Slide 1: TXMD Overview
TXMD Overview August 2016 THER-0086 8/16
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation by TherapeuticsMD, Inc. (referred to as “we” and “our”) may contain forward-looking statements. Forward- looking statements may include, but are not limited to, statements relating to our objectives, plans and strategies, as well as statements, other than
Slide 3: TXMD: women's health company
(TXMD) Innovative women’s health company exclusively focused on developing and commercializing products for women throughout their life cycles Drug candidate portfolio is built on SYMBODA™ technology for the solubilization of bio-identical female hormones 3
Slide 4: Compelling Investment Opportunity
Compelling Investment Opportunity Worldwide commercial rights for multiple hormone therapy products in phase 3 and earlier stages Well-known chemical entities with established safety and efficacy thresholds Large U.S. markets with favorable competitive and regulatory dynamics Additional early
Slide 5: Investigational Pipeline
Investigational Pipeline Pre-Clinical Phase 1 Phase 2 Phase 3 NDA Filing Yuvvexy™ (17ß-estradiol Vaginal Softgel Capsule) TX-004HR 07/07/2016 Oral Combination: 17ß-estradiol + Progesterone TX-001HR Q4 2016 Transdermal Progesterone TX-005HR Q4 2016 Transdermal 17ß-estradiol + Progesterone TX-006HR Q4
Slide 6: Key Accomplishments and Anticipated Milestones
Key Accomplishments and Anticipated Milestones Submitted New Drug Application for YuvvexyTM (TX-004HR) for all Expected YuvvexyTM three doses (4 mcg, 10mcg, 25mcg) PDUFA date 505(b)(2) pathway July ‘16 4Q ‘16 1H ‘17 Expected to report phase 3 Replenish Trial topline results (TX-001HR) Proj
Slide 7: Yuvvexy TX-004HR | Vulvar and Vaginal Atrophy (VVA) Program
YuvvexyTM TX-004HR | Vulvar and Vaginal Atrophy (VVA) Program 7
Slide 8: Overview – Vulvar and Vaginal Atrophy (VVA)
Overview – Vulvar and Vaginal Atrophy (V VA) Chronic and progressive condition characterized by thinning of vaginal tissue from decreased estrogen levels Diagnosed in approximately 50% of postmenopausal women1 Primary symptom = dyspareunia Secondary symptoms include: dryness, itching, irrita
Slide 9: Current VVA Market Overview
Current VVA Market Overview 32MM Women with VVA Symptoms1,2 ~50% of women seek treatment for VVA4 OTC Product Users 7%, or 2.3MM women, are currently being treated today with Rx hormone therapy (HT)3 Not Seeking 25% 18%, or 5.7MM women, have tried HT and Treatment were unsatisfied/unsuccessful4
Slide 10: Current FDA-Approved VVA Competitive Landscape
Current FDA-Approved VVA Competitive Landscape 1 U.S. sales more than doubled since 2008 4 Global market expected to be $2.1 billion in 2022 Currently no generic competition – Vagifem AG expected October 2016 7% current market penetration 2015 TRx 2015 U.S. Sales 2 Product Company Compound (
Slide 11: Current FDA-Approved VVA Product Use Falls Short
Current FDA-Approved VVA Product Use Falls Short VVA Market Market Size Perceived Product Shortcomings Opportunity Long-term safety concerns1 2.3MM Women2 Efficacy1 Current HT Users 7% of VVA Population Messiness1 >$1.5B Need for applicator1 Unsatisfied / unsuccessful with past 5.7MM Women
Slide 12: Yuvvexy – TX-004HR
YuvvexyTM – TX-004HR Small, digitally inserted, rapidly dissolving softgel capsule No applicator Proposed dose packaging to optimize compliance and convenience Submitted NDA on July 7, 2016 under 505(b)(2) pathway Prototype Starter Pack 0.69 x 0.3 inch Prototype Maintenance Pack YUVVEXY™ is
Slide 13: Yuvvexy – Potential Best In Class VVA Therapy
YuvvexyTM – Potential Best In Class VVA Therapy Premarin® Vagifem® Estrace® Osphena® Yuvvexy® (if approved) Products Method of Admin Vaginal Cream Vaginal Tablet Vaginal Cream Oral Tablet Vaginal Capsule Reusable Reusable Application Vaginal Applicator Oral Daily SERM Digitally Inserted Softgel Vagi
Slide 14: Yuvvexy - Designed for Long Term Compliance
YuvvexyTM - Designed for Long Term Compliance Current Market Yuvvexy Vaginal Creams: Reasons Women Stop Muco-adhesive, Dissolves Quickly and Completely Messiness1 Mean Duration No Applicator and No Dose Preparation Reusable Applicator1 of Use: 1.5 Months2 Long-term Safety1 Onset-of-Action (Efficacy
Slide 15: Co-Primary and Key Secondary Endpoints
Co-Primary and Key Secondary Endpoints LS Mean Change from Baseline to Week 12 Compared to Placebo 4 mcg 10 mcg 25 mcg Superficial Cells <0.0001 <0.0001 <0.0001 Parabasal Cells <0.0001 <0.0001 <0.0001 Vaginal pH <0.0001 <0.0001 <0.0001 Severity of Dyspareunia 0.0149 <0.0001 <0.0001 Severity of Vagin
Slide 16: Co-Primary and Key Secondary Efficacy Endpoints TX-004HR 4 mcg
Co-Primary and Key Secondary Efficacy Endpoints TX-004HR 4 mcg Arithmetic Mean Estradiol Serum Concentrations - LS Mean Change from Baseline to Week 12 Unadjusted TX-004HR 4 mcg (N=18) LS Mean Change from 4 mcg Baseline to Week 12 P-value 4 mcg Placebo Superficial Cells 17% 6% <0.0001 Parabasal Cell
Slide 17: Co-Primary and Key Secondary Efficacy Endpoints TX-004HR 10 mcg
Co-Primary and Key Secondary Efficacy Endpoints TX-004HR 10 mcg Arithmetic Mean Estradiol Serum Concentrations - LS Mean Change from Baseline to Week 12 Unadjusted TX-004HR 10 mcg (N=19) LS Mean Change from 10 mcg Baseline to Week 12 P-value 10 mcg Placebo Superficial Cells 17% 6% <0.0001 Parabasal
Slide 18: Co-Primary and Key Secondary Efficacy Endpoints TX-004HR 25 mcg
Co-Primary and Key Secondary Efficacy Endpoints TX-004HR 25 mcg Arithmetic Mean Estradiol Serum Concentrations - LS Mean Change from Baseline to Week 12 Unadjusted TX-004HR 25 mcg (N=18) LS Mean Change from 25mcg Baseline to Week 12 P-value 25 mcg Placebo Superficial Cells 23% 6% <0.0001 Parabasal C
Slide 19: Severity of Dyspareunia
Unadjusted Change From Baseline Severity Score Dyspareunia Based on Pivotal Clinical Data - Not Head-to-Head Comparative Studies Severity of Dyspareunia -1.2* -1.4 -1.48 -1.55 -1.5 *Composite score of most bothersome symptoms, including dyspareunia Vagifem [package label] http://www.novo-pi.com/vagi
Slide 20: Dyspareunia and Vaginal Dryness By Study Visit
Dyspareunia and Vaginal Dryness By Study Visit Statistical Significance of Severity of Dyspareunia Statistical Significance of Severity of Vaginal Dryness LS Mean Change from Baseline (by Study Visit) LS Mean Change from Baseline (by Study Visit) 4 mcg 10 mcg 25 mcg 4 mcg 10 mcg 25 mcg Week 2 0.026
Slide 21: Efficacy and Onset of Action
Efficacy and Onset of Action Not Head-to-Head Comparative Studies Premarin® Vagifem® Estrace® Osphena® Estring® Onset of Action* Week 4+ Week 12 Dyspareunia Approval Approval without without Week 8 dyspareunia dyspareunia (composite score) and dryness and dryness Onset of Action* Not Not data data D
Slide 22: Yuvvexy Qualitative Attributes
YuvvexyTM Qualitative Attributes Ease of Use 4 mcg 10 mcg 25 mcg Placebo (N=181) (N=181) (N=184) (N=185) Easy to Use 171 (94.5%) 172 (95.0%) 175 (95.1%) 164 (88.9%) Overall p-value = 0.035 Patient Satisfaction 4 mcg 10 mcg 25 mcg Placebo (N=181) (N=181) (N=184) (N=185) Very Satisfied 74 (40.1%) 84 (
Slide 23: Physical and Clinical Attributes Enable Market Expansion
Physical and Clinical Attributes Enable Market Expansion YuvvexyTM Attributes Could Address YuvvexyTM Perceived Shortcomings of Current Products Market Opportunity Negligible systemic profile may give comfort for long term use REJOICE data: first efficacy observation for dyspareunia and Current
Slide 24: Favorable Regulatory Dynamics Driven by Change in Treatment Paradigm
Favorable Regulatory Dynamics Driven by Change in Treatment Paradigm Citizen’s Petition, spearheaded by NAMS, Citizen’s Petition Supporters: for modification of black box warnings Removal of Nov. 2015 – FDA “boxed warnings” Black Box workshop provided an opportunity for Warning FDA to obtain inp
Slide 25: Future VVA HT Market
Future VVA HT Market TherapeuticsMD VVA Market Goals Potential launch of Yuvvexy Increase market awareness for VVA and the associated symptoms Convert unsatisfied past users of HT therapy to satisfied patients on drug Increase market penetration among OTC product users Increase duration of
Slide 26: Foundation Built for a Strong Launch
Foundation Built for a Strong Launch Operational leverage of OB/GYN relationships in key markets Map Legend: Current TXMD Sales Presence Highest Prescribing Physicians for VVA 50 Sales Representatives; Planned Increase to 150 With Launch of Yuvvexy 26
Slide 27: TX-001HR | Combination Estrogen + Progesterone (E+P) Program
TX-001HR | Combination Estrogen + Progesterone (E+P) Program 27
Slide 28: Menopause Overview
Menopause Overview Menopause represents the natural life-stage transition when women stop having periods as the production of Estrogen (E) and Progesterone (P) decreases Average age of menopause 51 years1 Women will spend approximately half of their lives in this state May result in physical and
Slide 29: Evolution of U.S. HT Market Post WHI Study
Evolution of U.S. HT Market Post WHI Study July 2002 - Women’s Health Initiative (WHI) study showed that synthetic hormones increased the risk of breast cancer, stroke, heart attack and blood clots Post WHI, women shifted to Bio-Identical Hormone Therapy (BHT) containing Natural Estradiol (E2) and N
Slide 30: Bio-Identical Hormones Are What Women and Doctors Want
Bio-Identical Hormones Are What Women and Doctors Want FDA-Approved Compounded Synthetic and Separate E&P Market1 Bio-identical Hormone Therapy Market2,3 120,000,000 35,000,000 30,000,000 100,000,000 25,000,000 Prescriptions Prescriptions 80,000,000 20,000,000 60,000,000 15,000,000 40,000,000 10,000
Slide 31: Compounded Bio-Identical HT: Why Has It Been So Successful?
Compounded Bio-Identical HT: Why Has It Been So Successful? Synthetic Progestins Bio-identical Progesterone References No benefits on sleep properties Favorable CNS Profile Freeman, E, et al.1 Increased risk of breast cancer Favorable breast profile E3N-EPIC2 Increased risk of MI, Stroke, VTE Favora
Slide 32: But…..Compounded Products Pose Significant Risks
But…..Compounded Products Pose Significant Risks Medical Societies’ global consensus statement declares that the use of Custom-Compounded HT is not recommended1 ACOG and ASRM Committee Opinion states compounded hormones may pose additional risks compared to FDA-approved products2 Lack of effic
Slide 33: Rationale for TX-001HR
Rationale for TX-001HR Target Goals Preliminary Supportive Data Potential for first and only FDA-approved Meet patient demand for natural estradiol plus natural progesterone bio-identical hormones combination softgel capsule Meet FDA requirements for Multiple FDA guidance documents safe, effective,
Slide 34: TX-001HR Estradiol + Progesterone U.S. Development Timeline
TX-001HR Estradiol + Progesterone U.S. Development Timeline Q1 ’15 Q2 ’15 Q3 ’15 Q4 ’15 Q1 ’16 Q2 ’16 Q3 ’16 Q4 ’16 Q1 ’17 Q2 ’17 Q3’17 Q4’17 Q1’18 Phase 3 Vasomotor & Endometrial Safety NDA Prep/Filing/PDUFA Phase 3 Trial1: ~100 U.S. sites Subjects: ~1750 fully enrolled as of October 2015 Fou
Slide 35: Total HT Market = 38+MM Prescriptions
Total HT Market = 38+MM Prescriptions U.S. women using FDA-approved Combinations of Estradiol, 3 custom-compounded Estrogens, Progesterones & Progestins 1-2.5MM menopausal hormone (8.1MM prescriptions)1 therapy Compounded Bio-Identical Hormones (30MM prescriptions)2,3 1) Symphony Health Solutions PH
Slide 36: Potential First and Only FDA-Approved Bio-Identical Combination Product
Potential First and Only FDA-Approved Bio-Identical Combination Product FDA Approved If Approved Activella® Compounded Generic 17b Prempro® TX – 001HR Separate E+P FemHRT® Duavee® Brisdelle® E+P + Progestins Premphase® Products Angeliq® 25,000 compounding pharmacies Bio-Identical Saf
Slide 37: Adverse Reimbursement Changes for Compounded Drugs
Adverse Reimbursement Changes for Compounded Drugs May 30, 2014: CVS/Caremark forces compounding pharmacies to include NDC numbers for each ingredient used and two scientifically valid studies in peer-reviewed journals supporting clinical efficacy of the additional ingredients1 June 3, 2014: ESI lau
Slide 38: Non-FDA-Approved BHT Market Represents Significant Opportunity
Non-FDA-Approved BHT Market Represents Significant Opportunity for First FDA-Approved Product 2 Annual custom Average 30MM -compounded $49 1 monthly $1.5B Current Annual prescriptions cash cost Revenues Average net 2 Annual 30MM $150 4 monthly Potential Future Annual branded prescriptions branded $4
Slide 39: Regulatory Environment Continues to Favor FDA-Approved Products
Regulatory Environment Continues to Favor FDA-Approved Products October 2012 2014 2016 July 2018 Contaminated Creation of “Do Not USP-800 finalized, Final implementation compounded Compound” list and addressing of USP-800 drugs made at established Pharmacy hazardous drugs NECC kill 77 Compounding in
Slide 40: Regulatory Tailwinds for FDA-Approved Products
Regulatory Tailwinds for FDA-Approved Products Drug Quality and Security Act (DQSA)1 Prohibits compounding of essential copies of an FDA-approved drug except in limited circumstances such as drug shortages Requires collaboration between the FDA and state boards of pharmacy to inspect, enforce, a
Slide 41: Compounding Pharmacies Need An FDA-Approved Product
Compounding Pharmacies Need An FDA-Approved Product Compounded BHT TX-001HR (if approved) Third-Party Reimbursement No Yes Required Capital Expenditure to Dispense Yes No Manufacturing and Compliance Investment Yes No Legal & Regulatory Risk Yes No If approved, compounding pharmacies who dispense Hi
Slide 42: TX-001HR Could Fulfill Therapeutic Gap For All Participants
TX-001HR Could Fulfill Therapeutic Gap For All Participants Patients • Meet demand for natural bio-identical hormone therapy • Assurance of safety and efficacy • Reduction of out-of-pocket costs via insurance coverage • Convenience of one combination product • Widely acceptable at all pharmacies and
Slide 43: TXMD: Financial Snapshot
TXMD: Financial Snapshot Listing Exchange Debt $0MM Shares Outstanding Cash 196.5MM $166.5MM (as of August 1, 2016) (as of June 30, 2016) 43
Slide 44: Worldwide Patent Filings
Worldwide Patent Filings* Strong IP Portfolio with 135 Patent Applications, including 72 international filings, and 17 issued U.S. patents *Not all patent filings filed in all jurisdictions. 44
Slide 45: THANK YOU!
TherapeuticsMD THANK YOU! TherapeuticsMD”
Slide 46: Appendix
Appendix 46
Slide 47: Seasoned Management Team with a Proven Track Record of Commercial Execution
Seasoned Management Team with a Proven Track Record of Commercial Execution • Former U.S. Secretary of • Co-founded vitaMedMD • Co-founded CareFusion • Former CFO of American • Co-founded vitaMedMD • Former Clinical Lead of Health and Human Services in 2008 • Held executive sales and Wireless, Teleg
Slide 48: TX-004HR vs. Vagifem Phase 1 Single Dose PK Studies
TX-004HR vs. Vagifem® Phase 1 Single Dose PK Studies Key Findings Tmax ~2 hours with TX-004HR and ~8 hours with Vagifem Systemic absorption of estradiol AUC (0-24 hours) is 2- to 3-fold lower with TX-004HR relative to Vagifem Vagifem is a registered trademark of Novo Nordisk A/S Corp. Pickar, et