Zonalta (Z-endoxifen hydrochloride) / Jina Pharma, National Cancer Institute, Intas - LARVOL DELTA

Z-Endoxifen Hydrochloride in Treating Patients With Metastatic or Locally Recurrent Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1 | N=62 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Atossa Therapeutics Announces Regulatory Strategy Aimed at Accelerating Development of Low-Dose (Z)-Endoxifen for Breast Cancer Risk Reduction (PRNewswire) - "Atossa...announced today it has requested a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a regulatory strategy aimed at accelerating development of low-dose (Z)-endoxifen for breast cancer risk reduction....Atossa has now filed this meeting request and expects to update shareholders on the outcome of the meeting before year end 2025, based on standard agency timelines."

FDA event • Breast Cancer

Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients (clinicaltrials.gov) - P3 | N=490 | Active, not recruiting | Sponsor: Jina Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Dec 2025

Enrollment closed • Trial completion date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=81 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • NCOA3

Z-Endoxifen Hydrochloride in Treating Patients With Metastatic or Locally Recurrent Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov) - P1 | N=62 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • EGFR • ER • HER-2 • IGF1R • mTOR • NCOA3 • PGR • PI3K

Atossa Therapeutics Reports Positive KARISMA-Endoxifen Trial Results (Atossa Therapeutics Press Release) - P2 | N=240 | KARISMA-Endoxifen (NCT05068388) | Sponsor: Atossa Therapeutics, Inc. | "The relative significant density change was -19.3 percent and -26.5 percent for the 1 and 2 mg arms, respectively, using the placebo arm as a reference. No significant difference was seen comparing the 1 and 2 mg arms. In a 2011 study, women with a breast density decrease of 10 percent or greater after taking tamoxifen for one year had a 62 percent reduction in breast cancer incidence after 5 years. No changes in hematological safety tests or vital signs were noted during the trial period. The mean endoxifen plasma concentration was 5.18 ng/mL in the 1 mg arm and 10.87 ng/mL in the 2 mg arm after one month of therapy. Plasma concentrations stayed the same at three and six months. The number of women that discontinued the study because of side effects related to the drug were 4, 5 and 12 in the placebo, 1 and 2 mg arms, respectively."

P2 data • Women's Health

Atossa Therapeutics Releases Promising Preliminary Analysis Demonstrating (Z)-Endoxifen’s Potential to Rapidly Reduce Ki-67 and Tumor Volume in ER+/HER2- Breast Cancer (GlobeNewswire) - P2 | N=5000 | I-SPY 2 (NCT01042379) | Sponsor: QuantumLeap Healthcare Collaborative | "A preliminary data analysis from this study...showed that (Z)-endoxifen met the primary endpoint with 95 percent (19/20 patients) receiving > 75 % of planned treatment. The data also demonstrated (Z)-endoxifen activity in rapidly reducing key biomarkers such as Ki-67 by 69 percent from baseline and a 30.4 percent reduction in functional tumor volume (FTV) from baseline after 3 weeks of treatment...(Z)-endoxifen was well tolerated in this study with the most common side effects being mild, including hot flushes, insomnia, and fatigue. No dose reductions or discontinuations due to treatment related adverse events were observed in this study."

P2 data • Breast Cancer • Oncology • Solid Tumor

Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients (clinicaltrials.gov) - P3 | N=490 | Recruiting | Sponsor: Jina Pharmaceuticals Inc.

New P3 trial • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients (clinicaltrials.gov) - P3 | N=124 | Completed | Sponsor: Jina Pharmaceuticals Inc. | Recruiting ➔ Completed

Trial completion • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Atossa Therapeutics Completes Enrollment of 80mg Pharmacokinetic Run-In Cohort in Phase 2 EVANGELINE Clinical Trial Evaluating (Z)-Endoxifen as a Neoadjuvant Treatment for ER+ / HER2- Breast Cancer (GlobeNewswire) - "Atossa Therapeutics, Inc...today announced that the 12-patient 80mg pharmacokinetic (PK) run-in cohort of the Phase 2 EVANGELINE (Endoxifen Versus exemestANe GosEreLIn) study has fully enrolled. EVANGELINE is a randomized non-inferiority trial of Atossa’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 study is expected to enroll approximately 175 patients at up to 25 sites across the United States."

Enrollment status • Breast Cancer • Oncology • Solid Tumor

Endoxifen in Adults With Hormone Receptor Positive Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2024 ➔ Jun 2026

Trial completion date • Breast Cancer • Desmoid Tumors • Endometrial Cancer • Gynecologic Cancers • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • HER-2

Atossa Therapeutics Announces Expanded Research Agreement with Weill Cornell Medicine to Further Evaluate Synergy Between Antibody Drug Conjugates (ADCs) and (Z)-Endoxifen (GlobeNewswire) - "Atossa Therapeutics, Inc...today announced an expanded research agreement with Weill Cornell Medicine to explore the potential synergy between antibody drug conjugates (ADCs) and (Z)-endoxifen...The expanded research agreement with Weill Cornell will build on previously conducted in silico research that determined a strong clinically relevant anti-tumor effect when combining ADCs and (Z)-endoxifen....The Weill Cornell research will focus on the combination of (Z)-endoxifen and two FDA-approved ADCs, TRODELVY and ENHERTU....'Once we have this data, we expect to move quickly into a clinical study investigating a (Z)-endoxifen / ADC combination in patients with late-line metastatic breast cancer.'"

Licensing / partnership • 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

Atossa Therapeutics Provides Five-Year (Z)-Endoxifen Treatment Update on FDA-Approved “Expanded Access“ Program for a U.S. Breast Cancer Patient (GlobeNewswire) - "Atossa Therapeutics, Inc...announced that the pre-menopausal, Estrogen Receptor positive (ER+) / Human Epidermal Growth Factor Receptor 2 negative (HER2-), breast cancer patient who received neoadjuvant and adjuvant (Z)-endoxifen therapy under an FDA-approved 'expanded access' program has completed five years of treatment. As of the date of this press release, the patient remains cancer-free and has reported no significant safety or tolerability issues over the course of her treatment."

Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=81 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2024 ➔ Feb 2025

Metastases • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • NCOA3

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: Evaluation of dermal safety, intra-mammary drug distribution, and biologic effects. (PubMed, Biomed Pharmacother) - "We formulated the tamoxifen metabolite (E/Z)-endoxifen for transdermal delivery and tested it in a placebo-controlled, double-blinded Phase I trial with dose escalation from 10 to 20 mg daily. At the endoxifen doses and duration used, and the tissue concentration achieved, we observed a non-significant overall reduction of tumor proliferation (Ki67 LI) and significant downregulation of gene signatures known to promote cancer invasion (FN1, SERPINH1, PLOD2, PDGFA, ITGAV) (p = 0.03). Transdermal endoxifen is an important potential breast cancer prevention agent but formulations with better dermal penetration are needed."

Journal • P1 data • Breast Cancer • Obesity • Oncology • Solid Tumor • PDGFA • PLOD2 • SERPINH1

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: evaluation of dermal safety, intra-mammary drug distribution, and biologic effects (SABCS 2023) - "We formulated the tamoxifen metabolite (E/Z)-endoxifen in a hydroalcoholic/oleic acid gel for transdermal delivery. our evaluation of transdermal (E/Z) endoxifen 10 and 20 mg in hydroalcoholic/oleic acid formulation demonstrates lack of early dermal toxicity, and good tolerability over a month or so of therapy. Our findings warrant development of transdermal formulations of (Z)-endoxifen with better dermal permeation for a Phase 2 breast cancer prevention trial compared to low-dose oral SERMs so that women at high-risk for breast cancer may have a range of cancer prevention options available to them."

Clinical • P1 data • Breast Cancer • AURKA • BIRC5 • CCNB1 • CDK1 • CEP55 • COL11A1 • COL1A1 • FN1 • IGF1 • MKI67 • MYBL2 • PDGFA • PLK1 • PLOD2 • PTTG1 • RRM2 • SERPINH1 • SPP1 • TOP2A • UBE2C

Presurgical Oral Tamoxifen vs Transdermal 4-Hydroxytamoxifen in Women With Ductal Carcinoma In Situ: A Randomized Clinical Trial. (PubMed, JAMA Surg) - P2b | "The median 4-hydroxytamoxifen concentrations deep in the breast were nonsignificantly higher in the oral tamoxifen group (5.7 [IQR, 4.0-7.9] vs 3.8 [IQR, 1.3-7.9] ng/g), whereas endoxifen was abundant in the oral tamoxifen group and minimal in the 4-hydroxytamoxifen gel group (median, 13.0 [IQR, 8.9-20.6] vs 0.3 [IQR, 0-0.3] ng/g; P < .001). New transdermal approaches must deliver higher drug quantities and/or include the most potent metabolites. ClinicalTrials.gov Identifier: NCT02993159."

Clinical • Journal • Oncology • ER

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=81 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2023 ➔ May 2024

Metastases • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Atossa Therapeutics and Quantum Leap Healthcare Provide Enrollment Update for (Z)-Endoxifen Arm of Ongoing I-SPY 2 Clinical Trial (PRNewswire) - "'With the ISPY 2.2 TRIAL, we have focused on optimizing treatments for the fast-growing breast cancers; that focus has allowed us to make great progress. But one of the biggest challenges in breast cancer is the hormone positive breast cancers that are slow growing. They can recur for up to 15 years or more, and we urgently need to find predictors of response so that we can prevent late recurrence. And we know that women suffer from the side effects of years of extended endocrine therapy, especially when they have larger tumors. So, we have a great need to find more effective and more tolerable agents so that women with live longer and better. The goal of the endocrine optimization pilot is to test these new and exciting hormone directed therapies like endoxifen,' said Dr. Laura Esserman..."

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Endoxifen in Adults With Hormone Receptor Positive Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Breast Cancer • Desmoid Tumors • Gynecologic Cancers • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • HER-2

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=81 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2022 ➔ May 2023

Metastases • Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Atossa Therapeutics and Quantum Leap Healthcare Announce New Study Arm to Evaluate (Z)-Endoxifen in the Ongoing I-SPY 2 Clinical Trial (PRNewswire) - "'(Z)-endoxifen is one of the most active metabolites of tamoxifen. Tamoxifen is known to be effective in treating and preventing ER+ breast cancer, but may be most effective in those patients who can adequately metabolize it,' said Dr. Laura Esserman...'(Z)-endoxifen may overcome some of the shortcomings of tamoxifen, as it is already the active metabolite. Perhaps most exciting is that it may be effective in premenopausal women without the need for ovarian suppression. Ovarian suppression in premenopausal women and aromatase inhibitors in postmenopausal women are associated with both short-term and potential long-term side effects that diminish adherence. (Z)-endoxifen holds promise of being a more effective and tolerable alternative to targeting the estrogen receptor in women with early-stage breast cancer.'"

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Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients (clinicaltrials.gov) - P3 | N=124 | Recruiting | Sponsor: Jina Pharmaceuticals Inc. | Unknown status ➔ Recruiting | Trial completion date: May 2021 ➔ May 2024 | Trial primary completion date: Mar 2021 ➔ Jul 2023

Enrollment open • Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Evaluation of tumor and circulating cell free (cf) DNA mutations in women with hormone refractory metastatic breast cancer (MBC) enrolled in a phase I study of Z-Endoxifen (MC093C). (ASCO 2017) - P1; "Prior endocrine therapy included aromatase inhibitors (37/38, 97%), fulvestrant (22/38, 58%) and tamoxifen (26/38, 68%). The absence of cfDNA mutations in patients with endocrine resistant, MBC treated with Z-Endoxifen was associated with significantly longer PFS. Given the discordance between tumor and cfDNA sequence data, future studies must determine which approach maximizes prognosis and prediction of benefit for estrogen-targeted therapy."

Biomarker • Clinical • P1 data • Biosimilar • Hormone Receptor Breast Cancer