COLUMBUS, Ohio, and SAN FRANCISCO, Feb. 15, 2023 -- Sermonix Pharmaceuticals Inc. and Quantum Leap Healthcare Collaborative™ today announced that Sermonix’s investigational next-generation targeted endocrine therapy, lasofoxifene, will be evaluated in a new study arm of the ongoing I-SPY endocrine program sponsored by Quantum Leap. This portion of the study targets patients with newly diagnosed estrogen receptor-positive (ER+)invasive cancer.
The arm is part of the I-SPY 2 Endocrine Optimization Platform (EOP), whichis focused on patients with clinically high risk (stage 2/3) estrogen receptorpositive (ER+)/HER2- breast cancer, but molecularly low risk (MammaPrint lowrisk signature). These patients often have substantial risk for recurrence thatoccurs later (after five years), and thus are in great need of novel agentsthat are more tolerable and more effective treatments than the current standardof care.
Quantum Leap opened the EOP program in 2021 to specifically address theneed for better options for this subset of patients, and to find an earlyendpoint to measure success of therapy. I-SPY 2 had previously only focused onwomen with high clinical and molecular risk where complete pathologic responseis highly predictive of treatment efficacy.
“Sermonix is delighted to be a part of the truly groundbreaking I-SPY 2clinical trial, working alongside such esteemed researchers to investigate anarea of unmet medical need,” said Dr. David Portman, founder and chief executiveofficer of Sermonix. “To date, we have successfully identified activity fromlasofoxifene, and will soon be initiating a Phase 3 registrational trial. It isexciting to be included in I-SPY and potentially generate additional data thatcould confirm activity of lasofoxifene in early-stage adjuvant settings as wellas support differentiated quality-of-life outcomes.”
EOP is a sub-study within the main I-SPY-2clinical trial utilizing neoadjuvant endocrine therapy in patients whose tumorsare predicted to be sensitive to endocrine therapy but for whom chemotherapy isexpected to provide little or no benefit. Lasofoxifene will be evaluated alongwith other investigational agents in separate study arms as part of theplatform trial.
“Lasofoxifene is a novel endocrine treatmentthat has demonstrated activity in patients with heavily pre-treated ER+/HER2-metastatic breast cancer, including patients harboring tumors with ESR1mutations,” said Dr. Laura Esserman ofthe University of California San Francisco, founder andleader of the I-SPY Program. “This agent is very well tolerated and thuswould be a true advancement for the significant percentage of breast cancerpatients who struggle or fail to complete the recommended five years ofaromatase inhibitor (AI) therapy.”
Dr. Jo Chien, the EOP study’s principalinvestigator, added: “Lasofoxifene is reported to promote vaginal and sexualhealth benefits, which are known and challenging side effects of AIs. Shouldlasofoxifene prove more efficacious and better tolerated than AIs in theneoadjuvant setting, this could have broad implications for both the survivaland quality of life for women in the metastatic and early-stage adjuvantsettings. Using the I-SPY model, we can accelerate the development of newcancer treatments and target new and innovative treatments to the patients whowill benefit most, and we are eager to see data from lasofoxifene-treatedsubjects in this trial.”
In two successfully completed Phase 2 studies(ELAINE-1 and ELAINE-2), lasofoxifene was found to be safe and well tolerated and demonstrated compelling anti-tumor activity, both as monotherapy (ELAINE-1)and in combination with abemaciclib (ELAINE-2). Of particular note, Sermonix shared a case study from ELAINE-1 detailing the first ever known finding of a durable complete response that could be characterized as 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. Additionally, lasofoxifene-treated patients in ELAINE-2 demonstrated mean progression-free survival over 13 months. Full results from the ELAINE-1 and ELAINE-2, which provide strong support for a Phase 3 combination study in 2023, were presented at ESMO 2022 and ASCO 2022, respectively.
Sermonix will supply lasofoxifene and provide financial support to Quantum Leap for this study. Quantum Leap is sponsor of the I SPY program, which includes 30 open sites and at least 10 more expected to be added in the first quarter of 2023. All I SPY sites have the EOP program open.
Lasofoxifene 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 abemaciclib 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 ESR1mutations, 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.
Sermonix 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.
Quantum Leap Healthcare Collaborative is a501c(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our mission is to integrate care and research, and to foster high-impact trials with embedded clinical processes and systems technology and improved data management, greater access to clinical trial matching, and greater benefit to patients, providers, and researchers. Our goal is to improve and save lives. Quantum Leap provides operational, financial, and regulatory oversight to I-SPY. For more information, visit https://www.quantumleaphealth.org/.
The I-SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2) (I-SPY 2 TRIAL) was designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 30 major U.S. cancer research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations. For more information, visit www.ispytrials.org.
Managing Director, Investor Relations Corporate Communications
Quantum Leap Healthcare Collaborative Media Contact:
Director, Marketing and Communications