Announcement • May 08
Atossa Therapeutics Announces Publication of KARISMA Endoxifen Trial Demonstrating Significant Reduction in Mammographic Breast Density in Healthy Premenopausal Women Atossa Therapeutics, Inc. had announced the publication of results from the KARISMA Endoxifen trial in the Journal of the National Cancer Institute. The randomized, double-blind, placebo-controlled Phase 2 study evaluated daily oral Endoxifen and demonstrated that low-dose Endoxifen significantly reduced mammographic breast density, a key risk factor for breast cancer. The article titled "Endoxifen for Mammographic Density Reduction – Results from the KARISMA Endoxifen Trial" highlighted data collected by investigators at Karolinska Institutet (Stockholm, Sweden) and collaborators, from a study funded by Atossa. The study evaluated placebo, 1 mg, and 2 mg Endoxifen administered daily for six months in 240 healthy premenopausal women enrolled through the Swedish national mammography screening program. Elevated mammographic breast density is an established risk factor for breast cancer and a recognized pharmacodynamic marker of response to endocrine risk-reduction therapy. In the KARISMA Endoxifen trial, both the 1 mg and 2 mg Endoxifen dose levels produced statistically significant reductions in mammographic breast density compared with placebo. The 1 mg dose reduced mammographic breast density by 19.3% versus placebo (p=0.004), while the 2 mg dose reduced mammographic breast density by 26.5% (p<0.001) versus placebo. These reductions were comparable to those previously reported with standard-dose tamoxifen, but were achieved using direct administration of Endoxifen, the most therapeutically active metabolite of tamoxifen. Both levels demonstrated a favorable tolerability profile. The similar tolerability profile between the 1 mg dose and placebo with effective mammographic breast density reduction is significant for potentially addressing future breast cancer risk reduction. Discontinuations due to adverse events considered related to the study drug were similar between placebo and 1 mg Endoxifen, occurring in 4 placebo participants and 5 participants receiving 1 mg Endoxifen, compared with 11 participants receiving 2 mg Endoxifen. No clinically significant changes in hematologic safety tests, serum chemistry, coagulation, urinalysis, blood pressure, heart rate, or physical examination findings were observed during the trial. Adverse events were generally vasomotor in nature, consistent with those previously reported for tamoxifen. The study also provides important dose-selection insight. Investigators observed that meaningful mammographic breast density reduction appeared to occur at relatively low Endoxifen plasma concentrations, with the response reaching an approximate 20% decrease at concentrations of roughly 3–4 ng/mL, and with no substantial additional density reduction at higher concentrations. In contrast, vasomotor symptoms appeared more prominent at higher concentrations, supporting the 1 mg dose as the preferred candidate for future prevention studies. The authors concluded that both 1 mg and 2 mg Endoxifen significantly reduced mammographic breast density to a degree comparable to the established 20 mg dose of tamoxifen, and that the 1 mg dose indicated superior tolerability. The authors also noted that future studies are needed to determine whether Endoxifen reduces incidences of breast cancer in women at increased risk. Atossa believes these results strengthen the rationale for advancing Endoxifen as a potential mammographic breast density reduction therapy, particularly for women with elevated mammographic breast density or other risk factors who may benefit from endocrine risk reduction but are reluctant to use currently available options. The KARISMA Endoxifen trial was a proof-of-concept, dose-determining, double-blind, randomized, placebo-controlled Phase 2 clinical trial conducted in Sweden. The study enrolled 240 healthy premenopausal women aged 40 to 55 years who were participating in the national mammography screening program in Stockholm, Sweden. Participants were randomized 1:1:1 to receive placebo, 1 mg Endoxifen, or 2 mg Endoxifen daily for six months. The primary objective was to evaluate the effect of Endoxifen on mammographic breast density. Safety and tolerability were also assessed. The study is registered at www.ClinicalTrials.gov under identifier NCT05068388. Announcement • May 06
Atossa Therapeutics Receives FDA Rare Pediatric Disease Designation For (Z)-Endoxifen For McCune-Albright Syndrome Atossa Therapeutics, Inc. announced that the U.S. Food and Drug Administration has granted Rare Pediatric Disease designation to (Z)-endoxifen for the treatment of McCune-Albright Syndrome in females. RPD designation is granted to drug candidates intended to treat serious or life-threatening diseases that primarily affect individuals from birth to 18 years of age. Upon approval of a qualifying marketing application, drugs with RPD designation may be eligible for a Priority Review Voucher, which can be used to obtain priority review for a future application or may be sold or transferred to another sponsor. In the last 18–24 months, disclosed PRV sales have ranged from approximately $100–$205 million. RPD designation provides a valuable regulatory pathway and opportunities for enhanced engagement with the FDA as we evaluate development strategies for MAS. The FDA's RPD designation is reserved for serious or life-threatening diseases that primarily affect individuals from birth to 18 years old and that meet the definition of a rare disease or condition under Section 526 of the Federal Food, Drug & Cosmetic Act. MAS qualifies as a rare pediatric disease due to its serious manifestations, including gonadotropin-independent precocious puberty, accelerated bone maturation, and endocrine abnormalities affecting children and adolescents. Drugs granted RPD designation may be eligible for a PRV upon FDA approval of a qualifying New Drug Application or Biologics License Application, provided all statutory criteria are met. A PRV may be used by the sponsor or sold or transferred to another company. MAS is an extremely rare genetic disorder caused by activating mutations in the GNAS gene, leading to mosaic endocrine dysregulation. The disease is characterized by a triad of symptoms: Polyostotic Fibrous Dysplasia: replacement of normal bone with weak, fibrous tissue, leading to fractures, deformities, and pain; Café-au-lait Spots: hyperpigmented skin patches with irregular, "jagged" borders (often described as the "Coast of Maine") that typically respect the body's midline; and Hyperfunctioning Endocrinopathies: commonly known as precocious puberty, where children (especially girls) may begin puberty as early as age two. In pediatric patients, MAS commonly presents with gonadotropin-independent precocious puberty, particularly in females, which can result in accelerated growth, premature epiphyseal closure, and reduced adult height. Additional complications may include thyroid dysfunction, growth hormone excess, and other endocrine abnormalities. There are currently limited effective treatment options, highlighting the need for new therapeutic approaches. (Z)-Endoxifen is a potent Selective Estrogen Receptor Modulator/Degrader with demonstrated activity across multiple mechanisms of interest. Atossa is evaluating its potential applications in oncology and rare diseases. The Company's proprietary oral formulation has shown a favorable safety profile and pharmacology distinct from tamoxifen, including ER-targeted effects and PKC inhibition. Atossa's (Z)-endoxifen is not approved for any indication. Atossa has previously received Orphan Drug Designation, as well as RPD for (Z)-endoxifen for the treatment of Duchenne Muscular Dystrophy from the FDA. Upon approval of a qualifying marketing application, drugs with RPD designation may be eligible for a PRV, which can be used to obtain priority review for a future application or may be sold or transferred to another sponsor. In the last 18-24 months, disclosed PRV sales have ranged from $100-$205 million. Atossa's (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including multiple recently issued U.S. patents and numerous pending applications worldwide. Breakeven Date Change • Apr 19
Forecast to breakeven in 2028 The 3 analysts covering Atossa Therapeutics expect the company to break even for the first time. New consensus forecast suggests the company will make a profit of US$22.6m in 2028. Average annual earnings growth of 58% is required to achieve expected profit on schedule. 
