Z-endoxifen / Atossa Therap - LARVOL DELTA

Atossa Therapeutics Announces Full Results from I‑SPY 2 Endocrine‑Optimization Sub‑Study Evaluating Low‑Dose (Z)‑Endoxifen (BioSpace) - P2 | N=5,000 | I-SPY (NCT01042379) | "Atossa Therapeutics, Inc...today reported full results from the Phase 2 Endocrine Optimization Pilot (EOP) sub‑study within the I‑SPY 2 TRIAL evaluating low‑dose oral (Z)‑endoxifen (10 mg daily) as a neoadjuvant treatment in 20 women with stage II/III estrogen‑receptor–positive (ER+), HER2‑negative breast cancer....95 percent of participants (19/20) completed at least 75 percent of planned dosing, far exceeding the predefined 75 percent threshold. Median Ki‑67 fell from 10.5 percent at baseline to 5 percent by Week 3 (prior to ovarian suppression); 65 percent of patients achieved Ki‑67 ≤ 10 percent at that time point, and suppression was maintained at surgery. Median functional tumor volume (FTV) measurement (performed at baseline, week 3, week 12, and at surgery) decreased 77.7 percent (range 9.0 cc → 1.2 cc) from baseline to surgery, and the longest tumor diameter from baseline to preoperative MRI was reduced by 36.8 percent."

P2 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Atossa Therapeutics Announces First Quarter 2025 Financial Results and Provides a Corporate Update (PRNewswire) - "Announced Strategic Decision to Pursue Metastatic Breast Cancer Indication: Atossa announced plans to target metastatic breast cancer as its lead program for (Z)-endoxifen.....Significantly Strengthened (Z)-endoxifen Patent Portfolio with Three New U.S. Patents: Atossa continued to bolster the intellectual property portfolio of (Z)-endoxifen with the grant of three new U.S. patents covering 31 claims directed at: sustained release compositions of (Z)-endoxifen (U.S. Patent No. 12,201,591); enteric oral formulations of (Z)-endoxifen and salts thereof as well as their use in treating hormone-dependent breast and reproductive tract disorders (U.S. Patent No. 12,275,684); and 58 claims covering (Z)-endoxifen formulations, including various levels of purity and stability as well as methods of using those formulations (U.S. Patent No. 12,281,056)."

Patent • Pipeline update • Breast Cancer

SMART 2.0 Interval breast cancer reduction study: A phase 3 randomized, double-blind, placebo-controlled trial of oral Z-endoxifen in women at high risk for breast cancer (AACR 2025) - "Endocrine therapies such as tamoxifen reduce mammographic density and lower the risk of breast cancer in healthy women. All data will be summarized using proportions/percentages for categorical data and means/medians with standard deviations/inter-quartile ranges for quantitative outcomes. Additionally, a multivariate logistic regression model will assess this endpoint, adjusting for treatment group and relevant covariates, and testing for multiplicative interaction terms as necessary.Outcome: The goal of this study is to achieve regulatory approval for low-dose (Z)-endoxifen as a therapy to reduce the incidence of interval breast cancer in high-risk women, identified by an AI-based mammogram screening algorithm."

Clinical • P3 data • Breast Cancer • Oncology • Solid Tumor • PRKCB

Novel (Z)-endoxifen-related chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer (AACR 2025) - "(Z)-Endoxifen (ENDX), an active metabolite of tamoxifen, is a potent, orally bioavailable selective estrogen receptor modulator with a favorable safety profile now under development for breast health applications. Its synthesis yields endoxifen-related byproducts that are new chemical entities (NCEs), including AT416E, AT416Z, AT402E and AT402Z...These findings highlight four NCEs with notable anti-cancer activity, with some matching or surpassing ENDX in several cancer-relevant cellular readouts, marking them as novel candidates for ERα+ breast cancer therapy. Further studies will advance one or more of these NCEs into in vivo models to confirm their therapeutic efficacy and potential for clinical application."

Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics Announces Issuance of U.S. Patent No. 12,275,684, Further Strengthening (Z)-endoxifen Portfolio (Atossa Therapeutics Press Release) - "Atossa Therapeutics, Inc...announced that the United States Patent and Trademark Office (USPTO) has granted a new patent (U.S. Patent No. 12,275,684) directed to enteric oral formulations comprising (Z)-endoxifen as well as methods of treating subjects with those oral formulations. This newly granted patent further fortifies Atossa’s intellectual property portfolio surrounding its proprietary (Z)-endoxifen formulations, encompassing novel compositions and methods related to (Z)-endoxifen, a potent Selective Estrogen Receptor Modulator (SERM). Specifically, the patent covers enteric oral formulations of (Z)-endoxifen and salts thereof as well as their use in treating hormone-dependent breast and reproductive tract disorders."

Patent • Breast Cancer

Atossa Therapeutics Announces Plans to Pursue Metastatic Breast Cancer Indication for (Z)-Endoxifen and Continued Engagement with FDA on Additional Indications (Atossa Therapeutics Press Release) - "Atossa Therapeutics, Inc...announced its strategic decision to pursue a metastatic breast cancer indication for (Z)-endoxifen. Atossa believes that pursuing a metastatic indication may offer a more efficient regulatory pathway to deliver (Z)-endoxifen to women in urgent need, and simultaneously plans to work with the FDA to advance additional indications, such as breast cancer prevention and neoadjuvant therapy, that often require larger and longer clinical trials."

Pipeline update • Breast Cancer

Atossa Therapeutics to Present…Tolerability Data from Phase 2 EVANGELINE Trial at the 2024 San Antonio Breast Cancer Symposium (Atossa Therapeutics Press Release) - P2 | N=180 | EVANGELINE (NCT05607004) | Sponsor: Atossa Therapeutics, Inc. | "The second poster...focuses on patient-reported outcomes from (Z)-endoxifen treatment in patients enrolled onto the PK run-in. Findings include: Tolerability: The QOL data presented supports (Z)-endoxifen as generally well-tolerated. Most patient-reported side effects were low grade. Symptoms like hot flashes and reduced libido were reported as mildly to moderately bothersome. Amenorrhea and menstrual suppression were common but generally reported as manageable."

P2 data • Patient reported outcomes • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Atossa Therapeutics to Present Pharmacokinetic…Data from Phase 2 EVANGELINE Trial at the 2024 San Antonio Breast Cancer Symposium (Atossa Therapeutics Press Release) - P2 | N=180 | EVANGELINE (NCT05607004) | Sponsor: Atossa Therapeutics, Inc. | "The first poster...discusses findings from the pharmacokinetic (PK) run-in phase of the trial....Primary Endpoint Achieved: 50 percent of patients (3/6) in the group that received 80 mg of (Z)-endoxifen with goserelin met the target steady-state plasma concentrations (Css) of 500–1000 ng/mL. Approximately 38 percent of patients (3/8) in the 80 mg/day (Z)-endoxifen only group reached target Css levels....Antitumor Activity: Substantial tumor suppression was observed across all dosing levels, with or without ovarian function suppression (OFS). The 4-week Ki-67 ≤10 percent response rate was generally above 85 percent across dose levels, with or without the presence of OFS."

P2 data • PK/PD data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

A Randomized Phase 2 Non-inferiority Trial of (Z)-endoxifen and Exemestane + Goserelin as Neoadjuvant Treatment for Premenopausal Women with ER+/HER2- Breast Cancer (EVANGELINE) (Atossa Therapeutics Press Release) - "Study Design: Based on adverse events reported in 80 mg/day groups, as well as the findings reported on (Z)-endoxifen tissue and plasma Css, overall tolerability, and antitumor activity, EVANGELINE is expected to proceed based on an amended protocol as a randomized trial that compares (Z)-endoxifen 40 mg/day plus OFS to exemestane plus OFS, using the 4-week Ki-67 reduction as the primary endpoint....Next Steps: The process for trial initiation has begun and recruitment for this cohort is expected to begin in 2025, now that the PK run-in phase has been concluded."

Clinical protocol • Enrollment status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Atossa Therapeutics Announces Full Results from Phase 2 KARISMA-Endoxifen Study Demonstrating Statistically Significant Reductions in Mammographic Breast Density (GlobeNewswire) - P2 | N=240 | KARISMA-Endoxifen (NCT05068388) | Sponsor: Atossa Therapeutics, Inc. | "Results showed that the 1 mg dose of (Z)-endoxifen reduced MBD by 17.3 percentage points (p<0.01), while the 2 mg dose achieved a reduction of 23.5 percentage points (p<0.01), compared to a minimal change in the placebo group of 0.27 percentage points. Plasma concentrations for (Z)-endoxifen were measured at 4.8 ng/mL and 9.7 ng/mL for the 1 mg and 2 mg arms, respectively, highlighting the effectiveness of the lower dose in achieving significant reductions. Importantly, no significant differences in adverse events were observed between the 1 mg dose and placebo."

P2 data • Breast Cancer

Atossa Therapeutics Presents Data from Study Investigating Anti-Cancer Activity of (Z)-Endoxifen-Related Compounds at AACR Special Conference in Cancer Research (GlobeNewswire) - "Atossa Therapeutics, Inc...announced the presentation of research investigating the anti-cancer activity of (Z)-endoxifen and its byproducts at the American Association for Cancer Research (AACR) Special Conference in Cancer Research, taking place in Toronto from December 9-11. The poster...outlines results from a study investigating four (Z)-endoxifen byproducts for their anti-estrogenic and anti-tumor effects in estrogen receptor-positive (ERα+) breast cancer cell lines, including those with ESR1 mutations (Y537S and D538G) associated with endocrine resistance. Notably, compounds AT416E and AT402E demonstrated strong anti-proliferative activity, with AT416E also showing enhanced inhibition of cell migration and invasion. All four byproducts exhibited greater anti-proliferative effects than (Z)-endoxifen in estrogen-deficient conditions, while (Z)-endoxifen remained the most potent at inducing cell cycle arrest and apoptosis, reinforcing its potential as a therapeutic agent."

Preclinical • Estrogen Receptor Positive Breast Cancer

Atossa Therapeutics Announces Five Abstracts Highlighting (Z)-Endoxifen Research Accepted for Presentation at the 2024 San Antonio Breast Cancer Symposium (GlobeNewswire) - "Atossa Therapeutics, Inc...announced that five abstracts featuring data on (Z)-endoxifen have been accepted for presentation at the San Antonio Breast Cancer Symposium (SABCS), taking place December 10-13, 2024, in San Antonio, Texas. The presentations will showcase significant findings from various studies evaluating the use of (Z)-endoxifen in breast cancer prevention and treatment, including phase 2 trials and innovative combination therapy research."

P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics and Quantum Leap Healthcare Collaborative Dose First Patient in I-SPY 2 Trial Combining (Z)-Endoxifen with Abemaciclib for ER+/HER2- Breast Cancer (GlobeNewswire) - "Atossa Therapeutics, Inc...announced the first patient has been dosed in their clinical trial evaluating Atossa’s proprietary (Z)-endoxifen in combination with abemaciclib (VERZENIO), a cyclin-dependent kinase (CDK) 4/6 inhibitor marketed by Eli Lilly and Company, as a neoadjuvant treatment in high-risk 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 oncology with a focus on breast cancer....Data from the study, anticipated in 2026, is expected to further validate the growing body of evidence that (Z)-endoxifen is safe and highly efficacious in both premenopausal and postmenopausal breast cancer patients."

P2 data • Trial status • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics Announces Support of Clinical Study Testing New, Artificial Intelligence, Breast Cancer Risk Assessment Model (GlobeNewswire) - "Atossa Therapeutics, Inc...announced support for a new Phase 2 study designed to validate an innovative, artificial intelligence driven, breast cancer risk assessment model. The SMART (Stockholm MAmmography Risk stratified Trial) study will test an individualized, imaging-based screening model designed to identify women with the highest risk of developing breast cancer in the next two years. If the model is validated for therapeutic use, it could serve as the foundation for a future, Phase 3, trial investigating (Z)-endoxifen in the breast cancer prevention setting."

Clinical • Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics Announces Last Patient, Last Dose in its Phase 2 Karisma-Endoxifen Clinical Trial (GlobeNewswire) - "Atossa Therapeutics, Inc...announced that the last patient in the Company’s Karisma-Endoxifen clinical trial received their final dose of study medication....'We look forward to seeing the breast density reduction data in the coming months and sharing it with regulatory authorities as it will allow us to further progress plans for a potential Phase 3, registrational study'."

P2 data • Trial status • Breast Cancer • Oncology

Atossa Therapeutics Announces Support of New Breast Cancer Screening Guidelines (GlobeNewswire) - "Atossa Therapeutics, Inc...announced its support of new guidelines released by the U.S. Preventive Services Task Force (USPSTF) recommending that women begin breast cancer screening starting at age 40....The updated guidelines recommend women undergo biennial mammography screening beginning at the age of 40 until the age of 74....The announced changes from USPSTF also come in advance of a September 2024 deadline mandated by U.S. FDA requiring mammogram facilities to provide women with detailed information regarding their breast density, as part of routine mammograms....Karisma-Endoxifen study, is investigating (Z)-endoxifen’s ability to reduce mammographic breast density in premenopausal women with measurable density. The trial fully enrolled in November 2023 and data is expected in the second half of 2024."

Clinical guideline • P2 data • Breast Cancer • Oncology • Solid Tumor

Data from Atossa’s Phase 2 EVANGELINE Clinical Trial to be Presented at American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Atossa Therapeutics, Inc...announced today that data from the 40mg pharmacokinetic (PK) run-in cohort of the ongoing Phase 2 EVANGELINE (Endoxifen Versus exemestANe GosEreLIn) study will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 5-10, 2024, in San Diego, California. The EVANGELINE study is investigating (Z)-endoxifen as a neoadjuvant treatment for premenopausal women diagnosed with 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."

P2 data • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Dr Goetz on the Early Pharmacokinetic Data With Neoadjuvant (Z)-endoxifen in ER+/HER2– Breast Cancer (OncLive) - P2 | N=180 | EVANGELINE (NCT05607004) | Sponsor: Atossa Therapeutics, Inc. | "Matthew P. Goetz...discusses pharmacokinetic data for neoadjuvant (Z)-endoxifen derived from the phase 2 EVANGELINE trial (NCT05607004) of premenopausal patients with metastatic estrogen receptor (ER)–positive, HER2-negative breast cancer...A total of 7 women were enrolled onto the pharmacokinetic run-in portion of the study and received 40 mg of the study drug per day, he states....Results from the pharmacokinetic run-in, which were presented at the 2024 AACR Annual Meeting, demonstrated that concentrations observed with the 40 mg dose ranged between 200 to 400 ng/ml, which was slightly below the target range, Goetz reports. As a result, the study is progressing to evaluate the 80 mg per day dose of (Z)-endoxifen to achieve optimal therapeutic concentrations, he explains. Enrollment to this portion of the study is ongoing."

P2 data • PK/PD data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics Presents Data from 40mg Cohort of Phase 2 EVANGELINE Clinical Trial Showing 100% Disease Control Rate After 24-Weeks of Treatment with (Z)-Endoxifen (GlobeNewswire) - P2 | N=180 | EVANGELINE (NCT05607004) | Sponsor: Atossa Therapeutics, Inc. | "Atossa Therapeutics, Inc...announced promising safety and efficacy data from the Company’s Phase 2 EVANGELINE (Endoxifen Versus exemestANe GosEreLIn) clinical trial....even women were enrolled in the cohort and treated daily for 28 days. At 28 days, six of the seven had Ki-67 levels below 10% and stayed on treatment for an additional five months. Per the study protocol, the seventh patient, whose Ki-67 decreased 19% but stayed above 10%, discontinued treatment and had surgery....Ki-67 for the 40mg cohort patients was reduced from an average of 14.5% at screening to 5.3% at 28 days and 1.2% at 24-weeks. This represents a reduction of 63% at 28 days and 92% at 24 weeks. Ki-67 is a cellular marker for proliferation and indicates how fast the tumor is growing."

P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Data from Atossa’s Phase 2 EVANGELINE Clinical Trial to be Presented at American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Atossa Therapeutics, Inc...announced today that data from the 40mg pharmacokinetic (PK) run-in cohort of the ongoing Phase 2 EVANGELINE (Endoxifen Versus exemestANe GosEreLIn) study will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 5-10, 2024, in San Diego, California."

P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Atossa begins trial for non-surgical DCIS treatment (Investing.com) - "Atossa Therapeutics, Inc...has announced the initiation of a Phase 2 trial involving a non-surgical approach for treating Ductal Carcinoma In Situ (DCIS). The first patient received a dose of Atossa's proprietary Selective Estrogen Receptor Modulator (SERM), (Z)-endoxifen, as part of the RECAST DCIS study, which aims to assess the possibility of long-term active surveillance of DCIS without surgery."

Trial status • Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics Announces Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "R&D expenses for the nine months ended September 30, 2023, were $11,680, an increase of $1,583 from total R&D expenses for the nine months ended September 30, 2022 of $10,097. Key changes were as follows: The increase in R&D expense was primarily due to increased spending on clinical and non-clinical trials of $1,467 compared to the prior year period due to increased spending on (Z)-endoxifen trial costs."

Commercial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology

Quantum Leap Healthcare Collaborative Initiates Landmark Phase 2 RECAST DCIS Platform Trial to Evaluate Alternative DCIS Treatments with Atossa Therapeutics, Havah Therapeutics, and the Menarini Group (PRNewswire) - "Quantum Leap Healthcare Collaborative...announces the enrollment launch for the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS), a Phase 2 platform study aimed at preventing the progression of DCIS to breast cancer."

Licensing / partnership • Trial status • Breast Cancer • Oncology • Solid Tumor

Atossa Therapeutics' upcoming breast cancer trial results expected to drive stock higher (Proactiveinvestors) - "Near-term data readouts include the Phase 2 80mg pharmacokinetic (PK) data readout from EVANGELINE for premenopausal women with ER+/HER2- breast cancer guided for the first quarter of 2024; the Phase 2 data readout from Phase 2 I-SPY 2 study in neoadjuvant ER+ breast cancer guided for the third quarter of 2024; and the Phase 2 data from Atossa’s Karisma-Endoxifen study guided for the second half of 2024."

P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Atossa to initiate breast cancer combo therapy trial in Canada (Clinical Trials Arena) - "Atossa Therapeutics has received approval from Health Canada to initiate the Phase II Endoxifen Versus exemestANe GosEreLIn (EVANGELINE) study in pre-menopausal women with breast cancer. With the ‘No Objection Letter’ from Health Canada, the company will enrol patients throughout Canada and open sites to conduct the study."

Trial status • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor