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Year-end 2024 Business Update March 25, 2025 NASDAQ:ATOS www.atossatherapeutics.com
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Disclaimer • This presentation may contain certain forward-looking statements related to or Atossa Therapeutics, Inc. (the “Company”) that involve risks and uncertainties. • Actual results and events may differ significantly from results and events discussed in forward-looking statements. • Factors that might cause or contribute to such differences include, but are not limited to, those discussed in “Risk Factors” in the Company’s Annual Reports on Form 10-K and subsequent Quarterly Reports on Form 10- Q filed with the Securities and Exchange Commission. • The Company undertakes no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date they were made. • This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdictions in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. • The Company may not yet have received clearance from the FDA or any other regulatory agency for some of the products described in this presentation.
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Problem: High unmet need for ET in breast cancer ~40-50% Patients Discontinue Adjuvant Endocrine Therapy Improved efficacy Reduced resistance Induced apoptosis ~60% Patients Do Not Benefit from 2L fulvestrant monotherapy ~50% Patients Do Not Respond to 1L Aromatase Inhibitors + CDK4/6 Although, endocrine therapy remains the mainstay treatment for patients, there are numerous UNMET NEEDS that still exist for new treatment options References: 1) Annals of Oncology 29: 1541–1547, 2018. 2) IBRANCE Label. 3) KISQALI label. 4) VERENZIO label. 5) Annals of Oncology 29: 1541–1547, 2018. 6) N Engl J Med 2016;375:1925-36. 7) JCO35, 3638-3646(2017). 8) CancerNetwork, December 8, 2022. 9) OncLive Ph3 CAPItello-291 Trial Data, January 4, 2023. 10) AstraZeneca Press Release, December 8, 2022. 12) Faslodex Package Insert. 11) Breast Cancer Res Treat.2022; 193(3): 567–577. Improved adherence
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(Z)-endoxifen is a novel, next-generation anti-estrogen with best-in-class potential across the breast cancer treatment paradigm Superior ER Antagonist 100-fold more potent vs other SERMs Superior antitumor efficacy in preclinical + clinical studies PKCβ1 Inhibition Binds to and inhibits protein kinase C beta one (PKCβ1, a known oncogenic protein) Downregulates AKT pathway and induces apoptosis in breast cancer cells ESR1 Mutant Inhibition Inhibits clinically relevant ESR1 mutants, an acquired resistance mechanism to aromatase inhibitors Improved safety & tolerability Potential to avoid current negative “on target off tissue” effects May increase adherence Superior Combination Partner Potential to be preferred endocrine combination partner (Z)-endoxifen’s points of differentiation PIK3CA AKT 1 PT EN
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(Z)-endoxifen – Metastatic Path for 1 st Indication High Unmet Clinical Need • Significantly improved progression-free survival (PFS) in CDK4/6i-naïve patients: (Z)-endoxifen more than doubled the median PFS compared to tamoxifen (7.2 vs. 2.4 months). • Substantial activity observed even after tamoxifen progression: Patients in the crossover arm who progressed on tamoxifen and switched to (Z)-endoxifen experienced clinical benefit, including partial responses and prolonged stable disease exceeding 2-3 years in some cases. • Favorable safety profile: Despite its higher potency, (Z)-endoxifen has not shown unexpected safety concerns beyond what is typically seen with tamoxifen and has been generally well-tolerated. Efficient Regulatory and Clinical Path • Potentially allows Atossa to more rapidly bring (Z)-endoxifen to patients who need it most. • Strengthens foundation for the expansion of (Z)-endoxifen into earlier-stage disease settings, where (Z)-endoxifen has already shown significant promise in reducing tumor proliferation and preventing recurrence.
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(Z)-endoxifen: Metastatic ClinicalSuperior anti-tumor activity In previous clinical studies, (Z)- endoxifen demonstrated promising anti-tumor activity in endocrine- refractory metastatic breast cancer patients In a Phase II trial comparing (Z)- endoxifen with tamoxifen, CDK4/6 inhibitor naïve patients had improved PFS with (Z)-endoxifen compared to tamoxifen. (Z)-endoxifen demonstrates promising efficacy in the relapsed/refractory setting References: J Clin Oncolo 2017 Oct 20; 35 (30): 3391-3400; Cancer Res 80(4 Suppl): Abstract nr GS4-04 Tumor shrinkage with (Z)-endoxifen treatment in tamoxifen, aromatase inhibitor, fulvestrant and Everolimus refractory breast cancer after 9 months Extended PFS demonstrated by (Z)-endoxifen in a Phase II randomized clinical trial, in the relapse/refractory metastatic setting. n=40 evaluable patients in each arm (Z)-endoxifen Tamoxifen HR= 0.42 (95% CI 0.22-0.80) Log rank test P=0.002 Median PFS (Z)-endoxifen 7.2 months Tamoxifen 2.4 months (Z)-endoxifen Tamoxifen Progression Free Survival (PFS) in Postmenopausal Women (Z)-endoxifen leads to disease regression
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Prevention Neoadjuvant KARISMA: • Unmet need to prevent breast cance rs. • (Z)-endoxifen has demonstrated 1 mg dose of (Z)-endoxifen reduced MBD by 17.3 percentage points (p<0.01) , compared to a minimal change in the placebo group of 0.27 percentage points. • Plasma concentrations for (Z)-endoxifen was measured at 4.8 ng/mL for the 1 mg , 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 EVANGELINE: • Unmet need for safer, more efficacious neoadjuvant therapies • (Z)-endoxifen has demonstrated 1 CR and 5 PRs in the first 6 patients at 40 mg • Expected readout: 80 mg data will be presented at SABCS 2024 I-SPY2: • Unmet need for safer , more efficacious neoadjuvant therapies • Monotherapy and combination therapy with abemaciclib • Expected readout: monotherapy Q4 2024, combination Q1 2026 • In collaboration with Quantum Leap Healthcare Collaborative (Z)-endoxifen (Z)-endoxifen: Parallel Regulatory Path
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EVANGELINE OVERVIEW Clinical 5 PR and 1 CR were observed in the neoadjuvant setting with (z) - endoxifen treatment in post -menopausal ER+/HER2 - breast cancer patients. Superior anti-tumor activity In an ongoing neoadjuvant clinical study, (Z)-endoxifen has demonstrated promising early efficacy with 1 CR and multiple PRs. The 4-week Ki-67 ≤10% response rate was generally above 85% across dose levels, with or without the presence of OFS. Endocrine therapies are generally observed to be cytostatic and do not cause tumor shrinkage. (Z)-endoxifen demonstrates promising efficacy in the neoadjuvant setting References: Cancer Res(2024) 84 (7_Supplement): CT205. One pt discontinued due to wk4 Ki -67 (marker for cell proliferation) remaining > 10%. The remaining 6 had endocrine sensitive disease and underwent surgery after 24 weeks. 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0Ki67 (%) Prior to Cycle 1, Day 1 Cycle 1, Day 28 0% 20% 40% 60% 80% 100% Percent Decrease From Baseline Patient % Decrease in Tumor Size at Cycle 3, Day 28 by MRI Imaging Ki67 From Baseline to Cycle 1, Day 28 EVANGELINE estimated enrollment will be ~180 patients
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(Z)-endoxifen dose Tamoxifen dose Variables 0 mg 1 mg 2 mg 5 mg 20 mg No. of premenopausal women 80 80 80 72a 79a Percent density change (from a regression model) 0.27 -17.3* -23.5* -19.6* -18.5* Mean (Z)-endoxifen concentration at end of study ng/mL - 4.8 9.7 2.5b 12.6b No. of early terminations (%) because of an adverse event related to the IMP# 4 (5.0) 5 (6.3) 11 (13.8) 5 (6.9) 7 (8.9) Mean change in Likert score from baseline to end of treatment Hot Flashes 0.10 0.26 0.45** 0.23* 0.67** Night Sweats 0.10 0.26 0.58** 0.60* 0.70** Cold Sweats 0.04 0.12 0.10 0.12 0.33** Vaginal discharge -0.06 0.05 0.03** -0.12 0.18 Genital itching 0.05 0.21 0.12 0.16* 0.22 Pain or cramps in legs and feet 0.14 0.20 0.17 0.22* 0.38* a premenopausal women in the intention to treat population, * p<0.01, **p<0.05, b for normal CYP2D6 metabolites, IMP#= Investigational Medicinal Product KARISMA-Endoxifen Trial References: Hall et. al. Primary breast cancer prevention using oral endoxifen. SABCS 2024; Li et. al. J Clin Oncol. 2013 Jun 20;31(18):2249-56; Eriksson et. al Cancers (Basel). 2021 Jan 15;13(2):E302; Eriksson et. al. J Clin Oncol. 2021 Mar 18:JCO2002598.; Hammarström et al. . Influence of endoxifen on mammographic density - results from the KARISMA trial. Accepted for publication. J Natl Cancer Inst.; Mocellin et. al. Cochrane Database of Systematic Reviews 2019, Issue 4. Art. No.: CD012191. No. of participants, percent density change, (Z)-endoxifen concentrations, no. of early terminators and change in side effects by (Z)-endoxifen and tamoxifen doses• Significant decrease in mammographic breast density in the 1 mg and 2 mg (Z)- endoxifen arms • Decrease is similar to data with 20mg tamoxifen • The discontinuation rates and adverse event profiles were similar between 1mg (Z)-endoxifen and placebo • Women in the 2mg (Z)-endoxifen arm reported significantly more hot flashes, night sweats, and vaginal discharge than the placebo group. • (Z)-endoxifen adverse event profile appeared to be more favorable than KARISMA-tamoxifen data. • No issues related to skin rashes, itching (other than genital), dry mouth, fatigue, depression, or sexual interest were reported with (Z)- endoxifen.
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Well-positioned across the treatment paradigm Prevention Neoadjuvant Adjuvant Metastatic Value Proposition • Earlier detection in patients with dense breast tissue • Prevention of cancer in at-risk patients • Phase 2 trial completed Value Proposition • Potential Improvement in Breast Conservation Rate • Premenopausal women may avoid ovarian function suppression (OFS), which results in higher use and compliance • Phase 2 underway Value Proposition • Many patients are refractory to Tamoxifen / contraindicated for aromatase inhibitors • Improved safety / tolerability profile and avoid OFS Value Proposition • PD effects and stable- disease responses from Ph1 study reinforce it as a potential next-generation ET. • Tolerable safety profile makes it a promising backbone for combination regimens • Phase 2 reporting underway (Z)-endoxifen
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2024 Year End Financial Update
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Income Statement
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Q&A
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Thank you.