Female breast cancer recently surpassed lung cancer as the most commonly diagnosed cancer worldwide1, representing approximately 30% of all new diagnoses of cancer in women.2 In the last year alone, the American Cancer Society estimated that there were approximately 287,850 new cases of invasive female breast cancer in the United States.3 For many of these women, treatment is intended to prolong and preserve quality of life; sadly however, many will ultimately succumb to their cancer.
There has been meaningful progress in treating breast cancer over the past two decades. However treatment options for women with metastatic or advanced breast cancer, which affects nearly a third of patients who were initially diagnosed with early-stage disease,4 are especially limited, with the 5-year survival rate hovering around 28%.5 For the approximately 80% of breast cancer categorized as estrogen receptor-positive (ER+),6 the treatment of choice is endocrine therapy that directly or indirectly targets estrogen receptor (ER) activation.
While existing endocrine therapies are clinically effective, most patients with metastatic breast cancer will progress on available therapies, and new treatment options are desperately needed. Despite this need, no new endocrine therapies have been approved in nearly 20 years since fulvestrant, which is a highly insoluble compound that must be administered monthly in large volumes via intramuscular injections. Additionally, fulvestrant has been shown to demonstrate limited drug exposure, which may negatively impact its anti-tumor effectiveness.
Fortunately, there are new innovative agents under investigation that have the potential to address limitations in current therapies, improve the patient experience, and advance the standard of care.
Taking a complete approach
Currently available FDA-approved endocrine treatments seek to stop estrogen from fueling cancer growth by either preventing the body from producing estrogen or by attempting to block the estrogen receptor. Some therapies are only able to partially block the receptor, leaving the ER vulnerable to transcriptional activation which could lead to cancer cell growth and proliferation.
Our team at Olema has spent the past decade characterizing the structure and function of the estrogen receptor to develop more potent therapies that completely inactivate this signaling pathway. Our lead product candidate, OP-1250, is a novel oral compound that is a potent and complete estrogen receptor antagonist, or a CERAN, that completely blocks the estrogen receptor and the signaling pathway, which we believe could lead to more durable and deeper anti-tumor activity.
The pursuit of more effective and convenient treatment options
Through our investigative work, we are focused on addressing the challenges of existing agents for ER+ breast cancer and generating data to guide the development of next generation therapies. We recently presented first-in-human data for OP-1250 from our ongoing Phase 1/2 clinical trial in patients with advanced breast cancer. The promising early data demonstrated that OP-1250 is an active drug that can achieve sufficient exposure levels to completely antagonize the ER and block the ER-mediated cancer cell growth and proliferation signal.
The initial data provide strong proof-of-concept supporting OP-1250’s potential as a once-daily oral monotherapy in women with recurrent, locally advanced, or metastatic ER+/human epidermal growth factor receptor 2‑negative (HER2-) breast cancer, with attractive pharmacokinetics and oral bioavailability, favorable tolerability, and clear efficacy signals in a heavily pretreated patient population.
Based on these encouraging early data, we are moving ahead with plans to initiate Phase 2 evaluation for OP-1250 as a monotherapy and have initiated a combination trial to evaluate OP-1250 with palbociclib, a CDK4/6 inhibitor. We also plan to initiate additional combination studies with CDK4/6 and PI3Ka inhibitors, and evaluate the possibility of treating CNS metastases associated with breast cancer given OP-1250’s capability of crossing the blood-brain barrier, as we look to generate additional evidence in support of OP-1250’s differentiated profile.
Commitment to data-driven innovation
Olema is dedicated to developing new therapies with the goal of transforming the standard of care for women living with cancer. We have looked at the treatment landscape and know that we are not satisfied with the status quo. We believe OP-1250’s oral formulation and CERAN mechanism of action directly address the limitations of current endocrine therapies and position it as a potential endocrine therapy of choice for the treatment of ER+ breast cancers.
This possibility inspires us to continue to push the boundaries of science to improve both the treatment experience and health outcomes for millions of women around the world.
To learn more about Olema’s science and our recent advancements, visit www.olema.com.
1. American Cancer Society. Female Breast Cancer Surpasses Lung as the Most Commonly Diagnosed Cancer Worldwide. Available at: http://pressroom.cancer.org/GlobalCancerStats2020
2. BreastCancer.org. U.S. Breast Cancer Statistics. Available at: https://www.breastcancer.org/symptoms/understand_bc/statistics
3. American Cancer Society. Key Statistics for Breast Cancer. Available at: https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html
4. Redig, A. J., & McAllister, S. S. (2013). Breast cancer as a systemic disease: a view of metastasis. Journal of internal medicine, 274(2), 113–126. https://doi.org/10.1111/joim.12084
5. American Cancer Society. Survival Rates for Breast Cancer. Available at: https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-survival-rates.html
6. BreastCancer.org. How to Read Hormone Receptor Test Results. Available at: https://www.breastcancer.org/symptoms/diagnosis/hormone_status/read_results