Z-endoxifen / Atossa Therap - LARVOL DELTA

Atossa Therapeutics Receives FDA Rare Pediatric Disease Designation for (Z)-Endoxifen for Duchenne Muscular Dystrophy (PRNewswire) - "Designation expands (Z)-Endoxifen program into rare pediatric neuromuscular disease and may qualify Atossa for a future Priority Review Voucher upon approval."

FDA event • Duchenne Muscular Dystrophy

Atossa Therapeutics and Quantum Leap Healthcare Announce I-SPY 2 Clinical Trial to Evaluate (Z)-Endoxifen in Combination with Abemaciclib (VERZENIO) in Women with ER+/HER2- Breast Cancer (Atossa Therapeutics Press Release) - "Atossa Therapeutics...and Quantum Leap Healthcare Collaborative...announced the initiation of a new study to evaluate Atossa’s proprietary (Z)-endoxifen in combination with abemaciclib (VERZENIO), a cyclin-dependent kinase (CDK) 4/6 inhibitor marketed by Eli Lilly and Company, in women with ER+/HER2- breast cancer....The new study arm will enroll approximately 20 women with newly diagnosed Estrogen Receptor positive (ER+) / Human Epidermal Growth Factor Receptor 2 negative (HER2-) invasive breast cancer. Participants will receive 40mg (Z)-endoxifen once daily in combination with 150mg abemaciclib twice daily for a total of 24 weeks prior to surgery."

Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Atossa Therapeutics Announces Year-End 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "(i) Full enrollment of Phase 2 Karisma-Endoxifen Clinical Trial:...Full enrollment was achieved in November 2023 and data is expected in the second half of 2024; (ii) Full enrollment of Phase 2 I-SPY 2 Clinical Trial:....Full enrollment was achieved in February 2024 and data is expected in the second half of 2024; (iii) First patient dosed with (Z)-endoxifen in RECAST DCIS study - the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS) study is an ongoing Phase 2 platform study designed to offer women diagnosed with DCIS six months of neoadjuvant endocrine therapy..."

P2 data • Trial status • Breast Cancer

Atossa Therapeutics Announces Issuance of U.S. Patent Covering Enteric Oral (Z)-Endoxifen Formulations and Methods of Treating Patients Using (Z)-Endoxifen (PRNewswire) - "The newly issued patent includes 100 claims directed to enteric oral formulations of highly pure (Z)-endoxifen free base, as well as methods of using those compositions to treat a range of hormone-dependent breast disorders and other estrogen-related conditions. The patent also covers specific solid oral dosage forms and stable formulations providing therapeutically meaningful and sustained systemic exposure to (Z)-endoxifen....New patent further strengthens global intellectual property estate supporting Atossa's lead program across the breast cancer spectrum and other hormone-driven conditions."

Patent • Breast Cancer

A Phase 2 Trial of (Z)-endoxifen + Goserelin as Neoadjuvant Treatment for Premenopausal Women with ER+, HER2-, Breast Cancer (EVANGELINE) (SABCS 2025) - P2 | "Problematically, only 41% of patients reach this threshold with tamoxifen compared to 78% with AI+OFS (Nitz JCO 2022)...Eligible patients are premenopausal women with Stage IIA/IIB ER+/HER2- breast cancer.• Part 1 (PK Run-in): assessed 40mg vs 80mg ENDX (+/- OFS) in 22 patients.• Part 2: patients with baseline Ki-67 >10% were randomized to 40 mg ENDX + goserelin or exemestane + goserelin for 6 months with the primary objective being 4-week ESD rate...EVANGELINE is the first trial to evaluate (Z)-endoxifen + OFS as neoadjuvant therapy in premenopausal ER+/HER2- breast cancer. By targeting both ER and PKC pathways, ENDX may offer a well-tolerated alternative to AI-based regimens and expand endocrine therapy options for this population. Clinical Trial Registration: NCT05607004"

Clinical • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PRKCB

(z)-endoxifen maintains erα antagonist function against esr1 mutants via inactive conformation stabilization and reversal of mutant esr1-associated transcriptional signatures (SABCS 2025) - "In this in silico modeling study, we examined the biophysical behavior and downstream transcriptional impacts of (Z)-endoxifen, an active tamoxifen metabolite, a selective estrogen receptor modulator (SERM), across ESR1 variants to further elucidate its mechanism of action and therapeutic potential. (Z)-Endoxifen demonstrates robust biophysical and functional activity against ESR1 mutations. It stabilizes inactive ERα conformations and reverses mutant-driven transcriptional programs, showing greater transcriptional breadth than next-generation SERDs like elacestrant. These findings support (Z)-endoxifen's potential as a precision therapy for ESR1-mutant ER+ MBC and justify further clinical investigation in endocrine-resistant settings."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • ER • GLIS2

Atossa Therapeutics Details Accelerated FDA Strategy to Advance (Z)-Endoxifen Across Breast Cancer Continuum (PRNewswire) - "During the meeting, the FDA provided the Company feedback on potential expedited regulatory pathways and development options across metastatic disease, neoadjuvant treatment, and breast cancer risk-reduction settings...This includes multiple high-value clinical settings, including: Metastatic breast cancer (mBC): A dose-ranging study is in preparation as part of the Company's strategy to support registrational development; Neoadjuvant ER+/HER2- breast cancer: Enrollment and data generation continue in the Phase 2 EVANGELINE trial; Breast cancer risk-reduction: Development includes a low-dose strategy targeting mammographic breast density and overall breast cancer risk....The Company also anticipates additional IND submissions in 2026 to advance combination strategies and explore opportunities beyond monotherapy and breast cancer."

FDA event • IND • Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Atossa Therapeutics Selects PSI as Contract Research Organization for Pivotal Dose-Ranging Study of (Z)-Endoxifen in Metastatic Breast Cancer (PRNewswire) - "The global Phase 2, multi-center dose-ranging study is designed to evaluate (Z)-endoxifen monotherapy for safety, pharmacokinetics/pharmacodynamics, and preliminary anti-tumor activity. Patient enrollment is expected to follow the Investigational New Drug (IND) filing in Q4 2025, with topline data anticipated in 2026."

New P2 trial • Breast Cancer

I-SPY 2 - Endocrine Optimization Pilot Analysis (Combination therapy of 40 mg (Z)-endoxifen and Eli Lilly’s abemaciclib) (Atossa Therapeutics Press Release) - "Patient recruitment continues at a faster rate than anticipated, with 41 patients initiated as of July 29, 2025."

Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Atossa Therapeutics Announces Positive FDA Feedback, Advances Toward IND for (Z)-Endoxifen Clinical Program in ER+/HER2- Metastatic Breast Cancer (PRNewswire) - "Atossa Therapeutics...announced positive written feedback from the U.S. Food and Drug Administration (FDA) regarding the company's proposed dose optimization trial of (Z)-endoxifen for the treatment of estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer...The FDA has provided highly constructive responses ahead of the scheduled pre-Investigational New Drug (IND) meeting, affirming key elements of Atossa's clinical development plan, negating the need for a virtual meeting, and paving the way for a potential IND submission targeted for the fourth quarter of 2025...FDA agreed that existing clinical and nonclinical data are sufficient to initiate Part A (monotherapy) of the proposed dose optimization study and provided clear guidance on randomization cohort sizes and study design enhancements....Agreement on Cardiac Safety Assessments for Monotherapy."

FDA event • IND • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Atossa Therapeutics Announces Full Results from I‑SPY 2 Endocrine‑Optimization Sub‑Study Evaluating Low‑Dose (Z)‑Endoxifen (Nasdaq) - 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

Join Atossa Therapeutics' Exclusive Live Investor Webinar and Q&A Session on May 22 (ACCESSWIRE) - "Attendees will gain insight into Atossa's strategic approach to redefining breast cancer treatment through its lead clinical candidate, (Z)-endoxifen - a next-generation SERM with best-in-class potential.... The presentation will highlight recent progress across key development programs, upcoming milestones, and how the Company's differentiated science and capital-efficient model are designed to deliver both clinical impact and long-term shareholder value."

Clinical data • 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