Atossa Genetics (NASDAQ:ATOS) was the focus of a Rodman & Renshaw discussion centered on the company’s lead breast cancer program, (Z)-endoxifen, and broader efforts to accelerate breast cancer drug development through adaptive clinical trials.
Michael King, managing director at Rodman & Renshaw, hosted the conversation with Dr. Laura Esserman, surgical oncologist and director of the UCSF Carol Franc Buck Breast Cancer Center. Steven Quay, founder, chairman, CEO and president of Atossa Therapeutics, also joined the call.
“The pace of execution is quite slow, and the number of steps it takes to put something into practice is enormous,” Esserman said. She added that I-SPY has evaluated 35 different drugs over 15 years and now operates with a central review process that can allow a new arm to begin enrolling across 48 sites in about a month.
Focus on ER-Positive, HER2-Negative Breast Cancer
Much of the discussion focused on estrogen receptor-positive, HER2-negative breast cancer, particularly luminal B tumors, which Esserman described as an area where progress has lagged. She said I-SPY’s overall complete response rate has risen from 19% to close to 55%, but that improvement has been driven largely by immune-responsive subtypes rather than endocrine-driven cancers.
“ER-positive cancers, we are not” figuring out how to cure in the same way as HER2-positive and triple-negative breast cancers, Esserman said, adding that the field needs better combinations, better endpoints and more tolerable therapies.
Esserman said tolerability is central in endocrine therapy because many patients discontinue treatment. She cited aromatase inhibitors as causing significant joint pain and said that after three years, 60% of women stop taking standard endocrine drugs.
Endoxifen Viewed as a Tolerability Opportunity
Esserman said she initially expected endoxifen, an active metabolite of tamoxifen, to be as toxic or more toxic than tamoxifen. Instead, she said her clinical experience has shown it to be “extremely well-tolerated.” King noted that endoxifen does not require conversion through CYP2D6, and Esserman said the compound’s tolerability may help distinguish it from tamoxifen.
Quay said tamoxifen produces numerous metabolites in the blood, while endoxifen alone produces one. “I think it’s one of those others that’s causing the mischief,” Quay said. Esserman agreed that the tolerability profile was notable, saying, “It’s clearly not the active ingredient that is driving that toxicity.”
Esserman also discussed experience with endoxifen in the RECAST DCIS trial, which is evaluating endocrine therapy and active surveillance approaches for stage 0 breast lesions. She said patients who remain on therapy provide an important signal of tolerability, because patients who dislike endocrine treatment may instead choose surgery.
Combination Strategies and Early Endpoints
The call also addressed combinations involving endoxifen. Esserman said an endoxifen-abemaciclib combination appears promising, with side effects primarily attributable to abemaciclib. “There’s no added toxicity whatsoever, and the combination appears to work just as well,” she said.
Esserman said the I-SPY group is working to refine early endpoints that could support faster development, including Ki-67, MRI-based functional tumor volume, background enhancement, residual cancer burden and patient-reported tolerability measures such as FACT-GP5.
She also discussed an endocrine optimization effort involving endoxifen, abemaciclib and elagolix, but emphasized that the elagolix data have not yet been formally presented. In a small 10-patient-per-arm evaluation, she said investigators saw similar drops in cell turnover and functional tumor volume, while patient-reported symptom burden appeared better with elagolix than with ovarian suppression.
Regulatory Path and Broader Trial Strategy
Esserman said the FDA still tends to prefer traditional drug-versus-drug trials, while I-SPY is designed as a signal-finding platform that could support seamless movement into confirmatory studies. She argued that better validated early endpoints could reduce the time needed to evaluate therapies, particularly in hormone-positive breast cancer.
“We must really work towards saying we need early markers of effectiveness,” Esserman said. “We need early markers of measurements of tolerability.”
She said I-SPY has screened almost 6,000 patients and enrolled about 3,800 across I-SPY2 and I-SPY2.2. She also described the platform as a model that could become more broadly replicable in other disease areas.
The discussion closed with Esserman highlighting additional work expected at upcoming oncology meetings, including I-SPY presentations involving immunotherapy combinations and findings from the Wisdom Study on personalized breast cancer screening. She also pointed to prevention-oriented efforts aimed at rethinking how hormonal interventions across a woman’s life could potentially reduce breast cancer risk.
About Atossa Genetics (NASDAQ:ATOS)
Atossa Genetics, Inc is a clinical-stage biotechnology company based in Seattle, Washington, focused on developing therapeutics and diagnostic products for breast cancer and other breast-related conditions. The company’s mission centers on delivering targeted, minimally invasive solutions that address early detection, treatment, and prevention in women at risk for or diagnosed with breast malignancies.
The company’s pipeline includes Z-Endoxifen, an oral formulation of endoxifen designed to treat and prevent estrogen receptor–positive breast cancers, particularly in patients with ductal carcinoma in situ or those at high risk of recurrence.
