Olema Pharmaceuticals (NASDAQ:OLMA) is focused on developing endocrine therapies aimed at improving outcomes for patients with estrogen receptor (ER)-positive, HER2-negative breast cancer, CEO Sean Bohen said during a company discussion hosted by Brad Canino. Bohen described the disease area as a large unmet need, noting that breast cancer is the most common cancer diagnosis in women worldwide and the second most common cause of cancer death, with ER-positive, HER2-negative disease representing roughly 70% of cases.
Pipeline overview and upcoming milestones
Bohen said Olema’s lead program is palazestrant, which he described as a “complete estrogen receptor antagonist.” He said endocrine therapy remains the backbone of treatment in ER-positive, HER2-negative breast cancer and is used through multiple lines of therapy with the goal of delaying chemotherapy as long as possible.
- OPERA-01, a monotherapy trial in the second/third-line setting, which Bohen said is expected to read out in the fall.
- OPERA-02, a first-line trial combining palazestrant with ribociclib, which he said is currently enrolling.
Bohen also highlighted a second program, OP-3136, a KAT6 inhibitor he characterized as “KAT6/7,” with KAT5 and KAT8 activity “dialed out” relative to Pfizer’s lead compound. He said initial data from this molecule is expected late in the second quarter and will be primarily monotherapy data across breast cancer, castration-resistant prostate cancer, and non-small cell lung cancer. He added that combination work has begun with fulvestrant and palazestrant, though he said the company does not yet have a maximum tolerated dose and does not expect to share combination data in Q2.
Executive change and preparations for commercialization
Bohen addressed a recent management change, saying the company’s CFO/COO, Shane Kovacs, departed “by mutual agreement” after nearly six years with Olema. He framed the change in the context of Olema approaching a Phase 3 readout and preparing for a potential next stage as a commercial organization.
According to Bohen, Olema has made its first commercial hires and is preparing to build a commercial organization and sales force, with a stated vision of becoming a fully integrated oncology company. He said the company intends to launch and promote palazestrant in the U.S. if approved, while seeking a collaborator for markets outside the U.S. Bohen said a launch could occur as early as next year.
Why management believes palazestrant can stand out among oral SERDs
Asked what supports palazestrant’s potential as a best-in-class oral SERD, Bohen emphasized past clinical results and differentiated pharmacologic attributes. He described palazestrant as having higher exposure than other agents, an eight-day half-life, and an oral once-daily profile that allows sustained exposure, supported by a tolerability profile he said enables combination use.
Bohen said the drug has been combined with ribociclib, palbociclib, everolimus, and abemaciclib, and is now being combined with Pfizer’s CDK4-selective atirmociclib as well as Olema’s own KAT6 inhibitor. He added that Olema has been able to administer “full doses” of combination agents.
On efficacy, Bohen cited Phase 2 monotherapy results in ESR1-mutant and ESR1 wild-type disease, stating palazestrant showed median progression-free survival (PFS) of seven months in ESR1-mutant patients and 5.5 months in wild-type patients. He also referenced a ribociclib-plus-palazestrant dataset in a setting he described as first-line “post-CDK4/6 with AI,” stating the combination showed one year of PFS, which he called an “outstanding result” supporting OPERA-02.
How lidERA and fulvestrant-era studies shape thinking about the class
The discussion also touched on Roche’s giredestrant results in the adjuvant lidERA study, which Bohen said “beat both tamoxifen and an AI.” He said key opinion leaders are still digesting where an oral SERD fits into the evolving treatment paradigm, particularly as many patients now receive CDK4/6 inhibitors in earlier-stage disease.
When asked how he would design an adjuvant study today, Bohen said he would not prioritize monotherapy in a moderate-to-severe risk adjuvant population. Instead, he suggested combining an endocrine agent such as palazestrant with a CDK4/6 inhibitor and comparing against an aromatase inhibitor (AI). He discussed tradeoffs between CDK4/6 options, noting that adjuvant treatment is sensitive to quality of life and referencing diarrhea as a side effect associated with abemaciclib, while describing ribociclib at 400 mg as “pretty well tolerated.” He added that conducting an adjuvant trial is feasible but expensive, requiring thousands of patients, and suggested it would likely require substantial capital or a partner.
Bohen also argued that older fulvestrant data, including PARSIFAL, should not be viewed as a strong surrogate for modern oral agents. He called fulvestrant a “terrible drug” from an exposure and administration standpoint, while asserting that giredestrant at 30 mg achieves far higher exposure than fulvestrant and that lidERA showed a clearly different magnitude of benefit than earlier fulvestrant comparisons. He also suggested that control-arm outcomes with AI plus CDK4/6 inhibitors may have improved over time, which he said will be important to watch in trials such as Roche’s persevERA.
OPERA-02 trial design and timing
Detailing OPERA-02, Bohen said the study targets endocrine-sensitive, first-line metastatic disease. He said most enrolled patients will have completed adjuvant endocrine therapy and remained disease-free for at least a year before developing metastatic disease, with the remainder expected to be de novo metastatic patients.
The trial randomizes patients to ribociclib plus letrozole (the standard-of-care arm) versus ribociclib plus palazestrant (the experimental arm). Bohen described it as blinded and placebo-controlled with PFS as the primary endpoint, enrolling about 1,000 patients. He said the earliest potential readout would be 2028, though it could take longer depending on event accumulation. He also disputed the idea that adding a CDK4/6 inhibitor would “wash away” an oral SERD’s superiority over AI, arguing that CDK4/6 inhibitors rely on synergy with endocrine therapy and that differences between settings may be driven more by patient population than combination biology.
Looking beyond first-line development, Bohen said Olema is evaluating whether to study ribociclib plus palazestrant in the second/third-line setting, citing physician interest in combinations and describing a potentially large market opportunity tied to duration of therapy. He also discussed competitive dynamics in KAT6 inhibition, arguing Olema’s molecule could differentiate via selectivity and tolerability, while acknowledging Pfizer’s role in validating the target and calling Pfizer’s reported combination activity “quite compelling.”
About Olema Pharmaceuticals (NASDAQ:OLMA)
Olema Pharmaceuticals, Inc, a clinical-stage biopharmaceutical company, focuses on the discovery, development, and commercialization of therapies for women’s cancers. Its lead product candidate is OP-1250, an estrogen receptor (ER) antagonist and a selective ER degrader, which is in Phase 3 clinical trial for the treatment of recurrent, locally advanced, or metastatic estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer; and OP-1250 combine with CDK4/6 inhibitors palbociclib, ribociclib, and alpelisib in Phase 1/2 clinical trial for the treatment of recurrent, locally advanced, or metastatic estrogen receptor-positive human epidermal growth factor receptor 2-negative breast cancer, as well as develops OPERA-01 for the of ER+/HER2- advanced or metastatic breast cancer.
