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Olema Oncology Laying Groundwork for 2027 Launch of Palazestrant

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NEW YORK – Olema Oncology shared recent data from ongoing trials of several investigational breast cancer therapies and provided a commercialization timeline for the estrogen receptor antagonist palazestrant at the 43rd annual JP Morgan Healthcare Conference on Tuesday.

Palazestrant combines the activity of a selective estrogen receptor degrader (SERD) and an estrogen receptor antagonist, which Olema believes will give it an advantage in the marketplace against competing SERDs, such as Menarini's Orserdu (elacestrant), AstraZeneca's camizestrant, and Roche's giredestrant.

The San Francisco-based company is evaluating palazestrant in five clinical trials as a monotherapy and in combination with CDK4/6 inhibitors, and it is planning an additional Phase III trial of the compound in combination with Novartis' CDK4/6 inhibitor Kisqali (ribociclib), slated to start in mid-2025.

At the 2024 San Antonio Breast Cancer Symposium in December, Olema reported early data from an ongoing Phase Ib/II trial of palazestrant with Kisqali in patients with advanced or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. In the trial, which was conducted by Olema in partnership with Novartis, patients on the combo therapy had a six-month progression-free survival rate of 73 percent among all patients and 68 percent among those who had received a prior CDK4/6 therapy with endocrine therapy. In patients with an ESR1-mutation, the six-month progression-free survival rate was 81 percent, and in those with ESR1 wild-type cancer, the six-month progression-free survival rate was 70 percent. Median progression-free survival results were not yet mature at data cutoff in November 2024.

The company also shared data from a Phase II trial of palazestrant in patients with ER-positive, HER2-negative advanced or metastatic breast cancer who have relapsed or progressed on one or two prior lines of therapy. In that trial, ESR1-mutant patients on palazestrant had a 7.3-month median progression-free survival and wild-type patients lived 5.5 months without disease progression or death.

Encouraged by data from those two trials, Olema has decided to move forward with the Phase III trial, which the company said is fully funded after raising $130 million in a private placement of stock in September 2023. Olema CEO Sean Bohen noted in his presentation at the meeting that progression-free survival for patients on palazestrant compares favorably with other drugs in its class including Orserdu, camizestrant, and giredestrant, which in their respective trials have shown 2.8-month, 3.7-month, and 5.5-month median progression-free survival.

In addition, Olema is conducting a Phase III trial, dubbed OPERA-01, of palazestrant as a monotherapy and anticipates results in 2026.

"We know that the existing endocrine therapies are inadequate," Bohen said. "They do not fully turn off the estrogen receptor signal. A complete estrogen receptor antagonist with favorable peak oral daily dosing, eight-day half-life exposure, and ability to combine at full doses without enhancement of toxicity is needed."

Olema is hoping to launch palazestrant in the US in the second- and third-line setting in 2027 following a readout from the OPERA-01 trial. The firm estimates 40,000 patients will be eligible for palazestrant each year in the US and between $3 billion to $5 billion in annual sales.

The company is also advancing the KAT6 inhibitor OP-3136, which it is evaluating in a Phase I trial in ER-positive, HER2-negative metastatic breast cancer alone and in combination with fulvestrant, palazestrant, or palazestrant plus Kisqali. In the initial, dose-escalation part of the trial, investigators are also enrolling patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer based on preclinical activity seen in those cancer types. In preclinical animal studies, OP-3136 had synergistic anti-tumor activity with palazestrant and was well tolerated, causing no significant changes in body weight and no mortality.

"The ability to combine with palazestrant and have both of these molecules in our portfolio allows for a unique opportunity to present a new treatment option," Bohen said.