8-K: Atossa Therapeutics Presents Promising Phase 2 Data for Breast Cancer Drug at San Antonio Symposium

Atossa Therapeutics announced the presentation of pharmacokinetic and tolerability data from their Phase 2 EVANGELINE trial of (Z)-endoxifen at the San Antonio Breast Cancer Symposium, showing promising results for premenopausal women with ER+/HER2breast cancer.

Summary

• Atossa Therapeutics presented three posters at the San Antonio Breast Cancer Symposium (SABCS) regarding their Phase 2 EVANGELINE trial of (Z)-endoxifen.
• The EVANGELINE trial is investigating (Z)-endoxifen as a neoadjuvant treatment for premenopausal women with estrogen receptor-positive (ER+)/HER2-negative breast cancer.
• The first poster focused on the pharmacokinetic (PK) run-in phase, evaluating 40 mg and 80 mg doses of (Z)-endoxifen, with and without goserelin for ovarian function suppression (OFS).
• 50% of patients receiving 80 mg of (Z)-endoxifen with goserelin achieved target steady-state plasma concentrations (Css) of 500-1000 ng/mL, while 38% of patients on 80 mg (Z)-endoxifen alone reached these levels.
• The average plasma Css level for all patients receiving 80mg/day of (Z)-endoxifen was 484 ng/mL.
• Tissue Css levels were more than double the plasma levels at the 80 mg dose, surpassing the 500 ng/g target in 90% of patients.
• Substantial tumor suppression was observed across all dosing levels, with Ki-67 10% response rates generally above 85%.
• The second poster highlighted patient-reported outcomes, indicating that (Z)-endoxifen was generally well-tolerated with mostly low-grade side effects.
• The third poster outlined the design of the randomized trial, which will compare 40 mg/day (Z)-endoxifen plus OFS to exemestane plus OFS, using 4-week Ki-67 reduction as the primary endpoint.
• The trial is expected to begin recruitment in 2025.

Sentiment

Score: 8

Explanation: The document presents positive data from the Phase 2 trial, showing good pharmacokinetic results, tumor suppression, and tolerability. The company has a clear plan for the next phase of the trial, and management is optimistic. However, it is still early-stage data, and there are risks associated with clinical trials.

Positives

• The 80 mg dose of (Z)-endoxifen achieved target plasma and tissue concentrations in a significant portion of patients.
• Tissue concentrations of (Z)-endoxifen were more than double the plasma concentrations, indicating good drug penetration into the tumor.
• Substantial tumor suppression was observed across all dosing levels.
• (Z)-endoxifen was generally well-tolerated with mostly low-grade side effects.
• The trial design has been optimized based on the PK run-in data.

Negatives

• Four gynecologic events were reported in the 80 mg groups, including one Grade 3 hemorrhagic cyst.
• Some patients reported mild to moderate bothersome symptoms like hot flashes and reduced libido.
• Amenorrhea and menstrual suppression were common side effects.

Risks

• The trial is still in Phase 2, and further studies are needed to confirm the efficacy and safety of (Z)-endoxifen.
• There are risks associated with clinical trials, including the possibility of unexpected adverse events or failure to meet endpoints.
• The company's ability to successfully develop and commercialize (Z)-endoxifen is subject to regulatory approvals and market acceptance.
• The company's financial performance and ability to raise capital could impact the development of (Z)-endoxifen.

Future Outlook

Atossa plans to advance the randomized portion of the EVANGELINE trial in 2025, seeking to demonstrate the potential of (Z)-endoxifen to improve outcomes and provide a better-tolerated option for premenopausal women with ER+/HER2breast cancer.

Management Comments

• We are encouraged by the breadth of data being presented at SABCS, which collectively advances our understanding of (Z)-endoxifens safety, efficacy, and impact on patient quality of life, said Steven Quay, M.D., Ph.D., Atossas President and Chief Executive Officer.
• We believe we now have a clear plan for the randomized portion of the EVANGELINE trial, including a defined (Z)-endoxifen dose and study design.

Industry Context

This announcement is relevant to the broader oncology field, particularly in breast cancer treatment. The development of new hormonal therapies like (Z)-endoxifen is important for patients who may not respond well to existing treatments or who experience significant side effects. The focus on premenopausal women with ER+/HER2breast cancer addresses a specific unmet need.

Comparison to Industry Standards

• The use of Ki-67 reduction as a primary endpoint is a common practice in neoadjuvant breast cancer trials, allowing for early assessment of treatment efficacy.
• The target plasma concentrations of 500-1000 ng/mL for (Z)-endoxifen are based on preclinical and early clinical data, aiming to achieve therapeutic levels.
• The reported tissue concentrations exceeding 500 ng/g are significant, as they indicate good drug penetration into the tumor, which is crucial for effective treatment.
• The 85% Ki-67 response rate is promising and compares favorably to other neoadjuvant hormonal therapies, such as aromatase inhibitors, which typically show response rates in the 60-80% range.
• The tolerability profile of (Z)-endoxifen, with mostly low-grade side effects, is also a positive sign, as many hormonal therapies are associated with significant side effects that can impact patient compliance.
• Companies like AstraZeneca with their drug 'Faslodex' and Novartis with 'Kisqali' are competitors in the hormonal therapy space for breast cancer, but (Z)-endoxifen's unique mechanism of action and potential for better tolerability could provide a competitive advantage.

Stakeholder Impact

• Shareholders may view the positive trial data as a positive development for the company.
• Patients with ER+/HER2breast cancer may benefit from the development of a new treatment option.
• Employees may be motivated by the progress of the clinical trial.
• The company's suppliers and partners may see increased business opportunities.

Next Steps

• The company will make the poster presentations available on their website on December 11.
• The process for trial initiation has begun, and recruitment for the randomized portion of the EVANGELINE trial is expected to begin in 2025.

Key Dates

Keywords

Z-endoxifen, breast cancer, EVANGELINE trial, pharmacokinetics, tolerability, neoadjuvant treatment, ER+, HER2-, San Antonio Breast Cancer Symposium, Ki-67, ovarian function suppression, SERM