Atossa Therapeutics Inc (NASDAQ:ATOS), which is developing medicines aimed at oncology and breast cancer, revealed that the pharmacokinetic (PK) run-in cohort of the Phase 2 EVANGELINE study, evaluating Endoxifen versus exemestANe GosEreLIn, has now fully enrolled.
The Seattle-based clinical-stage biopharma’s EVANGELINE study is one of two ongoing Phase 2 trials investigating Atossa’s proprietary (Z)-endoxifen as a neoadjuvant treatment, for women with estrogen receptor positive breast cancer.
A neoadjuvant treatment is usually given as a first step to shrink a tumor before the main treatment, which is usually surgery.
Atossa noted that EVANGELINE is a randomized trial of the company’s patented Selective Estrogen Receptor Modulator (SERM) (Z)-endoxifen, and exemestane plus goserelin as a neoadjuvant treatment for pre-menopausal women with Grade 1 or 2 Estrogen Receptor positive (ER+)/Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer.
The PK run-in cohort consists of six patients, all of whom will be treated with (Z)-endoxifen at 40 mg a day for four weeks, said the company.
Seeing if 40mg dose works
The goal of the PK run-in cohort is to determine if the 40mg dose delivers steady-state plasma concentrations (Css) between 500-to-1000 ng/mL, which are optimal to target PKCβ1 inhibition and enhance (Z)-endoxifen’s antitumor mechanism of action.
Once the optimal dose of (Z)-endoxifen is determined, the Atossa said the treatment cohort will start. Participants in the treatment cohort will receive neoadjuvant treatment for up to six months, followed by surgery. The study is expected to enroll around 175 patients at up to 25 sites across the US.
"We are excited to fully enroll the EVANGELINE PK run-in cohort and look forward to seeing data in the 3Q of this year,” said Steven Quay, Atossa’s CEO.
“The data will show us if the 40mg dose delivers the steady-state plasma concentrations required to effectively target PKCβ1 inhibition and enhance (Z)-endoxifen’s antitumor mechanism of action, or if we need to further optimize the dose. Identifying the optimal dose is an important milestone as it will allow us to activate additional sites in the US and advance plans to open sites outside of the US, which will increase the speed of recruitment for the EVANGELINE treatment cohort.”
According to Atossa, breast cancer is the most frequently diagnosed cancer in premenopausal women and accounts for almost half of the cancers that occur in women aged 15-49.
Nearly 75% of premenopausal breast cancer falls under luminal A (ER+/HER2-) or B (ER+/HER2+) subtypes. Ovarian function suppression, when combined with either tamoxifen or an aromatase inhibitor, is the first line of treatment for Stage 2 and 3 premenopausal ER+/HER2- breast cancer.
Atossa said (Z)-endoxifen is the most active metabolite of the FDA-approved selective estrogen receptor modulator tamoxifen. Studies have shown that the therapeutic effects of tamoxifen are driven in a concentration-dependent manner by (Z)-endoxifen.
Atossa is developing a proprietary oral formulation of (Z)-endoxifen that does’t 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 said its (Z)-endoxifen is protected by two issued US patents and numerous pending patent applications.
Contact the author Uttara Choudhury at uttara@proactiveinvestors.com
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