Atossa Therapeutics, Inc. · NASDAQ:ATOS
Atossa Therapeutics — Atossa Genetics — Corporate Update (October 2017)
51 slides from Atossa Therapeutics's corporate update, Oct 25, 2017
Slide 1: Preliminary Oral Endoxifen Phase 1 Results: All Objectives Successfully Met
Preliminary Oral Endoxifen Phase 1 Results All Objectives Successfully Met October 25, 2017 107 Spring Street • Seattle, WA 98104 USA
Slide 2: Forward-looking Statements
Some of the information presented herein may contain projections or other forward - looking statements regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management’s current expectations and
Slide 3: Discussion Topics
Discussion Topics • Atossa Genetics Overview • Endoxifen • Phase 1 Study Summaries – Safety – Tolerability – Pharmacokinetics • Upcoming Milestones 3
Slide 4: Atossa Genetics Overview
Atossa Genetics Overview GENETICS
Slide 5: About Atossa Genetics
About Atossa Genetics (NASDAQ: ATOS) 5 - Clinical - stage company - Novel pharmaceuticals - Novel drug delivery methods - Breast cancer & other breast conditions
Slide 6: Recent capitalization improvements
Corporate Update 6 Recent capitalization improvements: • April 2017 financing included 6M warrants and convertible Preferred • All April warrants have now been exercised • All April preferred stock has now been converted • Outstanding capital now includes only 14M shares of common stock
Slide 7: Breast Cancer Risk Factors & Treatment Approaches
Tamoxifen (Rarely used) Factors that Increase Breast Cancer Risk Lifestyle Genetic Dense Breasts Increased mammograms Enhanced imaging Risk Mitigation Lifestyle Modification Breast Cancer Diagnosis & Treatment Diagnosis _______ Treatment (Surgery, Chemo, Radiation) Routine Screening Long - term Ther
Slide 8: Our Drug and Delivery Programs
Our Drug and Delivery Programs 8 Drug Programs Using our Proprietary Endoxifen : • Topical Endoxifen For mammographic breast density (MBD) reduction All Phase 1 objectives met Phase 2 for MBD in Sweden commencing Q1 2018 • Oral Endoxifen For “ tamoxifen - refractory” patients All Phase 1 objectives
Slide 9: Our Drug and Delivery Programs, Cont.
Our Drug and Delivery Programs, Cont. 9 Two Programs Using Proprietary Microcatheter Technology: • Microcatheters for Transpapillary CAR - T Delivery (TRAP CAR - T) – In R&D phase with goals of reducing toxicity, improving efficacy and the potential of T - cells migrating along the lymphatic pathway
Slide 10: The Unmet Need
The Unmet Need 10 Intraductal Microcatheters Provides alternative to Systemic delivery, which has: • Systemic adverse effects • Limited tumor drug level ATOS microcatheter technology may: • Increase drug to tumor ratio • Improve efficacy • Reduce toxicity • CAR - T cells may follow lymphatic migrati
Slide 11: Breast Cancer Timeline
Suspicious Lump Biopsy Surgery and Radiation/ Chemotherapy Diagnosis Breast Cancer Timeline Tamoxifen (5 years) Intraductal : - Fulvestrant - TRAP CAR - T Oral Endoxifen Neoadjuvant Phase Adjuvant Phase Prevention Window Topical Endoxifen High Density via Mammography 11
Slide 12: Program Pipeline
Program Pipeline 12 Pivota l Preclinical Phase 1 NDA* Market Drug/Device Program * Estimated FDA or Ex - US submission Phase 2 Phase 3 TRAP CAR - T Microcatheters Ph. 2 Underway Microcatheters Fulvestrant - DCIS and BC R&D 2019 2020 Ph. 2 starts in Q1 ‘18 Breast Density Refractory t o Tamoxifen Ph.
Slide 13: Endoxifen
Endoxifen @Atossa GENETICS 13
Slide 14: Endoxifen - Overview
Endoxifen - Overview 14 • Most active metabolite of tamoxifen • Tamoxifen has been widely studied • Tamoxifen is a pro - drug • Up to 50% of patients can’t make enough E ndoxifen (1) Tamoxifen Endoxifen (1) Breast Care (Basel): Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast C
Slide 15: Why Endoxifen?
Low levels of circulating Endoxifen during tamoxifen adjuvant therapy correlate to an increased risk of recurrent or new breast cancers • Identified as an independent risk factor • Known and unknown causes for low endoxifen levels during tamoxifen therapy • Most active tamoxifen metabolite • It may
Slide 16: Endoxifen – Rationale for Development
Endoxifen – Rationale for Development 16 • Develop TWO formulations for two large unmet medical needs: – Topical to reduce density – less than 5% of high risk patients will take oral t amoxifen because of actual or perceived side effects (1) – Oral – up to 50% of patients taking tamoxifen are refrac
Slide 17: High Breast Density Masks Tumors
High Breast Density Masks Tumors Source: http ://woodtv.com/2015/05/11/are - you - dense - know - your - numbers / 17
Slide 18: High Breast Density Correlates With Breast Cancer
High Breast Density Correlates With Breast Cancer http://slideplayer.com/slide/1557508/ 18
Slide 19: Current Paradigm for Tamoxifen Use in U.S.
Current Paradigm for Tamoxifen Use in U.S. 1 million breast cancer patients take oral tamoxifen for at least five years 10 million patients with a high risk of breast cancer are indicated for chemoprevention with oral tamoxifen Source: Freedman AN, Graubard BI, Rao SR, McCaskill - Stevens W, Ballard
Slide 20: Many Drugs Limit Liver Endoxifen Production from Tamoxifen
Many Drugs Limit Liver Endoxifen Production from Tamoxifen • SSRI drugs like Prozac and Paxil (paroxetine) stop liver metabolism of tamoxifen to endoxifen • Before : 20 mg/day tamoxifen yields 12.4 ng/mL plasma endoxifen • After : four weeks of 10 mg/day of paroxetine is administered • Plasma endoxi
Slide 21: Emerging Unmet Medical Need
• Tamoxifen Refractory Patients – Up to 50% of patients fail to achieve therapeutic endoxifen blood levels • Approximately 30 nM is therapeutic threshold – Only option is aromatase inhibitors • Significant adverse drug effects Emerging Unmet Medical Need 21
Slide 22: Large Market Opportunities
Large Market Opportunities 22 Intraductal Fulvestrant : $800M U.S. market in DCIS pre - surgery and replacement to surgery (Defined Health 1/17) TRAP CAR - T: TBD U.S. Market Triple neg. – 37k patients/yr.; can’t use hormone therapy The Need: Breast Cancer Statistics • 250,000+ cancers and 60,000 DC
Slide 23: Phase 1 Study
Phase 1 Study @Atossa 23 NM GENETICS
Slide 24: Preliminary Phase 1 Oral Results
• Study objectives achieved • Demonstrated: - Safety - Tolerability - Verification of therapeutic blood levels Supports continued development Preliminary Phase 1 Oral Results 24
Slide 25: Product Development Timeline
Q2 2016 • Contracted to develop endoxifen API Q3 2016 • First batch of API for clinical use Q4 2016 • Topical formulation development in US • Retained CRO in Australia Q1 2017 • Retained CMO in Australia (for topical and oral presentations) Q2 2017 • Approval to start study • First cohort enrolled •
Slide 26: Preliminary Study Conclusions
• All study objectives successfully achieved – Safety: There were no clinically significant safety signals and no clinically significant adverse events in participants receiving oral Endoxifen . – Tolerability: Oral Endoxifen was well tolerated at each dose level and for the dosing duration utilized
Slide 27: Study Design Summary
Two - part double - blinded, placebo controlled, dose escalation trial investigating the safety and pharmacokinetics of (Z) - Endoxifen in healthy female volunteers – Part A: Topical – liquid applied to the breasts – Part B: Capsule – taken orally Study Design Summary 27
Slide 28: Phase 1 Study Design
PART A (Topical). Cohorts, dose levels and number of participants. Cohort Dose Level Number of Participants (mg per breast) (Total mg) (Z) - Endoxifen Placebo 1 1 2 6 2 2 3 6 6 2 3 5 10 6 2 PART B (Oral). Cohorts, dose levels and number of participants. Dose Level (mg/day) (Z) - Endoxifen Placebo 4
Slide 29: Oral Study Demographics
Oral Study Demographics Table 14.1.2-B Sunmary of Demographics, Part B oral Administration Cohort 4 Cohort 5 Cohort 6 1 ng 2 mg 4 ng Parameter Statistic (N=6) (es) os=6) Age (Years) N 6 6 6 18 6 24 Mean 39.3 22.8 33.5 31.9 27.5 30.8 sD 14.4 1.9 ADA 12.7 Dot 16 Median 36.5 22.5 28.5 27.0 26.0 27.0 Mi
Slide 30: Safety Summary
Safety Summary 30 There were no clinically significant safety signals and no clinically significant adverse events in participants receiving oral Endoxifen.
Slide 31: Safety Summary – Oral Study
• No safety signals observed in weekly assessments of/in: – Blood chemistry – Coagulation parameters – Hematology parameters – Urinalysis – Vital Signs – Heart – Physical Examinations Safety Summary – Oral Study 31
Slide 32: Serious Adverse Events None Reported
Serious Adverse Events None Reported Safety Summary – Oral Study 32
Slide 33: Safety Summary – Oral Study
• AEs deemed Probable as relationship to study drug: – in 5 of 18 subjects receiving oral Endoxifen (28%, 7 AEs ) – in 3 of 6 subjects receiving oral placebo (50%, 6 AEs) – All were assessed as “Mild” • AEs deemed probably related to study drug for oral administration were: – 1 mg : Vomiting (n = 1
Slide 34: Tolerability Summary
Tolerability Summary 34 Oral Endoxifen was well tolerated at each dose level and for the dosing duration utilized in the study.
Slide 35: Tolerability Summary – Oral Study
Tolerability Summary – Oral Study Based on responses from a validated questionnaire, oral endoxifen was well tolerated and similar to the placebo capsules Question: “I am bothered by side - effects of treatment” 35
Slide 36: FACT-ES Validated Questionnaire of Endocrine Symptoms
FACT - ES Validated Questionnaire of Endocrine Symptoms Current therapy has a substantial effect on the FACT - ES Score Tolerability Summary – Oral Study 36
Slide 37: Pharmacokinetics Summary
Pharmacokinetics Summary 37 Oral Endoxifen demonstrated blood levels that have been associated with a therapeutic effect in the adjuvant setting in women with breast cancer.
Slide 38: Pharmacokinetics Objective
Pharmacokinetics Objective • The typical plasma endoxifen levels after 20 mg daily tamoxifen in women who are poor metabolizers of tamoxifen (PM), intermediate metabolizers (IM), and excellent metabolizers (EM) • Reference : https:// www.ncbi.nlm.nih.gov/pubmed/22955113 Therapeutic level is reported
Slide 39: Single Dose Pharmacokinetics
Single Dose Pharmacokinetics Time, hours Pharmacokinetics Summary – Oral Study 39
Slide 40: Pseudo-Steady State Levels
Pseudo - Steady State Levels: 21 Day Sample EM IM PM Plasma endoxifen levels after 20 mg/day tamoxifen, based on CYP2D6 status, published data Pharmacokinetics Summary – Oral Study 40
Slide 41: Preliminary Study Conclusions
Preliminary Study Conclusions • All primary and secondary endpoints successfully met – Safety: There were no clinically significant safety signals and no clinically significant adverse events in participants receiving oral endoxifen. – Tolerability: Oral endoxifen was well tolerated at each dose lev
Slide 42: Oral Endoxifen – Refractory Clinical Trial Design
Oral Endoxifen – Refractory Clinical Trial Design 42 Entry Criteria: ER + breast cancer patients on tamoxifen Measure Endoxifen Levels >TBD nM Endoxifen Continue on tamoxifen (20 mg/day) ≤TBD nM Endoxifen Add Oral Endoxifen (1 - 2 mg/day)
Slide 43: Endoxifen Regulatory Pathway
Endoxifen Regulatory Pathway 43 Program could qualify for designation under the 505(b)(2) status. Advantages: A single clinical study of safety and efficacy Limited additional clinical or pre - clinical studies Leverage published clinical study data Multi - year market exclusivity possible
Slide 44: Intraductal Microcatheters
Intraductal Microcatheters 44
Slide 45: Intraductal Microcatheters
Intraductal Microcatheters 45 • Potential advantages: higher local drug/CAR - T exposure; lower systemic concentrations (lower toxicity) vs systemically delivered agents; potential for lymphatic migration of T - cells • 1 issued and 3 pending patent app’s (US and PCT) for intraductal delivery of dru
Slide 46: Intraductal Microcatheters - Fulvestrant
Intraductal Microcatheters - Fulvestrant 46 • Phase 2 study for delivery of fulvestrant in patients with DCIS or breast cancer (initiated at Columbia; transferred to Montefiore) • Advantages: potentially higher local drug exposure and lower systemic concentrations vs systemically delivered agents •
Slide 47: Microcatheter Fulvestrant - Clinical Trial Study Design
Microcatheter Fulvestrant - Clinical Trial Study Design Thirty women with ER + DCIS or Invasive Breast Cancer 6 24 Drug Administered 30 - 45 days B efore S urgery Assessments Efficacy Safety Pharmacokinetics Pathological Response, Ki - 67 Expression FACT - ES Tolerability Tissue and Blood Levels of
Slide 48: Microcatheters – TRAP CAR-T
Microcatheters – TRAP CAR - T 48 Source: NIH Step 1 : Remove blood and genetically modify T - cells to kill cancer Step 2 : Atossa’s Transpapillary (TRAP) microcatheters delivery CAR modified T - cells to breast ducts containing cancer cells
Slide 49: Upcoming Milestones
TRAP CAR - T - Seeking partners Topical Endoxifen: Phase 2 study of MBD to start in Q1 ‘18 with Karolinska Institute Investigator in Stockholm Oral Endoxifen : Phase 2 study for patients refractory to Tamoxifen is planned to start Q1 ‘18 Upcoming Milestones 49
Slide 50: Seasoned Management
50 Seasoned Management Steven Quay, MD, PhD Chairman, CEO and President Kyle Guse, CPA, ESQ, MBA CFO and General Counsel Janet Rose Rea, MSPH, RAC VP Regulatory, Quality and Clinical Affairs
Slide 51: MScenerics
MScenerics Atossa GENETICS NASDAQ: ATOS 51