Data Needed for Phase III Trials
Q: How much more data do you need to initiate Phase III?
A: We need a mature progression-free survival (PFS) assessment from more mature observations to finalize trial design and statistical power, along with FDA input. These are key elements for making a final go decision on pivotal trials for RMC-6236. "

PFS Improvement in Pancreatic Cancer
Q: What PFS bar do you need in PDAC to proceed?
A: While we've not specified a particular number, we aim to be superior to second-line chemotherapy, where median PFS is around 3 to 3.5 months. Our goal is to exceed well-accepted benchmarks for second-line pancreatic cancer. "

Capital Allocation Strategy
Q: How will you effectively spend your $1.85 billion cash?
A: Our top priority is advancing RMC-6236 into pivotal trials for second-line pancreatic and lung cancer, which will receive the lion's share of our capital. We also prioritize expanding the reach of 6236 and advancing our mutant-selective inhibitors 6291 and 9805 into late-stage development. "

Partnership Opportunities
Q: How are you thinking about partnering, in the U.S. and abroad?
A: In the U.S., we plan to build our own franchise and are not keen on partnering. Outside the U.S., we are open to partnerships to handle the complexities of global development and commercialization when the right opportunity arises. "

Confirmed Response Rates Update
Q: How are confirmed response rates for 6236 trending post ESMO?
A: We've seen favorable trends; most responses have been confirmed, except where patients progressed or discontinued treatment. We cannot provide specific confirmed rates today but will share more precise information later in the year. "

Upcoming Data Disclosures
Q: What is the sequence and timing of data disclosures?
A: While we have ideas on how data might roll out, it's too early to set a schedule. The most important event in the second half is the go decision and details about pivotal trial plans. Other information will be disclosed as appropriate. "

KRAS Combo Data Expectations
Q: What would be good data from the 6236/6291 combo?
A: First, we need to ensure the combination is safe and tolerated. We'll then look for clinical activity signals such as increased frequency, depth, or durability of response. Preclinical data suggests benefits, but we need to validate in humans. "

Regulatory Considerations for Trial Design
Q: Do you need activity data in G12X/Q61 mutations for FDA buy-in?
A: We're working with the FDA on final trial design. If we have activity data in these mutations, we'll include it in our discussions. Preclinical data shows all mutant forms of RAS tested show sensitivity to 6236, and we're gathering more information on other genotypes. "

Tumor-Agnostic Development Path
Q: What's the regulatory path for 6236 in a tumor-agnostic setting?
A: We're anchoring on demonstrated activity in non-small cell lung and pancreatic cancers. We're enrolling patients with colorectal cancer, melanoma, and other solid tumors. Our aspiration is to help as many as 30% of patients with solid tumors carrying RAS mutations. This will drive our decisions on pursuing tissue-agnostic approvals. "

Investigator Trial Enrollment Decisions
Q: How do investigators decide between NRAS and RAS-selective trials?
A: The need for these compounds is high, and there are more patients than our trials can support. Investigators enroll patients based on specific eligibility criteria, and patient availability is not limiting. Demand reflects the significant need in oncology. "