Erasca, Inc. Q4 FY2023 earnings call

• Ended Q4 2023 with $322 million cash, plus $45 million oversubscribed equity financing revising cash runway to second half of 2026.
• Lead clinical program Naporafenib to initiate global Phase 3 trial; preclinical ERAS-4 Pan-KRAS program focused on KRAS mutant solid tumors.
• Matured OS data from Phase 1/2 trials of Naporafenib plus Trametinib in NRAS mutant melanoma, showing PFS and OS potential vs benchmarks.
• Naporafenib's selectivity for BRAF and CRAF, safety profile with rash prophylaxis, and dose optimization plans for SEACRAFT-1 and 2.
• Pan-KRAS inhibitor program with internal/external compounds showing promising in vitro potency and in vivo PK; upcoming milestones like SEACRAFT-1 data readout Q2-Q4 2024 and SEACRAFT-2 Phase 3 initiation in H1 2024.

No traditional product segment performance with revenue contribution % discussed; focus is on pipeline programs including Naporafenib and Pan-KRAS inhibitor initiatives.

• Cash runway revised from first half of 2026 to second half of 2026 due to equity financing.
• Plan to initiate global Phase 3 trial for Naporafenib in first half of 2024.
• SEACRAFT-1 expected data readout Q2-Q4 2024.

• Limitations in cross-trial comparison affecting interpretation of OS and PFS data.
• Rapidly evolving landscape in Pan-KRAS inhibitor space posing competitive and development risks.
• Uncertainty in regulatory approval and reimbursement based on trial results.

Q: In SEACRAFT-2 on the dual primary endpoint of PFS and OS. Is there a hierarchy here? Or and do you have regulatory sign-off on this?

A: Yes, thanks for the question in terms of dual primary, there's not really a hierarchy, but in terms of winning on on either or both from a statistical and clinical benefit. And we do have regulatory alignment from the global health authorities both in the US and Europe.

Q: How should we be thinking about the ORR rate between the 201 versus the 400.5 regimens? Is there any evidence suggests potentially broader responses at the higher tremendous. Thanks [indiscernible] A: Yes, good question. Maybe I'll take a first cut and then Shannon, feel free to chime in in terms of the ORR. first of all, it's small patient numbers. And it's important to know that this is a very aggressive disease in the second-line plus setting post-IO and so there is some variability there. But really, the most important metric is progression-free survival. And so if you look at actually the DCR, which includes both ORR as well as stable disease, both of which get captured in PFS. You can see that they're relatively similar DCR rates. And so we do think that with PFS, that's going to be the main driver. But Shannon, do you want to comment further on that?

Q: On the dual primary endpoint of PFS and OS in SEACRAFT-2, is there a hierarchy? And do you have regulatory sign-off?

A: Yes, thanks for the question in terms of dual primary, there's not really a hierarchy, but in terms of winning on on either or both from a statistical and clinical benefit. And we do have regulatory alignment from the global health authorities both in the US and Europe.

Q: How does the OS data compare to your internal expectations when you design a SEACRAFT-2? And a second question, you've compared the Kaplan-Meier curve with Napo with some of the control regimens. Understood. They're all cross-trial comparisons, but it looks like it enables a couple of has a longer tail. And I was wondering, technically, is it possible to sort of like derive a hazard ratio out of these cross-trial comparisons, at least directionally?

A: Yes, I think so we don't comment specifically on hazard ratios, but what I will say is that the biometrics and and broader Naporafenib and his team at Erasca basically assumed worst case. We really all of our power assumptions and calculations were predicated on the control arm performing on par with what was historically seen with NEMO. And you can see for various reasons that Shannon mentioned during our formal remarks that could be an overestimate of what the quote-unquote natural history of disease could be. So if the control arm performs more in line with benchmarks two and three, which is probably a more relevant benchmark, given that those are post-IO settings versus the NEMO trial, which was pre IO or 80% of the patients received and either Chemo or MEK inhibition from before receiving IO. But that said, all of our power calculations are predicated on the control arm performing in line with NEMO. So that's why we're even more excited about the possibility to show both statistical and clinical benefit. If if the control arm performs more in line with benchmarks two and three, which is that roughly seven months OS range versus the 10 to 11. Does that answer your question?