ORIC: We See an Attractive Risk/Reward into MEVPRO-1; Positive Data Could Drive Meaningful Re-rating

Research evidence excerpt

ORIC: We See an Attractive Risk/Reward into MEVPRO-1; Positive Data Could Drive Meaningful Re-rating

Biotechnology Equity Research

Exhibit 9 - Phase 1 Cross-Trial Efficacy Comparison

Source: PFE and ORIC Presentations, Wells Fargo Securities, LLC

Cross-Trial Safety Comparison: Mevrometostat vs. Rinzimetostat

If efficacy between mevrometostat and rinizmetostat ends up looking similar at comparable

timepoints, the real separation likely comes down to safety—and that’s where we expect

rinizimetostat to differentiate. At a high level, rinzimetostat looks cleaner than mevrometostat across

most of the key tolerability metrics, likely driven by its longer half-life and therefore, less Cmax driven

toxicity.

That said, it’s important to flag key caveats:

• The AE reporting thresholds differ across programs, so the per-event rows are not perfectly

comparable. Mevrometostat only reports TEAEs occurring in ≥20% of patients, so lower-frequency

events like the blood creatinine increase seen with rinzimetostat simply may not be captured.

• Rinizimetostat's dataset is still early (4.9 months follow-up vs. ~9-12 months for mevrometostat)

and toxicity may build over time. However, in the TALAPRO-2 study (talazoparib + enzalutamide in

1L mCRPC) clinically meaningful AEs— particularly hematologic events manifested within the first

1–3 months, so we think rinzimetostat's follow-up window is long enough to capture severe safety

signals.

• While rinzimetostat’s dataset is smaller than mevrometostat's randomized cohort (n=18 vs. n=41,

respectively), it’s in the same ballpark as the Cohort 2C group (n=14), which is also the population

and dose PFE is taking forward into Phase 3.

• The ARPI partner is not held constant—rinzimetostat is paired with darolutamide, while