Olema president and CEO Sean Bohen spoke with BioSpace about why he believes his company’s approach with a SERD and ER antagonist can successfully treat an advanced form of breast cancer.
Olema President and CEO, Sean Bohen/courtesy of Olema Oncology
Sean Bohen, M.D., Ph.D., president and chief executive officer of Olema Oncology, is excited about the progress his company is making on the development of OP-1250, a potential treatment for metastatic breast cancer.
In a conversation with BioSpace, Bohen pointed out that OP-1250 is both a selective ER degrader (SERD), as well as a complete estrogen receptor (ER) antagonist (next generation CERAN). It’s that combined approach to targeting a tumor that Bohen believes will be critical to the clinical development of OP-1250, which is designed to treat estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. While there are multiple drugs on the market for breast cancer, Bohen said there is still a “large unmet need” in the space.
“Our competition isn’t another company. Our competition is the disease, and the disease is much craftier than we are,” Bohen said. “There’s an unmet need and a big market out there. Breast cancer is the most common cancer in women.”
As an example, he pointed out that pharma giant Sanofi saw a failure with its cornerstone oncology SERD asset amcenestrant, which flunked a Phase III study in patients with this same type of breast cancer. Sanofi wasn’t alone in seeing a SERD failure. In April, Roche also announced that the Phase II acelERA trial assessing its oral SERD, giredestrant, failed to meet the primary endpoint of progression-free survival in people with a certain form of advanced breast cancer.
Bohen said the space to treat this form of breast cancer is wide open and he’s confident that OP-1250, which is both a SERD and an ER antagonist, has the opportunity to establish a strong clinical reputation. Early data suggests the company is on track. Despite an odd 2021 incidence of what the company called “falsified information” that caused some investors to dump company stock, Bohen has expressed confidence in the development of the asset and its promise as a potential breast cancer treatment.
Last year, ahead of Olema’s presentation of data, an individual who claimed to have been a participant in the Phase Ia portion of a clinical study posted data online that the company was forced to refute. That particular individual claimed to have not received a high dose of the medication and said they, therefore, did not see any benefits. The post purportedly contained images from a poster presentation online. When Olema posted its own data that was not as robust as some of what the individual claiming to be a patient shared, the company’s stock cratered.
Olema’s data showed strong proof-of-concept for OP-1250, as well as highly attractive pharmacokinetics and favorable safety data. Among those patients who were treated in the early study, Olema said there were three partial responses, two of which have been confirmed, as well as “robust target lesion reduction up to 100%.” All three responses occurred in patients with ESR1 mutations who had previously received CDK4-6 and aromatase inhibitors, and fulvestrant, a selective estrogen receptor degrader. Bohen said the data demonstrates that OP-1250 is an active drug and achieved sufficient exposure levels to block the ER-mediated cancer cell growth and proliferation signal.
Bohen told BioSpace that he considered the investor reaction that caused company stock to drop by nearly 50% to be an “overreaction” to the falsified data. He speculated that the response was part of the current market environment in biotech that creates significant swings in prices.
He explained that in the Phase Ia single-agent study, there were 41 patients, with most having been heavily pretreated. He said the company did not reach a maximum tolerable dose. Also, Olema saw clear evidence of tumor shrinkage at the starting dose of 30mg. However, there were four cases of Grade IV neutropenia (low white blood cell counts). All four patients discontinued the study and all four recovered. Bohen said the trial investigators dove into the data and have been unable to determine what caused the neutropenia. “The cases were unusual,” he said.
Earlier this year, Olema presented updated data from the ongoing Phase I/II clinical study that provided strong proof of concept supporting OP-1250’s potential as a once-daily oral monotherapy in women with recurrent, locally advanced or metastatic ER+ / HER2- breast cancer. OP-1250 demonstrated highly attractive pharmacokinetics, favorable tolerability and clear efficacy signals in a heavily pretreated patient population, the company reported.
That data was further supported in a Phase Ib study where OP-1250 was assessed as a monotherapy and also partnered with Pfizer’s Ibrance (palbociclib), a CDK4-6 inhibitor. As a monotherapy, OP-1250 showed favorable tolerability with encouraging anti-tumor activity. There was no grade III or IV neutropenia.
Bohen said the company aims to select the recommended dose for a Phase II study and soon begin to enroll the trial for these advanced breast cancer patients.
“I really think we’re going to advance the treatment for this form of cancer,” Bohen said. “We are progressing the molecule and we are progressing quickly. We know how to get OP-1250 to patients and improve upon existing care.”
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