development.
Mark Goldsmith: Thank you, Jack.
Mark Goldsmith: Revolution Medicines entered the second half of the year by fulfilling one of many important clinical milestones for our organization.
Speaker Change: We are well-capitalized and remain focused on delivering key data and actions to advance RMC6236 into its first registrational studies while evaluating several opportunities to move into earlier lines of treatment for patients living with RAS-addicted cancers.
Speaker Change: We are also laying the groundwork to move our first two RASOM mutant selective inhibitors into late-stage development.
Mark Goldsmith: This important work and the progress we've made would not be possible without the support of our patients and caregivers, clinical investigators, scientific and business collaborators, advisors, shareholders, and the tireless efforts of RedMed employees on behalf of patients. This concludes our prepared remarks for today, and I'll now turn the call over to the operator for the Q&A. Thank you. At this time, we will conduct a question and answer session. As a reminder, to ask a question during this session, you need to press star one, one on your telephone and wait for your name to be announced.
Speaker Change: This important work, and the progress we've made, would not be possible without the support of our patients and caregivers, clinical investigators, scientific and business collaborators, advisors, shareholders, and the tireless efforts of RedMed employees on behalf of patients.
Speaker Change: This concludes our prepared remarks for today, and I'll now turn the call over to the operator for the Q&A session.
Operator: To withdraw your question, please press star one one again. We ask that you please limit your questions to one and one follow-up. Please stand by while I compile the Q&A roster. Our first question comes from Marc Frahm from TD Cowen. Please go ahead.
Speaker Change: Thank you. At this time, we will conduct a question and answer session. As a reminder, to ask a question,
Speaker Change: During this session, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. We ask that you please limit your questions to one question and one follow-up. Please stand by while I compile the Q&A roster.
Marc Frahm: Yes, thanks for taking my questions. Maybe just to start off, when you think about the PFS data you released in pancreatic cancer the other day, it looks a little bit better than what was achieved kind of with the G12C inhibitors in that subpopulation of pancreatic patients. Do you think that similar gap should kind of be expected when we look at monotherapy data in other settings where we have mature G12C inhibitor data, whether that's lung cancer or ultimately some other settings like colorectal cancer, or is just the biology just way too different across the board? Thanks, Marc.
Speaker Change: Our first question comes from Marc Frahm from TD Cowen. Please go ahead.
Mark Fromm: Yes, thanks for taking my questions. Maybe just to start off, when you think about the PFSA that you released in pancreatic cancer the other day, you know, it looks a little bit better than what was achieved kind of with the G12C inhibitors in that subpopulation of pancreatic patients.
Speaker Change: do you think that similar gap should kind of be expected when we look at mmotherotherap dat in other settings where we kindi have maturure you told ysee in hiptor data whether that's
Speaker Change: lung cancer or ultimately some other settings like colorectal cancer or is just the biology just way too different across tumors.
Mark Goldsmith: I appreciate your question. I think at this point, given that data will be rolling out in the coming months and over the next year, I think it's best just to let the data speak for themselves. Obviously, there are many differences in the subtle aspects of biology comparing one tumor type to another.
Speaker Change: Thanks, Marc. Appreciate your question.
Speaker Change: I think at this point, given that data will be rolling out, you know, in coming months and over the next year, I think it's best just to let the data speak for themselves. There's obviously, there are many differences in the subtle aspects of biology, comparing one tumor type to another.
Marc Frahm: Whether or not that nets out in any particular direction, I think, can just be determined in period. Okay, thanks, I'll go, and then if you... Maybe thinking about first line and pancreatic cancer, just, you know, how much more data do you need to gather to kind of know what the plan is there, rather than just saying you want to do it, whether it's monotherapy, do you need a fair amount of combo data with chemo or even with the G12D inhibitor to just kind of figure out what the what the design looks like to move to first line?
Speaker Change: Whether or not that nets out in any particular direction I think can just be determined empirically.
Speaker Change: Okay. Thanks. I'll go and then, if you...
Speaker Change: Maybe thinking about first line and pancreatic cancer, just, you know, how much more data do you need to gather to kind of
Speaker Change: know what the plan is there, rather than just saying you want to do it, whether it's monotherapy, do you need a fair amount of combo data with chemo or even with the G12D inhibitor to just kind of figure out what the design looks like to move to first line?
Marc Frahm: Yeah, I mean, I think we've said before, I know you and I talked about that. The monopair PRMC 6236, I think it already qualifies to be included in such a trial, and really the question is around what role chemotherapy should play. Should that be an arm in the study? And if so, how should that be done?
Speaker Change: Yeah, I mean, I think we said before, and I know you and I talked about that the monotherapy RMC 6236 I think already qualifies.
Speaker Change: to be included in such a trial. And really the question is around what.
Speaker Change: How to play with chemotherapy. What role should that play? Should that be an arm in the study? And if so, how should that be done? And that's principally a safety and tolerability question more than it is an efficacy question.
Mark Goldsmith: And that's principally a safety and tolerability question, an efficacy question, clearly is a broad-based inhibitor of RAS, by design. It's generally well-tolerated and safe, but it does have some side effects. It comes with side effects, and so when you put those two together, we need to have confidence going into the study going into a registration study that that combination will not blow up in patients. So that's really what we're doing is trying to figure that out. There are many combinations, as you point out, that we couldn't pursue.
Speaker Change: RMC6636 clearly is a broad-based inhibitor of RAS. It's by design. It's generally well-tolerated and safe, but it does have some side effects. Chemotherapy is typically
Speaker Change: replete with side effects. And so when you put those two together, we need to have confidence going into the study.
Speaker Change: going into a registration study that
Speaker Change: That combination will not blow up for patients. So that's really what we're doing is trying to figure that out. There are many combinations, as you point out, that we couldn't pursue. I wouldn't consider RMC 9805 specifically part of that determination for 6236.
Michael Schmidt: I wouldn't consider RMC 9805 specifically part of that determination for 6236. Going into Frontline, it's its own entity, and how we'll deal with that, we'll describe over time as we reveal data about that interesting, Okay, thanks a lot. Thank you. One moment for our next question. Our next question comes from Michael Schmidt from Guggenheim. Please go ahead.
Speaker Change: By going into Frontline, it's its own entity, and how we'll deal with that we'll describe over time as we reveal data about that interesting compound.
Speaker Change: Okay, thanks a lot.
Speaker Change: Thank you. One moment for our next question.
Michael Smith: Our next question comes from Michael Schmidt from Guggenheim. Please go ahead.
Michael Schmidt: Hey, thanks for taking my questions. I had one on the potential phase three study in second line non-small cell lung cancer for 6236. I mean, one would think that the easiest, the simplest design would just be a one-to-one randomization compared to dosy-TAP cell, but I'm just curious. There may be a scenario where CRIZATI gets full FDA approval in G12C positive patients at some point in the future, based on the CRISPR-12 study, and I was just wondering to what degree that might factor into the potential trial design.
Michael Smith: Hey, thanks for taking my questions. I had one on the potential phase 3 study in second line non-small cell lung cancer 46036.
Speaker Change: I mean, one would think that the easiest, the simplest design would just be a...
Speaker Change: One-to-one randomization compared to Dosey-Taxel. But I'm just curious, there may be...
Speaker Change: a scenario where Crevati has full FDA approval in G12C positive patients at some point in the future and based on the CRISPR-12 study. And I was just wondering...
Mark Goldsmith: Would you, for example, allow CRIZATI in the control arm for G12C positive patients, assuming that the trial obviously would include those patients, or is that something that is not feasible, in your opinion? Thanks, Michael. Good to hear from you.
Speaker Change: To what degree that might factor into the potential trial design? Would you, for example, allow Krizati in the control arm for G12C positive patients, assuming that the trial obviously would include those patients, or is that something that is...
Speaker Change: Not feasible, in my opinion.
Wei Lin: Maybe I'll just say something brief about it, and then if either Steve or Wei wants to add anything, that maybe my general comment is G-12C is clearly the most complicated part of the lung cancer trial for our 6, and there are subtleties associated with that, as you just alluded to. We have not described our plan yet for lung cancer. We put forth sort of a prototype last October, but we have not.
Michael Smith: Thanks, Michael. Good to hear from you. Maybe I'll just say something brief about it, and then if either Steve or Wei wants to add something, they can do that. Maybe my general comment is, G12C is clearly the most complicated part of...
Speaker Change: the lung cancer trial for RMC 6236.
Speaker Change: there are ceties associating with that it just uded to
Speaker Change: We've not described our plan yet for lung cancer. We put forth a sort of a prototype last October , but we've not
Mark Goldsmith: We would not lay that out, and our expectation is to do that in conjunction with disclosure of the data that would support it. So I think we'd be getting out a little bit of our skis to commit today, but whether there are any... Yige Guo wants to add to that. Actually, if you only came higher, one higher, I think you'd get it, will end up being a consideration from the FDA if they were to prove Khrisati.
Speaker Change: We've not laid that out, and our expectation is to do that in conjunction with disclosure of the data that would support it. So I think we'd be getting out a little bit of our skis to commit today. But whether there are any principles that Stephen really wants to add to that.
Speaker Change: ated
Speaker Change: I think the only thing I want out of it is that I think it's great.
Speaker Change: It will end up being a consideration from the FDA if they were to prove Frizzati.
Mark Goldsmith: Today's lead at 1.6 months of PFS improvement, is ProSTI the standard care for G12 patients or just another standard care in addition to docetaxel? And that would dictate whether ProSTI is required, the Comparator, or Don't Be Tough, Always Do What You Love, and Dan Taft.
Speaker Change: to basically lead the 1.6-month PFS improvement, if that's PSADI, as the standard care for G12 sleep patients, or just another standard care in addition to docetaxel. And that would dictate whether PSADI...
Speaker Change: is required to be the comparator or those who have tolls to be acceptable, so that'd be a negative.
Michael Schmidt: Thank you. Okay. Okay.
Eric Joseph: And then, yeah, very curious about the combination of 6236 and 6291, where I think you committed to presenting data later in the fourth quarter. And yeah, just want to understand a little bit better what types of patients are enrolled in the study. Are these predominantly second-line or later patients, or perhaps some treat-the-knife patients included there as well? And what efficacy bar are you looking for to potentially advance that dual?
Speaker Change: Thank you for all your views.
Speaker Change: Okay, okay, thank you, and then...
Speaker Change: Yeah, very curious about the combination of 6336 with 6291, where I think you committed to presenting data later in the fourth quarter. And yeah, just want to understand a little bit better what types of patients are enrolled in this study. Are these predominantly second-line or later patients, or perhaps some treat-the-nice patients included there as well? And
Speaker Change: What efficacy bar are you looking for to potentially advance that dual combination?
Mark Goldsmith: to more registration-directed studies. OK, so the first question is one of eligibility for the trial. Maybe Wei can answer that, and then maybe I can comment on that. Combination 6236 plus 6291, what types of patients are they for? Starr, Ben Hutrof.
Speaker Change: Okay so the first question is one of sort of eligibility for the for the trial maybe Wei can answer that and then I maybe I can comment on the
Wade: The second part of the question is, with combination 6236 plus 6291, what types of patients and tumors are in the trial? Yeah, so, if the patient, or Alec goes,
Eric Joseph: Yeah. So, the patient, or Alec was... any patient with a T12C previously treated. John Lee, so far, will be enrolling.
Wei: Any patient with a T12c previously treated tumor predominantly so far will be enrolling
Mark Goldsmith: 12k Pneumonia treatment in 2013, have a lung cancer or a colorectal cancer, just given the predominant... I think if you look at 100 patients with solitum or T12C mutations, 70 of them will probably have lung cancer, and the other 20 will be colorectal cancer, with the remaining 10% being the other. That's kind of the distribution, and so just by that natural distribution, we end up emulating predominantly colon cancer. Mao, and so and so that second line plus given that they have to have been previously treated with, And then your second question was, what's the efficacy bar?
Speaker Change: T-PALT patients.
Speaker Change: who have a lung cancer for a coront cancer just giving the predominance of those t or types of war i think to you look at one hundred patients with solitu or chieffe see mutations se of them probably be
Speaker Change: Lung cancer and the other 20 will be colorectal cancer, the remaining 10% being the other. That's kind of the distribution, and so just by that natural distribution, we end up emulating predominantly colon cancer.
Speaker Change: And so that second line plus, given that they have to have been previously treated with G12C powder.
Speaker Change: And then your second question was, what's the efficacy bar?
Mark Goldsmith: Yeah, well, it's a fairly subtle topic here, you know, really to compare two things and prove that they're different requires a randomized control trial with hundreds of patients. So there's not going to be a number that's going to come out of this that will allow it. Player, you know, victory at that level, of course.
Speaker Change: Yeah, well, it's a fairly subtle topic here, you know, really to compare two things and prove that they're different requires a randomized control trial with, you know, hundreds of patients. So, there's not going to be a number that's going to come out of this that will allow us.
Speaker Change: to declare, you know, victory at that level, of course.
Eric Joseph: What we're looking for, though, is can we see some level of differentiation? qualitatively informed, and what that is will emerge over time. We'll see what we see, and we'll communicate it at that time. But there's not a preset.
Speaker Change: What we're looking for, though, is can we see some level of differentiation?
Speaker Change: It's qualitatively informative and, you know, what that is.
Speaker Change: will emerge over time, you know, we'll see what we see.
Speaker Change: and we'll communicate it at that time, but there's not a preset.
Speaker Change: Response Rate, PFS, or OS number that we can associate with this and ever ascribe it to this particular combination in and of itself.
Mark Goldsmith: Response Rate, PFS, or OS number that we can associate with this and always ascribe it to this particular combination, in and of itself. Okay, great. Thank you. Thank you. One moment for our next question. Our next question comes from Eric Joseph from J.P. Morgan. Please go ahead.
Speaker Change: Okay, great. Thank you.
Speaker Change: Thank you. One moment for our next question.
Speaker Change: Our next question comes from Eric Joseph from J.P. Morgan. Please go ahead.
Jonathan Chang: Hi, thanks for taking the questions. I'm hoping you could just help us level set expectations for the phase one non-small cell lung cancer update in the fourth quarter in terms of patient numbers. You know, just kind of following up from the update that we saw in July in pancreatic cancer, should we expect a similar ramp up in the number of evaluable patients across doses 160 to 300 milligrams? And then... As a follow-up in pancreatic cancer, Marc, I guess how should we be thinking about sort of additional updates either kind of within the data set that you presented in July, perhaps at medical meetings, or sort of Thank you. Yeah, thanks, Eric.
Speaker Change: sp
Eric Joseph: All right, thanks for taking the questions. I'm hoping you could just...
Eric Joseph: to help us level set expectations into the Phase 1 non-small cell lung cancer update in fourth quarter in terms of patient numbers.
Speaker Change: You know, just kind of drafting from the update that we saw in July in pancreatic, should we expect a similar ramp up in the number of evaluable patients across doses 160 to 300 milligrams?
Speaker Change: And then.
Speaker Change: Bye.
Speaker Change: Just as a follow-up in pancreatic cancer, Mark, I guess how should we be thinking about sort of...
Speaker Change: Additional updates, either kind of within the data set that you presented in July , perhaps at medical meetings, or...
Speaker Change: sort of follow-on updates as that trial matures. Thank you.
Speaker Change: Yeah, thanks, Eric. Nice to talk with you.
Mark Goldsmith: Nice to talk with you, on the second question about PDAC, I think we've made a pretty clear commitment to providing an update to those data, a meaningful update. But we've not been able to share a specific timeline or setting in which that will happen, so the drama, with regard to lung cancer data. You know, it's hard, it's hard really to go into that level of forecasting about what we'll communicate.
Speaker Change: On the second question, PDAC, I think we've made a pretty clear commitment to provide an update to those data.
Speaker Change: We have a meaningful update, but we've not been able to share a specific timeline or setting in which that will happen. So I don't think we have anything to add to that today.
Speaker Change: with regard to the lung cancer data.
Speaker Change: um
Speaker Change: You know, it's hard, it's hard really to go into that level of forecasting, what we'll communicate.
Jonathan Chang: I think, generally speaking, we're going to be in the ballpark of the kinds of numbers that we've enrolled previously for pancreatic cancer, but the analysis, we'll just have to speak for ourselves. Okay, thanks. Maybe just one follow-up in lung cancer, if I could just pick up on a prior question about the phase three strategy. It sounds sort of like one, Option that you're contemplating is an integrated trial where G12C patients can go on to either a G12C inhibitor or a taxane.
Speaker Change: You know, I think, generally speaking, we're going to be in the ballpark of the kinds of numbers that we've enrolled previously for pancreatic cancer, but the analysis, we'll just have to speak for ourselves, you know, at the time.
Speaker Change: Okay, thanks. Maybe just one follow-up in lung cancer, if I could, just picking up on a prior question about the phase 3 strategy. It sounds sort of like one
Speaker Change: Option that you're contemplating is an integrated trial where G12C patients can go on to either a G12C or can be compared to a G12C inhibitor or a taxane.
Jonathan Chang: I just wonder operationally, is there sort of a scenario where you conduct two phase three trials, one in sort of G12X minus C and then another in G12, another that's focused on G12C patients? Thank you. Well, yeah, there are a lot of possible scenarios.
Speaker Change: I just wonder, operationally, is there sort of a scenario where you conduct two phase three trials, one in sort of G12X minus C, and then another in G12, another that's focused in G12C patients?
Mark Goldsmith: I don't think I can give any hints today about what the scenario is that we'll pursue. I think that's just done at the time that we share the data and describe it. I think that Wei's comment earlier was more one of concept.
Speaker Change: Well yeah, there are a lot of possible scenarios. I don't think I can give any hints today about what the scenario is that we'll pursue. I think that's just done at the time that we share the data and describe it. I think that Wei's comment earlier was more one of concept.
Chris Shibutani: If that's an FDA, ultimately that's an FDA question: what will they treat as the standard of care? Will, would Khrisati if it's approved? Be declared as the standard of care for G12C patients or just launch several treatments that are that are acceptable, in which case, Joseph Hax, and Silken David Comparator. You know, that's a topic, you know, really, really for discussion with the FDA. It's not so much that we're considering A, B, or C. But just as a concept, that's how one would have to think about it. And also, I think the other factor that would go into that is... Valley gets approved, Proof, Relative. Okay, I got it. I appreciate the color, and thanks for taking the question.
Speaker Change: Ultimately, that's an FDA question. What will they treat as the standard of care?
Will Wood-Crisale: and Will Wood-Crisale, if it's approved.
Speaker Change: be declared as the standard of care for G12C patients or just want several treatments that are that are acceptable, in which case, does the tax facility be a good comparator? You know, that's that's a topic.
Speaker Change: you know really really for discussion with the FDA it's not so much that we're considering A, B, or C, but just as a concept that's how one would have to think about it and also I think the other factor that would go into that is the timing.
Speaker Change: as to if Frisati gets approved, when is it going to be approved relative to the to that study.
Speaker Change: Okay, got it. I appreciate the color and thanks for taking the questions.
Mark Goldsmith: Thank you. One moment for our next question. Our next question comes from Jonathan Chang, from Lear Inc. Partners. Please go ahead. Hi guys.
Speaker Change: Thank you. One moment for our next question.
jonathan changin: Our next question comes from Jonathan Chang from Learing Partners. Please go ahead.
Wei Lin: Thanks for taking the question. Given that there are multiple data updates now expected in 4Q, how should we be thinking about the cadence and venue of these disclosures? Will they happen sequentially? Do you have an order in mind? Or could these be bundled together in a combined way?
jonathan changin: Hi guys, thanks for taking the question.
Speaker Change: Given that there are multiple data updates now expected in 4Q, how should we be thinking about the cadence and venue of these disclosures? Will it happen sequentially? Do you have an order in mind or could these be bundled together in a combined way? Thank you.
Chris Shibutani: Thank you. Yeah, thanks, Jonathan. The answer to your question is yes. So you gave a list of possibilities, and that is the list of possibilities. I think we won't be able to provide more clarity. We're glad that we can at least narrow it down to a quarter.
Speaker Change: Yeah, thanks, Jonathan. The answer to your question is yes. So you gave a list of possibilities, and that is the list of possibilities. I think we won't be able to provide more clarity. We're glad that we can give you at least narrow it down to a corner. That's a step forward, but beyond that, we'll save the format for the right moment.
Mark Goldsmith: That's a step forward, but beyond that point, we'll save the format for the right. Understand? Thank you. Thank you. One moment for our next question. Our next question comes from Chris Shibutani, from Goldman Sachs. Please go ahead.
Speaker Change: and
Jonathan: Understood. Thank you.
Speaker Change: Thank you. One moment for our next question.
Jonathan: Our next question comes from Chris Shibutani.
Eliana Merle: Oh, thank you very much. I know that Marc and the team had a discussion of the data, but perhaps, for the purposes of this audience at this point, for the second line PDAC readout, thinking about dropouts and censorship, is the level of censorship in an expected range? Is there something that might have accounted for in some idiosyncratic way, potentially, the investigation site or trial or any aspect of treatment of the patients? And then how should we think about this as possibly being relevant at all as we think about the larger phase three multi-institutional trial? Thanks. Yeah, thanks, Chris. It's nice to talk to you.
Speaker Change: from goldinsects please go it
Chris Shubbatani: Thank you very much. I know that, Marc, you and the team had a discussion of the data, but perhaps if you could just, for the purposes of this audience at this point, for the second line PDAC readout, thinking about dropouts and censorship,
Speaker Change: Is the level of censorship in an expected range? Is there something that might have accounted in some idiosyncratic way, potentially, for an investigation, site, or trial, or any aspect or treatment of the patients? And then how should we think about this as possibly being relevant at all as we think about the larger phase three multi-institutional trial? Thanks.
Mark Goldsmith: Thanks for the question. Yeah, there was some censorship, some censoring that went on in both the PFS and OS analyses, and maybe Wei can address both of your questions. What type of censorship was it? Was it unusual?
Eliana Merle: Did it indicate anything? And how does it affect our view of how to translate that information? on it. There's nothing unusual about the sensoring.
Mark Goldsmith: The patient will get standard sensory due to the fact that some patients will go later than other patients and at the time of the data cutoff, they have not had a progression event. And so that's the reason for the century that you saw for the patient, throughout both the Kavanaugh curve for the PFS and the OS.
Alec Stranahan: As we follow through and have later data cut with more maturity to the data, then it will essentially move out, and hopefully even beyond the median PFS line. Furthermore, we have the PSS event in terms of translation to the... Ultimate Retreational Trial in a recurrence, in an early life study.
Speaker Change: As we follow through and make a cup.
Speaker Change: With more mature for the data.
Speaker Change: Essentially.
Speaker Change: <unk>.
Jonathan: And.
Jonathan: Hopefully you're going beyond the median PFS.
Jonathan: As estimate and Furthermore.
Jonathan: At that event and how we see it.
Jonathan: In terms of translation to the <unk>.
Jonathan: Ultimate Registrational trial.
Jonathan: Because.
Jonathan: In a hurry line study.
Mark Goldsmith: We can observe the data in real time, and we can cover up data.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, There will be a pre-specified number of PFS and OS events that we define that will actually, University Date at which time we read out the study, and so we would not be looking at the data in real time, not presenting data in an immature state, in this case, so we would not expect. And so at that time, the PFS and OS, when we do read out, will be a fairly stable recognition, but fine. I didn't think, um, there's... to Law, Lack of Translatability.
Jonathan: We can observe data real time and take up.
Jonathan: Other data.
Jonathan: And so you do see a early data cut which was presented with some strange you Chi.
Jonathan: E.
Jonathan: Debt maturity lack thereof of the data.
Jonathan: Setting up a registration trial. This we now no longer be an issue because.
Speaker Change: Specify number of PFS and OS.
Jonathan: Fine that would actually be.
Speaker Change: We used eight.
Jonathan: Eight at which time we.
Jonathan: The study.
Speaker Change: And so we would not be looking at the data in real time.
Speaker Change: It will be not presenting data in mature stages.
Jonathan: So we're not expecting.
Jonathan: And so at that time, the PFS and OS.
Jonathan: Yes.
Jonathan: <unk>.
Speaker Change: So I cant income.
Jonathan: Yes.
Jonathan: Any.
Jonathan: Lack of translate ability.
Speaker Change: Looking at cash throughout the year.
Jonathan: Okay.
Gabe: Sure Gabe.
Speaker Change: Got it.
Gabe: Got it for the questions.
Alec Stranahan: If I could just add one point to the first part of the presentation, question, which is patients who are censored because they started on the trial more recently. We did look at those patients' profiles.
Jonathan: Thanks, Wayne if I could just step one 1.2.
Jonathan: As part of the.
Jonathan: Question wishes.
Speaker Change: Those patients were censored because they started on the trial more recently.
Speaker Change: We did look at those patients.
Speaker Change: It profiles to determine whether they showed any different characteristics than patients who have been enrolled earlier you also spoke with investigators asked them about those patients and the general consensus was.
Mark Goldsmith: We also spoke with investigators and asked them about those patients. The General Consensus was... They're not different patients, they're just patients who enroll later into those cohorts. Forced to be Censored at Planet Street.
Speaker Change: Not different patients patients with later.
Jonathan: In two dose cohorts.
Jonathan: Yes.
Speaker Change: To be censored.
Speaker Change: Yes.
Peter Lawson: Thank you. That's reassuring clarification. I appreciate it.
Speaker Change: Thank you that's reassuring clarification I appreciate it.
Mark Goldsmith: Thank you. One moment for our next question. Our next question comes from Eliana Merle from UBS. Please go ahead. Hi, this is Elliot Bosco. I'm on behalf of Ellie Merle, UBS.
Speaker Change: Thank you one moment for our next questions.
Speaker Change: Our next question comes from Eliana Merle from UBS. Please go ahead.
Kelly Shee: First one, what's your view on what would be competitive PFS data for the upcoming 6236 non-small cell lung cancer update? In particular, could you clarify what would be competitive when thinking about both CRAF and non-CRAF targeted therapies? Yeah, thanks for your question. I mean, it's pretty straightforward.
Jonathan: Hi, This is Elliott bus go on for Ellie Merle UBS.
Speaker Change: First one what's your view on what would be a competitive competitive PFS data for the upcoming six two to three six non small cell lung cancer update.
Speaker Change: In particular could you clarify what would be competitive when thinking about both craft and non crafts targeted therapies.
Mark Goldsmith: We think that the first thing we have to do is make sure that we clear the standard care bar, and I know you're asking more than that, which is by how much it has to be cleared. It's a little bit difficult for us to give you an answer to that while we're in the midst of gathering and analyzing data. It's very hard to separate, then, our view of the data from that.
Speaker Change: Yes. Thanks for your question I mean, it's pretty straightforward, we think that the.
Speaker Change: The first thing we introduced make sure that we clear the standard of care.
Speaker Change: And I know youre, asking more than that which is by how much does Apache declared its a little bit difficult for us to give you an answer to that.
Speaker Change: While we are in the midst of gathering and analyzing data, it's very hard to separate in our view of those data from that we of course have to target product profiles that are a feature of our.
Kelly Shee: We, of course, have target product profiles that are internal. I think it's really a tricky question at this stage, so the best thing to do is to wait and see. We do have experience, of course, with RAS inhibitors as to what they previously considered sufficient, and investors have had opinions about that, and everybody's had an opinion about it. And we'll present ours in the context of the data that we have, and will everybody enter the dogfight? Okay, and then just one more. For the ongoing 6236 monotherapy and combo studies in colorectal cancer, could you provide a sense of when we might see data? Is that likely to be 2025 events?
Terry: Terry but nonetheless for a conversation like this I think it's really a tricky question at this stage. So thats 80 days to wait and see we do have.
Speaker Change: <unk> of course with <unk> as to what.
Speaker Change: Previously considered sufficient and investors have had opinions about that and everybody kind of opinion about it.
Speaker Change: Presenters into context.
Speaker Change: The data that we have today.
Speaker Change: Okay.
Speaker Change: She was a dog fight.
Speaker Change: Yeah.
Speaker Change: Okay, and then just one more for the ongoing six two or three six monotherapy and combo studies in colorectal cancer could you provide a sense of when we might see data is that likely to be 2025 of them.
Mark Goldsmith: Yeah, we haven't provided any guidance on timing for that, so I'll attempt to just do it off the cuff here. I think the one concept that I think Steve has communicated a number of times, and Wei has as well, is that we consider colorectal cancer to be primarily a combination strategy play. That's been the story.
Speaker Change: Yes, we haven't provided any guidance on timing for that so they tend to just do it off of off the cuff here.
Speaker Change: The one concept that I think Steve has communicated a number of times that way as well.
Speaker Change: Bidder.
Speaker Change: Colorectal cancer to be primarily a combination strategy play.
Speaker Change: That's been the history.
Speaker Change: Essentially forever.
Jay Olson: Forever, and it will be as well, so that goes. That's more the horizon to be thinking about, enough to say present some monotherapy data, but we do believe that fundamentally changes the biology of colorectal cancer. Okay, thanks for taking the question. Thank you. One moment for our next question. Our next question comes from Alec Stranahan from Bank of America. Please go ahead. Hey guys. Thanks for taking our questions. First one from us:
Speaker Change: And it will be as well so that goes.
Speaker Change: That's more of the horizon to be thinking about.
Speaker Change: Not to say, we maybe not presents a monotherapy data, but we do believe that fundamentally the biology.
Speaker Change: And of course.
Speaker Change: Okay.
Speaker Change: Okay. Thanks for taking the question.
Speaker Change: Sure.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from Alec Stranahan from Bank of America. Please go ahead.
Alec Stranahan: Hey, guys. Thanks for taking our questions.
Alec Stranahan: First one from us.
Jay Olson: Here's some of the nested trial design in RAS Salute 302. Any signals you'd highlight from either your Phase I or preclinical work for the activity of 6236, specifically in the G13X, the G61X, and especially the RAS wild-type patients? Would you view these as maybe higher-hanging fruit from a mechanistic perspective?
Speaker Change: Some of the nested trial design and resolute 302, any signals you'd highlight from either your phase one of our preclinical work for the activity of $63 six specifically in the 16, how does the <unk>.
Speaker Change: <unk> X <unk>, 60, onex, and especially the Ras Wild type patients would you view these as maybe higher hanging fruit from a mechanistic perspective, I know you saw some preclinical activity in.
Mark Goldsmith: I know you saw some preclinical activity in the RAS wild-type in your Nature paper earlier this year. Yeah, maybe Steve wants to comment on that, but not G-12X versus T-12X. Alright. Well, think about it, and the best thing is that if it isn't, she said.
Alec Stranahan: In the Ras Wild type nature paper earlier this year.
Speaker Change: Yes, maybe Steve wants to comment on that but not launching 12 extra space both exited.
Speaker Change: How do we think about that.
Alec Stranahan: Yeah.
Alec Stranahan: Hi.
Alec Stranahan: Well.
Speaker Change: And we think about it in the vesting is back.
Alec Stranahan: Okay.
Alec Stranahan: Okay.
Jay Olson: It isn't in the inner core, as she described it, whether that is based on firm data or whether it is based on more of a conceptual approach to the whole disease. The concept of rats driving the disease, I think, is something that we don't really know yet. I mean, the assessment of... Any of our compounds, including RMC6236 in rats, mutations outside of the G12 mutations, was a somewhat later event, and therefore the emergence of data in those mutations is going to be somewhat behind the main body of data on which we base our decision-making, and so we're a little less confident there. I think it's more about confidence than it is about science. Benson, and I doubt that was all of them.
Alec Stranahan: It isn't so.
Alec Stranahan: Cool.
Alec Stranahan: Okay.
Speaker Change: Where the space on firm date, so whether it is based on.
Speaker Change: More of a more of a conceptual approach to the to the whole disease.
Alec Stranahan: Call Center as well as driving driving.
Alec Stranahan: Driving the disease I think is something that.
Speaker Change: We don't really know yet I mean the.
Alec Stranahan: The assessments of.
Speaker Change: Any of our competitors, including RMB $63, six and Ras mutations iron side with the gene mutations was a somewhat later event.
Alec Stranahan: And therefore, the emergence of data in those mutations is going to be somewhat behind the.
Alec Stranahan: The main body of data on which we base our decision, making and so we're a little less comfortable there I think it's more of a confidence that it is about science and medicine.
Alec Stranahan: All of them.
Mark Goldsmith: I'd love to be able to give you a proper scientific answer to that question, but at the moment, we're remaining silent. And I would just add to that that in the data we presented, we did show the overall RAS mutated group. The PFS value for that was 7.6 months, so if there are differences that we haven't yet developed clarity around, they don't seem to compromise, you know, looking at the whole
Alec Stranahan: Energy costs, so I'd love to be able to give you a trough of scientific analysis the customers love it.
Speaker Change: And I would just add to that.
Speaker Change: In the <unk>.
Alec Stranahan: Data that we presented we did show the overall Ras mutated group.
Alec Stranahan: The PFS value for that was $7 six months so.
Speaker Change: If there if there are differences that we haven't yet developed clarity around.
Alec Stranahan: They don't seem to compromise looking at that looking at it.
Laura Prendergast: You know, and also keeping in mind that 85% of pancreatic cancer is attributable to a RAS G12X mutation, so the majority of the disease that we're trying to treat here is still in the core population, offers something more broad. That makes sense. And then one more, if I may, obviously, launching and supporting your ongoing and planned studies is a top priority. But in terms of capital allocation, in the next 12 months or so, how do you plan to move forward with the earlier Wave 2 pipeline in order to realize the ultimate potential of the RASP-ON approach?
Alec Stranahan: And also keep in mind that 85% pancreatic.
Greg: Hey, Greg cancer is attributable to a T 12 last 12 expectation. So the majority of the disease that we're trying to treat here is still in the core population but.
Alec Stranahan: We'd like to offer something more broadly than that.
Alec Stranahan: Yes.
Greg: Got it that makes sense.
Speaker Change: Then one more if I may.
Speaker Change: Obviously, you're launching and supporting your ongoing and planned studies as is the top priority, but in terms of capital allocation next 12 months or so.
Speaker Change: How do you plan to move forward with the earlier.
Alec Stranahan: Wave two pipeline in order to realize the ultimate potential for restaurant approach right.
Alec Stranahan: Yeah.
Laura Prendergast: So we, thanks for that question. I mean, we define wave one RASL inhibitors as being the 6236, 6291, and 9805. And then we have lots of other inhibitors behind that. We haven't formally called them wave two, but I think that would be a natural progression. We have not declared any sort of public guidance about what, where, when, and how.
Speaker Change: So thanks for that question I mean, we define wave one.
Speaker Change: So I would say, but here's the thing.
Speaker Change: 669 to 195.
Alec Stranahan: And then we have lots of other inhibitors, but behind that we havent formally call. The wave two but I think that would be at ash rule.
Alec Stranahan: Progression.
Alec Stranahan: And.
Alec Stranahan: We have not declared any sort of public guidance about what where when and how there's so much to chew on with the first three.
Mark Goldsmith: There's so much to chew on with the first three assets, both as mama therapy, combinations, multiple lines of therapy, and multiple tumor types. That's a lot of a story for people to digest, and we've allocated capital largely accordingly to just what we've identified as the Wave 1 assets, and within that, most of that is actually our C6236. So all I can say is stay tuned. This is a company with an incredibly
Speaker Change: <unk>, both as monotherapy and combinations multiple lines of therapy multiple tumor types.
Alec Stranahan: That's a lot of storage for people to digest and the allocated capital larger.
Speaker Change: Largely accordingly.
Speaker Change: There is no money spent on other things but.
Alec Stranahan: Really the drivers of our spending.
Alec Stranahan: Just what we've identified is the wave one assets.
Alec Stranahan: And within that most of that is actually RMB 63, six so all I can say is stay tuned.
Alec Stranahan: Yes.
Speaker Change: Currently a relatively productive flips.
Laura Prendergast: Joint Discovery Organization that sort of delivers effectively more high-quality, interesting information. Assist, and any organization could move forward in parallel. We've done some prioritizing, but we keep a very close eye on that productivity. And, by the way, we also want to understand how those first three assets perform in order to understand where the gaps are. That's not something that's just a matter of defining it preclinically, what we want to see in it, where the gaps are, what sorts of combinations, and what next-generation compounds make sense, and how to develop them.
Alec Stranahan: Drug discovery organization that delivers.
Alec Stranahan: For a more high quality interesting.
Alec Stranahan: Assets than any organization to move forward.
Alec Stranahan: Well, we've got some prioritizing, but we keep a very close eye on that productive.
Alec Stranahan: Early pipeline.
Alec Stranahan: And we'll move things forward as they make sense and by the way we also want to understand.
Alec Stranahan: First the assets performing in order to understand where the gaps are and thats not something thats, just a matter of designing it three clinically, but we want to see in the clinic, where the gaps are what sorts of combinations.
Alec Stranahan: To us what next generation.
Alec Stranahan: Makes sense.
Mark Goldsmith: So stay tuned. We'll all be learning. Appreciate the color.
Alec Stranahan: So stay tuned we will all be learning as we go.
Speaker Change: Appreciate the color. Thank you.
Joe Cantazaro: Thank you. Thank you. One moment for our next question. Our next question comes from Peter Lawson, from Barclays. Please go ahead. Hi. Good afternoon. This is Alex on behalf of Peter.
Speaker Change: Thank you one moment for our next question.
Alec Stranahan: Our next question comes from Peter Lawson.
Speaker Change: From Barclays. Please go ahead.
Mark Goldsmith: Thanks for taking our questions. I just had one on the combination data with PEMBRO in lung cancer in the second half for 6236. So, I understand that, you know, safety data for the combination is going to help you inform your strategy in the first-line metastatic setting. But I'm wondering if that data would also enable potential studies in earlier lines of therapy in lung cancer, like the adjuvant setting, for example, and if that's something that's also of interest for RevMed. Thank you. Yeah, thanks a lot, Alex.
Alex: Hi, Good afternoon. This is Alex on for Peter Thanks for taking our questions just had one on the on the combination data with <unk> in lung cancer in the second half for $6 three six so I understand that safety data for the combination is going to help you inform your strategy in the first line.
Alex: Metastatic setting.
Speaker Change: I'm wondering if that data would also enable potential studies in earlier lines of therapy in lung cancer like the adjuvant setting for example, if that's something that's also of interest for revenue. Thank you.
Speaker Change: Yes, Thanks, a lot Alex I think.
Joe Cantazaro: I think Dr. Lin can answer that question. Yeah, I think, absolutely, we have thought about this. And I think you're absolutely correct. I think the current regimen that's Angel Plus chemotherapy is used both in the first line as well as in the actual paratherapy setting by starting with 3TEI activity. That combination in the first-line setting would also enable us to move into our next slide.
Dr. Glenn: Dr. Glenn can answer that question, yes.
Dr. Glenn: Yes, I think absolutely we have thought about this.
Glenn: You are absolutely correct I think that.
Tom: The current regimen that Tom.
Speaker Change: <unk> plus chemotherapy issues <unk> first line itself the actual care optical states so by stopping the safety and activity of that combination in the first line setting that would also enable us to engage or say something very much on my mind.
Mark Goldsmith: That is something that I mentioned online. Thank you. One moment for our next question. Our next question comes from Kelly Shee from Jeffries. Please go ahead.
Alex: Yeah.
Alex: Sure.
Speaker Change: Thank you.
Speaker Change: Our next question.
Speaker Change: Our next question comes from Kelly <unk> from Jefferies. Please go ahead.
Operator: Thank you for taking my questions. So for the G12D data in the fourth quarter, what tumor types would be included in this first data discloser? And also, for the 6236 Pembroke combo in lung, for the data discloser, do we expect only second line class settings? Thank you. I didn't quite understand the first question.
Kelly: Hi, Thank you for taking my questions. So far then Keith while the data.
Speaker Change: Our fourth quarter, what's your guys have suitable include <unk>.
Speaker Change: Carlo I'll call for that.
Speaker Change: Hornbill combo in lung.
Speaker Change: So that buildup of color great quarter.
Speaker Change: Second line class settings. Thank you.
Speaker Change: I didn't quite understand the first question I didn't really.
Mark Goldsmith: I didn't, did somebody catch exactly what was being asked about the 90 to five, tumor type C, 90 to five. Ah, tumor types. I'm sorry, I just didn't hear that word. Yeah, I mean, it's a solid tumor study, so we'll have a mix of G12D solid tumors. G12D is most common in gastrointestinal tumors, although it does appear in lung cancer and others, but less frequently. So, to my knowledge, the representation in the study is sort of the representation in the world. Those tuners are nasty tuners, no matter what type they are, so they're going to show up for...
Speaker Change: Catch exactly what was being asked.
Speaker Change: 92.
Speaker Change: Tumor tissue 90 Eagle package tumor types I'm, sorry to hear that word.
Speaker Change: Yeah, I mean, it's just.
Speaker Change: Solid <unk> solid tumor studies. So it will have a mix of <unk> solid tumors Jacoby is most common in gastrointestinal tumors, although it does appear in lung cancer and others, but less frequently.
Speaker Change: So.
Speaker Change: To my knowledge.
Speaker Change: Our representation in the study.
Speaker Change: Representation in the world.
Speaker Change: Those figures are nasty juniors matter what types. They are what they are going to show up for <unk>.
Speaker Change: It's available so I think it'd be a mix.
Operator: The second question about 63.6 in non-small cell lung cancer was whether those patients are all previously treated or not, or are they second line and later, or are there first line patients as well? So the trial design says that in initial dose isolation, we will previously treat it in expansion, and once we establish a safe and tolerable dose, produced by Spatial Expanding Field Burst Pumps.
Speaker Change:
Speaker Change: And then the second question about $63 six in non small cell lung cancer. It was whether those patients are all previously treated or not the second.
Speaker Change: In line with later or their first line patients as well.
Speaker Change: Yes, so the <unk> initial dose escalation we will.
Speaker Change: Previously treated and expansion once we establish stays safe and tolerable dose.
Speaker Change: After dose that patient expanding so first months.
Speaker Change: Thanks.
Speaker Change: Okay. Thank.
Speaker Change: Thank you one moment before our next question.
Operator: Thank you. One moment for our next question. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Hey, congrats on all the progress and shout out to Ryan. AC is great to reconnect.
Speaker Change: Our next question comes from Jay Olson from Oppenheimer. Please go ahead.
Jay Olson: Oh, Hey, congrats on all the progress and shout out to Ryan Acs great to reconnect.
Operator: We were curious about any long-term plans for combination studies, and specifically the combination of your molecules with ADCs, and then I had a follow-up question. Yeah, there are, I mean, there are a lot of possibilities. It's almost infinite, for successful in Establishing RMC6236 as a Backbone Targeted Therapy. I would imagine a lot of things will be combined, but things that we... Prioritized, things that investigators prioritize, and things that... Who Knows Who Else ultimately decides to study things that are done outside of the context of the company. We have no plans as of today relating to ADCs, and, you know, I think we'll want to keep watching the ADC space and see which compounds emerge, potentially being complementary, and have tolerability profiles that.
Speaker Change: Curious.
Jay Olson: <unk> about any long term plans for combination studies and specifically the combination of your molecules with Adcs and then I had a follow up question.
Speaker Change: Yes, I mean, there are a lot of possibilities, it's almost infinite.
Speaker Change: And if we're successful at establishing RMC $63 six of the backbone targeted therapy.
Speaker Change: We would imagine a lot of things will be combined with things that we buy.
Speaker Change: Aratana is things that investigators prioritized and things that we know.
Speaker Change: Who else ultimately decides to study instead of done outside of the context of the company.
Speaker Change: We have no plan to disclose today relating to adcs.
Speaker Change: And I think.
Speaker Change: While.
Speaker Change: Keep watching the ADC space, Mtc, which compounds emerge.
Speaker Change: Potentially complementary tolerability profiles.
Speaker Change: Adjusted by wanting to combine <unk> with it.
Speaker Change:
Operator: So we're open to it. We're interested in your plans to discuss. Great, thank you. And then, as a follow-up, for your internal combinations, are you planning to formulate any fixed-dose combinations? You know that's possible at some point.
Speaker Change: So we are open to interested clients.
Speaker Change: Great. Thank you and then as a follow up for your internal combinations are you planning to formulate any fixed dose.
Speaker Change: Fixed dose combinations.
Speaker Change: That's possible at some point.
Operator: You know, there are a lot of combinations that we're talking about that we really have to establish the doses first before you create those combinations. We also have some compounds that are, Deeds, and Thomas Sutter BID. Those aren't exactly amenable to fixing those combinations. So I don't know that that's going to be a major part of our commercial strategy. But our competitors certainly have it on their radar and will move when it makes like that, but it really is going to add convenience and not just add.
Speaker Change: There are a lot of combinations that we're talking about really how to establish.
Speaker Change: The doses first before you create those combinations.
Speaker Change: Allow for step downs for dose modifications, which creates a little bit of complexity access realm. We also have some compounds that are.
Speaker Change: QD sometime et cetera.
Speaker Change: So those arent exactly amenable to a fixed dose combination. So I don't know that thats going to be a major part of our commercial.
Speaker Change: Strategy, but.
Speaker Change: Our team certainly has it on their radar and will will move when it makes sense to do something like that but it really just going to add convenience and not just active bucket.
Operator: Great, thanks for taking the questions. Please take one moment for our next question. Our next question comes from Laura Prendergast, from Raymond James. Please go ahead. Hey, guys, congrats on the progress. I was curious, you know, some KOLs did note that, you know, the deepening of response over time seen with the PDAC patients was, you know, interesting to them. And, you know, I actually refer to that as a phenomenon.
Speaker Change: Great. Thanks for taking the questions.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from lower printer grasp from Raymond James. Please go ahead.
Operator: Do you think this could be due to the unique mechanism of action of the drug? And do you think it's going to translate to other indications or other RAS inhibitors? Any color there would be helpful.
Speaker Change #101: Hey, guys congrats on the progress.
Speaker Change: I was curious if you saw some kols didn't know that the deepening of response.
Speaker Change #105: Overtime as seen with the pediatric patients.
Speaker Change: Interesting development.
Speaker Change: I actually referred to that as a phenomenon.
Speaker Change: This can be due to the unique mechanism of action of the drug and do you think it's going to translate to other indications or other rasp inhibitors any color there would be helpful.
Operator: Thank you, Laura. That's an interesting question. I don't know the exact question. Spector.
Laura: Thank you Laura.
Speaker Change: An interesting question.
Speaker Change: Who wants to take that question.
Speaker Change: Yep.
Speaker Change: Yeah.
Operator: The observation that the responses deepen over time is much more evident in pancreatic cancer than it appears to be in Non-Small Cell Lung Cancer, which are the two... 36. And so. Having said that, it's clearly more obvious with RMC6236 than it is with chemotherapy. So I think it may be a combination of both the mechanism of action of the drug, which could include a multitude of different effects on both the tumor cells themselves and the immune microenvironment, and possibly also the particular biology and histology of pancreatic cancer, which traditionally is a very large mixture or a pleiotropic mixture of different cell types Sometimes, the dominant one is the epithelial tumor cell itself, and sometimes it isn't.
Speaker Change: The observation that the response to see over time is much more evident in pancreatic cancer.
Speaker Change: The.
Speaker Change: Multiple cell lung cancer, which are the two diseases, which we have the most experience right now with obviously 63 six.
Speaker Change: And so.
Speaker Change: Having said that it's clearly more Lps with RMB 63, six than it is with chemotherapy. So I think it may be a combination of both the mechanism of action of the drug.
Speaker Change: She could include.
Speaker Change: A multitude of different.
Speaker Change: Effects on the tumor cells themselves.
Speaker Change: In my career environment.
Speaker Change: And possibly also the particular biology, and histology of pancreatic cancer, which traditionally is a very large mixture trophic mixture of different cell types.
Speaker Change: Sometimes which the dominant one is is the FCC auction the cell itself and sometimes it is it is it's a minority component of a mishmash of nothing.
Operator: It's a minority component of a mishmash of immune cells and fibrotic cells and a whole lot of other things. So you can imagine that if your tumor is... has a very mixed histology, and there are a lot of things going on. It may take quite some time for that remodeling to occur such that when you look at it with a very crude imaging modality like CT scanning, which, let's face it, has been around for about 50 years.
Speaker Change: <unk> sells in fibrotic cells.
Speaker Change: A whole lot of other things. So you can imagine that if you will.
Schumer: Schumer is.
Speaker Change: It's a very mixed histology and there's a lot of things going on at night and take quite some time for that remodeling to occur such that when you.
Speaker Change: Look at it with a very crew imaging.
Speaker Change: That's a very cute imaging modality, like Cte scanning, which let's face it.
Speaker Change: Been around for about 50 years.
Operator: ,,,,,,,, then it could take some time for the observations that we apply to that to take effect. And I superimposed on top of that, of course, is the... The dichotomization of responses is lack of response. You know, a patient can go from 0% Tumor Reduction to 31% Tumor Reduction, and they're called a response. But if they go from 29% Tumor Reduction to 29.5% Tumor Reduction, they're not a response.
Speaker Change: Then it could take some time for the observations that we that we applied to that too.
Speaker Change: The night superimposed on top of that of course is the.
Speaker Change: The.
Speaker Change #102: The dichotomy monetization of response versus lack of response, a patient can go through them.
Speaker Change: Zero percent tumor reduction to 31% tumor reduction in that cohort resolved. So they go from 29% tumor reductions of 29, 5% G&A reduction then other response.
Operator: And so the deepening of responses over time is really, in our data set, has only been applied to the dichotomous conversion of patients from a lack of response to response, and from a response to a response with a higher percentage of Tumor Reduction. But in fact, this is happening in the linear continuum in all patients, irrespective of whether they qualify for RESS's response or not. So the answer is, we don't know, but I suspect it's a 50-50 mixture of the biology of pancreatic cancer and the mechanism of action of the drug.
Speaker Change: And so the deepening of responses over time is really.
Speaker Change: Data set has there any been applied to the dichotomous conversion of patient strong not lack of response to response and from a response to a response.
Speaker Change #108: A higher percentage of extreme reduction, but in fact this is happening even though they may have continue in all patients irrespective of whether they qualify for aggressive response, the response or not so the answer is we don't know, but I suspect as a 50 50 mixture of the <unk>, but for all of <unk> of pancreatic cancer.
Speaker Change #101: The mechanism of action of the drug.
Operator: And it isn't quite as obvious in lung cancer, which makes me say that. That's really helpful. Thanks for all the color.
Speaker Change #101: Isn't quite as obvious in lung cancer, which makes me.
Speaker Change: Makes me say that.
Speaker Change #101: That's really helpful. Thanks for all the color.
Operator: Thank you. One moment for our next question. Our next question comes from Joe Cantazaro, from Piper Sandler. Please go ahead.
Speaker Change #100: Thank you one moment for our next question.
Speaker Change #101: Our next question comes from Joe <unk> Zero from Piper Sandler. Please go ahead.
Operator: Hey, thanks for taking my question. I had a quick one here on 6236 and combinability with pembrolizumab, and maybe even with other combination approaches you're looking at, and it primarily relates to 6236-mediated rash. When you look at historical data sets for other map kinase pathway inhibitors that also see rash, is there anything there that informs how the addition of pembrolizumab and or chemotherapy could impact or not the rate and severity of rash when you start combining?
Speaker Change #101: Hey, Thanks for taking my question I had a quick one here on 63, six and combinability with timber lithium mab and maybe even with other combination approaches you're looking at and then.
Speaker Change #106: Primarily as it relates to 63 six mediated grass when you look at historical datasets for other map kinase pathway inhibitors that also see RASK is there anything there that informs how the addition of <unk> chemotherapy.
Speaker Change #101: Could impact or not the rate and severity of <unk> when you start combining thanks.
Speaker Change #106: I'm seeing shaking heads here I don't think that we think there is much of a connection there.
Operator: Thanks. I don't think that we think there is much of a connection there, you know, the effect on rash, the mechanism of rash, probably due to the direct effects on... Epidermal, that has to do with intimidate grasp.
Speaker Change #108: The effect on rash.
Speaker Change #106: The mechanism of rash.
Speaker Change #102: Probably to the direct effects on.
Speaker Change #108: Epidermal cells.
Speaker Change #102: And.
Speaker Change #101: That's inhibiting Ras I don't know that hasnt into it with that.
Speaker Change #101: With chemotherapy.
Operator: Yeah, I think the immune-mediated type of rats are slightly different than the type of rat that we observe more commonly. Ours is more... Act Inform, and uh.., truly responsive to mechanical everything... that's quite different from the massive pathways that are more common here. There's always a mix, but I'm talking about what's actually more predominant.
Speaker Change #101: Yeah.
Speaker Change #105: I think they mean mediated packet rash are slightly different.
Speaker Change #108: We observed more calming rcp's more frequently at the forum.
Speaker Change #107: And again for the sponsors antibiotics.
Speaker Change #102: Uh huh.
Speaker Change #102: Feedback so far.
Speaker Change #108: That's quite different than E. Massive outflows that are more commonly occur here. So it's always been mix, but im talking about what's actually what we dominate and E E.
Operator: I'm going to talk about feedback from the viewers. Netanyahu, B.J. Armitager, or Rasmus, I think, all tend to be down in form.
Speaker Change #108: I know you talked about <unk>.
Speaker Change #108: Net income for each operating here.
Scott: <unk> dialing in for Scott.
Operator: When we combine the two, it may be true-true, but you're probably going to see each creating its own type of rash. Burnett achieved mutual enchantment. Okay, thanks. That's helpful. Thanks for taking the question. Thank you. I am showing no further questions at this time.
Speaker Change #102: When we combine the two in a truthful.
Speaker Change #110: Probably going to each creating its own type of rash, but.
Speaker Change #102: At fixed rate did not indicate.
Speaker Change #102: Combining issue mutually enhance irrespective of ash.
Speaker Change #121: Okay. Thanks.
Speaker Change #122: Hello, Thanks for taking the question.
Speaker Change #111: Thank you.
Speaker Change #102: I am showing no further questions at this time I will now turn it over to Mark goes smooth.
Operator: I will now turn it over to Marc Goldsmith for closing remarks. Thank you, Operator, and thank you to everyone for participating today and for your continued support of Revolution. This does conclude the program. You may now disconnect. [music] Thank you for watching!
Mark: For closing remarks.
Operator: Good day, and thank you for standing by. Welcome to Revolution Medicine's Q2 2024 earnings conference call. At this time, our participants are in listen-only mode.
Speaker Change #120: Thank you operator, and thank you to everyone for participating today and for your continued support resolution medicines.
Speaker Change #121: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Speaker Change #120: Yes.
Speaker Change #111: [music].
Speaker Change #111: Okay.
Speaker Change #111: Okay.
Speaker Change #111: Yes.
Speaker Change #111: [music].
Speaker Change #111: [music].
Speaker Change #111: [music].
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you need to press star 1 1 on your telephone. You will then hear an automated message advising that your hand is raised.
Speaker Change #111: Good day, and thank you for standing by.
Speaker Change #129: Welcome to the Revolution, Medicine's Q2, 2024 earnings conference call.
Speaker Change #130: At this time all participants are in listen only mode. After the speaker's presentation, there will be a question and answer session.
Speaker Change #129: To ask a question. During this session you will need to press star one on your telephone.
Speaker Change #129: Dan here, an automated message and advising your hand is raised.
Speaker Change #129: To withdraw your question. Please press star one again please.
Speaker Change #111: Please be advised that today's conference is being recorded.
Speaker Change #129: I'd now like to hand, the conference over to your first speaker today.
Speaker Change #129: Ryan AC senior Vice President of Corporate Affairs. Please go ahead.
Operator: To withdraw your question, please press star 1 1 again. Thank you, and welcome everyone to the second quarter 2024 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines Chairman and Chief Executive Officer, and Jack Anders, our Chief Financial Officer. Dr. Steve Kelsey, our President of R&D, and Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call. I'll note 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, and as a result, may differ materially from those in the forward-looking statements.
Speaker Change #130: Thank you and welcome everyone to the second quarter 2024 earnings call. Joining me on today's call are Dr. Mark Goldsmith Revolution, medicines, Chairman and Chief Executive Officer, and Jack Anders <unk>, Our Chief Financial Officer, Dr. Steve <unk>, our president of R&D and Dr. Wei Lin our Chief Medical Officer will join us for the Q&A portion of today's call.
Speaker Change #129: <unk>.
Speaker Change #134: I'll note that certain statements we make during this call will be forward looking.
Speaker Change #129: We're going to 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.
Operator: For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly report on Form 10-Q, which are filed with the U.S. Securities and Exchange Commission. This afternoon, we released financial results for the quarter ended June 30, 2024, and recent corporate updates.
Operator: This press release is available on the investor section of our website at resmed.com. With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicines Chairman and CEO. Thanks, Ryan. It's good to be with you this afternoon.
Speaker Change #142: This afternoon, we released financial results for the quarter ended June 32024, 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 Dr. Mark Goldsmith Revolution medicines, Chairman and CEO Mark.
Mark Goldsmith: Thanks, Bryan it's good to be with you this afternoon.
Operator: Given our recent webcast in which we provided an update on our clinical progress in pancreatic cancer, we will keep our remarks relatively brief today. I'll share a quick summary of the data we presented last month, highlight recent progress we've made across the rest of our pipeline, and discuss several corporate updates. I'll then turn the call over to Jack, who will provide highlights of our financial results before we open the line for questions.
Speaker Change #131: Given our recent webcast in which we provided an update on our clinical progress in pancreatic cancer, we will keep our remarks relatively brief today.
Speaker Change #111: I'll share a quick summary of the data we presented last month.
Speaker Change #111: Highlight recent progress we've made across the rest of our pipeline and discuss several corporate updates.
Mark Goldsmith: I will then turn the call over to Jack who will provide highlights of our financial results before we open the line for questions.
Operator: We've made meaningful progress with our pioneering RAS-on inhibitor pipeline, notably preparing RMC6236, our RAS-on multi-selective inhibitor, to move into its first pivotal monotherapy studies in common, difficult-to-treat cancers driven by oncogenic RAS variants. We kicked off the second half of the year with an important clinical milestone for RMC6236. We disclosed recent data from the RMC6236-001 trial showing compelling preliminary progression-free survival and overall survival for patients with metastatic pancreatic cancer receiving RMC6236 monotherapy.
Jack Anders: We have made meaningful progress with our pioneering rason inhibitor pipeline, notably preparing RMC 63, six or Ras on multi selective inhibitor to move into its first pivotal monotherapy studies and common difficult to treat cancers, driven by oncogenic grafts variance.
Jack Anders: We kicked off the second half of the year with an important clinical milestone for RMC six to $3 six.
Jack Anders: We disclosed recent data from the RMC $63, six or one trial, showing compelling preliminary progression free survival and overall survival for patients with metastatic pancreatic cancer, receiving RMC 63, 6% mono therapy.
Operator: These data have increased our confidence in the promise of this program and reinforced our commitment to initiate our first registrational study this year. I'll take a few minutes to walk through some of the key findings from the pancreatic cancer results we shared last month. The full details of these results can be found in the investor section of our website at redmed.com. The data, with a May 11, 2024 cutoff date, reflect patients with previously treated pancreatic cancer across the RMC6236 160mg to 300mg daily dose cohort.
Jack Anders: These data have increased our confidence in the promise of this program.
Jack Anders: And reinforce our commitment to initiate our first Registrational study this year.
Jack Anders: I'll take a few minutes to walk through some of the key findings from the pancreatic cancer results. We shared last month. The full detail of these results can be found on the investors section of our website at <unk> Dot com.
Jack Anders: The data with a May 11, 2024 cutoff date reflect patients with previously treated pancreatic cancer across the RMC 63, 6% 160 milligrams to 300 milligram daily dose cohorts.
Operator: The safety findings were promising. The most common adverse events are believed to be on target and associated with the inhibition of wild-type RAS in normal tissue. Most adverse events were low-grade, with approximately 22% of patients experiencing a grade 3 or higher treatment-related adverse event. The most common treatment-related adverse events observed were rash and gastrointestinal-related toxicity.
Jack Anders: The safety findings were promising.
Jack Anders: The most common adverse events are believed to be on target and associated with the inhibition of wild type Ras in normal tissue.
Jack Anders: Most adverse events were low grade with approximately 22% of patients experiencing grade three or higher treatment related adverse events.
Jack Anders: The most common treatment related adverse events observed were rash and gastrointestinal related toxicities.
Operator: There were no discontinuations due to treatment-related adverse events, and dose modifications of any kind occurred in only 28% of patients. The anti-tumor durability data were quite compelling as well. Historical progression-free survival benchmarks in pancreatic cancer are poor overall and deteriorate with advancing lines of therapy. In a progression-free survival analysis of second-line patients, which is consistent with the patient population we plan to evaluate in our PACE re-study, we observed an initial median progression-free survival of 8.1 months in patients with KRAS G12X tumors and 7.6 months in patients with RAS-mutated tumors broadly.
Jack Anders: There were no discontinuation due to treatment related adverse events.
Jack Anders: Dose modifications of any kind of occurred in only 28% of patients.
Speaker Change #134: The answer to antitumor durability data were quite compelling as well.
Jack Anders: Historical progression free survival benchmarks in pancreatic cancer are poor overall and deteriorate with advancing lines of therapy.
Jack Anders: And a progression free survival analysis of second line patients, which is consistent with the patient population, we plan to evaluate in our phase III study.
Jack Anders: We observed an initial median progression free survival of eight one months in patients with <unk> <unk> X tumors.
Jack Anders: Seven six months in patients with Ras mutated tumors broadly.
Operator: While these data continue to mature with longer patient follow-up, these preliminary findings compare favorably to standard of care in this patient population. We also showed an early interim look at overall survival in these patients. As of the cutoff date, the median overall survival had not been reached for patients with either KRAS G12X mutations or other RAS mutations. And importantly, the lower bound of the 95 percent confidence interval for the median overall survival estimate is above the standard of care benchmark for median overall survival in second line metastatic pancreatic cancer.
Jack Anders: While these data continue to mature with longer patient follow up these preliminary findings compare favorably to standard of care in this patient population.
Jack Anders: We also showed an early interim look at overall survival in these patients as of the cutoff date. The median overall survival had not been reached for patients with either <unk> 12 X mutations or other asby patients and importantly, the lower bound of the 95% confidence interval for the median overall survival.
Jack Anders: Estimate is above the standard of care benchmark for median overall survival in second line metastatic pancreatic cancer.
Operator: As we noted in July, while early overall survival estimates represent a relatively immature data set, in the context of the strong progression-free survival data, we believe these observations provide a meaningful complement to the overall efficacy story of RMC6236 in metastatic pancreatic cancer. We anticipate that these two measures, progression-free survival and overall survival, will be dual primary endpoints in our planned Phase 3 study. Additional metrics and more detail regarding these data can be found on our website.
Jack Anders: As we noted in July while early overall survival estimates represents a relatively immature data set.
Jack Anders: In the context of the strong progression free survival data. We believe these observations provide a meaningful complement to the overall efficacy story of RMC 63, six in metastatic pancreatic cancer.
Jack Anders: We anticipate that these two measures progression free survival and overall survival will be dual primary endpoints in our planned phase III study.
Jack Anders: Additional metrics in more detail regarding these data can be found on our website.
Operator: Given the strength of these data and based on initial feedback from the Food and Drug Administration, including alignment around high-level study design and the selection of 300 milligrams as our go-forward dose for pancreatic cancer, we plan to initiate our first global, registrational Phase III study this year. This phase 3 study, called RAS-ELUTE-302, will evaluate RMC6236 as a second-line therapy for patients with metastatic pancreatic cancer. Of course, while we are excited to initiate this study shortly on behalf of patients, our ambitions for ARMC6236 go well beyond second-line pancreatic cancer as we explore or plan to explore other tumor types and earlier lines of therapy. Data from the non-small cell lung cancer portion of the RMC6236 monotherapy study continue to mature.
Jack Anders: Given the strength of these data and based on initial feedback from the food and drug administration, including alignment around high level study design and the selection of 300 milligrams as our go forward dose for pancreatic cancer, we plan to initiate our first global Registrational Phase III study this year.
Jack Anders: This phase III study called Resolute <unk>.
Jack Anders: We will evaluate RMC 63, 6% as a second line therapy for patients with metastatic pancreatic cancer.
Jack Anders: Of course, while we are excited to initiate this study shortly on behalf of patients our ambitions for RMC 63, six go well beyond second line pancreatic cancer as we explore or plan to explore other tumor types in earlier lines of therapy.
Jack Anders: Data from the non small cell lung cancer portion of the RMC six to $3 six monotherapy study continue to mature.
Operator: In the fourth quarter, we expect to provide updated safety and anti-tumor activity data, including durability data, and to initiate a second registrational study evaluating RMC6236 monotherapy for patients with previously treated non-small cell lung cancer. The strength of the data we've presented also enhances our commitment to expand the reach of RMC6236 into earlier lines of therapy, including first-line metastatic, locally-advanced unresectable Exploratory studies evaluating RMC6236 in combination with current standard of care chemotherapy in first-line pancreatic cancer and colorectal cancer are currently enrolling and will yield important insights that should inform dosing paradigms for potential first-line registrational paths. This area remains a significant focus for RevMed. Another important combination study in progress is evaluating RMC6236 with pembrolizumab, with or without chemotherapy, in patients with advanced RAS-mutated non-small cell lung cancer.
Jack Anders: In the fourth quarter, we expect to provide updated safety and antitumor activity, including durability data and to initiate a second registrational study evaluating RMC $63 six monotherapy for patients with previously treated non small cell lung cancer.
Jack Anders: The strength of the data we've presented also.
Jack Anders: Hence our commitment to expand the reach of RMC 63 six inch.
Jack Anders: Into earlier lines of therapy, including first line metastatic or locally advanced Unresectable and Resectable disease.
Jack Anders: Exploratory studies evaluating RMC $63 six in combination with current standard of care chemotherapy in first line pancreatic cancer and colorectal cancer are currently enrolling and will yield important insights that should inform dosing paradigms for a potential first line registrational paths.
Speaker Change #134: This area remains a significant focus for retina.
Jack Anders: Another important combination study in progress is evaluating RMC 63, six with <unk> with or without chemotherapy in patients with advanced Ras mutated non small cell lung cancer.
Operator: We expect to report initial data for this combination in the fourth quarter of 2024, although there is substantial focus and investment in RMC6236 as our most advanced RAS-on inhibitor in the clinic. We also continue to prioritize investment in qualifying our first two graphs on mutant selective inhibitors, RMC6291, our G12C selective inhibitor, and RMC9805, our G12D selective inhibitor, for late-stage development. First, we continue to make progress in our combination studies with the goal of moving RMC6291 into early lines of therapy for patients with RAS G12C tumors. The RAS-on inhibitor doublet of RMC6291 in This study is ongoing, and we expect to share initial data in the fourth quarter of this year. Another combination approach with KRAS G12C non-small cell lung cancer is RMC6291 with pembrolizumab with or without chemotherapy.
Jack Anders: We expect to report initial data for this combination in the fourth quarter of 2024.
Jack Anders: While there is substantial focus and investment in RMC 63, six as our most advanced Ras <unk> inhibitor in the clinic we.
Jack Anders: We also continue to prioritize investment in qualifying our first two rason mutant selective inhibitors RMC 691, our <unk> selective inhibitor and pharmacy $90 five RG 12, <unk> selective inhibitor for late stage development.
Operator: The study of this combination is ongoing, and we anticipate disclosing initial data for RMC6291 with Pemberlizumab in the first half of 2025. Second, the first in human monotherapy study of RMC9805, a Ras-on-G12 deselective inhibitor, continues to enroll well. Dose optimization is ongoing, and we are on track to share initial safety, tolerability, and anti-tumor activity data in the fourth quarter. Overall, we have a busy and exciting road ahead with the anticipated initiation of two RMC6236 monotherapy registrational studies, a number of important exploratory combination study data updates, and additional data maturation that may validate the potential to advance two clinical-stage RASOM mutant-selective inhibitor In addition to advancing our studies, we are also preparing the organization for the next phase of growth. We are pleased to announce that we have appointed Frank Clyburn to our board of directors.
Jack Anders: First we continued to make progress in our combination studies with the goal of moving RMC 69, one into early lines of therapy for patients with Ras <unk> tumors the.
Jack Anders: The rason inhibitor doublet of RMC 60, 91 in combination with RMC 63, six in patients with <unk> solid tumors, primarily non small cell lung cancer is a vanguard study of this sort of combination regimen.
Jack Anders: This study is ongoing and we expect to share initial data in the fourth quarter of this year.
Jack Anders: Another combination approach with <unk> non small cell lung cancer is RMC 69, one with <unk> map with or without chemotherapy.
Jack Anders: A study of this combination is ongoing and we anticipate disclosing initial data for RMC 60 to 91 with <unk> in the first half of 2025.
Jack Anders: Second the first.
Jack Anders: First in human monotherapy study of RMC $90, five <unk> 12, <unk> selective inhibitor continues to enroll well.
Jack Anders: <unk> dose optimization is ongoing and we are on track to share initial safety Tolerability and antitumor activity in the fourth quarter.
Jack Anders: Overall, we have a busy and exciting road ahead with the anticipated initiation of two RMC $63 six monotherapy Registrational studies, a number of important exploratory combination study data updates and additional data maturation that may validate the potential to advance two.
Jack Anders: Clinical stage Ras on mutant selective inhibitors into late stage development.
Jack Anders: In addition to advancing our studies. We are also preparing the organization for the next phase of growth. We are pleased to announce that we have appointed Frank Clyburn to our board of directors.
Operator: Frank is a distinguished commercial pharmaceutical leader who brings a wealth of experience to help Revolution Medicines advance toward late-stage clinical development and prelaunch commercial readiness. Notably, he was instrumental in building Merck's modern oncology business, leading the successful global launch and commercialization of Merck's Keytruda to create the dominant immuno-oncology franchise. These insights and experience will be invaluable as we move forward. We've also made several strategic leadership hires across medical affairs, research and development, program management, and corporate affairs to help scale our organization as we move closer to becoming a fully integrated commercial organization.
Speaker Change #137: Frank is a distinguished commercial pharmaceutical leader brings a wealth of experience to help revolution medicines advance towards late stage clinical development and prelaunch commercial readiness.
Jack Anders: Notably he was instrumental in building <unk> modern oncology business, leading the successful global launch.
Jack Anders: And commercialization of Merck's keytruda to create the dominant immuno oncology franchise is insights and experience will be invaluable as we move forward.
Speaker Change #138: We've also made several strategic leadership hires across medical Affairs Research and development program management and corporate affairs to help scale our organization as we move closer to becoming a fully integrated commercial organization.
Operator: In particular, I'd like to highlight two individuals who have joined RevMed's senior leadership team. First, Ryan Asay, who is hosting today's call, brings extensive business experience in the biopharmaceutical industry to his new role as our Senior Vice President for Corporate Affairs. Second, Dr. Mary Pinder Shank has joined the organization as our senior vice president and head of medical.
Speaker Change #137: In particular I'd like to highlight two individuals who have joined <unk> senior leadership team.
Jack Anders: First Ryan AC who is hosting today's call brings extensive business experience in the biopharmaceutical industry to his new role as our senior Vice President Corporate Affairs.
Speaker Change #138: Second Dr. Mary Pinder, Shane has joined the organization as our senior Vice President and head of Medical Affairs and.
Operator: In addition to being a well-respected board-certified medical oncologist, Dr. Pinder-Shank brings extensive U.S. and global medical affairs leadership experience to Rev. I'm highly confident in the strength of our team and the collective depth and breadth of experience we can apply to this transformative stage of the company. We continue to build the capabilities needed to drive the long-term sustainable growth of our business.
Speaker Change #135: In addition to being a well respected board certified medical oncologist, Dr. Pinder Shang brings extensive U S and global Medical Affairs leadership experience to revenue.
Speaker Change #137: I'm highly confident in the strength of our team and the collective depth and breadth of experience. We can apply to this transformative stage of the company.
Speaker Change #142: We continue to build the capabilities needed to drive the long term sustainable growth of our business. This team along with our robust pipeline of innovative programs and one of the most productive drug discovery organizations in the industry positioning us well for what lies ahead.
Operator: This team, along with our robust pipeline of innovative programs and one of the most productive drug discovery organizations in the industry, positions us well for what lies ahead. Now I'd like to turn the call over to Jack Anders, our Chief Financial Officer, to provide a financial update.
Jack Anders: Now I'd like to turn the call over to Jack Anders <unk>, Our Chief financial officer to provide a financial update.
Operator: Thank you, Marc. We ended the second quarter of 2024 with $1.59 billion in cash and investments. This compares to $1.7 billion at the end of Q1. The decrease in cash investments during the second quarter was primarily due to a net loss for the quarter. Turning to expenses, R&D expenses for the second quarter of 2024 were $134.9 million compared to $98.0 million for the second quarter of 2023. The increase in R&D expenses was primarily due to increases in clinical trial expenses for our first wave of Rasson inhibitors, pre-clinical portfolio expenses, personnel-related expenses associated with additional headcount, and stock-based compensation. BNA expenses for the second quarter of 2024 were $21.7 million The increase in GNA expenses was primarily due to increases in personnel-related expenses associated with additional headcount.
Jack Anders: Sure.
Jack Anders: Thank you Mark.
Jack Anders: We ended the second quarter of 2024 with $1 $5 9 billion in cash and investments.
Jack Anders: This compares to $1 7 billion at the end of Q1.
Speaker Change #148: The decrease in cash and investments during the second quarter was primarily due to net loss for the quarter.
Jack Anders: Turning to expenses R&D expenses for the second quarter of 2024, or $134 9 million compared to $98 zero million dollars for the second quarter of 2023.
Jack Anders: The increase in R&D expenses was primarily due to increases in clinical trial expenses for our first wave of rason inhibitors preclinical portfolio expenses.
Jack Anders: Personnel related expenses associated with additional headcount and stock based compensation expense.
Jack Anders: G&A expenses for the second quarter of 2024, or $21 7 million compared to $14 6 million for the second quarter of 2023.
Jack Anders: The increase in G&A expenses was primarily due to increases in personnel related expenses associated with additional head count.
Operator: Commercial Preparation Activities, and stock-based compensation expense. The net loss for the second quarter of 2024 was $133.2 million compared to $98.3 million for the second quarter of 2023. As previously disclosed on July 15th, we have updated our 2024 financial guidance and expect full year 2024 gap net loss to be between $560 million and $600 million, which includes estimated non-cash stock-based compensation expense of between $70 million and $80 million. That concludes the financial update. I'll now turn the call back over to Marc. Thank you, Jack.
Jack Anders: Commercial preparation activities.
Jack Anders: Stock based compensation expense.
Jack Anders: Net loss for the second quarter of 2024 was $133 2 million compared to $98 3 million for the second quarter of 2023.
Jack Anders: As previously disclosed on July 15th we have updated our 2024 financial guidance and expect full year 2024, GAAP net loss to be between $560 million and $600 million.
Jack Anders: Which includes estimated noncash stock based compensation expense.
Jack Anders: Between $70 million and $80 million.
Jack Anders: That concludes the financial update I will now turn the call back over to Mark.
Mark: Thank you Jack.
Operator: Revolution Medicines entered the second half of the year by fulfilling one of many important clinical milestones for our organization. We are well-capitalized and remain focused on delivering key data and actions to advance RMC6236 into its first registrational studies, while evaluating several opportunities to move into earlier lines of treatment for patients living with RAS-addicted cancer. We are also laying the groundwork to move our first two RASOM mutant-selective inhibitors into late-stage development.
Mark: Evolution medicines to enter the second half of the year by fulfilling one of many important clinical milestones for our organization.
Speaker Change #142: We are well capitalized and remain focused on delivering key data and actions to advance RMC $63 six into its first Registrational studies, while evaluating several opportunities to move into earlier lines of treatment for patients living with <unk> cancers.
Mark: We are also laying the groundwork to move our first two Ras mutant selective inhibitors into late stage development.
Operator: This important work and the progress we've made would not be possible without the support of our patients and caregivers, clinical investigators, scientific and business collaborators, advisors, shareholders, and the tireless efforts of RedMed employees on behalf of patients. This concludes our prepared remarks for today, and I'll now turn the call over to the operator for the Q&A. Thank you. At this time, we will conduct a question and answer session. As a reminder, to ask a question during this session, you will need to press star 1-1 on your telephone and wait for your name to be announced.
Jack Anders: This important work and the progress we've made would not be possible without the support of our patients and caregivers clinical investigators scientific and business collaborators advisers shareholders and the tireless efforts of Radnet employees on behalf of patients.
Speaker Change #137: This concludes our prepared remarks for today and I'll now turn the call over to the operator for the Q&A session.
Operator: To withdraw your question, please press star one one again. We ask that you please limit your questions to one and one follow-up. Please stand by while I compile the Q&A roster. Our first question comes from Marc Frahm from TD Cowen. Please go ahead.
Speaker Change #137: Thank you.
Speaker Change #149: At this time, we will conduct a question and answer session. As a reminder to ask a question.
Speaker Change #145: During this session you will need to press star one on your telephone and wait for your name to be announced.
Speaker Change #137: To withdraw your question. Please press star one again, we expect you. Please limit your questions to one question and one follow up please stand by while a compounded Q&A roster.
Operator: Yes, thanks for taking my questions. Maybe just to start off, when you think about the PFS data you released in pancreatic cancer the other day, it looks a little bit better than what was achieved kind of with the G12C inhibitors in that subpopulation of pancreatic patients. Do you think that similar gap should kind of be expected when we look at monotherapy data in other settings where we have mature G12C inhibitor data, whether that's lung cancer or ultimately some other settings like colorectal cancer, or is just the biology just way too different across the board? Thanks, Marc.
Speaker Change #145: Our first question comes from Mark from from TV Cowen. Please go ahead.
Mark: Yes, thanks for taking my questions maybe.
Mark: Maybe just to start off can you.
Mark: You think about the PFS data you are at least in pancreatic cancer and the other day.
Speaker Change #141: It looks a little bit better than what was achieved with the <unk> inhibitors in that subpopulation pancreatic patients.
Speaker Change #138: That similar gap should kind of be expected when we look at monotherapy data in other settings, where we have mature <unk> inhibitor data whether thats.
Speaker Change #141: Lung cancer or ultimately some other settings like colorectal cancer or is it just a biology way to different across tumors.
Operator: I appreciate your question. I think at this point, given that data will be rolling out in the coming months and over the next year, I think it's best just to let the data speak for themselves. Obviously, there are many differences in the subtle aspects of biology comparing one tumor type to another.
Speaker Change #141: Thanks, Mark I appreciate your question.
Speaker Change #143: I think at this point given that data will be rolling out in coming months over the next year, I think especially as to let the data speak for themselves. There is obviously.
Speaker Change #147: There are many differences.
Mark: Several aspects of biology, comparing one tumor type to another.
Operator: Whether or not that nets out in any particular direction, I think, can just be determined by period. Okay, thanks. Maybe thinking about first line and pancreatic cancer, just, you know, how much more data do you need to gather to kind of know what the plan is there? Rather than just saying you want to do it, whether it's monotherapy, do you need a fair amount of combo data with chemo or even with the G12D inhibitor to just kind of figure out what the design looks like to move to first line?
Speaker Change #141: Whether or not that nets out in any particular direction I think just speaks determined empirically.
Speaker Change #141: Okay.
Keith: And then Keith.
Keith: Maybe thinking about first line and pancreatic cancer, just how much more data do you need to gather to kind of know what the <unk>.
Keith: <unk> is there.
Keith: Rather than just saying you want to do it whether it's monotherapy do you need a fair amount of combo data with chemo or even with the <unk> inhibitor.
Keith: To just kind of figure out what the design looks like to move to first line.
Operator: Yeah, I mean, I think we've said before, I know you and I talked about this, The model PRMC-6236, I think it already qualifies to be included in such a trial, and really the question is around what role chemotherapy should play. Should that be an arm in the study? And if so, how should that be done?
Keith: Yes, I mean I think.
Keith: We said before.
Speaker Change #141: And I talked about that.
Keith: Monotherapy or FCC 36, I think already qualifies to be included in such a trial and really the question is around what.
Keith: Have a place to come with chemotherapy what role should that play.
Keith: Should that be an arm in this study and if so how should that be done.
Operator: And that's principally a safety and tolerability question, is an efficacy question. RMC-6237 clearly is a broad-based inhibitor of RAS, by design. It's generally well tolerated and safe, but it does have some side effects.
Speaker Change #138: And that's principally.
Speaker Change #138: A safety and Tolerability question more than it is in the efficacy question.
Speaker Change #138: Obviously 606 clearly is.
Speaker Change #151: A broad based and taking over assets by design.
Speaker Change #138: It is generally well tolerated and safe, but it does have some side effects chemotherapy is typically.
Operator: Female therapy is typically complete with side effects, and so when you put those two together, we need to have confidence going into the study, going into a registration study that that combination will not blow up patients. So that's really what we're doing is trying to figure that out. There are many combinations, as you point out, that we couldn't pursue.
Speaker Change #138: We're pleased with side effects and so when you put those two together we need to have confidence going into the study.
Speaker Change #138: Going into a registration study that that combination will not go up.
Speaker Change #141: So that's really what we're doing is trying to figure that out there are many combinations as you pointed out that we couldnt pursue I wouldn't consider RMC nominated five specifically part of that determination for 63 six.
Operator: I wouldn't consider RMC 9805 specifically part of that determination for 6236. Going Into Frontline is its own entity, and how we'll deal with that, we'll describe over time as we reveal data about that interest. Okay, thanks a lot. Thank you. One moment for our next question. Our next question comes from Michael Schmidt from Guggenheim. Please go ahead.
Speaker Change #144: Oems frontline its own entity and how we'll deal with that we will describe.
Speaker Change #138: Over time as you can reveal data.
Speaker Change #138: Net interest income.
Speaker Change #159: Okay. Thanks, a lot.
Speaker Change #152: Thank you one moment for our next question.
Speaker Change #152: Our next question comes from Michael Schmidt from Guggenheim. Please go ahead.
Operator: Hey, thanks for taking my questions. I had one on the potential phase three study in second line non-small cell lung cancer for 6236. I mean, one would think that the easiest, the simplest design would just be a one-to-one randomization compared to dosy-TAP cell, but I'm just curious. There may be a scenario where CRIZATI gets full FDA approval in G12C positive patients at some point in the future, based on the CRISPR-12 study, and I was just wondering to what degree that might factor into the potential trial design.
Michael Schmidt: Hey, Thanks for taking my questions I had one on the potential.
Speaker Change #149: The study in second line non small cell lung cancer for $60.
Speaker Change #156: I mean, one would think that the.
Speaker Change #147: The simpler design with VA.
Speaker Change #159: One to one randomization compared to Docetaxel.
Bill: Bill maybe.
Operator: Would you, for example, allow CRIZATI in the control arm for G12C positive patients, assuming that the trial obviously would include those patients, or is that something that is not, you know, not feasible in your opinion? Thanks, Michael. Good to hear from you.
Speaker Change #138: Okay.
Speaker Change #138: Scenario.
Speaker Change #138: T.
Speaker Change #138: It has full FDA approval and <unk> positive patients at some point in the future.
Speaker Change #138: Based on the clinical trial study and I was just wondering.
Speaker Change #138: To what degree that might.
Speaker Change #138: Factor into the potential trial design will give for example allow crowbar a control arm for <unk> positive patients assuming that the trial. Obviously would include both patients or is that something that is not.
Speaker Change #138: Bob.
Speaker Change #156: Not feasible.
Speaker Change #138: Onion.
Speaker Change #138: Thanks, Michael good to hear from you.
Operator: Maybe I'll just say something brief about it, and then if you do, Steve, you're away, watch this, that maybe my general comment is G-12C is clearly the most complicated part of the lung cancer trial for our 6. There are subtleties associated with that, as you just alluded to. We have not described our plan yet for lung cancer. We put forth sort of a prototype last October, but we have not.
Speaker Change #151: I will say some degree got it and then.
Speaker Change #138: Steve you may want to add something to that.
Speaker Change #205: Maybe my General comment is <unk> is clearly the most complicated part of the <unk>.
Speaker Change #181: Cancer trial for RMC 63, six.
Steve: <unk> associated with that as you just alluded to we've not described our plan yet for lung cancer, we put forth.
Speaker Change #138: Prototype last October, but we cannot.
Operator: We did not lay that out, and our expectation is to do that in conjunction with disclosure of the data that would support it. So I think we'd be getting out a little bit of our skis to commit today, but whether there are any... Yige Guo wants to add to that. Actually, if you only came out one time, I think you'd get..., will end up being a consideration from the FDA if they were to prove Khrisati.
Speaker Change #162: We've not laid that out in our expectation to do that in conjunction with disclosure of the data that would support it so I think getting out a little bit over our skis too to commit today.
Speaker Change #156: But whether there are any principles CBOE wants to add to that.
Speaker Change #160: Got it.
Speaker Change #170: Hi, <unk>.
Speaker Change #138: Okay.
Speaker Change #138: We will end up being a.
Speaker Change #156: The issue from the FDA.
Speaker Change #138: Pre Saudi to date, you need that $1 six month PFS.
Operator: The PFS improvement is that PSATI is the standard care for G12 patients or just another standard care in addition to docetaxel. And that would dictate whether PSATI is required to be approved. Compared to her, or doesn't he have follows to, Thank you.
Speaker Change #138: The statutory Saudi deep panic here six four for <unk> patients or just another issue to docetaxel and delegate whether casady.
Speaker Change #138: Required GBT.
Speaker Change #138: There were docetaxel will soon be accepted.
Speaker Change #138: Yes.
Speaker Change #198: If you wish.
Operator: Okay. Okay. And then, yeah, very curious about the combination of 6236 and 6291, where I think you committed to presenting data later in the fourth quarter. And yeah, just want to understand a little bit better what types of patients are involved in the study. Are these predominantly second-line or later patients, or perhaps some treat-the-knife patients included there as well? And what efficacy bar are you looking for to potentially advance that dual?
Speaker Change #145: Okay. Okay. Thank you.
Speaker Change #138: And then yes, very curious about the culmination of 16 please.
Speaker Change #145: With the 6% to 91.
Speaker Change #174: I think you've committed to presenting data later in the fourth quarter and two one I understand all that better what types of patients is ongoing we will study all of these people.
Speaker Change #156: Dominantly second line or later patients, perhaps some treatment naive patients included there as well and.
Speaker Change #138: What.
Speaker Change #147: What efficacy bar are you looking for to potentially advance that do.
Speaker Change #147: <unk> combination into more.
Speaker Change #188: Registration directed study.
Operator: to more registration-directed studies. Okay, so the first question is one of sort of eligibility for the trial. Maybe Wei can answer that, and then maybe I can comment on it.
Speaker Change #159: Okay. So the first question is one of sort of eligibility for.
Speaker Change #145: For the trial, maybe we can answer that and then maybe I can comment on.
Speaker Change #138: The second.
Operator: County 6636 plus 6291, what types of patients, Starr, and Ben Hutchross. Yeah. So the big thing that Alec was.. any patient with a T-12T previously treated, predominantly so far, will be enrolling. Healthy Patients have lung cancer or colorectal cancer just given the predominant... or I think if you look at 100 patients with solid chamber T12C mutations, 70 of them will probably have lung cancer, and the other 20 will be colorectal cancer, with the remaining 10% being the other.
Speaker Change #138: It's a combination of $66 to $6 60 to 90, what types of patients in tumors.
Speaker Change #138: So.
Speaker Change #174: How we closed out any patients he treated tumor without me so far will be enrolling <unk> patients.
Speaker Change #138: In lung cancer and colorectal.
Speaker Change #138: Colorectal cancer cases, getting predominance of those tumor types, where I think if you look at it.
Speaker Change #138: Solid years.
Speaker Change #138: Mutations 70 of them will probably be lung cancer colorectal.
Speaker Change #138: Colorectal cancer.
Operator: So that's kind of the distribution. And so just by that natural distribution, we end up with a million predominant colonies. Ma, and so on and so forth, that second line plus given that they have to have been previously treated with chitosan. And then your second question was, "What's the efficacy bar?" Yeah, well, it's a fairly delicate topic here, you know, really to compare two things and prove that they're different requires a randomized control trial. We have hundreds of patients, so there's not going to be a number that's going to come out of this that will allow us to do that. Player, you know, victory at that level, of course.
Speaker Change #138: And thats kind of a distribution and so just by that math with distribution gains.
Speaker Change #138: To accompany Colin.
Speaker Change #138: And.
Speaker Change #138: And so that second line plus given that they have to have been previously treated with <unk>.
Speaker Change #168: And then your second question was what the efficacy bar.
Speaker Change #138: Yes.
Speaker Change #138: Well it does.
Speaker Change #138: It's a fairly subtle topic here.
Speaker Change #147: To compare two things and prove that they are different requires a randomized control trial.
Speaker Change #147: Hundreds of patients. So there is not going to be a number that's going to come out of this that will allow us.
Speaker Change #147: To declare.
Speaker Change #138: Victory at that level of course.
Operator: What we're looking for, though, is can we see some level of differentiation? qualitatively informed. And, what that is, will emerge over time. We'll see what we see, and we'll communicate it at that time. But there's not a preset.
Speaker Change #138: What we're looking for though is can we see some level of differentiation.
Speaker Change #138: Quantitatively informative and.
Speaker Change #138: What that is will emerge over time, we'll see what we see.
Speaker Change #138: And we will communicate at that time that theres not theres not a preset response rate PFS or OS number that we could associated with its an ever describe it to this particular combination.
Operator: The response rate, PFS, or OS number that we can associate with this and always ascribe it to. This particular combination, in and of itself. Okay, great. Thank you. Thank you. One moment for our next question. Our next question comes from Eric Joseph from J.P. Morgan. Please go ahead.
Speaker Change #138: So.
Speaker Change #179: Okay, great. Thank you.
Speaker Change #205: Thank you one moment for our next question.
Speaker Change #179: Our next question comes from Eric Joseph from Jpmorgan. Please go ahead.
Operator: All right. Thanks for taking the questions. I'm hoping you could just help us level set expectations for the phase one non-small cell lung cancer update in the fourth quarter in terms of patient numbers. You know, just kind of drafting from the update that we saw in July in pancreatic cancer, should we expect a similar ramp up in the number of evaluable patients across doses 160 to 300 milligrams? and then.
Eric Joseph: Good morning.
Eric Joseph: Alright, thanks for taking the questions.
Speaker Change #147: <unk> you could just help us level set expectations into the phase one.
Speaker Change #209: So lung cancer update and fourth quarter in terms of patient numbers.
Speaker Change #168: Just kind of drafting.
Speaker Change #148: Drafting from the uptick that we saw in July and pancreatic should we expect a similar ramp up in the number of evaluable patients across doses 160 to 300 milligrams.
Speaker Change #187: And then.
Operator: Just as a follow-up in pancreatic cancer, Marc, I guess how should we be thinking about sort of additional updates either kind of within the data set that you presented in July, perhaps at medical meetings, or sort of follow-on updates as that trial matures? Thank you. Yeah, thanks, Eric. Nice to talk with you.
Speaker Change #189: Just as a follow up.
Mark: Pancreatic cancer, Mark I guess, how should we be thinking about sort of.
Speaker Change #155: Additional updates either kind of within the data set that you presented in July perhaps at medical meetings or.
Speaker Change #312: Sort of follow on.
Speaker Change #155: Updates.
Speaker Change #148: As.
Speaker Change #242: That trial matures. Thank you.
Eric Joseph: Yes, Thank you Eric.
Speaker Change #148: With you.
Operator: On the second question about PDAC, I think we've made a pretty clear commitment to providing an update to those data, a meaningful update. But we've not been able to share a specific timeline or setting in which that will happen, so, Year at CHART, with regard to lung cancer data. You know, it's hard, it's hard really to go into that level of forecasting about what we'll communicate.
Speaker Change #148: On the second question, Peter I think we've been.
Speaker Change #148: It's pretty.
Speaker Change #147: Clear commitment to providing an update to those data.
Speaker Change #147: Have a meaningful update.
Speaker Change #225: But we've not been able to share a specific timeline youre setting in which that will happen.
Speaker Change #147: So.
Speaker Change #164: Good day.
Speaker Change #151: With regard to the lung cancer data.
Speaker Change #160: It's hard it's hard really to go into that level of forecasting we'll communicate.
Operator: You know, I think, generally speaking, we're going to be in the ballpark of the kinds of numbers that we've enrolled previously for pancreatic cancer, but the analysis, we'll just have to speak for ourselves. Okay, thanks. Maybe just one follow-up in lung cancer, if I could just pick up on a prior question about the phase three strategy, it sounds sort of like one option that you're contemplating is an integrated trial where G12C patients can go on to either a G12C inhibitor or a taxane. I just wonder operationally, is there sort of a scenario where you conduct two phase three trials, one in sort of G12X minus C and then another in G12, another that's focused on G12C patients?
Speaker Change #164: I think generally speaking we're going to be in the ballpark of the passenger numbers everything all the previous stage four pancreatic cancer, but.
Speaker Change #160: Analysis, and we'll just have to speak for itself.
Speaker Change #160: Wow.
Speaker Change #138: Okay. Thanks, maybe just one follow up in lung cancer, if I could just picking up on a prior question.
Speaker Change #187: About the phase III strategy, it sounds sort of like one.
Speaker Change #185: Option that you are contemplating as an integrated trial, where <unk> patients can go on to either.
Speaker Change #138: We'll see where it can be compared to a <unk> inhibitor or taxane.
Speaker Change #205: I just wonder operationally is there sort of.
Speaker Change #164: An area, where you conduct two phase III trials, one in sort of <unk> X minus C. And then another and cheese. Both another that's focused in <unk> patients. Thank you.
Operator: Thank you. Well, yeah, there are a lot of possible scenarios. I don't think I can give any hints today about what the scenario is that we'll pursue. I think that's done at the time that we share the data and describe it. I think that Wei's comment earlier was more one of concept. If that's an FDA issue, ultimately that's an FDA question: what will they treat as the standard of care? Will, would Khrisati if it's approved?
Speaker Change #179: Well, yes, there are a lot of possible scenarios.
Speaker Change #156: I don't think I can give you here today about what the scenario is that we will pursue I think thats been.
Speaker Change #151: At the time that we share the data and describe that I think that weights comment earlier, just more one concept that has an FDA ultimately that's an FDA question what will they treat as the standard of care.
Speaker Change #151: And we will would Chris Audi it's approved.
Operator: Be declared as the standard of care for G12C patients or just launch several treatments that are acceptable, in which case... Joseph Axelstiel, and David Comperator. You know, that's a topic. You know, really, really for discussion with the FDA, it's not so much that we're considering A, B, or C. But just as a concept, that's how one would have to think about it, and also I think the other factors would go into that as well. Ed. Zalik has approved. Relative, Okay, I got it.
Speaker Change #151: Be declared as the standard of care for <unk> patients or just launched several treatments that are that are acceptable in which case.
David: Taxes, David comparator.
Speaker Change #190: That's a topic.
Speaker Change #190: Really really for discussion with the FDA, it's not so much that we are considering a b or C.
Speaker Change #138: But just as a concept that's how one would have to think about it.
Speaker Change #138: So I think the other factor that would go on to that is the timing.
Speaker Change #138: As to.
Speaker Change #138: So it gets approved.
Speaker Change #138: Getting through relative to the to that study.
Operator: I appreciate the color and thanks for taking the question. Thank you. One moment for our next question. Our next question comes from Jonathan Chang, from Lear Inc. Partners. Please go ahead. Hi guys.
Speaker Change #251: Okay got it I appreciate the the.
Speaker Change #185: The color and thanks for taking my questions.
Speaker Change #138: Okay.
Speaker Change #189: Thank you one moment for our next question.
Speaker Change #138: Our next question comes from Jonathan Chang.
Speaker Change #189: From Leerink partners. Please go ahead.
Operator: Thanks for taking the question. Given that there are multiple data updates now expected in 4Q, how should we be thinking about the cadence and venue of these disclosures? Will they happen sequentially? Do you have an order in mind? Or could these be bundled together in a combined way?
Jonathan Chang: Hi, guys. Thanks for taking the question.
Jonathan Chang: Given that there are multiple data updates now expected in <unk>, how should we be thinking about the cadence and if any of these disclosures.
Speaker Change #179: Sequentially do you have an order in mind or could these be bundled together in a combined way. Thank you.
Speaker Change #179: Yes.
Operator: Thank you. Yeah, thanks, Jonathan. The answer to your question is yes. So you gave a list of possibilities, and that is the list of possibilities. I think we won't be able to provide more clarity. We're glad that we can at least narrow it down to a quarter.
Speaker Change #179: Yes, Thanks, Jonathan the answer to your question is yes. So you gave a list of possibilities and that is the list of possibilities.
Speaker Change #206: I think we won't be able to provide more clarity. We are glad that we can give you at least narrow it down to a quarter. That's a step forward, but beyond that it will save the format floor right now.
Operator: That's a step forward, but beyond that point, we'll save the format for the rest of the session. Okay. Thank you. Thank you. One moment for our next question. Our next question comes from Chris Shibutani, from Goldman Sachs. Oh, thank you very much. I know that Marc and the team had a discussion of the data, but perhaps, for the purposes of this audience at this point, for the second-line PDAC readout, thinking about dropouts and censorship, is the level of censorship in an expected range?
Speaker Change #179: Yeah.
Jonathan: Understood. Thank you.
Speaker Change #200: Thank you one moment for our next questioner.
Jonathan: Our next question comes from Chris Shaw with Tommy.
Speaker Change #240: From Goldman Sachs. Please go ahead.
Chris Shaw: Hello. Thank you very much I know that Mark you and the team had a discussion of the data, but perhaps if you could just for the purposes of this audience at this point for the second line PD readout thinking about dropouts and censorship.
Speaker Change #218: This is the level of censorship.
Speaker Change #156: Expected range is there something that might have accounted in some idiosyncratic way potentially invest.
Operator: Is there something that might have accounted in some idiosyncratic way, potentially, for an investigation site or trial or any aspect or treatment of the patients? And then how should we think about this as possibly being relevant at all as we think about the larger Phase 3 multi-institutional trial? Thanks. Yeah, thanks, Chris. Nice to talk to you.
Speaker Change #195: Investigations site or trial or any aspect of treatment of the patients and then how should we think about this as possibly being relevant at all as we think about the larger phase III multi institutional trial. Thanks.
Operator: Thanks for the question. Yeah, there was some censorship, some censoring that went on in both the PFS and OS analyses, and maybe Wei can address both of your questions. What type of censorship was it? Was it unusual?
Jonathan: Yeah, Thanks, Chris Nice to talk to you. Thanks for the question.
Speaker Change #151: Yes, there was some censorship.
Speaker Change #138: When some censoring that went on.
Speaker Change #138: Both PFS and OS analysis and maybe.
Speaker Change #158: <unk> can address both of your questions.
Speaker Change #201: Type of censorship was it wasn't unusual to indicate anything.
Operator: Did it indicate anything? And how does it affect our view of how to translate that information?
Speaker Change #229: Does it how does it affect our view of how to translate that information.
Operator: on your, There's nothing unusual about the censoring. The censoring, or the standard censoring, due to the fact that some patients were enrolled later than other patients, and at the time of the data cutoff, they have not had a progression event. And so that's the reason for the century that you saw for the patient, throughout both the Kavanaugh curve for the PFS and the OS.
Speaker Change #138: All right.
Speaker Change #257: And we're doing.
Speaker Change #138: So nothing unusual about the sensory entry will be a standard entry due to the fact that some patients who go.
Speaker Change #138: Later again other patients.
Speaker Change #211: The data cutoff.
Speaker Change #138: Progression bank and so thats the.
Speaker Change #138: The leasing for essentially that you saw for the patients.
Speaker Change #138: Banks have occurred now.
Speaker Change #138: Throughout the both the Kaplan Meier curve PFS OS.
Speaker Change #138: Alright.
Operator: As we follow through and have later day data cut with more maturity to the data, Minimalism Center will move out, and hopefully even beyond the median PFS line for the more, if they have a PSS event, you know, in terms of translation to the... Ultimate Retreational Trial in a nutshell, because In an early life study, we can observe the data in real time, and we can cover up the data. Continuously, and so you do see an early data cut, which we presented with some sensoring. In a setting of a registration trial, this would no longer be an issue because of the. There will be a pre-specified number of PFS and OS events that we define that would actually help. University.
Speaker Change #138: As we follow through and make a cup with more mature data.
Speaker Change #138: Essentially.
Speaker Change #138: <unk>.
Speaker Change #138: And.
Speaker Change #138: Hopefully you can be out and median PFS.
Speaker Change #138: As estimate.
Speaker Change #138: Furthermore.
Speaker Change #138: And how we see it.
Speaker Change #138: Sure.
Speaker Change #138: In terms of translation to the.
Speaker Change #138: The ultimate Registrational trial.
Speaker Change #138: Because.
Speaker Change #138: In a hurry line study.
Speaker Change #138: We can observe data real time and take all the.
Speaker Change #138: Data.
Speaker Change #138: And so you do see early data cut which was presented with some strange you Chi.
Speaker Change #138: Okay.
Speaker Change #138: Debt maturity lack thereof of the data.
Speaker Change #138: Setting up a registration trial. This we now no longer be an issue.
Speaker Change #138: Because.
Speaker Change #176: Specify number of PFS and OS.
Speaker Change #176: Fine that would actually.
Speaker Change #176: We used to.
Operator: State, at which time we read out the study, and so we would not be looking at the data in real time, not presenting data in an immature state, in this case, so we would not expect. And so at that time, the PFS and OS, when we do read out, will be a fairly stable recognition of the findings. I didn't think, um... Survive, lack of translatability earlier.
Speaker Change #176: Eight at which time, we readout the study.
Speaker Change #207: So we will not be looking at the data in real time and will be not presenting data.
Speaker Change #176: Data, we have so we're not expecting.
Speaker Change #138: And so at that time, the PFS and OS readout.
Speaker Change #176: Takeaway indications that final analysis.
Speaker Change #176: Income.
Speaker Change #176: Yes.
Speaker Change #176: Hi.
Speaker Change #176: Any.
Speaker Change #176: Lack of translate ability.
Speaker Change #176: Looking at cash throughout the year.
Gabe: Sure Gabe.
Gabe: Any questions.
Operator: Thank you. If I could just add one point to the first part of the presentation, question, which is, patients who are censored because they started on the trial more recently. We did look at those patients. Their profiles. We also spoke with investigators and asked them about those patients. The general consensus was that they're not different patients, they're just patients who enroll later into those cohorts. Forced to be Censored at Planet Street.
Speaker Change #176: Thanks, Wayne if I could just step one one point.
Gabe: <unk>.
Speaker Change #218: First part of the.
Speaker Change #219: Question wishes.
Speaker Change #187: Those patients were censored because they get started on the trial more recently.
Speaker Change #254: We did look at those patients.
Speaker Change #187: Their profiles to determine whether they showed any different characteristics than patients who have been enrolled earlier you also spoke with investigators asked them about those patients and the general consensus was.
Speaker Change #236: Not different patients Theyre just patients with later.
Speaker Change #138: In two dose cohorts.
Speaker Change #138: Yes.
Speaker Change #209: Forced to be censored.
Speaker Change #209: Right.
Operator: Thank you. That's reassuring clarification. I appreciate it.
Speaker Change #162: Thank you that's reassuring clarification I appreciate it.
Speaker Change #159: Thank you one moment for our next questions.
Operator: Thank you. One moment for our next question. Our next question comes from Eliana Merle from UBS. Please go ahead. Hi, this is Elliott Bosco on behalf of Ellie Merle, UBS.
Speaker Change #159: Our next question comes from Eliana Merle from UBS. Please go ahead.
Speaker Change #259: Hi, This is Elliott bus go on for Ellie Merle UBS.
Operator: First one, what's your view on what would be competitive PFS data for the upcoming 6.2.3.6 non-small cell lung cancer update? In particular, could you clarify what would be competitive when thinking about both CRAF and non-CRAF targeted therapies? Yeah, thanks for your question. I mean, it's pretty straightforward.
Speaker Change #184: First one what's your view on what would be a competitive competitive PFS data for the upcoming six two years to three six non small cell lung cancer update.
Speaker Change #284: In particular could you clarify what would be competitive when thinking about <unk>.
Speaker Change #242: <unk> crafts and non crafts targeted therapies.
Operator: We think that the first thing we have to do is make sure that we clear the standard care bar. And I know you're asking more than that, which is by how much it has to be cleared. It's a little bit difficult for us to give you an answer to that while we're in the midst of gathering and analyzing data. It's very hard, then, to separate, then, our view of the data from that. We, of course, have target product profiles that are internal.
Speaker Change #209: Yes. Thanks for your question I mean, it's pretty straightforward, we think that the.
Speaker Change #209: The first thing we introduced make sure that we clear the standard of care.
Speaker Change #236: And I know youre, asking more than that which is by how much did the Apache declared its a little bit difficult for us to give you an answer to that.
Speaker Change #231: While we are in the midst of gathering and analyzing data, it's very hard to separate in our view of those data from that.
Speaker Change #204: We of course have a target product profile generation Chevrolet proprietary, but and then less of a conversation like this I think it's a tricky question at this at this stage, so thats 80 days to wait and see.
Operator: I think it's really a tricky question at this stage, so the best thing to do is to wait and see. We do have experience, of course, with RAS inhibitors as to what they were previously considered sufficient, and investors have had opinions about that, and everybody has an opinion about it. And we'll present ours in the context of the data that we have, and I'll let everybody speak about the dogfight. Okay, and then just one more. For the ongoing 6236 monotherapy and combo studies in colorectal cancer, could you provide a sense of when we might see data? Is that likely to be 2025 events?
Speaker Change #309: Do have experienced a course of fasteners in years as to what.
Speaker Change #204: Previously considered sufficient and investors have had opinions about that and everybody kind of opinion about it.
Speaker Change #224: Presenters in the context of.
Speaker Change #209: The data that we have.
Speaker Change #161: Hello, everybody.
Speaker Change #197: Should a dogfight.
Speaker Change #197: Yeah.
Speaker Change #217: Okay, and then just one more for the ongoing 636 monotherapy and combo studies in colorectal cancer could you provide a sense of when we might see data is that likely to be 2025 events.
Operator: Yeah, we haven't provided any guidance on timing for that, so we tend to just do it off the cuff here. I think the one concept that I think Steve has communicated a number of times, and Wei has as well, is that we consider colorectal cancer to be primarily a combination strategy play. That's been the story.
Speaker Change #240: Yes, we haven't provided any guidance on timing for that so they tend to just do it off of off the cuff here I think.
Speaker Change #197: The one concept that I think Steve has communicated a number of times in warehouse as well.
Speaker Change #197: Bidder.
Speaker Change #197: Colorectal cancer to be primarily a combination strategy play.
Speaker Change #197: That's been the history.
Operator: Forever, and it will be as well, so that does. That's more the horizon to be thinking about. I'm not to say we present some monotherapy data, but we do believe that fundamentally changes the biology of colorectal cancer. Okay, thanks for taking the question. Thank you. Please take a moment for our next question. Our next question comes from Alec Stranahan from Bank of America. Please go ahead. Hey, guys. Thanks for taking our questions. First one from us. Here's some of the nested trial design in RAS Salute 302.
Speaker Change #189: Essentially forever.
Speaker Change #189: And it will be as well so that goes.
Speaker Change #197: Hi.
Speaker Change #161: That's more of the horizon to be thinking about.
Speaker Change #165: Not to say, we maybe not presents a monotherapy data, but we do believe that fundamentally the biology.
Speaker Change #165: Sure.
Speaker Change #165: Yeah.
Speaker Change #218: Okay. Thanks for taking the question.
Speaker Change #165: Sure.
Speaker Change #165: Thank you one more before our next question.
Speaker Change #180: Our next question comes from Alec Stranahan from Bank of America. Please go ahead.
Alec Stranahan: Hey, guys. Thanks for taking our questions.
Alec Stranahan: First one from us.
Speaker Change #227: Some of the nested trial design and resolute 302, any signals you'd highlight from either your phase one of our preclinical work for the activity of $63 six specifically in the 16, how does the <unk>.
Operator: Any signals you'd highlight from either your Phase I or preclinical work for the activity of 6236, specifically in the G13X, the G61X, and especially the RAS wild-type patients? Would you view these as maybe higher-hanging fruit from a mechanistic perspective? I know you saw some preclinical activity in the RAS wild-type in your Nature paper earlier this year. Yeah, maybe Steve wants to comment on that, but not G-12X versus T-12X. Well... Think about it, and the best thing is that. If it isn't, she told him.
Speaker Change #225: <unk> X <unk>, 60, onex, and especially the Ras Wild type patients would you view these as maybe higher hanging fruit from a mechanistic perspective, I know you saw some preclinical activity in.
Alec Stranahan: In the Ras Wild type nature paper earlier this year.
Speaker Change #165: Yes, maybe Steve wants to comment on that but not launching 12 extra space both exited.
Speaker Change #179: How do we think about that.
Speaker Change #179: Yes.
Speaker Change #179: Hi.
Speaker Change #179: Well.
Speaker Change #209: And we think about it in the vesting is.
Speaker Change #209: Okay.
Operator: It isn't in the inner core, as she described it, whether that is based on firm data or whether it is based on more of a conceptual approach to the whole disease. The concept of rats driving the disease, I think, is something that we don't really know yet. I mean, the assessment of... Any of our compounds, including RMC6236 in rats, mutations outside of the G12 mutations, was a somewhat later event. And therefore, the emergence of data on those mutations is going to be somewhat behind the..., the main body of data on which we base our decision-making, and so we're a little less confident there.
Speaker Change #179: So.
Speaker Change #179: Linda.
Speaker Change #179: <unk>.
Speaker Change #165: It's growing at.
Speaker Change #165: Where the.
Speaker Change #165: Space on firm dates or whether it is based on.
Speaker Change #165: More of a more of a concern.
Speaker Change #165: She will approach to the to the whole disease.
Speaker Change #165: Call centers last July.
Speaker Change #165: Driving the disease I think is something that we.
Speaker Change #255: We don't really know yet.
Speaker Change #165: <unk>.
Speaker Change #165: Assessments of.
Speaker Change #165: Any of our competitors, including RMB 63, six and Ras mutations iron side with the <unk> mutations was somewhat later event.
Speaker Change #165: And therefore, the emergence of data in those mutations is going to be somewhat behind.
Speaker Change #165: The main body of data on which we base our decision, making and so we're a little less comfortable there I think it's more of a confidence that it is evolves items.
Operator: I think it's more about confidence than it is about science, as mentioned, and no doubt that revolving. I'd love to be able to give you a proper scientific answer to the question, but at the moment, we remain silent.
Speaker Change #165: Medicine.
Speaker Change #165: Both of them.
Speaker Change #237: Engine costs, so I'd love to be able to give you a trough of sunset advances to customers, but at the moment.
Speaker Change #165: <unk>.
Speaker Change #165: Yes.
Operator: And I would just add to that that in the data we presented, we did show the overall RAS mutated group. The PFS value for that was 7.6 months, so if there are differences that we haven't yet developed clarity around, they don't seem to compromise, you know, looking at the whole group.
Speaker Change #247: And I would just add that in the in the data we presented we did show the overall Ras mutated group.
Speaker Change #165: And the PFS value for that was $7 six months so.
Speaker Change #255: If there if there are differences that we havent yet.
Speaker Change #247: Clarity around.
Speaker Change #165: They don't seem to compromise looking into looking at.
Operator: You know, and also keep in mind that 85% of the time it offers something more broadly. Got it. That makes sense. And then one more, if I may, obviously, launching and supporting your ongoing and planned studies is a top priority. But in terms of capital allocation, the next 12 months or so, how do you plan to move forward with the earlier Wave 2 pipeline in order to realize the ultimate potential of the RASP-ON approach? So we, thanks for that question.
Speaker Change #165: And also keep in mind that 85%.
Speaker Change #271: Hey, Grant of cancer is attributable to a <unk> 12 last 12 expectation. So the majority of the disease that we're trying to treat here is still in the core population.
Speaker Change #165: We'd like to offer something more broadly than that.
Speaker Change #165: Yes.
Speaker Change #282: Got it that makes sense.
Speaker Change #216: And then one more if I may.
Speaker Change #180: Obviously, launching and supporting your ongoing and planned studies as is the top priority, but in terms of capital allocation next 12 months or so.
Speaker Change #180: How do you plan to move forward with the earlier.
Speaker Change #165: Wave two pipeline in order to realize the ultimate potential for restaurant approach. Thanks.
Speaker Change #165: Yeah.
Speaker Change #246: So thanks for that question I mean, we define wave one.
Operator: I mean, we define wave one RASL inhibitors as being the 6236, 6291, and 9805. And then we have lots of other inhibitors behind that. We haven't formally called them wave two, but I think that would be a natural progression. We have not declared any sort of public guidance about what, where, when, and how.
Speaker Change #248: So I was just curious as being <unk>.
Speaker Change #246: 669 195.
Speaker Change #214: And then we have lots of other inhibitors, but behind that we havent formally call. The wave two but I think that would be a cash flow.
Speaker Change #214: Progression.
Speaker Change #214: And.
Speaker Change #214: We have not declared any sort of public guidance about what where when and how there's so much to chew on with the first three.
Operator: There's so much to chew on with the first three assets, both as mama therapy, combinations, multiple lines of therapy, and multiple tumor types. That's a lot of a story for people to digest, and we've allocated capital largely accordingly to just what we've identified as the Wave 1 assets, and within that, most of that is actually our C6236. So all I can say is stay tuned. This is a company with an incredibly productive workforce. Joint Discovery Organization that sort of delivers, effectively, more high quality interesting content.
Speaker Change #264: <unk>, both as monotherapy and combinations multiple lines of therapy in multiple tumor types.
Speaker Change #214: That's one that's a lot of storage for people to digest and the allocated capital larger.
Speaker Change #214: Largely accordingly.
Speaker Change #242: There is no money spent on other things but.
Speaker Change #214: Really the drivers of our spending or just what we've identified is the wave one assets.
Speaker Change #165: And within that most of that is actually RMB 63, six so all I can say is stay tuned.
Speaker Change #214: <unk>.
Speaker Change #165: Company a relatively productive.
Speaker Change #242: So a separate organization that delivers secondly, more high quality interesting.
Operator: We've done some prioritizing, but we keep a very close eye on that productive Early Pipeline Creation. And, by the way, we also want to understand how those first three assets perform in order to understand where the gaps are. That's not something that's just a matter of defining it preclinically what we want to see in it, where the gaps are, what sorts of combinations, what is best to use, what next generation compounds make sense, and how to develop them.
Speaker Change #165: Assets than any organization can move forward in parallel we've got some prioritizing, but we keep a very close eye on that productive.
Speaker Change #165: Pipeline.
Speaker Change #165: And we'll move things forward as they make sense and by the way. We also want to understand how those first three assets performing in order to understand where the gaps are and thats not something thats, just a matter of divining at three clinically, but we won't see in the clinic, where the gaps are what sorts of combinations to use what nextgen.
Speaker Change #165: Yeah.
Speaker Change #165: Makes sense.
Operator: So stay tuned. We'll all be learning. Appreciate the color.
Speaker Change #165: So stay tuned we will all be learning as we go.
Speaker Change #238: Appreciate the color. Thank you.
Operator: Thank you. Thank you. One moment for our next question. Our next question comes from Peter Lawson, from Barclays, please go ahead. Hi, good afternoon. This is Alex on behalf of Peter.
Speaker Change #238: Thank you one moment.
Speaker Change #259: Our next question.
Speaker Change #165: Our next question comes from Peter Lawson.
Speaker Change #224: From Barclays. Please go ahead.
Operator: Thanks for taking our questions. I just had one on the combination data with PEMBRO in lung cancer in the second half for 6236. So, I understand that, you know, safety data for the combination is going to help you inform your strategy in the first-line metastatic setting. But I'm wondering if that data would also enable potential studies in earlier lines of therapy in lung cancer, like the adjuvant setting, for example, and if that's something that's also of interest for RevMed. Thank you. Yeah, thanks a lot, Alex.
Alex: Hi, Good afternoon. This is Alex on for Peter Thanks for taking our questions just had one on the on the combination data with <unk> in lung cancer in the second half for $6 three six so I understand that safety data.
Speaker Change #190: The combination is going to help you inform your strategy in the first line metastatic setting.
Speaker Change #240: I'm wondering if that data would also enable potential studies in earlier lines of therapy in lung cancer like the adjuvant setting for example, if thats something Thats also of interest for relevant. Thank you.
Alex: Yes, Thanks, a lot Alex I think.
Operator: I think Dr. Lin can answer that question. Yeah, I think, absolutely, we have thought about this, and I think you're absolutely correct. I think the current regimen is... The Angle Plus Chemotherapy is used in the first line of the actual chiropractic setting as well as other therapeutic settings by establishing the CTEI.
Dr. Glenn: Dr. Glenn can answer that question, yes.
Dr. Glenn: Yes, I think absolutely we have thought about this.
Dr. Glenn: You are absolutely correct I think on the.
Tom: The current regimen that Tom.
Speaker Change #281: <unk> plus chemotherapy issues, both the first line of Salt asphalt care optical states, so it's happening with <unk> and <unk>.
Operator: Activity of that combination in the first-line setting that would also enable us to move into our..., that is something very much in my mind. Thank you. One moment for our next question. Our next question comes from Kelly Shee from Jeffries. Please go ahead.
Speaker Change #262: Cleaning activity of that.
Speaker Change #262: That combination in the first line setting that would also enable us to engage over here.
Speaker Change #259: Got it thank you very much.
Speaker Change #190: Sure.
Speaker Change #190: Thank you.
Speaker Change #284: My primary question.
Kelly <unk>: Our next question comes from Kelly <unk> from Jefferies. Please go ahead.
Operator: Thank you for taking my questions. So for the G12-D data in the fourth quarter, what tumor types would be included in this first data disclosure? And also, for the 62-36 Pembroke combo in the lung, for the data disclosure, do we expect only second line class settings?
Kelly: Hi, Thank you for taking my questions. So far the key to all the data.
Speaker Change #208: Fourth quarter, what's your guys have suitable include <unk>.
Speaker Change #208: Carlo I'll call for that.
Operator: Thank you. I didn't quite understand the first question. Did anybody catch exactly what was being asked about the 90 to five, tumor, x-ray, 90 to five? Ah, two more types. I'm sorry; I just didn't hear that word.
Speaker Change #208: Okay.
Speaker Change #280: Hornbill combo in lung.
Speaker Change #203: So that buildup of color great quarter.
Speaker Change #266: Second line class settings. Thank you.
Speaker Change #272: I didn't quite understand the first question I didn't.
Speaker Change #248: Catch exactly what was being asked.
Speaker Change #203: 92.
Speaker Change #203: Tumor tissue 90 Eagle five tumor.
Speaker Change #273: I'm, sorry, I, just didnt hear that.
Operator: Yeah, I mean, it's a solid tumor study, so we will have a mix of solid tumors. G12D is most common in gastrointestinal tumors, although it does appear in lung cancer and others, but less frequently. So, to my knowledge, the representation in the study is sort of representative of the representation in the world. Those swimmers are nasty tuners, no matter what type they are, so they're going to show up for...
Speaker Change #203: Yes.
Speaker Change #249: It's a <unk> solid tumors studies. So it will have a mix of <unk> solid tumors Jacoby is most common in gastro intestinal tumors, although it does appear in lung cancer and others, but less frequently.
Speaker Change #203: No.
Alex: To my knowledge.
Speaker Change #264: Representation in the study.
Alex: Representation in the world.
Alex: Those figures are nasty juniors matter what types. They are they going to show up for targeted therapy, because it's available. So I think it'd be a mix.
Operator: Therapy, et cetera. So I think you'll be next. The second question about 63.6 in non-small cell lung cancer was whether those patients are all previously treated or not, or are they second line and later, or are they first line patients as well? So the trial design says that in the initial dose saturation, we will treat it first in expansion. Then once we establish a safe and tolerable environment. Produced by Spatial Expansion for Earth Concepts.
Alex:
Speaker Change #224: And then the second question about $63 six in non small cell lung cancer. It was whether those patients are all previously treated or not or the SEC.
Speaker Change #224: Can line in later or their first line patients as well.
Speaker Change #254: Yes, so the trial design such that initial dose escalation we will.
Speaker Change #273: Please proceed.
Speaker Change #272: Pension gain once we establish a safe and tolerable dose.
Speaker Change #266: After dose that patient Spanish first months.
Alex: Thanks.
Speaker Change #249: Okay. Thank.
Operator: Thank you. One moment for our next question. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Well, hey, congratulations on all the progress and shout out to Ryan, AC. It's great to reconnect.
Speaker Change #288: Thank you one moment before our next question.
Alex: Our next question comes from Jay Olson from Oppenheimer. Please go ahead.
Jay Olson: Hey, congrats on all the progress and shout out to Ryan Acs great to reconnect.
Operator: We were curious about any long-term plans for combination studies, and specifically the combination of your molecules with ADCs, and then I had a follow-up question. Yeah, there are, I mean, there are a lot of possibilities. It's almost infinite, for successful in Establishing RMC6236 as a Backbone Targeted Therapy. I would imagine a lot of things will be combined, but things that we... Prioritized, and said investigators prioritized, and things that, Who Knows Who Else, ultimately decides to study things that are done outside of the context of the company. We have no plans as far as today relating to ADCs, and I think we'll want to keep watching the ADC space and see which compounds emerge, potentially being complementary, and have tolerability profiles that.
Jay Olson: We were curious.
Jay Olson: Any long term plans for combination.
Jay Olson: And specifically the combination of your molecules with Adcs and then I had a follow up question.
Speaker Change #251: Yes, I mean, there are a lot of possibilities, it's almost infinite.
Speaker Change #254: And if we're successful at establishing RMC $63 six of the backbone targeted therapy.
Jay Olson: We would imagine a lot of things will be combined with things that we.
Jay Olson: Prioritize things that investigators prioritized and things that.
Jay Olson: Those who else ultimately decides to study instead of done outside of the context of the company.
Jay Olson: We have no plans to dispose today relating to adcs.
Speaker Change #306: And I think.
Jay Olson: While.
Jay Olson: Keep watching the ADC space, Mtc, which compounds emerge.
Speaker Change #266: Potentially a complementary tolerability profiles.
Speaker Change #281: Adjusted by wanting to buy <unk>.
Jay Olson:
Operator: So we're open to it. We're interested. Great, thank you. And then, as a follow-up, for your internal combinations, are you planning to formulate any fixed-dose combinations? You know that's possible at some point.
Jay Olson: So we are open to interested clients.
Speaker Change #214: Great. Thank you and then as a follow up for your internal combinations are you planning to formulate any fixed dose.
Speaker Change #214: Fixed dose combinations.
Speaker Change #293: That's possible at some point.
Operator: You know, there are a lot of combinations that we're talking about that we really have to establish the doses first before you create those combinations. We also have some compounds that are, some comments that are B.I.D. Those aren't exactly amenable to fixed-cost accommodations, so I don't know that that's going to be a major part of our commercial, you know, strategy, but our company certainly has it on its radar and will move when it makes a move.
Speaker Change #198: There are a lot of combinations that we're talking about really how to establish.
Speaker Change #198: The doses first before you create those combinations you have to allow for step downs for dose modifications, which creates a little bit of complexity and fixed dose realm. We also have some compounds that are.
Speaker Change #198: QD, sometimes et cetera.
Alex: So those arent exactly amenable to a fixed dose combination. So I don't know that thats going to be a major part of our commercial.
Alex: <unk>, but.
Alex: Our team certainly has it on their radar and will will move when it makes sense to do something like that but it really just going to add convenience and not just with us.
Speaker Change #261: Great. Thanks for taking the questions.
Speaker Change #306: Thank you one moment for our next question.
Operator: Like That, when it really is going to add convenience and not just add. Great, thanks for taking the questions. Thank you one moment for our next question. Our next question comes from Laura Prendergast, from Raymond James. Please go ahead. Hey, guys, congrats on the progress. I was curious, you know, some KOLs did note that, you know, the deepening of response over time seen with the PDAC patients was, you know, interesting to them.
Speaker Change #261: Our next question comes from lower printer grasp from Raymond James. Please go ahead.
Operator: And, you know, I actually refer to that as a phenomenon. Do you think this could be due to the unique mechanism of action of the drug? And do you think it's going to translate to other indications or other RAS inhibitors? Any color there would be helpful.
Speaker Change #264: Hey, guys congrats on the progress.
Speaker Change #275: I was curious you some kols and noted that the deepening of response.
Speaker Change #295: <unk> seen with the pediatric patients.
Speaker Change #288: Interesting development.
Speaker Change #266: I actually referred to that as a phenomenon.
Speaker Change #273: This can be due to the unique mechanism of action of the drug and do you think it's going to translate to other indications or other rasp inhibitors any color there would be helpful.
Operator: Thank you, Laura. That's an interesting question. Exactly. Thank you, Pickett.
Laura: Thank you Laura.
Speaker Change #257: An interesting question.
Speaker Change #257: Who wants to take that question.
Alex: Yes.
Alex: Yes.
Operator: The observation that the responses deepen over time is much more evident in pancreatic cancer than it appears to be in Non-Small Cell Lung Cancer, which are the two we have the most experience right now with arms. And so, having said that, it's clearly more obvious with RNC6236 than it is with chemotherapy. So I think it may be a combination of both the mechanism of action of the drug, which could include a multitude of different effects on both the tumor cells themselves and the immune microenvironment, and possibly also the particular biology and histology of pancreatic cancer, which traditionally is a very large mixture or a cleotropic mixture of different cell types.
Speaker Change #259: The observation that the.
Speaker Change #288: We're starting to see the time is much more evident.
Speaker Change #268: Take accounts.
Alex: The.
Speaker Change #308: Multiple cell lung cancer, which are the two diseases, which we have the most experience right now with obviously 63 six.
Alex: And so.
Alex: Having said that it's clearly more Lps with RMB 63, six than it is with chemotherapy. So I think it may be a combination of both the mechanism of action of the drug.
Speaker Change #272: She could include <unk>.
Speaker Change #249: <unk> achieved its different.
Speaker Change #272: So on the tumor.
Speaker Change #284: <unk> sells for themselves.
Speaker Change #220: In my career environment.
Speaker Change #281: And possibly also the particular biology, and histology of pancreatic cancer, which traditionally is a very large mixture.
Speaker Change #220: Mixture of different cell types.
Operator: Sometimes, the dominant one is the epithelial tumor cell itself, and sometimes it isn't. It's a minority component of a mishmash of immune cells and fibrotic cells and a whole lot of other things. So you can imagine that if your tumor is... has a very mixed histology, and there are a lot of things going on, it may take quite some time for that remodeling to occur such that when you look at it with a very crude imaging, a very good imaging modality like CT scanning, which, let's face it, Since it's been around for about 50 years, it could take some time for the observations that we apply to it to take effect.
Alex: Sometimes which the dominant one is the FTC to obtain the cell itself and sometimes it isn't.
Alex: It's a minority component of a mishmash of.
Speaker Change #220: EMEA themselves in fibrotic cells.
Alex: On a whole lot of other things so you can imagine that.
Schumer: Schumer as.
Schumer: It's a very mixed histology and there's a lot of things going on it might take quite some time for that remodeling to occur such that when you.
Alex: Look at it with a very crew imaging.
Alex: That's a very cute imaging modality, like Cte scanning, which let's face it.
Schumer: Been around for about 50 years.
Schumer: Then it could take some time for the observations that we that we applied to that too.
Operator: And superimposed on top of that, of course, is the... The Dichotomization of responses is lack of response. You know, a patient can go from 0% tumor reduction to 31% tumor reduction, and they're called a response. If they go from 29% tumor reduction to 29.5% tumor reduction, they're not a response. And so the deepening of responses over time has only been applied to the dichotomous conversion of patients from lack of response to response, and from a response to a response with a higher percentage of tumor reduction.
Speaker Change #220: The night superimposed on top of that of course is the.
Speaker Change #220: The.
Speaker Change #291: The dichotomy monetization of responses is lack of response a patient can go through them.
Speaker Change #204: Zero percent tumor reduction to 31% tumor reduction in the quarter resolved. So they go from 29% tumor reductions of 29, 5% G&A reduction then other response.
Speaker Change #220: And so the deepening of responses over time is really.
Speaker Change #220: <unk> has there any been applied to the dichotomous conversion of patient strong not lack of response to resolve and from a response to a response.
Operator: But in fact, this is happening on the linear continuum in all patients, irrespective of whether they qualify for RESS's response or not. So the answer is we don't know, but I suspect it's a 50-50 mixture of the biology of pancreatic cancer and the mechanism of action of the drug. And it isn't quite as obvious in lung cancer, which makes me say that.
Alex: A higher percentage of extreme reduction, but in fact this is happening in India continue in all patients irrespective of whether they qualify for aggressive response. The response. So long. So the answer is we don't know, but I suspect. This is a 50 50 mixture of the ball, but for all of <unk> of pancreatic cancer.
Speaker Change #265: Mechanism of action of the drug.
Alex: Isn't quite as obvious in lung cancer, which makes me.
Alex: Makes me say that.
Operator: That's really helpful. Thanks for all the color. Thank you. Please take a moment for our next question. Our next question comes from Joe Catanzaro on behalf of Piper Sandler. Please go ahead. Hey, thanks for taking my question. I had a quick one here on 6236 and combinability with pembrolizumab, and maybe even with other combination approaches you're looking at, and primarily as it relates to 6236-mediated rash. When you look at historical data sets for other map kinase pathway inhibitors that also see rash, is there anything there that informs how the addition of pembrolizumab and or chemotherapy could impact or not the rate and severity of rash when you start combining them?
Speaker Change #309: That's really helpful. Thanks for all the color.
Speaker Change #280: Thank you one moment for our next question.
Speaker Change #274: Our next question comes from Joe <unk> Zero from Piper Sandler. Please go ahead.
Operator: Thanks. I don't think that we think there is much of a connection there, you know, the effect on rash, the mechanism of rash, probably due to the direct effects on... Epidermal, that has to do with intimidate grasp. I think the immune-mediated type of rats are slightly different than the type of rats that we observe more commonly.
Speaker Change #202: Hey, Thanks for taking my question I had a quick one here on 63, six and combinability with timber lithium mab and maybe even with other combination approaches you're looking at.
Speaker Change #265: Primarily as it relates to 63 six mediated grass.
Speaker Change #260: When you look at historical datasets for other map kinase pathway inhibitors that also see rash is there anything there that informs how the addition of <unk> chemotherapy.
Speaker Change #202: Could impact or not the rate and severity of Ratch when you start combining thanks.
Speaker Change #299: Shaking heads here I don't think that we think there is much of a connection there.
Speaker Change #295: The effect on rash.
Speaker Change #310: <unk> mechanism of rash.
Speaker Change #202: Probably to the direct effects on.
Speaker Change #272: Epidermal cells.
Speaker Change #202: And.
Speaker Change #202: That's inhibiting Ras I don't know there hasnt into it.
Speaker Change #202: With chemotherapy.
Speaker Change #202: Yes.
Speaker Change #209: I think they mean mediated packet rash are slightly different.
Speaker Change #270: We observed more calming ours is more predominantly acne form.
Operator: Ours is more... Impact Informed, and uh....../p>p begin="00.466.393.666.833">fully responsive to mechanical engineering customers, providing/p>p begin="00.466.933.600".>/p>font style="nern4">equitable, responsible, and clean quality services that are provided within the company./font>/u The warehouse division is one of our main provisions??/font>/b>/i>b upon??/b>font style="nern4">that it's quite different from the massive pathways that are more common here. There are so it's always a mix, but I'm talking about what's actually more predominant.
Speaker Change #209: And again for the sponsors antibiotics.
Speaker Change #209: Treatment so.
Speaker Change #209: That's quite different than E massive capital more commonly occur.
Speaker Change #265: It's always been mix, but im talking about what's actually what we dominate.
I'm going to talk about feedback from the viewers. Netanyahu, H.R. Garner, or Rasmus, who don't tend to be down-and-informed.
Speaker Change #207: I think.
Speaker Change #207: I think it's from a BRAF inhibitor.
Speaker Change #296: Each operating here.
Speaker Change #207: <unk>.
Speaker Change #207: Okay.
When we combine the two, it may be truthful, but you're probably going to see each creating its own type of rash, expressed, or did not indicate. Burnett achieved mutual enchantment. Okay, thanks. That's very helpful. Thanks for taking the time to answer the question. Thank you. I am showing no further questions at this time. I will now turn it over to Marc Goldsmith, for Occasional America. Thank you, Operator, and thank you to everyone for participating today and for your continued support of Revolution. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
Speaker Change #207: When we combine the two in a truthful.
Speaker Change #207: You're probably going to each creating its own type of rash, but.
Speaker Change #207: At fixed rate did not indicate.
Speaker Change #207: Combining issue mutually enhance their respective Josh.
Speaker Change #288: Okay. Thanks, that's helpful. Thanks for taking the question.
Speaker Change #265: Thank you.
Speaker Change #207: I am showing no further questions at this time I will now turn it over to Mark goes smooth.
Mark: For closing remarks.
Mark: Thank you operator, and thank you to everyone for participating today and for your continued support resolution medicines.
Speaker Change #262: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.