Atossa Therapeutics, Inc. announced protocol changes in the previously initiated study to evaluate Atossa?s proprietary (Z)-endoxifen in combination with abemaciclib (VERZENIO®), a cyclin-dependent kinase (CDK) 4/6 inhibitor marketed by Eli Lilly and Company. The study is investigating the combination as a neoadjuvant treatment in women with newly diagnosed Estrogen Receptor positive (ER+) /Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer. Atossa is a clinical stage biopharmaceutical company developing innovative medicines in areas of significant unmet medical need in oncology with a focus on breast cancer.

Based on accumulating data from the ongoing Phase 2 EVANGELINE study, the dose of (Z)-endoxifen in the combination study has been increased from 40 mg to 80 mg once daily. The change in study dose was determined following a review of safety, efficacy and pharmacokinetic (PK) data from participants currently enrolled in the 80 mg PK run-in cohort of the EVANGELINE study. The EVANGELINE study is enrolling premenopausal women with ER+/HER2- breast cancer.

The study began with a 40 mg pharmacokinetic (PK) run-in cohort. Data from this cohort, which was presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting, showed encouraging efficacy and an extremely favorable safety profile compared to currently approved endocrine therapies. Efficacy was measured by both reduction in Ki-67, a cellular marker for proliferation that indicates how fast the tumor is growing, and response (tumor shrinkage).

Participants treated for a total of 24-weeks experienced an average reduction in Ki-67 of 92% and an average target lesion decrease of 37%. The study is now enrolling an 80 mg PK cohort, which is expected to deliver the optimal drug concentrations required to fully target PKCß1 inhibition and further enhance (Z)-endoxifen?s antitumor efficacy. Additionally, the combination study will now enroll approximately 80 participants across two 40-participant cohorts.

Both cohorts will include pre-and-menopausal women who will receive 80 mg (Z)-endoxifen once daily in combination with 150 mg abemaciclib twice daily for up to 24-weeks prior to surgery. Premenopausal women in the second cohort will also receive ovarian function suppression (OFS). Increasing the number of study participants was done to ensure a statistically significant number of menopausal and premenopausal women are enrolled in each cohort.

The addition of OFS in premenopausal women enrolled in the second cohort of the study will allow for a direct comparison of safety and efficacy among the two treatment groups. This data is expected to further validate the growing body of evidence that (Z)-endoxifen is safe and highly efficacious in premenopausal women without the need for OFS. Under the terms of the study agreement, Atossa and Eli Lilly and Company are each responsible for supplying their respective study drugs.

(Z)-endoxifen is the most potent Selective Estrogen Receptor Modulator (SERM) for estrogen receptor inhibition and also causes estrogen receptor degradation. It has also been shown to have efficacy in the setting of patients with tumor resistance to other hormonal treatments. In addition to its potent anti-estrogen effects, (Z)-endoxifen has been shown to target PKCß1, a known oncogenic protein, at clinically attainable blood concentrations.

Finally, (Z)-endoxifen appears to deliver similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with standard treatments, like tamoxifen. Atossa is developing a proprietary oral formulation of (Z)-endoxifen that does not require liver metabolism to achieve therapeutic concentrations and is encapsulated to bypass the stomach, as acidic conditions in the stomach convert a significant proportion of (Z)-endoxifen to the inactive (E)-endoxifen. Atossa?s (Z)-endoxifen has been shown to be well tolerated in Phase 1 studies and in a small Phase 2 study of women with breast cancer.

(Z)-endoxifen is currently being studied in four Phase 2 trials: one in healthy women with measurable breast density, one in women diagnosed with ductal carcinoma in situ, and two other studies including the EVANGELINE study in women with ER+/HER2- breast cancer. Atossa?s (Z)-endoxifen is protected by three issued U.S. patents and numerous pending patent applications.