Seattle-based Atossa Genetics Inc. (ATOS) a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods to treat breast cancer and other breast conditions issued the following letter from Dr. Steven C. Quay, President, and CEO, to Atossa shareholders:
To Our Valued Shareholders:
I begin this letter with a sense of great pride about our accomplishments at Atossa. In 2018, we completed our transformation into a Phase 2 clinical-stage pharmaceutical company. Building on that momentum, our 2019 goals are a three-fold, laser-focused clinical program to continue the development of novel therapeutics and delivery methods to: 1) treat breast cancer, 2) reduce the risk of breast cancer, and 3) prevent/reduce gynecomastia.
Throughout 2018, we advanced our Endoxifen programs into Phase 2 clinical studies for estrogen receptor positive (ER+) breast cancer and executed a research and development program of immunotherapies (such as Chimeric Antigen Receptor Therapy, or CAR-T) intended for targeted delivery via our proprietary microcatheters for the potential treatment of “triple negative” breast cancer (TNBC) and BRCA+ breast cancer. Our key achievements in 2018 include:
Expanded Access Oral Endoxifen U.S. Clinical Study: Window of Opportunity. The FDA approved the use of our oral Endoxifen (4 mg per day) for a pre-menopausal, ER+ breast cancer patient awaiting surgery. Endoxifen has been reported in the literature to play an important role in reducing breast cancer cell activity. Additionally, higher endoxifen levels correlate to lower recurrence/new tumors in ER+ breast cancer patients after surgery.
We have previously reported that during our prior Phase I study of oral Endoxifen, a 4 mg daily dose reached steady-state, therapeutic blood levels within one week, which were over 200 percent higher than the endoxifen blood levels achieved with the current standard of care, 20 mg daily tamoxifen (as reported in the literature), in patients who metabolize tamoxifen effectively and over 900 percent higher in those who do not.
We look forward to reporting on progress.
Phase 2 Oral Endoxifen Study: Window of Opportunity. We commenced our Phase 2 clinical study in Australia using our proprietary oral Endoxifen in the “window of opportunity” between diagnosis of ER+ breast cancer and surgery, to determine if pre-surgical dosing actually reduces the biological activity of the tumor, as measured by the tissue biomarker, Ki-67, and other parameters.
We previously reported that oral Endoxifen administered in our Phase 1 study was not associated with a significant change in vasomotor symptoms, i.e., hot flashes and night sweats, and in fact had a level of endocrine symptoms that was not different from placebo. Current conventional hormone therapy (tamoxifen or aromatase inhibitors) are associated with a significant and substantial change in endocrine symptoms. If our oral Endoxifen continues to maintain this tolerance profile, it could provide a “gentler” approach to breast cancer therapy.
This study is open for enrollment.
Phase 2 Topical Endoxifen Study: Mammographic Breast Density. We have advanced our Phase 2 clinical study in Sweden using our proprietary topical Endoxifen in women with high mammographic breast density, or MBD. The study was fully enrolled in October 2018 and we expect to finish dosing by the end of the second quarter of 2019, and to report initial results thereafter.
In a study of woman taking oral tamoxifen, a 10 percent reduction of MBD at one year conferred a 63 percent reduction in breast cancer at five years.1
Phase 1 Study: Topical Endoxifen in Men. We completed a Phase 1 clinical study in male subjects with all safety and tolerance objectives achieved.
Intraductal Immunotherapy R&D. We launched our intraductal microcatheter immunotherapy R&D program. This is a novel approach using our proprietary intraductal microcatheter technology for the potential of TRAnsPapillary, or “TRAP,” delivery of genetically modified cells or immunomodulatory cytokines to attack breast cancer cells. This method has several potential advantages, such as: reducing potential toxicity by delivering the immunotherapy directly to the breast milk ducts, thus limiting systemic exposure; improving efficacy by placing the modified cells in direct contact with the target the malignant ductal epithelial cells; and, the potential for the modified cells to migrate through the regional lymphatic system and extending their cytotoxic actions, which could limit tumor cell dissemination.
During 2018, we received an opinion from the World Intellectual Property Organization that certain claims in our patent application for TRAP therapy were “novel.” The invention is related to: “A transpapillary method of adoptive cell therapy for treatment of a subject having or at risk of having a breast disorder comprising administering cells into a breast duct of the subject, wherein the cells comprise modified ceils expressing one or more recombinant receptors that bind a target antigen on a breast cell, wherein the one or more recombinant receptors comprises a chimeric antigen receptor (CAR).” While there can be no assurance this opinion will be upheld or that a patent will issue with this claim, it is gratifying that our ground-breaking science is being recognized.
Additional U.S. Manufacturing. We have contracted with an additional manufacturer in the United States for the production of Endoxifen.
Capital Raising. In May, we completed a rights offering that resulted in approximately $13.4 million in gross proceeds for our company. This financing significantly added to our capital resources, allowing us to execute on our ongoing clinical trials and other related activities.
Strategic Board. We formed a strategic advisory board comprised of prominent executives from the pharmaceutical industry and academia to play a key role in a number of important initiatives, including seeking key industry partners to accelerate the clinical development of our Endoxifen programs.
In 2019, we will continue to focus on advancing the clinical development of our proprietary Endoxifen and our intraductal microcatheter programs:
Oral Endoxifen. The 2019 goal for our oral Endoxifen program is to continue clinical studies to help us understand the full “metes and bounds” of the clinical potential of this therapeutic. Specifically, we plan to determine if Endoxifen has an improved safety and tolerability profile compared to other hormone treatments. If so, we will determine whether Endoxifen, because of clinical data suggesting superiority to other hormone therapies, might augment or even replace other hormone therapies in important, clinical settings. We hope to end the year with a pharmacological profile for oral Endoxifen that can inform both further clinical trials as well as partnering discussions.
Topical Endoxifen. The 2019 goal for our topical Endoxifen program is to determine whether an important, clinically-validated imaging biomarker — mammographic breast density — can be reduced by Endoxifen formulated for transdermal (through the skin) administration. We anticipate that dosing in the Phase 2 MBD study will conclude in the second quarter 2019 with initial results to follow. The results of this study will drive the further development of our proprietary topical Endoxifen, not only for MBD but also for preventing and/or reducing gynecomastia in men being treated for prostate cancer.
Intraductal Microcatheter Technology. We will continue to advance our intraductal microcatheter technology program: continuing the Phase 2 clinical study using our proprietary intraductal microcatheter technology to administer fulvestrant in the Window of Opportunity for women with ER+ breast cancer, and continuing our R&D program to develop TRAP to administer immunotherapies for women with triple negative breast cancer and/or BRCA+ breast cancer. We developed and validated preclinical methods to administer immunotherapy to the site of tumor initiation.
These studies are the first of several steps to develop our intraductal microcatheter technology to treat breast cancer with cell-based immunotherapy, and will form the basis for supporting human studies, with the ultimate goal of treating breast cancer by administering an immunotherapy with our proprietary microcatheter technology.
Atossa is an exceptional company focused on novel therapeutics and delivery methods for breast diseases for which additional or new treatments are needed. We look forward to reporting our progress on our priorities throughout the year and we thank you for your continued support of Atossa.
Dr. Steven C. Quay, MD, Ph.D.
President and Chief Executive Officer