Sermonix Pharmaceuticals & Quantum Leap Healthcare Announce New Study Arm to Evaluate Lasofoxifene in Ongoing I-SPY 2 Clinical Trial

Sermonix Pharmaceuticals Inc. and Quantum Leap Healthcare Collaborative recently announced 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), which is focused on patients with clinically high risk (stage 2/3) estrogen receptor positive (ER+)/HER2- breast cancer, but molecularly low risk (MammaPrint low risk signature). These patients often have substantial risk for recurrence that occurs later (after five years), and thus are in great need of novel agents that are more tolerable and more effective treatments than the current standard of care.

Quantum Leap opened the EOP program in 2021 to specifically address the need for better options for this subset of patients, and to find an early endpoint to measure success of therapy. I-SPY 2 had previously only focused on women with high clinical and molecular risk in which complete pathologic response is highly predictive of treatment efficacy.

“Sermonix is delighted to be a part of the truly groundbreaking I-SPY 2 clinical trial, working alongside such esteemed researchers to investigate an area of unmet medical need,” said Dr. David Portman, Founder and Chief Executive Pfficer of Sermonix. “To date, we have successfully identified activity from lasofoxifene, and will soon be initiating a Phase 3 registrational trial. It is exciting to be included in I-SPY and potentially generate additional data that could confirm activity of lasofoxifene in early stage adjuvant settings as well as support differentiated quality-of-life outcomes.”

EOP is a sub-study within the main I-SPY-2 clinical trial utilizing neoadjuvant endocrine therapy in patients whose tumors are predicted to be sensitive to endocrine therapy but for whom chemotherapy is expected to provide little or no benefit. Lasofoxifene will be evaluated along with other investigational agents in separate study arms as part of the platform trial.

“Lasofoxifene is a novel endocrine treatment that has demonstrated activity in patients with heavily pre-treated ER+/HER2- metastatic breast cancer, including patients harboring tumors with ESR1 mutations,” said Dr. Laura Esserman of the University of California San Francisco, founder and leader of the I-SPY Program. “This agent is very well tolerated and thus would be a true advancement for the significant percentage of breast cancer patients who struggle or fail to complete the recommended five years of aromatase inhibitor (AI) therapy.”

Dr. Jo Chien, the EOP study’s principal investigator, added “Lasofoxifene is reported to promote vaginal and sexual health benefits, which are known and challenging side effects of AIs. Should lasofoxifene prove more efficacious and better tolerated than AIs in the neoadjuvant setting, this could have broad implications for both the survival and quality of life for women in the metastatic and early-stage adjuvant settings. Using the I-SPY model, we can accelerate the development of new cancer treatments and target new and innovative treatments to the patients who will benefit most, and we are eager to see data from lasofoxifene-treated subjects 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 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.

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, MD, Vice President of Oncology Clinical Development, has many decades of experience at AstraZeneca in the breast cancer drug development arena. Barry Komm, PhD, Chief Scientific Officer, is recognized for his expertise in nuclear receptor biology. Miriam Portman, MD, is Co-founder and Chief Operating Officer, with expertise in clinical trial conduct and patient recruitment. Elizabeth Attias, MMSc, ScD, Chief Strategy and Development Officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, PhD, 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, PhD, former President of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. For more information, visit SermonixPharma.com.

Quantum Leap Healthcare Collaborative is a 501c(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 US FDA, industry, patient advocates, philanthropic sponsors, and clinicians from 30 major US 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.