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Dr. Sean Bohen, President and CEO of Olema Oncology, is looking for a better endocrine option, alone or in the context of a CDK 4/6 inhibitor, to treat ER-positive, HER2-negative breast cancer. Their oral pill OP-1250 does not have chemotherapy-like side effects and could be better tolerated than chemotherapy to aggressively target and turn off the estrogen receptor.

Sean explains, "In that respect, I'd say the estrogen receptor is probably one of the most validated therapeutic, molecular therapeutic targets in cancer, with tamoxifen first being approved in 1977. That said, that progress here has been relatively slow. Tamoxifen, approved in 1977, is not a complete antagonist. It turns on the receptor in some contexts, and turns it off in others. Fulvestrant is a complete antagonist. It has to be injected. That was approved in the early 2000s, and here in 2022, we're still working on getting a better estrogen-receptor targeting therapy."

"What happens, as is often the case in cancers, is that the ER-positive, HER2-negative breast cancer cell co-ops that normal growth and proliferation signal to promote an abnormal growth and proliferation of the cancerous cells. So that's why we are able to go back and try to turn that signal off and help treat the cancer, prevent progression and, sometimes, cause regression of the tumors by turning off that inappropriately-used estrogen receptor signal."

"We are currently treating three cohorts, 50 patients with measurable tumors, 15 patients without measurable tumors. In the context of ER-positive, HER2-negative breast cancer, that is usually bone-only involvement. Then we also have an interesting property with OP-1250. It crosses the blood-brain barrier, so which raises the possibility of being able to treat brain metastases. We have a cohort of 15 central nervous system metastasis patients that we are working on enrolling right now."

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