Atossa Therapeutics, Inc. announced that the pre-menopausal, Estrogen Receptor positive (ER+) /Human Epidermal Growth Factor Receptor 2 negative (HER2-), breast cancer patient who received neoadjuvant and adjuvant (Z)-endoxifen therapy under an FDA-approved "expanded access" program has completed five years of treatment. As of the date of this press release, the patient remains cancer-free and has reported no significant safety or tolerability issues over the course of her treatment. 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.

Patient /Treatment Background Diagnosis. In late 2018, a 51-year-old premenopausal woman was diagnosed with a moderately differentiated invasive ductal breast carcinoma with the most frequently reported subtype: ER+, PR+, and HER2-. The initial diagnostic biopsy demonstrated that 90% of the tumor cells were ER+ and 20% expressed Ki-67, a tumor proliferation antigen.

Pharmacogenomics analysis showed a CYP2D6 genotype of CYP2D6*4/*4, a nonfunctioning variant, suggesting tamoxifen would be a poor treatment option. Other than breast cancer, the patient had no comorbidities and took no medications. Her family history was strong for osteoporosis, a contraindication for aromatase inhibitor treatment.

Neoadjuvant treatment. Neoadjuvant treatment is given in the window of time between the diagnosis and the primary treatment, which in the case of locally advanced breast cancer is surgery. The intent of neoadjuvant therapy is to slow the growth of the cancer or even shrink the cancer prior to surgery.

The goal of this treatment is to help increase the effectiveness of surgery, and it has also been shown to reduce the likelihood that the cancer returns. The FDA authorized a single-patient study under its Expanded Access or compassionate use program for this woman to receive 4 mg/day oral (Z)-endoxifen for 20 days before surgery. Surgery.

The patient had a unilateral mastectomy. After (Z)-endoxifen neoadjuvant treatment, the Ki-67 expression in the tumor was reduced 50%, from 20% to 10%. Both the relative response, a 50% reduction, and the absolute value at the time of surgery have been found in large trials to be an indicator of favorable long-term outcomes.

Adjuvant treatment. Following surgery, her physician recommended adjuvant therapy but, like many women, she was not a candidate for tamoxifen due to her low liver enzyme (CYP2D6) activity. She also did not want to take drugs to suppress her ovarian function and go into early menopause, which meant aromatase inhibitors were not an option.

Given the strong and rapid response to (Z)-endoxifen, it was recommended that she continue taking (Z)-endoxifen. This led to an additional compassionate use authorization by the FDA to allow this patient to continue taking 4 mg/day (Z)-endoxifen in the adjuvant setting. She has now completed five years of daily (Z)-endoxifen.

As of the date of this press release, she has not had a recurrence of breast cancer or a new cancer in the contralateral breast, as assessed by clinical examination and mammography. Additionally, the treatment has been well tolerated, and there were no vasomotor symptoms commonly associated with tamoxifen (for example, night sweats and hot flashes). Under the FDA Expanded Access IND program, the use of Atossa's proprietary (Z)-endoxifen is restricted to this patient only.

(Z)-endoxifen is the most active metabolite of the FDA approved Selective Estrogen Receptor Modulator (SERM), tamoxifen. Studies have demonstrated that the therapeutic effects of tamoxifen are driven in a concentration-dependent manner by (Z)-endoxifen. In addition to its potent anti-estrogen effects, (Z)-endoxifen at higher concentrations has been shown to target PKCß1, a known oncogenic protein.

(Z)-endoxifen also appears to deliver similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with 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 greater 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.