Olema Pharmaceuticals (OLMA) presented its oncology pipeline at the H.C. Wainwright 28th Annual Global Investment Conference on September 16, 2026, detailing Phase III milestones for lead candidate palazestrant and updated clinical data for second asset OP-3136.
The stock traded at $9.73, having fallen 61% year to date, while the prior day's close registered at $10.22 with pre-market trading at $9.14.
Palazestrant, a complete estrogen-receptor antagonist, targets ER-positive, HER2-negative breast cancer — a subtype representing roughly 70% of all breast-cancer cases. The Phase III OPERA-01 study, in the second- and third-line setting for patients who progressed after first-line CDK4/6 inhibitor and aromatase-inhibitor therapy, is fully enrolled with a data readout expected in Q1 2027. The trial population is split approximately 40%-50% ESR1-mutant and 50%-60% wild-type.
Phase II progression-free survival data showed a median PFS of 5.5 months in ESR1 wild-type patients and 7.3 months in those with the ESR1 mutation.
"In ESR1 wild-type setting, we saw 5.5 months median PFS in phase II, and that's more than anyone's seen, even with a mutant, in that second line setting," CEO Sean Bohen said.
The OPERA-02 study, evaluating palazestrant plus ribociclib (KISQALI) in the first-line metastatic setting, is currently enrolling. In Phase II, the combination produced a median PFS of 15.5 months overall and 12.2 months in patients who had already progressed on prior CDK4/6 therapy — roughly 30% of whom had received two previous CDK4/6 inhibitors.
A separate Phase II trial combining palazestrant with atirmociclib, a CDK4-selective inhibitor developed with Pfizer, is also fully enrolled.
Bohen described palazestrant as having "very high exposure, favorable tolerability, and a unique ability to combine with other targeted agents at full dose without pharmacological PK effects and without enhancement of toxicity."
Against established comparators, elacestrant (ORSERDU) showed benefit only in ESR1-mutant patients and not in wild-type disease, while AstraZeneca's SERENA-4 and Roche's persevERA were statistically negative in the first-line setting, though persevERA showed some signal of activity. A two-month prolongation of PFS is generally regarded as clinically meaningful, with control arms expected in the two-to-three-month range.
Olema's second clinical asset, OP-3136, a KAT6 inhibitor, has shown single-agent activity in castration-resistant prostate cancer, according to Bohen. Phase I monotherapy data presented at ASCO 2024 demonstrated a tolerability profile with less myelosuppression and cytopenias compared to Pfizer's competing KAT6 inhibitor. Two combination studies are ongoing — with fulvestrant (data possible by end of 2024) and with palbociclib (data expected H1 2025). A combination trial with Bayer's darolutamide (NUBEQA) is expected to start in Q4 2024.
On the commercial front, Bohen estimated the second- and third-line ER-positive, HER2-negative breast-cancer market at roughly $5 billion annually, divided between approximately $2 billion in the ESR1-mutant subset and $3 billion in wild-type. The first-line metastatic opportunity was valued at more than $10 billion annually, with OP-3136 in breast cancer alone estimated at about $5 billion.
