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Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers harboring ESR1 mutations, today announced that a case report detailing a durable complete remission during its Phase 2 ELAINE-1 study was published in JCO Precision Oncology (JCO PO). The case marks the first-ever known finding of a complete clinical remission in a metastatic estrogen receptor-positive (ER+)/HER2- breast cancer patient with an ESR1 mutation after prior CDK4/6 inhibitor treatment upon participation in any single-agent hormonally based therapy trial.

The open-access case report, “Lasofoxifene Monotherapy Induces Durable Complete Remission in a Patient with ER+, HER2- Metastatic Breast Cancer with an ESR1 Mutation,” details a patient result that was reported during Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE-1, NCT03781063) study. The case was previously presented as a poster and brief talk at the annual Metastatic Breast Cancer Research Conference in September 2022. Topline results from the ELAINE-1 trial, including this patient, were reported at the European Society for Medical Oncology (ESMO) Congress 2022.

“To witness a study participant with advanced breast cancer achieve a durable complete remission for more than two years while taking lasofoxifene is a reminder to everyone at Sermonix why we do what we do; it drives our daily and long-term vision for this drug,” said Dr. David Portman, Sermonix founder and chief executive officer. “We are excited the details of this complete responder – the only one to our knowledge achieved in the post-CDK4/6i-ESR1 mutation setting with single-agent endocrine therapy – will be shared with a broader audience through JCO Precision Oncology and we look forward to lasofoxifene’s continued clinical development during our current Phase 3 ELAINE-3 registrational study.”

Mutations in the ESR1 gene have emerged as an important driver of resistance to endocrine therapies that form the backbone of treatment for patients with ER+/HER2- breast cancer.

ELAINE-1 was an open-label, randomized study that evaluated the efficacy of oral lasofoxifene versus intramuscular fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation and progression-free survival as the primary endpoint. ELAINE-1 demonstrated that lasofoxifene numerically prolonged median progression-free survival compared with fulvestrant (5.6 vs 3.7 months; P=0.138) in metastatic breast cancer patients with ESR1 mutations who had progressed taking a prior aromatase inhibitor (AI) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), with a favorable safety profile.

“To achieve a complete response during our ELAINE-1 study was exceedingly gratifying, bolstering our confidence in lasofoxifene’s potential to address the needs of patients with ESR1 mutations,” Dr. Einav Nili Gal-Yam, M.D., Ph.D., ELAINE-1 principal investigator and head of the Breast Oncology Institute at Chaim Sheba Medical Center in Ramat Gan, Israel. “We are excited to continue investigating the drug’s potential.”

Breast cancer is the most common solid tumor in women worldwide and a major cause of cancer mortality, and incidence rates in the U.S. are steadily increasing every year.1-3 Approximately 80% of all breast cancers are estrogen receptor positive (ER+)4, and evidence suggests estrogen receptor alpha (ERα, encoded by ESR1) and mutations of the receptor play a critical role in the initiation and progression of these tumors.5

JCO PO is a peer-reviewed, online-only journal publishing original research, case reports, opinions, and reviews that advance the science and practice of precision oncology and define genomics- and other biomarker-driven clinical care of patients with cancer.

To read the published case report, visit JCO PO website. To learn more about the ELAINE studies, visit ElaineStudy.com.

1Pfeiffer RM, Webb-Vargas Y, Wheeler W, et al: Proportion of U.S. Trends in Breast Cancer Incidence Attributable to Long-term Changes in Risk Factor Distributions. Cancer Epidemiol Biomarkers Prev 27:1214-1222, 2018.2Siegel RL, Miller KD, Fuchs HE, et al: Cancer Statistics, 2021. CA Cancer J Clin 71:7-33, 2021.3Sung H, Ferlay J, Siegel RL, et al: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209-249, 2021.4Hwang KT, Kim J, Jung J, et al: Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database. Clin Cancer Res 25:1970-1979, 2019.5Jeselsohn R, De Angelis C, Brown M, et al: The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer. Curr Oncol Rep 19:35, 2017.

About LasofoxifeneLasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

About SermonixSermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific oncology products and is currently undertaking two Phase 2 clinical studies of lasofoxifene, its lead investigational drug. The Sermonix management team, led by founder Dr. David Portman, has significant experience in all stages of the drug development, regulatory and commercialization processes. Paul Plourde, M.D., vice president of oncology clinical development, has many decades of experience at AstraZeneca in the breast cancer drug development arena. Barry Komm, Ph.D., chief scientific officer, is recognized for his expertise in nuclear receptor biology. Miriam Portman, M.D., is co-founder and chief operating officer, with expertise in clinical trial conduct and patient recruitment. Elizabeth Attias, M.M.Sc., Sc.D., chief strategy and development officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, Ph.D., vice president of operations, has over 30 years of experience in global drug development leadership. Sermonix non-executive chairman of the board is Anthony Wild, Ph.D., former president of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. Learn more at SermonixPharma.com.

Sermonix Contact:Monica Kozlowski, MSPHSermonix Product Managermkozlowski@sermonixpharma.com860-692-8548