On December 13, 2021 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat ESR1-mutated metastatic breast and gynecological cancers, reported that the company, in collaboration with Dr. Geoffrey Greene from the University of Chicago, presented compelling new data in a poster at the 2021 San Antonio Breast Cancer Symposium (SABCS) (Press release, Sermonix Pharmaceuticals, DEC 13, 2021, View Source [SID1234597212]). The symposium was held December 7-10 at the Henry B. Gonzalez Convention Center in San Antonio.

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The poster describes results from a pre-clinical study demonstrating that lasofoxifene alone or in combination with a CDK inhibitor may limit tumor progression in AI resistant tumors that are characterized by low levels of estrogen receptor (ESR1), elevated HER2 and genetic modifications other than activating ESR1 mutations.

Sermonix’s fully enrolled, ongoing Phase 2 Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) studies include the randomized ELAINE 1 study of lasofoxifene versus fulvestrant and the ELAINE 2 combination study of lasofoxifene with abemaciclib. The program aims to evaluate the safety and efficacy of lasofoxifene as a treatment option for breast cancer patients who develop AI resistance due to ESR1 mutations.

"These new pre-clinical data presented at this year’s SABCS move our development program a step further and suggest that lasofoxifene may have activity in non-ESR1-driven mechanisms of resistance as well," said David Portman, M.D., Sermonix founder and chief executive officer. "We intend to further evaluate a possible path forward in AI resistance not due to ESR1 mutations to complement our existing ESR1 mutation-focused programs."

"Widespread aromatase inhibitor use and selective pressure in the metastatic setting have together dramatically increased the incidence of endocrine therapy resistance, leading to deteriorating prognosis among these patients," said Dr. Geoffrey Greene. "These data, together with Sermonix’s current development program in AI resistance conferred by ESR1 mutations, suggest that lasofoxifene may have broad clinical utility across a number of resistance mechanisms. If proven in rigorously designed clinical trials, this could represent a significant leap forward in the treatment of metastatic breast cancer."

Poster details:

Title: Lasofoxifene as a Potential Treatment for Aromatase Inhibitor Resistant ER Positive Breast Cancer
Summary: First line treatment of breast cancer is primarily a long-term regimen with an aromatase inhibitor (AI), which is now also combined with a CDK 4/6 inhibitor. Treatment resistance is a relatively common result signaled by tumor progression and metastatic disease. Resistance in approximately 20-40% of those in treatment is associated with activating mutations of the estrogen receptor (ESR1) where we have shown in preclinical models that lasofoxifene more effectively inhibits these tumors’ proliferation and metastases compared to fulvestrant. However, treatment resistance may not be confined to those with ESR1 activating mutations. This study, performed by Dr. Geoffrey Greene’s research group at the University of Chicago, employed a model utilizing a metastatic cell line expressing low levels of ESR1 (MCF-7 LTLT-1) which are resistant to AI treatment, but not as a function of an ESR1 mutation. Lasofoxifene +/- palbociclib was significantly more effective than fulvestrant +/- palbociclib at inhibiting tumor progression, and all treatment combinations inhibited bone metastases except for fulvestrant alone.
Conclusion: These data support the hypothesis that lasofoxifene or lasofoxifene in combination with a CDK 4/6 inhibitor may effectively limit tumor progression and metastases in AI resistant tumors not resistant due to an ESR1 mutation.
The poster can be found on the Sermonix website here.

About Lasofoxifene
Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and 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 potent, oral SERM could, if approved, play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer.