Olema Pharmaceuticals (NASDAQ:OLMA) Chief Executive Officer Dr. Sean Bohen outlined the company’s plans for its KAT6 inhibitor and breast cancer programs during a session at TD Cowen’s Seventh Annual Oncology Innovation Summit, highlighting upcoming Phase 1 data for OP-3136 and later-stage readouts for palazestrant.
Speaking with TD Cowen Senior Biotech Analyst Tyler Van Buren, Bohen said Olema’s OP-3136 program is advancing in Phase 1, with an upcoming poster focused on the monotherapy dose-escalation portion of the trial. He said the presentation will include tolerability, pharmacokinetic and pharmacodynamic data, including histone acetylation, as well as early efficacy results.
OP-3136 Data to Show Early Activity and Tolerability
“What you’re going to see in the poster is clear evidence of anti-tumor activity,” Bohen said, adding that the majority of patients with measurable disease had some amount of tumor shrinkage.
OP-3136 is being evaluated across a wide dose range, from 2 milligrams to 45 milligrams, Bohen said. He noted that target engagement was seen at the 2-milligram dose and maintained across dose levels. As of the discussion, no dose-limiting toxicities had been observed, no maximum tolerated dose had been determined, and dose escalation was continuing.
Bohen said Olema believes OP-3136 may have a tolerability advantage because of its selectivity profile. He compared the program with Pfizer’s KAT6 program, which he said has shown activity but also toxicity, particularly cytopenias and neutropenia. Bohen said Olema’s molecule is designed to reduce inhibition of KAT5 and KAT8 while maintaining potent KAT6 and KAT7 inhibition at achieved exposures.
Combination Strategies in Breast and Prostate Cancer
Bohen said Olema does not expect KAT6 inhibitors to be used primarily as monotherapy over time, despite early evidence of tumor shrinkage. He said the broader strategy is to use OP-3136 in combinations with targeted agents.
In breast cancer, Bohen said combinations with endocrine-based therapies are ongoing, including fulvestrant and a “pala” combination that he described as a key area of focus. He said no combination data will be included in the upcoming OP-3136 poster because the studies are still early. The earliest possible update could come at the end of the year, though Bohen said he would not commit to that timing and said the first half of next year was more certain.
Bohen said Olema is also planning to start a combination study with NUBEQA in prostate cancer. He described prostate cancer as mechanistically similar to breast cancer in that it is driven by an endocrine pathway, with androgen signaling playing a role analogous to estrogen signaling in breast cancer.
Lung cancer remains an eligible tumor type in the OP-3136 trial, but Bohen said only one lung cancer patient had been enrolled so far. He said the company included lung cancer because preclinical xenograft data suggested potential activity, though he said it is less clear what combination approach would be most appropriate.
Palazestrant Readouts Remain Key Catalysts
Bohen also discussed Olema’s palazestrant program, including the OPERA-01 and OPERA-02 studies. He said OPERA-01 remains on track for a fall readout. The trial is designed to evaluate palazestrant in ESR1-mutant and ESR1-wild type populations, with intent-to-treat results included as an exploratory analysis.
In ESR1-mutant disease, Bohen said current standards of care generally improve median progression-free survival from about two months in the control arm to about four months in the treatment arm. He said that type of result can support approval but may not be meaningfully differentiated. He said a larger improvement, such as from roughly two months to six months, would be more meaningful.
For ESR1-wild type patients, Bohen said there is a significant opportunity because there are no approved oral monotherapy options in that setting after progression on CDK4/6 inhibitors plus aromatase inhibitors. He said a two-month progression-free survival delta could be meaningful if it provides an oral monotherapy option for the 50% to 60% of patients who are ESR1 wild type.
Bohen estimated the overall annual market opportunity for palazestrant monotherapy at about $5 billion, including roughly $2 billion in ESR1-mutant disease and about $3 billion in the wild type setting, if Olema can access it.
OPERA-02 Timeline May Depend on External Data
Bohen said OPERA-02, which is evaluating palazestrant with ribociclib, is actively enrolling and remains on target. However, he said he is becoming more hesitant about prior guidance that data could arrive as early as 2028, particularly if control-arm performance in comparable studies exceeds expectations.
Olema is watching external readouts including persevERA and SERENA-4, Bohen said. He said those data could help Olema assess whether to change OPERA-02’s assumptions or patient numbers before the trial is fully locked in. He said Olema has confidence in the palazestrant-ribociclib combination based on Phase 2 data showing more than 12 months of progression-free survival after CDK4/6 inhibitor progression.
Asked what investors may be underappreciating, Bohen pointed to OP-3136 while also citing Olema’s late-stage palazestrant assets. He said the company has a Phase 3 asset with a potential fall readout and additional longer-term opportunity through OPERA-02, while acknowledging his own bias as Olema’s chief executive.
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.
