Our Growth Strategy

Our goal is to become theWe are a women’s health care company recommended by health care providers to all patients by becoming the new standard in women’s health with a complete linecorporate culture designed to foster innovation in the development and commercialization of products all under one quality brand. Key elementsthat address the needs of patients, pharmacists, payers and providers in the twenty-first century.

We believe that building a culture of innovation around patient needs and opportunities, rather than focusing on specific drugs, will enable us to effectively develop and commercialize our strategy to achieve this goal are as follows:products.

Exclusive Focus on Women’s Health Issues. We plan toFor the last seven years, we have steadily developed relationships with many of the largest OB/GYN practices in the country through the sales of our line of prenatal vitamins. Our singular focus exclusively on women’s health issues towill enable us to continue to build long-term relationships with women as they move through their life cycles of birth control, pregnancy, child birth, and pre- and post-family planning through menopause.

Focus on Hormone Therapy Products. We plan to continue our focus on the development, clinical trials, and commercialization of hormone therapy products designed to (1) alleviate the systemssymptoms of, and reduce the health effects resulting from, menopause-related hormone deficiencies, including hot flashes, osteoporosis, and vaginal dryness, and (2) demonstrate equivalent clinical efficacy at lower doses, enabling an enhanced side effect profile compared with competing products. We believe there is a large unmet need in this segment of the market.

Penetrate BioidenticalCompounding Market with FDA-approved Products. As we are not aware of any current FDA-approved bioidentical hormone therapy combination products that are bioidentical to – or having the same chemical and molecular structure as - the estradiol and progesterone produced by the ovaries, we believe that our hormone therapy drug candidate for combined estradiol and progesterone, if approved by the FDA, will provide a safer and more effective alternative to non-FDA approved compounded bioidentical hormone therapy products, at a lower price to patients duesince most insurance companies do not provide coverage for non-FDA approved compounded products. We intend to insurance coverage.work with independent and community based pharmacies that currently compound bioidentical hormone therapy products to help them transition their patients to our hormone therapy products, if approved. We recently launched the BIO-IGNITE™ program, an outreach program to quantify the number of compounded bio-identical estradiol and progesterone prescriptions currently dispensed by the 3,000-3,500 high-volume compounding pharmacies and qualify their interests in dispensing our hormone therapy product candidates, if approved.  As part of the BIO-IGNITE™ program, we intend to work with compounding pharmacies to identify the number of compounded estradiol and progesterone prescriptions that are directly substitutable by the two potential doses of TX-001HR, if approved, and to enter into agreements with such pharmacies to dispense our hormone therapy products in lieu of compounding, if approved.

Multi-Channel Marketing Emphasis. We plan to maintain ancontinue our emphasis on large group OB/GYN practices that provide opportunities to reach large patient bases and that are receptive to the data and savings we provide. We believe this will effectively position us for the launch of our hormone therapy products, if approved.

In addition, proliferation of digital technology has dramatically increased the amount of information to available to patients and providers putting more power in their hands. We believe this makes patient/provider engagement and experience a more important lever for life sciences companies and that providing patients and providers with important information whenever and however they want it, on a real-time basis, is a critical piece of serving this market.

Multiple Distribution ChannelsSales Partners. We are pursuingplan to continue to pursue multiple distribution channels,sales partners, including physicianslarge chain pharmacies, independent community pharmacies, mail order and pharmacies,compounding and specialty pharmacies. We believe providing a higher level of customer care through ourunique programs targeted at each of these sales forcepartners can produce better outcomes and our website.value for the patient, provider and payer.

Geographical Expansion. We plan to expand our geographic market and sales team to cover the entire country by increasing our current 36 sales territories to 60 sales territories in the next 18 months.approximately 100 professionals.

Introducing New Products. We plancontinue to introduce a new prescription prenatal vitamin product under our branded vitaMedMD name and our generic Prena1 name in the first quarter of 2014, as well as the development ofdevelop our hormone therapy drug candidates consisting of a (1) bioidenticalan oral combination of progesterone and estradiol product, (2) an oral progesterone product, and (3) a suppository vulvar and vaginal atrophy estradiol product. Early pharmacokinetic, or PK, studies of our combination estradiol and progesterone drug candidate demonstrate that the product is bioequivalent to the reference listed(TX-001HR), and (2) a vaginal estradiol softgel drug (based on the criterion that the 90% confidence interval on the test-to-reference ratio is contained entirely within the interval 0.800 to 1.250)candidate (TX-004HR).

Our Current Product Lines

We offer a wide range of products targeted for women’s health specifically associated with pregnancy, child birth, nursing, post-child birth, and menopause, including prescription and over-the-counterOTC prenatal vitamins, iron supplements, vitamin D supplements,and a natural menopause relief products, and stretch mark creamsproduct under our vitaMedMD brand name and duplicateauthorized generic formulations of some of our prescription prenatal vitamin products referred to as “generic” formulations, under our BocaGreenMD Prena1 name. As of January 1, 2017, we decided to focus on selling our prescription vitamins and ceased manufacturing and distributing our OTC product lines, except for Iron 21/7, which sales have declined steadily over time resulting in immaterial sales.

For the years ended December 31, 2016, 2015, and 2014, approximately 99.8%, 99.5%, and 98%, respectively, of our consolidated revenue was generated by our prenatal vitamin products.

In March 2012, we launched our first prescription-onlyprescription prenatal vitamin, vitaMedMD Plus Rx, with subsequent launches of our second prescription-onlyprescription prenatal vitamin, vitaMedMD One Rx, in April 2012 and our third prescription-onlyprescription prenatal vitamin, vitaMedMDRediChew™,vitaMedMD RediChew™ Rx, in May 2012. In the fourth quarter of 2012, we launched our BocaGreenMD Prena1 line brand was launched and our first products includeof prescription prenatal vitamins, which included three prescription products Prena1 Plus, Prena1, and Prena1 Chew, which are duplicate, or “generic”prenatal vitamins that were authorized generic formulations of our vitaMedMD-branded prescription prenatals.prenatal vitamins. In the first quarter of 2014, we will introduce vitaPearl,introduced a new prescription prenatal vitamin. This “complete prenatal in one tiny pearl”vitamin product under our branded vitaMedMD name as vitaPearl and under our authorized generic Prena1 name as Prena1 Pearl, which features a unique, proprietary combination of FOLMAX™, FePlus™, and pur-DHA™. In January 2016 we launched vitaTrue. Our current product line is detailed below.

vitaTrue^TM

vitaTrue^TM is our newest prescription prenatal vitamin and is targeted at health-conscious consumers. vitaTrue^TM is the first and only vegan and kosher prenatal vitamin with 40% more folic acid than the leading prescription prenatal vitamin. vitaTrue^TM contains a complete multivitamin with 16 essential vitamins and minerals and 300 mg of plant based docosahexaenoic acid, or DHA. vitaTrue is fish, gluten, lactose, and sugar free.

vitaPearl™

vitaPearl is our leading prescription prenatal vitamin and is a complete prenatal vitamin in one tiny pearl. vitaPearl provides 40% more folic acid than the leading prescription prenatal vitamin. vitaPearl delivers 14 key vitamins and minerals plus 200 mg of DHA, providing comprehensive support for a woman and her body whether she is planning a pregnancy, pregnant, or nursing.

vitaMedMD Plus (Prenatal Women’s Multivitamin + DHA™)

vitaMedMD Plus Prenatal is a once-daily, two pill combo pack that contains a complete multivitamin with 16 essential vitamins and minerals and 300 mg of plant based DHA,DHA. As of January 1, 2017, we ceased manufacturing and is Vegan and Kosher certified. Based on recent medical and scientific research, we have optimized many of the nutrients found indistributing vitaMedMD Plus Prenatal. Plus. All minerals, including iron, zinc, and copper, are chelated to improve absorption.

vitaMedMD One Prenatal Multivitamin

vitaMedMD One One is a single-dose daily multivitamin that provides 14 vitamins and minerals and 200 mg of vegetarian, plant-based DHA. Each convenient, easy-to-swallow softgel also features 975 mcg of folic acid. As of January 1, 2017, we ceased manufacturing and distributing vitaMedMD One.

vitaMedMD Plus Rx Prenatal Multivitamin

vitaMedMD Plus Rx is a once-daily, two pill combo prescription-onlyprescription product containing one prenatal vitamin tablet with Quatrefolic^®, the fourth generation folate, and one plant-based DHA 300 mg capsule. Quatrefolic^® is a registered trademark of Gnosis S.P.A. All minerals, including iron, zinc, and copper, are chelated to improve absorption. As of end of third quarter of 2016, we ceased manufacturing and distributing vitaMedMD Plus Rx Prenatal Multivitamin and replaced it with vitaTrue.^TM.

vitaMedMD One Rx Prenatal Multivitamin

vitaMedMDOne Rx is a prescription-onlyprescription product with a single-dose daily multivitamin that provides 14 vitamins and minerals, Quatrefolic^®, and 200 mg of plant-based DHA.

vitaMedMD RediChew™RediChew® Rx Prenatal Multivitamin

vitaMedMDRediChew™ RediChew® Rx is a prescription-only,prescription, easy-to-chew, small, vanilla-flavored chewable tablet containing Quatrefolic,Folmax®, vitamin D3, to promote healthy birth weight, vitamin B2, to support bone, muscle, and nerve development, and vitamin B6, and vitamin B12 to help relieve nausea and morning sickness.B12. We believevitaMedMD RediChew Rx is an excellent option for women who have difficulty swallowing tablets or softgels, or are experiencing nausea and morning sickness.

vitaMedMD Iron 21/7

vitaMedMD Iron 21/7 is an iron replacement supplement with a 3-weeks-on/1-week-offthree weeks-on/one week-off dosing schedule intended to maximize absorption and enhance tolerability. It is formulated with 150 mg of chelated iron to help improve tolerability and limit typical side effects associated with iron replacements. Each easy-to-swallow single tablet serving also includes 800 mcg of folic acid, plus vitamins C and B12, and succinic acid to aid in absorption.

vitaMedMD Menopause Relief with Lifenol^® Plus Bone Support

vitaMedMD Menopause Relief with Lifenol^® Plus Bone Support offers a natural treatment for hot flashes, night sweats, and mood disturbances. Each single tablet dosage delivers 120 mg of Lifenol^®, a well-studied female hops extract recognized for its potency and support in alleviating hot flashes, plus plant phytoestrogens. It also includes calcium and vitamin D3 for added bone support. As of January 1, 2017, we ceased manufacturing and distributing vitaMedMD Menopause Relief with Lifenol^®.

vitaMedMD Vitamin D3 50,000 IU

vitaMedMD Vitamin D3 50,000 IU and Vitamin D3 2,000 IU

vitaMedMD Vitamin D3 50,000 IU and Vitamin D3 2,000 IU areis a dietary supplementssupplement provided in a small, easy-to-swallow gel capsule that help replenish and maintain beneficial levels of vitamin D in the body. Sustaining adequate levels of vitamin D in the body is essential to bone health, enhancing the absorption of calcium and phosphorus. Vitamin D3, also known as cholecalciferol, is considered the most preferred form of vitamin D as it is the most active form of the nutrient. We believevitaMedMDVitamin D3 50,000 IU and Vitamin D3 2,000 IU areis ideal for pregnant, breastfeeding, and menopausal women to sustain adequate levels of vitamin D.

As of January 1, 2017, we ceased manufacturing and distributing vitaMedMD Signature Collection Stretch Mark Body CreamVitamin D3 50,000 IU.

vitaMedMD Signature Collection Stretch Mark Body Cream contains naturally derived ingredients, including peptides, shea butter, sweet almond oil, and fruit extracts. This combination of ingredients hydrates, soothes, and pampers skin to make it softer, smoother, and younger-looking. It helps reduce the appearance of stretch marks, scars, and other skin irregularities by hydrating and replenishing the skin’s moisture, diminishing the look of fine lines and wrinkles, and encouraging the fading of age spots and sun spots.vitaMedMD Stretch Mark Body Cream is hypoallergenic, paraben-free, and non-comedogenic.

BocaGreenMD Prena1 PlusPearl

BocaGreenMD Prena1 Plus is a prescription-only, comprehensive single-dose dietary supplement containing one prenatal tablet with 16 vitamins and minerals, plus one softgel with 300 mg of plant-based life’s DHA.

BocaGreenMD Prena1

BocaGreenMD Prena1 Pearl is an authorized generic of vitaPearl, a prescription-only, convenient single-dose softgel with 14 vitamins, minerals and 200 mg of plant-based DHA.complete prescription prenatal vitamin in one tiny pearl.

BocaGreenMD Prena1 Chew

BocaGreenMD Prena1 Chew is an authorized generic of vitaMedMD RediChew Rx, a prescription-only,prescription, single daily easy-to-chew, vanilla-flavored, chewable tablet well-suited for women planning a pregnancy and those with difficulty swallowing tablets or capsules or when nausea or morning sickness make taking tablets or capsules difficult.tablet.

AllBocaGreenMD Prena1 multivitamins contain a combination of folic acid and Quatrefolic and are available by prescription only.

Our Hormone Therapy Drug Candidates

We have obtained FDA approvalacceptance of our IND applications to conduct clinical trials for fourfive of our proposed products: TX 12-001HR,hormone therapy drug candidates. In December 2016, we announced positive top-line results from the recently completed REPLENISH Trial, our oralphase 3 clinical trial of TX-001HR, our bio-identical hormone therapy combination of 17ß- estradiol and progesterone and estradiol; TX 12-002HR,in a single, oral softgel drug candidate, for the treatment of moderate to severe VMS due to menopause in post-menopausal women with an intact uterus. In December 2015, we completed the REJOICE Trial, our oral progesterone alone; TX 12-003HR,phase 3 clinical of TX-004HR, our oralapplicator-free vaginal estradiol alone; and TX 12-004HR, our estradiol alonesoftgel drug candidate for the treatment of moderate to severe dyspareunia (vaginal pain during sexual intercourse), a symptom of VVA in post-menopausal women with vaginal suppository.

TX 12-001HR

TX 12-001HR,linings that do not receive enough estrogen. On July 7, 2016, we submitted a NDA for all three doses of TX-004HR that were evaluated in the REJOICE Trial. In the fourth quarter of 2016 we submitted an IND for TX-006HR, our combination estradiol and progesterone drug candidate is undergoingin a topical cream form, and intend to commence phase 1 clinical trials of this drug candidate in 2017. In July 2014, we suspended enrollment in the SPRY Trial, our phase 3 clinical trial for TX-002HR, our oral progesterone alone drug candidate, and, in October 2014, we stopped the trial in order to update the phase 3 protocol based on discussions with the FDA. We have no current plans to conduct clinical trials for TX-003HR, our oral estradiol alone drug candidate, and the IND for this drug candidate is currently inactive.

TX-001HR

TX-001HR is our bio-identical hormone therapy combination of 17ß- estradiol and progesterone in a single, oral softgel drug candidate for the treatment of moderate to severe vasomotor symptomsVMS due to menopause, including hot flashes, night sweats and sleep disturbances and vaginal dryness, forin post-menopausal women with an intact uterus. The hormone therapy drug candidate is chemically identicalbioidentical to – or having the same chemical and molecular structure as - the hormones that naturally occur in a woman’s body, namely estradiol and progesterone, and is being studied as a continuous-combined regimen, (wherein which the combination of estrogen and progesterone are taken together in one product daily).daily. If approved by the FDA, we believe this would represent the first time a combination product of estradiol and progesterone the biologically identical or bioidentical to the estradiol and progesterone produced by the ovaries would be approved for use in a single combined product. According to Source Healthcare Analytics, the total FDA-approved market for menopause-related combination estrogen/progestin was approximately $625 million in U.S. sales for the 12 months ended December 31, 2013.

We previously conducted a pharmacokinetics, or PK, study of Therapeutics’TX 12-001HRTX-001HR to demonstrate that our drug candidate is bioequivalent to the reference listed drug based on the criterion that the 90% confidence interval on the test-to-reference ratio is contained entirely within the interval 80% to 125%. The study compared our combined capsule TX 12-001HRTX-001HR of 2 mg estradiol and 200 mg of progesterone to 2 mg of Estrace^® and 200 mg of Prometrium^®.

The study compared the mean plasma concentrations for free estradiol between TX 12-001HRTX-001HR and Estrace^® in 62 female test subjects. When the results of a single dose-fed study were compared over 48 hours by the test drug versus reference drug, the ratio was 0.93 with the standard deviation within the subject being 0.409 for an upper 95% confidence bound of -0.089. The maximum plasma concentration levels of free estradiol showed that the drug versus reference-versus -reference drug ratio was 0.88 with the standard deviation within the subject being 0.344 for an upper 95% confidence bound of -0.040 over 48 hours.

The study also compared the mean plasma concentrations for progesterone between TX 12-001HRTX-001HR and Prometrium^® in 62 female test subjects. When the results were compared over 48 hours of the test drug verses referencethat the drug-versus-reference drug, the ratio was 1.05 with the standard deviation within the subject being 0.956 for an upper 95% confidence bound of -0.542. The maximum plasma concentration levels of progesterone showed drug versus reference drug ratio as 1.16 with the standard deviation within the subject being 1.179 for an upper 95% confidence bound of -0.785 over 48 hours.

We believe these data are sufficient to demonstrate the bioequivalence of TX 12-001HR to Estrace^® and Prometrium^® based on the criteria for demonstrating bioequivalence established in connection with the study.

On September 5, 2013, we began enrollment of patients in the REPLENISH Trial, a multicenter, double-blind, placebo-controlled, phase 3 clinical trial of TX-001HR in postmenopausal women with an intact uterus. The trial was designed to measureevaluate the safety and effectiveness in treatingefficacy of TX-001HR for the symptomstreatment of moderate to severe VMS due to menopause and protecting the endometrium.endometrial safety of TX-001HR. Patients were assigned to one of five arms, four active and one placebo, and received study medication for 12 months. The primary endpoint for the reduction of endometrial hyperplasia was an incidence of endometrial hyperplasia of less than 1% at 12 months, as determined by endometrial biopsy. The primary endpoint for the treatment of moderate to severe VMS was the mean change of frequency and severity of moderate to severe VMS at weeks four and 12 compared to placebo, as measured by the number and severity of hot flashes. Only subjects experiencing a minimum daily frequency of seven moderate to severe hot flashes at screening were included in the VMS analysis, while all subjects were included in the endometrial hyperplasia analysis. The secondary endpoints included reduction in sleep disturbances and improvement in quality of life measures, night sweats and vaginal dryness, measured at 12 weeks, six months and 12 months. The trial evaluated 1,835 patients between 40 and 65 years old at 111 sites. On December 5, 2016, we announced positive topline data for the REPLENISH Trial.

The REPLENISH Trial evaluated four doses of TX-001HR and placebo; the doses studied were:

The REPLENISH Trial results demonstrated:

● TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5 mg/progesterone 100 mg both achieved all four of the co-primary efficacy endpoints and the primary safety endpoint. 

● TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5 mg/progesterone 100 mg both demonstrated a statistically significant and clinically meaningful reduction from baseline in both the frequency and severity of hot flashes compared to placebo. 

● TX-001HR estradiol 0.5 mg/progesterone 50 mg and TX-001HR estradiol 0.25 mg/progesterone 50 mg were not statistically significant at all of the co-primary efficacy endpoints. The estradiol 0.25 mg/progesterone 50 mg dose was included in the clinical trial as a non-effective dose to meet the recommendation of the FDA guidance to identify the lowest effective dose. 

● The incidence of consensus endometrial hyperplasia or malignancy was 0 percent across all four TX-001HR doses, meeting the recommendations established by the U.S. Food and Drug Agency’s (FDA) draft guidance.

As outlined in the FDA guidance, the co-primary efficacy endpoints in the REPLENISH Trial were the change from baseline in the number and severity of hot flashes at weeks four and 12 as compared to placebo. The primary safety endpoint was the incidence of endometrial hyperplasia with up to 12 months of treatment. General safety was also evaluated.

The results of the REPLENISH Trial are summarized in the table below (p-values of < 0.05 meet FDA guidance and support evidence of efficacy):

MITT = Modified intent to treat

^ŦPer FDA, consensus hyperplasia refers to the concurrence of two of the three pathologists be accepted as the final diagnosis

We anticipate that we will submit an NDA for TX-001HR to the FDA in the third quarter of 2017. Assuming that the NDA is accepted 60 days thereafter and an FDA review period of ten months from the receipt date to the Prescription Drug User Fee Act, or PDUFA, date for a non-new molecular entity, the NDA for TX-001HR could be approved by the FDA as soon as the first half of 2018.

According to Symphony Health Solutions, sales of FDA-approved combinations of estrogen and progestins were approximately $603 million and the sales of estradiol and progesterone on a stand-alone basis were approximately $955 million and approximately $360 million, respectively, in the United States for the 12 months ended December 31, 2016.

TX 12-002HRTX-002HR

TX 12-002HRTX-002HR is a natural progesterone formulation for the treatment of secondary amenorrhea without the potentially allergenic component of peanut oil. The product would be chemically identicalhormone therapy drug candidate is bioidentical to – or having the same chemical and molecular structure as - the hormones that naturally occur in a woman’s body. We believe it will be similarly effective to traditional treatments, but may demonstrate efficacy at lower dosages.

In January 2014, we began recruitment of patients in the SPRY Trial, a phase 3 clinical trial designed to measure the safety and effectiveness of TX-002HR in treatingthe treatment of secondary amenorrhea. AccordingDuring the first two quarters of 2014, the SPRY Trial encountered enrollment challenges because of Institutional Review Board, or IRB, approved clinical trial protocols and FDA inclusion and exclusion criteria. In July 2014, we suspended enrollment and in October 2014 we stopped the SPRY Trial in order to Source Healthcare Analytics,update the total FDA-approved market for oral progestin was approximately $364 millionphase 3 protocol based on discussions with the FDA. We are considering updating the phase 3 protocol to, among other things, target only those women with secondary amenorrhea due to polycystic ovarian syndrome and to amend the primary endpoint of the trial. We believe that the updated phase 3 protocol, if proposed by us and approved by the FDA, would allow us to mitigate the enrollment challenges in, U.S. sales forand shorten the 12 months ended December 31, 2013.duration of, the SPRY Trial. However, there can be no assurance that the FDA will approve the updated phase 3 protocol if we propose it. We have currently suspended further development of this drug candidate to prioritize our leading drug candidates.

TX-003HR

TX 12-003HR

TX 12-003HRTX-003HR is a natural estradiol formulation. This hormone therapy drug candidate would be chemically identicalis bioidentical to the hormones that naturally occur in a woman’s body. We currently do not have plans to further develop this hormone therapy drug candidate. AccordingOur IND related to Source Healthcare Analytics, the total FDA-approved market for oralTX-003HR is currently inactive.

TX-004HR

TX-004HR is our applicator-free vaginal estradiol was approximately $130 million in U.S. sales for the 12 months ended December 31, 2013.

TX 12-004HR

TX 12-004HR is a vaginal suppository estradiolsoftgel drug candidate for the treatment of vulvar and vaginal atrophy, ormoderate to severe dyspareunia, a symptom of VVA in post-menopausal women with vaginal linings that do not receive enough estrogen. We believe that our drug candidate will be at least as effective as the traditional treatments for VVA because of an early onset of action with less systemic exposure, inferring a greater probability of dose administration to the target tissue, and that it will have an added advantage of being a simple, easier to use dosage form versus traditional VVA treatments. In August 2013, weTX-004HR features our SYMBODA^TM technology. This allows for the production of cohesive, stable formulations and provides content uniformity and accuracy of dosing strengths for TX-004HR. We initiated the REJOICE Trial, a randomized, multicenter, double-blind, placebo-controlled phase 13 clinical trial during the third quarter of 2014 to assess the safety and efficacy of three doses — 25 mcg, 10 mcg and 4 mcg (compared to placebo) — of TX-004HR for the treatment of moderate to severe dyspareunia, or painful intercourse, as a symptom of VVA designeddue to measuremenopause.

On December 7, 2015, we announced positive top-line results from the effectREJOICE Trial. The pre-specified four co-primary efficacy endpoints were the changes from baseline to week 12 versus placebo in the percentage of TX 12-004HRvaginal superficial cells, percentage of vaginal parabasal cells, vaginal pH and severity of participants’ self-reported moderate to severe dyspareunia as the most bothersome symptom of VVA. The trial enrolled 764 postmenopausal women (40 to 75 years old) experiencing moderate to severe dyspareunia at approximately 89 sites across the United States and Canada. Trial participants were randomized to receive either TX-004HR at 25 mcg (n=190), 10 mcg (n=191), or 4 mcg (n=191) doses or placebo (n=192) for a total of 12 weeks, all administered once daily for two weeks and then twice weekly (approximately three to four days apart) for ten weeks.

The following table sets forth the statistical significance of the REJOICE Trial results for the four pre-specified co-primary efficacy endpoints, based on certain clinical endpoints, including a study candidate’s pH levels, vaginal cytology, andmean changes from baseline to week 12 compared to placebo.  Based on our analyses of the REJOICE Trial data, statistical significance of the results for the co-primary endpoint of severity of participants’ self-reported moderate to severe dyspareunia as the most bothersome symptom of VVA outhas improved for all three doses from the results originally reported.

The 25 mcg dose of TX-004HR demonstrated highly statistically significant results at the p < 0.0001 level compared to placebo across all four co-primary endpoints. The 10 mcg dose of TX-004HR demonstrated highly statistically significant results at the p < 0.0001 level compared to placebo across all four co-primary endpoints. The 4 mcg dose of TX-004HR also demonstrated highly statistically significant results at the p < 0.0001 level compared to placebo for the endpoints of vaginal superficial cells, vaginal parabasal cells, and vaginal pH; the change from baseline compared to placebo in the severity of dyspareunia was statistically significant at the p = 0.0149 level. The FDA has previously indicated to us that in order to approve the drug based on a single trial, the trial would need to show statistical significance at the 0.01 level or lower for each endpoint, and that a trial that is merely statistically significant at a higher level may not provide sufficient evidence to support an NDA filing or approval of a drug candidate where the NDA relies on a single clinical trial.

Statistical improvement over placebo was also observed for all three doses at the first assessment at week two and sustained through week 12 (see table below).

Vaginal dryness was a prespecified key secondary endpoint. The 25 mcg and 10 mcg doses of TX-004HR demonstrated highly statistically significant results at the p < 0.0001 level compared to placebo for the endpoint of vaginal dryness. The 4 mcg dose of TX-004HR demonstrated statistically significant results at the p = 0.0014 level compared to placebo (see table below).

The pharmacokinetic data for all three doses demonstrated negligible to very low systemic absorption of 17 beta estradiol, estrone and estrone conjugated, supporting the previous Phase 1 trial data. TX-004HR was well tolerated, and there were no clinically significant differences compared to placebo-treated participants with respect to adverse events. There were no drug-related serious adverse events reported.

We submitted the NDA for TX-004HR with the FDA on July 7, 2016. The FDA determined that the NDA is sufficiently complete to permit a substantive review and accepted the NDA for filing. The PDUFA target action date for the completion of the symptoms identifiedFDA’s review is May 7, 2017. The NDA submission was supported by the complete TX-004HR clinical program, including positive results of the phase 3 REJOICE Trial. The NDA submission included all three doses of TX-004HR (4 mcg, 10 mcg and 25 mcg) that were evaluated in FDA guidance. Based upon our phase 1 results, we believe we havethe REJOICE Trial. If approved, the 4 mcg formulation would represent a rapidly acting product that differs substantially fromlower effective dose than the reference listed drug Vagifem® soldcurrently available VVA therapies approved by Novo Nordisk. the FDA.

According to Source Healthcare Analytics,Symphony Health Solutions, the total FDA-approved market for VVA treatment was approximately $1$1.7 billion in U.S. sales for the 12 months ended December 31, 2013.2016.

On November 10, 2015, the FDA held a scientific workshop on labeling “lower” dose estrogen-alone products for symptoms of VVA to provide an opportunity for the FDA to obtain input from experts on several topics related to the product label of lower dose estrogen-alone products approved solely for the treatment of moderate to severe symptoms of VVA due to menopause. According to the FDA, lower-dose estrogen products means products that contain less than the 0.625 mg of conjugated estrogens used in the WHI study and estradiol products containing 0.0375 mg and below. Discussion topics at the workshop included the relevance of the boxed warnings based on data from the WHI to the lower dose estrogen-alone products; certain members in the scientific/medical community have questioned whether the boxed warnings section in the labeling, which is currently required to be included on all estrogen products, is applicable in whole or in part to these lower-dose estrogen products. The boxed warnings include: (1) an increased risk of endometrial cancer in women with a uterus who uses unopposed estrogens, (2) estrogen therapy with or without progestins should not be used for the prevention of cardiovascular disease or dementia, (3) an increased risk of stroke and deep vein thrombosis (DVT) in women treated with estrogen-alone, (4) an increased risk of probable dementia in postmenopausal women 65 years of age and older treated with estrogen-alone, (5) an increased risk of invasive breast cancer in women treated with estrogen plus progestin, and (6) to use the lowest effective dose for the shortest duration. It is unknown at this time what, if any, changes the FDA may propose with respect to the boxed warnings on lower dose estrogen-alone products for symptoms of VVA or whether such label changes would be applicable to TX-004HR, if approved.

As of December 31, 2016, we had 17 issued patents, which included 13 utility patents that relate to our combination progesterone and estradiol formulations, two utility patents that relate to TX-004HR, which establishes an important intellectual property foundation for TX-004HR, one utility patent that relates to a pipeline transdermal patch technology, and one utility patent that relates to our OPERA^® information technology platform.

Preclinical Development

Based upon leveraging our SYMBODA^TMhormone platform technology, we have sevenfour preclinical projects that include development of our proposeda progesterone-alone and combination estradiol and progesterone and progesterone-alone products in a topical cream form, which we refer to as TX-005HR and TX-006HR, respectively, and transdermal patch form.form, which we refer to as TX-007HR and TX-008HR, respectively. We plancompleted a proof-of-concept preclinical study of TX-005HR in 32 rats. The study used four groups of eight female ovariectomized rats, each of whom were treated with subcutaneous estradiol for eight days. On day four of treatment, they were also dosed with placebo, subcutaneous progesterone or TX-005HR topical progesterone cream. The results, presented at the NAMS meeting in October 2015, showed that the progesterone in TX-005HR penetrated the skin and opposed the effect of subcutaneous estradiol on the endometrium. We submitted an IND for TX-006HR in the fourth quarter of 2016 and intend to commence phase 1 clinical trials in 2017. We may in the future engage with a financing partner to advance these projects into the next stagesour topical cream and transdermal patch projects. We have recently conducted rat bioavailability studies on several novel, oral formulations of development as financial and personnel resources become available. Weprogesterone. In addition to menopausal treatments, we are also evaluating various other indications for our hormone technology, including oral contraception treatment of preterm birth, and premature ovarian failure. According to South Healthcare Analytics, the total FDA-approved menopause-related market for estrogen alone and in combination was approximately $3.3 billion in U.S. sales for the 12 months ended December 31, 2013.

Sales and Marketing

Although our direct national sales force is similar to that of a traditional pharmaceutical company in that sales representatives call on OB/GYN practices to provide education and sampling, we believe our sales representatives are more customer centriccustomer-centric in their sales approach by offering physicians more than just differences in our products from the competition; they are also able to offer an array of partneringphysicians opportunities to promote efficiency and cost savings.assist their patients in obtaining products in a cost-efficient manner.

Our national rollout strategy has been to focus first on the largest metropolitan areas in the United States. In order to accelerate the sales rampramp-up in a new territory, we employ a national sales/large practice sales effort to identify key practices in new or expanding markets. Concurrent with our provider sales effort, we work with commercial insurance payors for partnerships in which the payor can support the prescribingprescription and/or recommendation of our products for the benefit of the patient, physician, and payor, with an end result of providing better outcomes for all three constituents.

At the forefront of our sales approach is the philosophy that the physician should recommend or prescribe products based only on what is best for the patient. In general, a better outcome is achieved by providing patients with the best products and care at the best value. We believe having an assortment of high-quality product options that can be recommended or prescribed by both the physician and payor is the foundation of providing valuable options to the patient.

We believe our sales force has developed strong relationships and partnerships in the OB/GYN market to sell our current products. We have also established relationships with some of the largest OB/GYN practices in their respective markets. By delivering additional products through the same sales channel, we believe we can leverage our already deployed assets to increase our sales and achieve profitability. We intend to leverage and grow our current marketing and sales organization to commercialize our drug candidates in the United States assuming the successful completion of the FDA regulatory process. In addition, we may partner with licensors or other strategic partners to commercialize our drug candidates outside of the OB/GYN market or in non-U.S. markets.

Online Commerce

A vast majority of our over-the-counterOTC product sales arewere completed online. The Internet has continuedAs of January 1, 2017, we decided to increase its influencefocus on selling our prescription vitamins and ceased manufacturing and distributing our OTC product lines, except for Iron 21/7, which sales have declined steadily over communication, content, and commerce. We believe several factors will contributetime resulting in immaterial sales. As a result, as of January 1, 2017, we stopped selling our products through our websites directly to this continuing increase, including convenience, expanded range of available products and services, improved security and electronic payment technology, increased access to broadband Internet connections and widespread consumer confidence and acceptance of the Internet as a means of commerce.consumers.

Retail CommerceSales Concentration

The vast majoritySee Note 12 to the consolidated financial statements included in this Annual Report for a discussion of the concentration of sales of our prescription prenatal vitamin products.

Commercialization

We cannot market or promote a new product sales are completed through the traditional pharmacy distribution network. Although online and mail order pharmacy commerce continues to grow, the majority of products are still purchased directlyuntil a marketing application has been approved by the consumer locallyFDA. The PDUFA date is a target date and is usually set at traditional stores. As10 months after the NDA is accepted for filing. The NDA for our TX-004HR hormone therapy drug candidate has a PDUFA target action date of May 7, 2017. We believe that it will be possible for us to access the United States market through a specialty sales force. Subject to receiving marketing authorization in the United States, we expect to commence commercialization via our then-in-place sales and marketing organization. If approved, we plan to launch this divisionproduct in the fourth quarter of our business expands, we will continue to employ strategies that help us reduce inefficiencies in this channel and develop relationships that allow our products to be differentiated from the competition.2017.

Competition

Pharmaceutical Industry

The pharmaceutical industry is subject to intense competition and is characterized by extensive research efforts and rapid technological change. Competition in our industry occurs in a variety of areas, including developing and bringing new products to market before others, developing new technologies to improve existing products, developing new products to provide the same benefits as existing products at lower cost, and developing new products to provide benefits superior to those of existing products. Most major pharmaceutical companies, as well as numerous specialty pharmaceutical companies, sell products in the women’s health sector of the pharmaceutical industry, which is comprised of products designed for post-pubescent females and is generally considered very fragmented. There are many companies including generic manufacturers, drug compounding pharmacies, and largefocused on the women’s health sector of the pharmaceutical companies,industry that have significantly greater financial and other resources than we do.do, including generic manufacturers, drug compounding pharmacies, and large pharmaceutical companies. In addition, academic and other research institutions could be engaged in research and development efforts for the indications targeted by our products.

Hormone Therapy Market

The menopause hormone therapy market includes two major components: an FDA-approved drug market and a non-FDA approved drug market supplied by compounding pharmacies. On November 27, 2013, the DQSA became law and the FDA was given additional oversight over compounding pharmacies. We believe FDA-approved products are easily measured and monitored, while non-FDA approved hormone therapy drug products, typically referred to as “bioidenticals” when produced and sold by compounding pharmacies, are not easily measured or monitored. Our phase 3 clinical trials are intended to establish an indication of the safety and efficacy of our hormone therapy drug candidates at specific dosage levels. We intend our hormone therapy drug candidates, if approved by the FDA, to provide hormone therapies with well characterized safety and efficacy profiles that can be consistently manufactured to target specifications. This would provide an alternative to the non-FDA approved compounded bioidentical market. This aim is based on our belief that our drug candidates will offer advantages in terms of demonstrated safety and efficacy consistency in the hormone dose, lower patient cost due to the increased likelihood of insurance coverage and improved access as a result of availability from major retail pharmacy chains rather than custom order or formulation by individual compounders.

TX-001HR is our combination estradiol and progesterone drug candidate for the treatment of moderate to severe VMS due to menopause. The combination of estradiol and progesterone for the treatment of moderate to severe VMS due to menopause for postmenopausal women with an intact uterus is comprised of two components: the FDA-approved drug market and the non-FDA-approved compounded drug market. According to Symphony Health Solutions, sales of FDA-approved combinations of estrogen and progestins were approximately $603 million and the sales of estradiol and progesterone on a stand-alone basis were $955 million and $360 million, respectively, in the United States for the 12 months ended December 31, 2016.

The largest competitors in the FDA-approved market are Pfizer (PREMPRO), MYLAN, BARR (generic estradiol) and Noven (Minivelle), with sales of PREMPRO constituting a majority of such sales. None of the current FDA-approved drugs for the treatment of moderate to severe VMS due to menopause is bioidentical to the estradiol and progesterone produced by the ovaries. Based on various reports, including data recently presented at NAMS, "Knowledge, Use, and Prescribing of Custom-Compounded Bioidentical Hormones for Menopausal Women: It’s Not What You Think," by JoAnn V. Pinkerton, et al., we estimate that U.S. sales of non-FDA-approved compounded combination estradiol and progesterone products approximate $1.5 billion per year. The market for non-FDA-approved compounded hormone therapy products is generally considered very fragmented because the products are prepared and sold by individual compounding pharmacies. We believe that TX-001HR, if approved by the FDA, would represent the first time a combination product of estradiol and progesterone that is bioidentical to – or having the same chemical and molecular structure as - the estradiol and progesterone produced by the ovaries would be approved for use in a single combined product.

TX-004HR is our applicator-free vaginal estradiol softgel drug candidate for the treatment of moderate to severe dyspareunia, a symptom of VVA in post-menopausal women with vaginal linings that do not receive enough estrogen. According to Symphony Health Solutions, the FDA-approved U.S. market for treatment of VVA in post-menopausal women was approximately $1.7 billion for the 12 months ended December 31, 2016. Approximately $1.5 billion of such sales were by three products currently on the market: Pfizer (PREMARIN cream), Allergan (ESTRACE cream) and Novo Nordisk (Vagifem tablets). We believe that TX-004HR, if approved by the FDA, will be at least as effective as the existing treatments for VVA because of an early onset of action with less systemic exposure inferring a greater probability of dose administration to the target tissue, and it will have an added advantage of being a simple, easier to use dosage form versus traditional VVA treatments. An authorized generic for Vagifem was approved by the FDA and launched in the fourth quarter of 2016. Also, a new product – Intrarosa^@ prasterone – was approved by the FDA for the treatment of dyspareunia in November 2016 and was licensed for commercialization in early 2017.

Prenatal Vitamin Market

The prenatal vitamin market is highly fragmented, with dozens of companies selling hundreds of competitive products. Prenatal vitamin products are marketed as either OTC products or prescription products, with many companies marketing their products through both channels. According to Symphony Health Solutions, during the 12 months ended December 31, 2016, approximately 6.3 million prescriptions for prenatal vitamins were issued in the United States resulting in total sales of approximately $353.8 million.

Seasonality

The specialty pharmaceutical industry is not subject to seasonal sales fluctuation.

Products in Development

We introduced our branded prescription products in the first and second quarters of 2012 and introduced our first prescription generic product line in the fourth quarter of 2012. Our market objective is to develop an entire suite of products that are condition-specific and geared to the women’s health sector. Our focus is to introduce products in which we use proprietary or patented molecules or ingredients that will differentiate our products from the competition. We currently have numerous products in development, including our hormone therapy drug candidates as described above.

Manufacturing of Our Products; Availability of and Dependence Upon Suppliers; Raw Materials for Our Products

We will rely on third-party CMOs for the commercial supply of our hormone therapy drug candidates. The regulations for manufacturing of approved drugs are significantly more stringent than the standards for manufacturing supplements or drug product for clinical trials and we will rely on our CMOs to manufacture our products in accordance with our specifications and applicable regulatory requirements.  We have entered into long-term supply agreements with Catalent Pharma Solutions, LLC, or Catalent, for the commercial supply of our TX-001HR and TX- 004HR hormone therapy drug candidates, if approved. Under the terms of the agreements, we will be obligated to purchase certain minimum annual amounts of each product once we commence commercial sales of such product following regulatory approval of Catalent as a manufacturer of the product. We may terminate the agreement for a particular drug candidate in the event that we cease pursuit of regulatory approval for such drug candidate for certain specified reasons. If we are unable to obtain sufficient quantities of drug candidates or receive raw materials in a timely manner, we could be required to delay our manufacturing and seek alternative manufacturers, which would be costly and time-consuming. The hormone therapy drug candidates used in our recently completed phase 3 clinical trials for TX-001HR and TX-004HR were manufactured by a different CMO.

We acquire all raw materialsuse third-party manufacturers to manufacture and ingredients forpackage our proprietaryvitamin and supplement products, from a group of third-party suppliers specializing in raw material manufacturing, processing,as well as meet applicable contract and specialty distribution. Our primary manufacturer maintains multiple supply and purchasing relationships throughout the raw materials marketplace to provide an uninterrupted supply of product to meet our manufacturingregulatory requirements.

Availability of and Dependence Upon Suppliers

We currently obtain approximately 98% of our vitaMedMD and BocaGreen products from Lang Pharma Nutrition, or Lang, a full-service, private label and corporate brand manufacturer specializing in premium health benefit driven products, including medical foods, nutritional supplements, beverages, bars, and functional foods in the dietary supplement category. As a result, we are dependent on Lang and its subcontractors for the manufacture of most of our products. We believe the terms of our agreements with Lang are competitive with other suppliersvitamin and manufacturers. Although we anticipate continuing our relationship with Lang, we believe that we could obtain similar terms with other suppliers to provide the same services. We have experienced no difficulties in obtaining the products we need in the amounts we require and do not anticipate those issues in the future.

Manufacturing of Our Products

Our vitamin products are manufactured in accordance with FDA’s current Good Manufacturing Practice, or cGMPs, for dietary supplements. In addition, we employ an outside third party to enforce rigorous quality audits.

All of our manufacturing is performed by third-party manufacturers.supplement products.  In addition to manufacturing, substantially all of our products, Lang also provides a variety of additional services to us, including development processes, prototype development, raw materials sourcing, regulatory review, and packaging production.  We believe that Lang maintains multiple supply and purchasing relationships throughout the raw materials marketplace to provide an uninterrupted supply of product to meet our manufacturing requirements.

We have experienced no difficulties in obtaining the vitamin and supplement products we need in the amounts we require and do not anticipate those issues in the future.  We believe the terms of our agreements with Lang are competitive with other suppliers and manufacturers. At present, we believe our relationship with Lang is excellent, and we intend to continue to use Lang as our third-party manufacturer for most of our products. Invitamins and supplements.  Although we anticipate continuing our relationship with Lang, we believe that we could obtain similar terms with other suppliers to provide the same services in the event our relationship with Lang terminates for any reason, there are a number of other manufacturers available to us.terminates. Accordingly, we do not believe that such termination would have a material adverse effect on our business.

Quality Control for our Products

Our products are required to source key raw materials and manufacture and package our products. Thebe manufactured in accordance with the FDA’s current Good Manufacturing Practice, or cGMPs.  In order to approve an NDA, the FDA must approveassure that the proposed manufacturing facilityfacilities for our drug candidates are in compliance with the FDA’s cGMP regulations, before a New Drug Application,which may include an FDA Pre-Approval Inspection Process, or PAI. We depend on our third-party suppliers and manufacturers for continued compliance with cGMP requirements, which are higher standards than we have been required to comply with in the past. To comply with these drug commercialization standards, we have personnel with pharmaceutical development and manufacturing experience who are responsible for the relationships with our suppliers. In addition, we have contracted with Catalent, an established manufacturer of soft gel drug products, to manufacture the commercial supply for both our TX-001HR and TX-004HR hormone therapy drug candidates. Although Catalent has received Form 483 observations from FDA inspections in the past, we are not aware of any open FDA investigations into its manufacturing processes at the facilities that would be used to manufacture our products, if approved. We anticipate that as part of the PAI of our NDA for TX-004HR the FDA may inspect Catalent’s such facilities.

The CMO that manufactured the hormone therapy drug candidates used in our recently completed phase 3 clinical trials for TX-001HR and TX-004HR was recently inspected by the FDA, which issued it a newForm FDA-483 listing various observations, some of which pertained to the clinical supply of our TX-001HR and TX-004HR drug is approved. Accordingly,candidates. The CMO has submitted its written response to the Form 483 observations to the FDA, which we intendbelieve will satisfactorily address the FDA’s observations with respect to engage only those third-party contract manufacturersthe clinical supply of our TX-001HR and TX-004HR drug candidates. We do not believe that the observations made by the FDA with respect to the CMO will have consistently showna material adverse effect on the abilityFDA’s review of our NDA for TX-004HR or the timing of our anticipated submission of an NDA for TX-001HR. We believe the inspection was not conducted as part of the FDA’s review of our NDA for TX-004HR. As noted above, we have contracted with a different CMO, Catalent, to satisfy these requirements forprovide the commercial supply of our TX-001HR and TX- 004HR hormone therapy drug candidates.

Quality Control for Our Products

A quality assurance team establishes process controls that are designed to document and documents and teststest every stage of the manufacturing process to ensure wethat our contract manufacturers meet product specifications and that our finished dietary supplementsproducts contain the correct ingredients, purity, strength, and composition in compliance with FDA regulations. WeOur contractors test incoming raw materials and finished goods to ensure they meet or exceed FDA and U.S. Pharmacopeia standards (when applicable), including quantitative and qualitative assay and microbial and heavy metal contamination.

Our manufacturers’ quality and production standards are designed to meet or exceed current FDA regulations. To ensure the highest quality, our manufacturing operations are audited by AIB International, Inc., or AIB, among others, for independent cGMP certification. AIB is an independent, not-for-profit organization that offers programs and services to augment and support the work of regulatory officials around the country, including standards development, product testing and certification, and onsite audits and inspections. The manufacturing facilities we primarily use are also ISO 9001 certified, which is a family of standards related to quality management systems and are designed to help organizations ensure they meet the needs of customers.

contamination (as appropriate).

Distribution of our Products

We useDuring the third quarter of 2016, we centralized the distribution channel for both our retail pharmacy distributors and wholesale distributors, in order to facilitate sales to a varietybroader population of distribution channels dependent upon product type. We sell our prescription dietary supplement products to patients through theirretail pharmacies. Since the launch of our prescription products, inIn addition to third-party logistics providers, we use some of the same national and regional distributors as other pharmaceutical companies, including Cardinal, McKesson, AmerisourceBergen, H.D. Smith, and Smith Drug. Wholesaler product inventory is monitored daily and sales out is monitored weekly. National and regional retail chain pharmacies are also an area of focus to make sure our products are purchased and dispensed properly. We sell our OTC products directly to consumers via our website and phone sales and the products are shipped directly from us to the consumer’s home or office. In a few instances, we sell OTC product to physicians who then sell the products directly to their patients.

Customer Service

Our goal is 100% customer satisfaction by consistently delivering superior customer experiences before, during, and after the sale. To achieve this goal, we maintain a fully staffedfully-staffed customer care center that uses current customer relationship management software to respond to health care providers, pharmacies, and consumers and accept orders for non-prescription products via incoming and outgoing telephone calls, e-mails, and live-chat.consumers. We believe our customer service initiatives allow us to establish and maintain long-term customer relationships and facilitate repeat visits and purchases. We also facilitate repeat customer orders through our auto-ship feature.

Our representatives receive regular training so that they can effectively and efficiently field questions from current and prospective customers and are also trained not to answer questions that should be directed to a customer’s physician. Having a quality customer care center allows our representatives to provide an array of valuable data in the areas of sales, market research, quality assurance, lead generation, and customer retention.

Our Return Policy

We sell our prescription products through third-party logistics providers, majorwholesale distributors, and pharmacies,retail pharmacy distributors, all of whom may return a product within six months prior to orand twelve months after the expiration date of the product. Once customers buy a prescription product from the pharmacy, the product may not be returned. Non-prescription customers

Customers may return or exchange our non-prescription products for any reason by returning the product within 30 days of receipt. We will refund the entire purchase price, less shipping. The customer is responsible for the cost of returning the products to us, except in cases in which the product is being returned because of a defect or an error made in our order fulfillment. If the purchased product exceeded a 30-day supply, the unused product must be returned to receive the full refund. All unopened OTC products may be exchanged for different products; the customer will be responsible for the difference in price if the replacement product is more expensive or we will refund the difference if the replacement product is less expensive. As of January 1, 2017, we decided to focus on selling our prescription vitamins and ceased manufacturing and distributing our OTC product lines, except for Iron 21/7, which sales have declined steadily over time resulting in immaterial sales.

Our Quality Guarantee

We proudly stand behind the quality of our products. We believe our guarantee makes it easy, convenient, and safe for customers to purchase our products. Under our quality guarantee, wewe:

We value frequent communication with and feedback from our customers in order to continue to improve our offerings and services.

Research and Development

Our product development programs are concentrated in the area of advanced hormone therapy pharmaceutical products. We engage in programs to provide alternatives to the non-FDA approvedFDA and non-FDA-approved compounded bioidentical market for hormone therapy. Our programs seek to bring new products to market in unique delivery systems or formats that enhance the effectiveness, safety, and reliability of existing hormone therapy alternatives.

We intend for our hormone therapy drug candidates, if approved, to provide an alternative to the non-FDA approvednon-FDA-approved compounded bioidentical market based on our belief that our drug candidates will offer advantages in terms of proven safety, efficacy, and stability, lower patient cost as a result of insurance coverage, and improved access as a result of availability from major retail pharmacy chains rather than custom order or formulation by individual compounders.

Our research and development expenses were $13.6$53.9 million in 2013, $4.52016, $72.0 million in 2012,2015, and $0.1$43.2 million in 2011.2014.

Intellectual Property

Our success depends, in part, on our ability to obtain patents, maintain trade secret protection, and operate without infringing the proprietary rights of others. Our intellectual property portfolio is one of the means by which we attempt to protect our competitive position. We rely primarily on a combination of know-how, trade secrets, patents, trademarks, and contractual restrictions to protect our products and to maintain our competitive position. We are diligently seeking ways to protect our intellectual property through various legal mechanisms in relevant jurisdictions.

We have developed hormone products using our SYMBODA^® technology, which is our advanced hormone therapy technology that enables us to deliver bioidentical hormones through a variety of dosage forms and administrative routes.

       In addition to numerous pending patent applications, as of December 31, 2016, we had 17 issued patents, including:

As of December 31, 2016, we had filed several39 non-provisional and 30 provisional patent applications with the U.S. Patent and Trademark Office, or the USPTO, with respect to our hormone therapy drug candidates. We intend to file additionalcandidates, including issued patents, and 74 international patent applications when appropriate; however, we may not file any such applications or, if filed, the patents may not be issued. with respect to our hormone therapy drug candidates, including Patent Cooperation Treaty (PCT) and national stage filings.

We hold multiple U.S. trademark registrations and have numerous pending trademark applications. Issuance of a federally registered trademark creates a rebuttable presumption of ownership of the mark; however, it is subject to challenge by others claiming first use in the mark in some or all of the areas in which it is used. Federally registered trademarks have a perpetual life as long as they are maintained and renewed on a timely basis and used properly as trademarks, subject to the rights of third parties to seek cancellation of the trademarks if they claim priority or confusion of usage. We believe our patents and trademarks are valuable and provide us certain benefits in marketing our products.

We intend to actively protect our intellectual property with patents, trademarks, trade secrets, or other legal avenues for the protection of intellectual property.

We intendproperty and to aggressively prosecute, enforce, and defend our patents, trademarks, and proprietary technology. The loss, by expiration or otherwise, of any one patent may have a material effect on our business. Defense and enforcement of our intellectual property rights can be expensive and time consuming, even if the outcome is favorable to us. It is possible that the patents issued or licensed to us will be successfully challenged, that a court may find that we are infringing on validly issued patents of third parties, or that we may have to alter or discontinue the development of our products or pay licensing fees to take into account patent rights of third parties.

OPERA is our patented information technology platform used in our business. We believe the deployment of OPERA™OPERA and the further development and deployment of related technology creates a sustainable competitive advantage in clinical development and product improvement. We are actively filing new patent application, when appropriate, that reflects incremental developments in our technologies.

As we continue to develop proprietary intellectual property, we will expand our protection by applying for patents on future technologies. As we examine our current product offerings and new product pipeline, we are in the process of modifying and developing new formulations that will enable us to gain patent protection for these products.

While we seek broad coverage under our patent applications, there is always a risk that an alteration to the process may provide sufficient basis for a competitor to avoid infringement claims. In addition, patents expire and we cannot provide any assurance that any patents will be issued from our pending application or that any potentially issued patents will adequately protect our intellectual property.

Government Regulation

In the United States, the FDA regulates pharmaceuticals, dietary supplements, and cosmetics under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations. These products are also subject to other federal, state, and local statutes and regulations, including federal and state consumer protection laws, laws protecting the privacy of health-related information, and laws prohibiting unfair and deceptive acts and trade practices.

Pharmaceutical Regulation

The process required by the FDA before a new drug product may be marketed in the United States generally involves the following:

	•	completion of or reference to extensive preclinical laboratory tests and preclinical animal studies, all performed in accordance with the FDA’s Good Laboratory Practice, or GLP, regulations;
	•	submission to the FDA of an IND application under which the holder may begin conducting human clinical trials, provided that the FDA does not object; the IND must be updated annually;
	•	performance of adequate and well-controlled human clinical trials to establish the safety and efficacy of the drug candidate for each proposed indication; and
	•	submission to the FDA of an NDA after completion of all pivotal clinical trials.

An IND application is a request for authorization from the FDA to administer an investigational drug product to humans. We currently have effective INDs for all of our hormone therapy drug candidates, although we have no current plans to conduct clinical trials for TX 12-003HR.

TX-003HR.

Clinical trials involve the administration of the investigational drug to human subjects under the supervision of qualified investigators in accordance with current Good Clinical Practices, or cGCPs, which include the requirement that all research subjects provide their informed consent for their participation in anythe clinical trial. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. Additionally, approval must also be obtained from each clinical trial site’s Institutional Review Board, or IRB before the trials may be initiated, and the IRB must monitor the study until completed.completed and re-assess and approve the study at least annually. There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries.

Clinical trials are usually conducted in three phases. Phase 1 clinical trials are normally conducted in small groups of healthy volunteers to assess safety and find the potential dosing range. After a potentially safe dose has been established, the drug is administered to small populations of sick patients (Phase(phase 2) to look for initial signs of efficacy in treating the targeted disease or condition and to continue to assess safety. Phase 3 clinical trials are usually multi-center, double-blind controlled trials in hundreds or even thousands of subjects at various sites to assess as fully as possible both the safety and effectiveness of the drug.

During the course of a clinical trial, we are required to inform the FDA and the IRB about adverse events associated with our drug candidate. The FDA, the IRB, or the clinical trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee, or DSMB. This group reviews unblendedunblinded data from clinical trials and provides authorization for whether or not a trial may move forward at designated check points based on access to certain data from the study. We may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.

climates.

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, detailed investigational drug product information is submitted to the FDA in the form of an NDA requesting approval to market the product for one or more indications. The application includes all relevant data available from pertinent preclinical and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among other things.

Once the NDA submission has been accepted for filing, the FDA’s goal is to review applications within 10ten months of filing.filing or 12 months of filing for a new molecular entity. However, the review process is often significantly extended by FDA requests for additional information or clarification. The FDA may refer the application to an advisory committee for review, evaluation, and recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it typically follows such recommendations.

After the FDA evaluates the NDA and conducts inspections of manufacturing facilities in which the drug product will be formulated and its active pharmaceutical ingredient, or API, will be produced, it may issue an approval letter or, instead, a Complete Response Letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response Letter may require additional clinical data and/or an additional pivotal Phasephase 3 clinical trial(s), and/or other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. Even if such additional information is submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. The FDA could also approve the NDA with a Risk Evaluation and Mitigation Strategies, or REMS, plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate controls and specifications, or a commitment to conduct one or more post-market studies or clinical trials. Such post-market testing may include Phasephase 4 clinical trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

After regulatory approval of a drug product is obtained, we arewould be required to comply with a number of post-approval requirements. As a holder of an approved NDA, we would be required to report, among other things, certain adverse reactions and production problems to the FDA, to provide updated safety and efficacy information, and to comply with requirements concerning advertising and promotional labeling for any of our products. Also, quality control and manufacturing procedures must continue to conform to cGMP after approval to ensure and preserve the long-term stability of the drug product. The FDA periodically inspects manufacturing facilities to assess compliance with cGMP, which imposes extensive procedural, substantive, and record keeping requirements. For example, Catalent Pharma Solutions, LLC, or Catalent, the contract manufacturing organization, or CMO, that we have contracted with for the commercial supply of our TX-001HR and TX-004HR hormone therapy drug candidates, if approved, was issued a Form FDA-483 in 2016 with respect to its softgel manufacturing plant that will be used for the manufacture of the commercial supply of TX-001HR and TX- 004HR, if approved.  The corrective actions identified in Catalent’s response to the Form 483 have been completed and we are not aware of any open FDA investigations into Catalent’s manufacturing processes at this facility.

In addition, changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our drug candidates. Future FDA and state inspections may identify compliance issues at our facilities or at the facilities of our contract manufacturers that may disrupt production or distribution, or require substantial resources to correct. In addition, discovery of previously unknown problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer, or holder of an approved NDA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action that could delay or prohibit further marketing. Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications, and also may require the implementation of other risk management measures. Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

Our hormone therapy drug candidates may compete with unapproved hormone therapy products supplied by compounding pharmacies. Pharmacy compounding is a practice in which a licensed pharmacist combines, mixes, or alters ingredients in response to a prescription to create a medication tailored to the medical needs of an individual patient. The medications created by the compounding pharmacy are technicallytheoretically “new drugs” that would otherwise be subject to the new drug approval requirements of the FDCA.

However, for approximately 50 years, the FDA left regulation of compounding pharmacies to the states. In 1992, in response to various safety concerns, the FDA issued a Compliance Policy Guide, which announced that the “FDA may, in the exercise of its enforcement discretion, initiate federal enforcement actions...when the scope and nature of a pharmacy’s activities raises the kinds of concerns normally associated with a manufacturer and...results in significant violations of the new drug, adulteration, or misbranding provisions of the Act.” Thereafter, Congress enacted the Food and Drug Administration Modernization Act of 1997, or FDAMA, which sought to clarify FDA’s regulatory authority over compounding pharmacies. FDAMA exempted “compounded drugs” from the FDA’s standard drug approval requirements as long as the providers of those drugs abide by several restrictions, including that they refrain from advertising or promoting particular compounded drugs. In 2002, though, the Supreme Court declared this provision of FDAMA to be unconstitutional under the First Amendment, effectively re-instating the pre-FDAMA regime. Shortly thereafter, the FDA issued its 2002 Compliance Policy Guide 460.200, which states that the FDA will exercise enforcement discretion to exclude compounded drugs from the new drug approval requirements except where compounding pharmacies act more akin to traditional drug manufacturers.

To further clarify the FDA’s jurisdiction, Congress enacted and the President signed into law the DQSA, which among other things, formalized the relationship between the FDA and compounding pharmacies by exempting compounding pharmacy products from the FDA approval requirements and the requirement to label products with adequate directions for use, but not the exemption from cGMP requirements. To qualify for this exemption, a compounding pharmacy must register with the FDA as an “outsourcing facility,” subject to FDA inspection and other requirements. The FDA does not exercise the same authority to regulate compounding pharmacies as pharmaceutical manufacturers. For example, compounding pharmacies are not required to report adverse events associated with compounded drugs, while commercial drug manufacturers are subject to stringent regulatory reporting requirements.

505(b)(2) Applications

Application

We intend to submit NDAs for our hormone therapy drug candidates, assuming that the clinical data justify submission, under section 505(b)(2) of the FDCA.FDCA, or Section 505(b)(2). Section 505(b)(2) permits the filing of an NDA when at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. The applicant may rely upon published literature and the FDA’s findings of safety and effectiveness based on certain pre-clinical or clinical studies conducted for an approved product. The FDA may also require companies to perform additional studies or measurements to support the change from the approved product. The FDA may then approve the new drug candidate for all or some of the label indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant. In regards to TX 12-001HR,TX-001HR, we are required to conduct phase 3 studies for vasomotor symptomsVMS versus placebo and an endometrial protection study.

Phase 3 clinical trials for secondary amenorrhea versus placebo will be required for TX 12-002HR. TX 12-003HRTX-002HR. TX-003HR would be required to undergo phase 3 studies of vasomotor symptomsVMS compared to placebo, though we currently do not have plans to continue development of this drug candidate.

candidate

As part of our NDA submission, we intend to certify that all of the patents for approved products referenced in the NDA for each of the hormone therapy drug candidates as listed in the FDA’s Orange Book have expired and that we will not be compelled to certify that any patent is invalid, unenforceable, or will not be infringed by the new product. If, in fact, this assessment is incorrect, it can have a serious and significant adverse effect on our ability to obtain FDA approval or market our new product. If we are compelled to certify that a patent is invalid, unenforceable, or not infringed, then the holder of that patent can initiate a patent infringement suit against us and the FDA is precluded from approving our product for 30 months or until a court decision or settlement finding that the patent is invalid, unenforceable or not infringed, whichever is earlier.

Marketing Exclusivity

A Section 505(b)(2) NDA applicant may be eligible for its own regulatory exclusivity period, such as a three-year exclusivity. The first approved Section 505(b)(2) NDA applicant for a particular condition, of approval, or change to a marketed product, such as a new extended release formulation for a previously approved product, may be granted three-year Hatch-Waxman exclusivity if one or more clinical studies, other than bioavailability or bioequivalence studies, was essential to the approval of the application and was conducted/conducted or sponsored by the applicant. Should this occur, the FDA would be precluded from making effective any other application for the same condition of use or for a change to the drugmarketing product that was granted exclusivity until after that three-year exclusivity period has run. Additional exclusivities may also apply.

Additionally, the Section 505(b)(2) NDA applicant may have relevant patents in the Orange Book, and if it does, it can initiate patent infringement litigation against those applicants that challenge such patents, which could result in a 30-month stay delaying those applicants.

Dietary Supplement and Cosmetic Regulation

Our currently marketed products are regulated as dietary supplements and cosmetics.supplements. The processing, formulation, safety, manufacturing, packaging, labeling, advertising, and distribution of these products are subject to regulation by one or more federal agencies, including the FDA and the Federal Trade Commission, or the FTC, and by various agencies of the states and localities in which our products are sold.

Generally, our nutritional product formulations are proprietary in that in designing them, we attempt to blend an optimal combination of nutrients that appear to have beneficial impact based upon scientific literature and input from physicians; however, we are generally prohibited from making disease treatment and prevention claims in the promotion of our products that use these formulations.

The Dietary Supplement Health and Education Act of 1994, or DSHEA, amended the FDCA to establish a new framework governing the composition, safety, labeling, manufacturing, and marketing of dietary supplements. Generally, under the FDCA, dietary ingredients that were marketed in the United States prior to October 15, 1994 may be used in dietary supplements without notifying the FDA. “New” dietary ingredients (i.e., dietary ingredients that were “not marketed in the United States before October 15, 1994”) must be the subject of a new dietary ingredient notification submitted to the FDA unless the ingredient has been “present in the food supply as an article used for food” without being “chemically altered.” A new dietary ingredient notification must provide the FDA evidence of a “history of use or other evidence of safety” establishing that use of the dietary ingredient “will reasonably be expected to be safe.” A new dietary ingredient notification must be submitted to the FDA at least 75 days before the initial marketing of the new dietary ingredient. The FDA may determine that a new dietary ingredient notification does not provide an adequate basis to conclude that a dietary ingredient is reasonably expected to be safe. Such a determination could prevent the marketing of such dietary ingredient. The FDA recently issued draft guidance governing the notification of new dietary ingredients. FDA guidance is not mandatory and companies are free to use an alternative approach if the approach satisfies the requirements of applicable laws and regulations. However, FDA guidance is a strong indication of the FDA’s “current thinking” on the topic discussed in the guidance, including its position on enforcement. The draft guidance on new dietary ingredients is expected to be significantly revised when published in final form. Moreover, Congress can amend the dietary supplement provisions of the FDCA to impose additional restrictions on labeling and marketing of dietary supplements. Such action would have material adverse impact on our business and growth prospects.

The FDA or other agencies could take actions against products or product ingredients that in its determination present an unreasonable health risk to consumers that would make it illegal for us to sell such products. In addition, the FDA could issue consumer warnings with respect to the products or ingredients in such products. Such actions or warnings could be based on information received through FDCA-mandated reporting of serious adverse events. The FDCA requires that reports of serious adverse events be submitted to the FDA, and based in part on such reports, the FDA has issued public warnings to consumers to stop using certain third party dietary supplement products.

The FDCA permits “statements of nutritional support” to be included in labeling for dietary supplements without premarket approval. Such statements must be submitted to the FDA within 30 days of marketing. Such statements may describe how a particular dietary ingredient affects the structure, function, or general well-being of the body, or the mechanism of action by which a dietary ingredient may affect body structure, function, or well-being, but may not expressly or implicitly represent that a dietary supplement will diagnose, cure, mitigate, treat, or prevent a disease. A company that uses a statement of nutritional support in labeling must possess scientific evidence substantiating that the statement is truthful and not misleading. If the FDA determines that a particular statement of nutritional support is an unacceptable drug claim, conventional food claim, or an unauthorized version of a “health claim,” or, if the FDA determines that a particular claim is not adequately supported by existing scientific data or is false or misleading, we would be prevented from using the claim.

In addition, DSHEA provides that so-called “third-party literature,” such as a reprint of a peer-reviewed scientific publication linking a particular dietary ingredient with health benefits, may be used “in connection with the sale of a dietary supplement to consumers” without the literature being subject to regulation as labeling. The literatureliterature: (1) must not be false or misleading; (2) may not “promote” a particular manufacturer or brand dietary supplement; (3) must present a balanced view of the available scientific information on the subject matter; (4) if displayed in establishment, must be physically separate from the dietary supplements; and (5) should not have appended to it any information by sticker or another method. If the literature fails to satisfy each of these requirements, we may be prevented from disseminating such literature with our products, and any dissemination could subject our product to regulatory action as an illegal drug.

In June 2007, pursuant to the authority granted by the FDCA as amended by DSHEA, the FDA published detailed cGMP regulations that govern the manufacturing, packaging, labeling, and holding operations of dietary supplement manufacturers. The cGMP regulations, among other things, impose significant recordkeeping requirements on manufacturers. The cGMP requirements are in effect for all manufacturers, and the FDA is conducting inspections of dietary supplement manufacturers pursuant to these requirements. There remains considerable uncertainty with respect to the FDA’s interpretation of the regulations and their actual implementation in manufacturing facilities. In addition, the FDA’s interpretation of the regulations will likely change over time as the agency becomes more familiar with the industry and the regulations. The failure of a manufacturing facility to comply with the cGMP regulations renders products manufactured in such facility “adulterated,” and subjects such products and the manufacturer to a variety of potential FDA enforcement actions. In addition, under the Food Safety Modernization Act, or FSMA, which was enacted on January 2, 2011, the manufacturing of dietary ingredients contained in dietary supplements will be subject to similar or even more burdensome manufacturing requirements, which will likely increase the costs of dietary ingredients and will subject suppliers of such ingredients to more rigorous inspections and enforcement. The FSMA will also require importers of food, including dietary supplements and dietary ingredients, to conduct verification activities to ensure that the food they might import meets applicable domestic requirements.

The FDA has broad authority to enforce the provisions of federal law applicable to dietary supplements, including powers to issue public Warning Letters or Untitled Letters to a company, publicize information about illegal products, detain products intended for import, require the reporting of serious adverse events, request a recall of illegal or unsafe products from the market, and request that the Department of Justice initiate a seizure action, an injunction action, or a criminal prosecution in the U.S. courts. The FSMA expands the reach and regulatory powers of the FDA with respect to the production and importation of food, including dietary supplements. The expanded reach and regulatory powers include the FDA’s ability to order mandatory recalls, administratively detain domestic products, require certification of compliance with domestic requirements for imported foods associated with safety issues and administratively revoke manufacturing facility registrations, effectively enjoining manufacturing of dietary ingredients and dietary supplements without judicial process. The regulation of dietary supplements may increase or become more restrictive in the future.

Our cosmetic products, such as our topical creams, are also subject to regulation by the FDA. Such products and their ingredients do not require premarket approval prior to sale, but are subject to specific labeling regulations. While the FDA has not promulgated specific cGMPs for the manufacture of cosmetics, the FDA has provided guidelines for cosmetic manufacturers to follow to ensure that their products are neither misbranded nor adulterated.

The FTC exercises jurisdiction over the advertising of dietary supplements and cosmetics. In recent years, the FTC has instituted numerous enforcement actions against companies for failure to have adequate substantiation for claims made in advertising or for the use of false or misleading advertising claims.

In recent years, the FTC has instituted numerous enforcement actions against dietary supplement companies for making false or misleading advertising claims and for failing to adequately substantiate claims made in advertising. These enforcement actions have often resulted in consent decrees and the payment of civil penalties and/or restitution by the companies involved. The FTC also regulates other aspects of consumer purchases, including promotional offers of savings compared policies, telemarketing, continuity plans, and “free” offers.

We are also subject to regulation under various state, local, and international laws that include provisions governing, among other things, the formulation, manufacturing, packaging, labeling, advertising, and distribution of dietary supplements and drugs. For example, Proposition 65 in the state of California is a list of substances deemed to pose a risk of carcinogenicity or birth defects at or above certain levels. If any such ingredient exceeds the permissible levels in a dietary supplement, cosmetic, or drug, the product may be lawfully sold in California only if accompanied by a prominent warning label alerting consumers that the product contains an ingredient linked to cancer or birth defect risk. Private attorney general actions as well as California attorney general actions may be brought against non-compliant parties and can result in substantial costs and fines.

Other U.S. Health Care Laws and Compliance Requirements

We are also subject to additional health care regulation and enforcement by the federal government and the states in which we conduct our business. Applicable federal and state health care laws and regulations include the following:

Efforts to ensure that our business arrangements with third parties comply with applicable health care laws and regulations could be costly. Although we believe that our business practices are structured to be compliant with applicable laws, it is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations, or case law involving applicable fraud and abuse or other health care laws and regulations. If our past or present operations, including activities conducted by our sales team or agents, are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal, and administrative penalties, damages, fines, exclusion from third party payor programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations. If any of the physicians, providers, or entities with whom we do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil, or administrative sanctions, including exclusion from government funded health care programs.

Many aspects of these laws have not been definitively interpreted by the regulatory authorities or the courts, and their provisions are open to a variety of subjective interpretations that increases the risk of potential violations. In addition, these laws and their interpretations are subject to change. Any action against us for violation of these laws, even if we successfully defend against it, could cause us to incur significant legal expenses, divert our management’s attention from the operation of our business, and damage our reputation.

In addition, from time to time in the future, we may become subject to additional laws or regulations administered by the FDA, the FTC, or by other federal, state, local, or foreign regulatory authorities, to the repeal of laws or regulations that we generally consider favorable, such as DSHEA, or to more stringent interpretations of current laws or regulations. We are not able to predict the nature of such future laws, regulations, repeals, or interpretations, and we cannot predict what effect additional governmental regulation, if and when it occurs, would have on our business in the future. Such developments could, however, require reformulation of certain products to meet new standards, recalls or discontinuance of certain products not able to be reformulated, additional record-keeping requirements, increased documentation of the properties of certain products, additional or different labeling, additional scientific substantiation, additional personnel, or other new requirements. Any such developments could have a material adverse effect on our business.

The growth and demand for eCommerce could result in more stringent consumer protection laws that impose additional compliance burdens on online retailers. These consumer protection laws could result in substantial compliance costs and could interfere with the conduct of our business.

There is currently great uncertainty in many states whether or how existing laws governing issues such as property ownership, sales and other taxes, and libel and personal privacy apply to the Internet and commercial online retailers. These issues may take years to resolve. For example, tax authorities in a number of states, as well as a Congressional advisory commission, are currently reviewing the appropriate tax treatment of companies engaged in online commerce and new state tax regulations may subject us to additional state sales and income taxes. New legislation or regulation, the application of laws and regulations from jurisdictions whose laws do not currently apply to our business, or a change in application of existing laws and regulations to the Internet and commercial online services could result in significant additional taxes on our business. These taxes could have an adverse effect on our results of operations.

Employees

As of December 31, 2013,2016, we had 69 full-time159 full time employees, foursix of whom are executive officers. Additionally, from time to time, we hire temporary contract employees. None of our employees are covered by a collective bargaining agreement, and we are unaware of any union organizing efforts. We have never experienced a major work stoppage, strike, or dispute. We consider our relationship with our employees to be good.

Our History

On October 3, 2011, we changed our name to TherapeuticsMD, Inc. On October 4, 2011, we closed a reverse merger with VitaMedMD LLC, a Delaware limited liability company, or VitaMed, pursuant to which (1) all outstanding membership units of VitaMed were exchanged for shares of our common stock, (2) all outstanding VitaMed options and warrants were exchanged and converted into options and warrants to purchase shares of our common stock, and (3) VitaMed became our wholly owned subsidiary. As of December 31, 2011, we determined that VitaMed would become the sole focus of our company and services previously performed relative to the aforementioned licensing agreement discussed in the following paragraph were discontinued.

We were incorporated in Utah in 1907 under the name Croff Mining Company.Company, or Croff. Prior to 2008, Croff’s operations consisted entirely of oil and natural gas leases. Due to a spin-off of its operations in December 2007, Croff had no business operations or revenue source and had reduced its operations to a minimal level although it continued to file reports required under the Securities Exchange Act of 1934, or the Exchange Act. As a result of the spin-off, Croff was a “shell company” under the rules of the Securities and Exchange Commission, or the SEC. In July 2009, Croff (i) closed a transaction to acquire America’s Minority Health Network, Inc. as a wholly owned subsidiary, (ii) ceased being a shell company, and (iii) experienced a change in control in which the former stockholders of America’s Minority Health Network, Inc. acquired control of our company. On June 11, 2010, we closed a transaction to acquire Spectrum Health Network, Inc. as a wholly owned subsidiary. On July 20, 2010, we filed Articles of Conversion and Articles of Incorporation to redomicile in the state of Nevada. On July 31, 2010, we transferred the assets of America’s Minority Health Network, Inc. to a secured noteholder in exchange for the satisfaction of certain associated debt. On February 15, 2011, we transferred the assets of Spectrum Health Network, Inc. to a secured noteholder in exchange for the satisfaction of associated debt and in exchange for a licensing agreement under which we subsequently sold subscription services and advertising on the Spectrum Health Network for commissions.

Available Information

We are a Nevada corporation. We maintain our principal executive offices at 6800 Broken Sound Parkway NW, Third Floor, Boca Raton, Florida 33487. Our telephone number is (561) 961-1900. We maintain websites atwww.therapeuticsmd.com,www.vitamedmd.com,www.vitamedmdrx.com, andwww.bocagreenmd.com. The information contained on our websites or that can be accessed through our websites is not incorporated by reference into this Annual Report or in any other report or document we file with the SEC.

We file reports with the SEC, including Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and any other filings required by the SEC. Through our website, we make available free of charge our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and all amendments to those reports, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

The public may read and copy any materials we file with, or furnish to, the SEC at the SEC’s Public Reference Room at 100 F Street, NE, Washington, DC 20549. The public may obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330. The SEC maintains an Internet site (www.sec.gov) that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC.

The following table sets forth certain information regarding our executive officers as of December 31, 2013:Risk Factors

Robert G. Finizio has served as Chief Executive Officer and a director of our company since October 2011. As co-founder of VitaMed, Mr. Finizio served as its Chief Executive Officer and a director from April 2008 to October 2011. Mr. Finizio has 16 years of successful early stage company development experience in the health care industry. Mr. Finizio co-founded and served from August 2001 to February 2008 as President of Care Fusion, LLC and then as Chief Executive Officer of CareFusion, Inc., which was acquired by Cardinal Health, Inc. Mr. Finizio’s early business experience was with Omnicell, Inc. (formerly known as Omnicell Technologies, Inc.) and Endoscopy Specialists, Inc. in the healthcare IT and surgical space, respectively. Mr. Finizio earned a B.A. from the University of Miami.

John C.K. Milligan, IV has served as President, Secretary, and a director of our company since October 2011. From December 2008 to October 2011, Mr. Milligan served as President and Director of VitaMed. Prior to VitaMed, Mr. Milligan co-founded CareFusion, LLC, serving as President and General Manager from August 2001 to February 2008, and then as President and Chief Operating Officer of CareFusion, Inc. From 1997 to 2001, Mr. Milligan was Vice President, Sales and Operations for Omnicell, Inc., a provider of pharmaceutical supply chain management systems and services. Prior to Omnicell, Mr. Milligan also held executive management positions at Serving Software Inc. and HBO & Co., both subsequently acquired by McKesson Corporation. Mr. Milligan is a graduate of the U.S. Naval Academy.

Daniel A. Cartwright has served as Chief Financial Officer, Vice President of Finance, and Treasurer of our company since October 2011. From July 2011 to October 2011, Mr. Cartwright served as Chief Financial Officer of VitaMed. From May 1996 to July 2011, Mr. Cartwright served as Chief Financial Officer and Executive Vice President of Circle F Ventures, LLC, an Arizona venture capital firm that made investments in more than 50 companies. During the same period, Mr. Cartwright served as Chief Financial Officer and Treasurer of Fleming Securities, formerly a registered broker dealer involved with raising capital for public and private companies. From 1993 to 1996, Mr. Cartwright served as Chief Financial Officer of American Wireless Systems, Inc., a provider of entertainment video services. Mr. Cartwright currently serves as a member of the board of directors of Primetrica, Inc., a private information research company for the telecommunications industry, and formerly served on the board of directors of Antenna Technologies Company, Inc. and WEB Corp. Mr. Cartwright earned his B.S. in Accounting from Arizona State University.

Mitchell L. Krassan has served as Executive Vice President and Chief Strategy Officer of our company since October 2011. From April 2010 to October 2011, Mr. Krassan served as Chief Strategy and Performance Officer of VitaMed. Mr. Krassan has been a partner with EquiMark Limited, a private investment partnership, since October 1997. From November 1994 to July 1997, Mr. Krassan served as Chief Financial Officer and Chief Operating Officer of The Reich Group/Telespectrum Worldwide, a fully integrated direct marketing firm that provided clients expertise in market research and analysis, strategic planning, marketing, creative, and production services, telemarketing and database development. The Reich Group became a leading company in a roll-up and $180 million initial public offering of Telespectrum Worldwide. Mr. Krassan earned a B.S. in Accounting from University of Maryland, received his certification as a CPA in the state of Maryland, and earned his M.B.A. in Management from New York University.

Non-Executive Officers

Dr. Brian Bernick has served as Chief Clinical Officer of our company since November 2012 and has served as a director of our company since October 2011. Dr. Bernick also has served as the Chief Medical Officer of our company from February 2012 until 2013. As co-founder of VitaMed, Dr. Bernick served on VitaMed’s board of directors from April 2008. Dr. Bernick is a practicing and board certified obstetrician/gynecologist with 20 years of clinical medical experience. Dr. Bernick is the past Chairman of the Department of Obstetrics and Gynecology at Boca Raton Regional Hospital and has served as a member of its Medical Executive Board. He has served on the board of directors of the Palm Beach Medical Society and VitalMD Group Holding, LLC, the largest physician-owned and managed group of obstetricians/gynecologists in Florida covering more than 250 physicians/practices. Dr. Bernick is an Associate Professor of Medicine at Florida Atlantic University and provides medical education in conjunction with Emory University and Florida Atlantic University School of Nursing and Medicine. Dr. Bernick earned a B.A. in economics from Northwestern University and a doctorate in medicine from the University of Chicago Medical School. He completed his residency at the University of Pennsylvania.

Julia Amadiohas served as Chief Product Officer of our company since January 16, 2012. Ms. Amadio has a 25-year background in general management and leading pharmaceutical marketing and product development organizations. From June 2011 to January 2012, Ms. Amadio was President of JMA Consulting, LLC, her own consulting company that she formed in 2008. From June 2009 to May 2011, she served as Global Vice President of Marketing for MeadWestvaco Healthcare Division. Previously, Ms. Amadio was President of a start-up, Patients’ & Consumers’ Pharma, in 2007. She was Vice President of Marketing & Marketing Services with Daiichi Pharmaceutical from 2004 to 2006; Vice President of Aventis Pharmaceutical from 1997 to 2004; Senior Director, New Products Women’s Health at Wyeth from 1991 to 1997; and started her career at J&J’s McNeil Pharmaceutical. Ms. Amadio is an active member and leader in the Healthcare Businesswomen’s Association. She was an adjunct lecturer at St. Joseph’s University in the pharmaceutical MBA program and authored a chapter on Marketing, Market Research and insights in the book Pharmaceutical Development for Woman (Wiley & Sons). Ms. Amadio earned a B.S. in Accounting from St. Joseph’s University and a Masters in Business Administration from Drexel University.

Dr. Joel Krasnow has served as the Chief Scientific Officer of our company since December 2013. Dr. Krasnow has 15 years of pharmaceutical industry experience in clinical development and medical affairs. Mr. Krasnow was Chief Safety Officer for Intarcia Therapeutics in 2013. From 2010 to 2012, Dr. Krasnow served as Vice-President and Chief Medical Officer of Eisai Pharmaceuticals, Frontier Business Unit. He led the Actemra® (tocilizumab) and Boniva® (ibandronate sodium) development teams at Roche Pharmaceuticals, resulting in several global product approvals between 2006 to 2010. From 2004 to 2006, Dr. Krasnow led the global development team at Novartis for Zometa® (zoledronic acid), resulting in multiple regulatory approvals. Dr. Krasnow’s experience as a Medical Director in women’s health includes the development of contraceptive, hormone replacement, and fertility treatments while at Organon. In a medical affairs capacity at Pharmacia/Pfizer, Dr. Krasnow worked with Activella® (estradiol/norethindrone acetate), Vagifem® (estradiol vaginal tablets), Depo-Provera (medroxyprogesterone acetate injectable suspension), and Detrol® (tolterodine tartrate). Dr. Krasnow pursued his residency training in OB-GYN at the University of Chicago; a fellowship in Reproductive Endocrinology at Baylor College of Medicine; and was on faculty in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh from 1991 to 1996. After receiving a Masters of Business Administration from the University of Pittsburgh, Dr. Krasnow worked in the healthcare practice at Deloitte Consulting.

Dr. Sebastian Mirkin has served as the Chief Medical Officer of our company since November 2013. Dr. Mirkin has more than 15 years of experience and leadership in clinical development and medical affairs in Women’s Health in global pharmaceutical companies. From October 2009 to November 2013, Dr. Sebastian was Clinical Lead and Global Clinical Lead of Women’s Health, Clinical Research at Pfizer. From October 2005 to October 2009, he was Director and Senior Director, Clinical Research, Women’s Health at Wyeth, and from October 2004 to October 2005 was Global Lead Medical Services, Women’s Health at Organon. Dr Mirkin oversaw the development and successful marketing authorization of several novel medicines, including Duavee®, Conbriza®, Lybrel®, and Premarin Vaginal Cream® in the United States, Europe, and Japan. Dr. Mirkin holds a Doctor in Medicine degree from National University, Argentina. Trained in Obstetrics/Gynecology, Dr. Mirkin completed his fellowship in Reproductive Medicine at The Jones Institute of Reproductive Medicine in Norfolk, Virginia, USA.

Jason Spitzhas served as Vice President - Marketing of our company since December 2011. Mr. Spitz has a 24-year career in marketing, advertising, and general management experience in pharmaceutical and biopharmaceutical markets. From June 2008 to December 2010, Mr. Spitz served as Managing Director, Oncology & Hematology at Beacon Healthcare Communications, a company specializing in pharmaceutical and health care advertising. From September 2004 to June 2008, he served as General Manager, Canada and Commercial Strategy and Development at MGI Pharma (later acquired by Eisai, Inc.), a company specializing in oncology and cancer supportive care products. From February 2004 to September 2004, he served as Vice President of Marketing and Sales at Aesgen, Inc., a company specializing in cancer products and drug delivery systems that was acquired by MGI Pharma. Mr. Spitz began his career at Schering Plough as a sales representative, rising within the organization over 15 years to lead a global pharmaceutical franchise. Mr. Spitz earned his Bachelor of Business Administration in Marketing from The University of Texas at Austin and his Master of Business Administration in Pharmaceutical Studies from Fairleigh Dickinson University.

Michael Donegan has served as Vice President – Finance of our company since April 2013. Mr. Donegan has a 23-year background in accounting and finance. From August 2012 to April 2013, Mr. Donegan served as an independent consultant exclusively for our company, where he conceptualized, designed and executed our Sarbanes-Oxley 404 compliance program. From August 2007 to August 2012, Mr. Donegan served as an independent consultant designing and implementing Sarbanes-Oxley 404 compliance programs for various non-accelerated filers and executed on pre-designed Sarbanes-Oxley 404 compliance programs for certain large accelerated filers. From January 2005 to August 2007, Mr. Donegan served as an independent consultant exclusively for Tyco International, where he enhanced and executed the Sarbanes-Oxley 404 compliance model with their corporate headquarters group. From November 2001 to December 2004, Mr. Donegan was Manager of Financial Systems at Tyco International at its global headquarters. From 1994 to 2001, Mr. Donegan held various positions in the global consolidation/SEC Reporting group at Sensormatic Electronics Corporation culminating with the acquisition of Sensormatic Electronics Corporation by Tyco International in the fall of 2001 when he was the Manager of Financial Systems. Mr. Donegan began his career at Ernst & Young, LLP where he worked in both the audit and tax departments. Mr. Donegan earned his Bachelor of Science in Accounting and his Master of Accounting from the University of Florida.

Christian Bloomgrenhas served as Vice President - Sales of our company since June 2011. Mr. Bloomgren has 14 years of leadership experience in the pharmaceutical, bio-technology, and diagnostic industry. From 2005 to 2011, Mr. Bloomgren served as Region Manager at ViaCell, Inc., a biotechnology company dedicated to enabling the widespread application of human cells as medicine, later acquired by PerkinElmer, Inc. While at ViaCell, Mr. Bloomgren built a successful national sales channel and helped lead the Specialty Diagnostics business. From 2000 to 2002, Mr. Bloomgren served as a specialty Account Manager at Eli Lilly & Co. and from 2002 to 2005 as District Manager at KV Pharmaceutical. Mr. Bloomgren served as an Officer in the United States Air Force and holds a Bachelor of Science degree from California State University and a Master of Science degree from Troy State University.

Marlan Walkerhas served as Corporate and Intellectual Property Counsel since June 2013. Mr. Walker’s experience is focused in the life science industries, including long-term portfolio strategy and management, patent preparation and prosecution, contract negotiation and drafting, life-cycle management, and Hatch-Waxman. After law school, he took a position at Greenberg Traurig LLP in August 2005. In March of 2009, he moved to Luce Forward Hamilton & Scripps. Mr. Walker accepted an in-house position as Intellectual Property Counsel for Medicis Pharmaceutical Corp. in June 2011, which was acquired by Valeant Pharmaceutical International, Inc. in December 2012. In February 2013, Mr. Walker accepted a position at Kilpatrick Townsend & Stockton, but chose to move in-house again in June 2013, when he accepted a position at our company. Mr. Walker graduated from Arizona State University’s Sandra Day O’Conner College of Law with his J.D. in 2004, and an LL.M. in Intellectual Property Law at The George Washington University Law School in 2005. He holds a Master’s Degree in Molecular Biology and a Bachelor of Science degree, both earned from Brigham Young University.

Risk Factors

Item 1A.Risk Factors

Investing in our common stock involves a high degree of risk. You should carefully consider the following risk factors, together with all of the information included in this Annual Report before you decide to purchase shares of our common stock. We believe the risks and uncertainties described below are the most significant we face. Additional risks and uncertainties of which we are unaware, or that we currently deem immaterial, also may become important factors that affect us. If any of the following risks occur, our business, financial condition, or results of operations could be materially and adversely affected. In that case, the trading price of our common stock could decline, and you may lose all or part of your investment.

Risks Related to Our Business

We have incurred significant operating losses since inception and anticipate that we will incur continued losses for the foreseeable future.

We have incurred recurring net losses, including net losses of $28$90 million, $35,$85 million, and $13$54 million for the years ended December 31, 2013, 2012,2016, 2015, and 2011,2014, respectively. As of December 31, 2013,2016, we had an accumulated deficit of approximately $81$310 million. We have generated limited revenue and have funded our operations to date primarily from public and private sales of equity and private sales of debt securities. We expect to incur substantial additional losses over the next severalfew years as a result of our research, development, and clinical trial activities increase, especially those related to our hormone therapy drug candidates.and commercialization activities. As a result, we may never achieve or maintain profitability, unlesseven if we successfully commercialize our products, in particular, our hormone therapy drug candidates. If we are unable to make required payments under any of our obligations for any reason, our creditors may take actions to collect their debts, including foreclosing on our intellectual property that collateralizes our obligations. If we continue to incur substantial losses and are unable to secure additional financing, we could be forced to discontinue or curtail our business operations, sell assets at unfavorable prices, refinance existingthen-existing debt obligations on terms unfavorable to us, or merge, consolidate, or combine with a company with greater financial resources in a transaction that might be unfavorable to us.

Our independent registered public accounting firm, in its audit reports related to our financial statements for the years ended December 31, 2012 and 2011, expressed substantial doubt about our ability to continue as a going concern.

As a result of our continued losses, our independent registered public accounting firm has included an explanatory paragraph in its reports on our financial statements for the years ended December 31, 2012 and 2011, expressing substantial doubt as to our ability to continue as a going concern. The inclusion of a going concern explanatory paragraph in the report of our independent registered public accounting firm may make it more difficult for us to secure additional financing or enter into strategic relationships on terms acceptable to us, if at all, and may materially and adversely affect the terms of any financing that we might obtain.

We currently derive all of our revenue from sales of our women’s health care products, and our failure to maintain or increase sales of these products wouldcould have a material adverse effect on our business, financial condition, results of operations, and growth prospects.

We currently deriveIn 2016, we derived virtually all of our revenue from sales of women’s health care products, including prenatal and women’s multi-vitamins, iron supplements, vitamin D supplements, and natural menopause relief, and scar reduction creams.relief. While sales of our vitamin products grew from 2010 through 2013,2016, we cannot assure you that we will be able to sustain such sales or that such sales will continue to grow. In addition to other risks described herein, our ability to maintain or increase existing product sales is subject to a number of risks and uncertainties, including the following:

If revenue from sales of our existing prescription and over-the-counter dietary supplements and cosmeticsOTC prenatal vitamins does not continue or increase, we may be required to reduce our operating expenses or to seek to raise additional funds, which could have a material adverse effect on our business, financial condition, results of operations, and growth prospects, or we may not be able to commence or continue clinical trials to seek approval for and commercialize our hormone therapy drug candidates or any other products we may choose to develop in the future.

If our products or drug candidates do not have the effects intended or cause undesirable side effects, our business may suffer.

Although many of the ingredients in our current dietary supplement products are vitamins, minerals, and other substances for which there is a long history of human consumption, they also contain innovative ingredients or combinations of ingredients. AlthoughWhile we believe that all of these products and the combinations of ingredients in them are safe when taken as directed, the products could have certain undesirable side effects if not taken as directed or if taken by a consumer who has certain medical conditions.conditions, such as the potential effect of high doses of folic acid masking pernicious anemia. In addition, these products may not have the effect intended if they are not taken in accordance with certain instructions, which include certain dietary restrictions. Furthermore, there can be no assurance that any of the products, even when used as directed, will have the effects intended or will not have harmful side effects in an unforeseen way or on an unforeseen cohort. If any of our products or products we develop or commercialize in the future are shown to be harmful or generate negative publicity from perceived harmful effects, our business, financial condition, results of operations, and prospects wouldcould be harmed significantly.

Our future success will depend in large part on our ability to commercialize our hormone therapy drug candidates designed to alleviate the symptoms of and reduce the health risks resulting from menopause, including hot flashes, osteoporosis,VMS and vaginal dryness.VVA.

Our future success will depend in large part on our ability to successfully develop and commercialize our hormone therapy drug candidates designed to alleviate the symptoms of and reduce the health risks resulting from menopause, including hot flashes osteoporosis, and vaginal dryness.dyspareunia. We have submitted IND applications for our fourfive hormone therapy drug candidates, which the FDA has made effectiveallowed to proceed, and which permit us to conduct clinical testing on these proposed products. In December 2015, we completed a phase 3 clinical trial of our TX-004HR drug candidate and in December 2016 we completed a phase 3 clinical trial for our TX-001HR drug candidate. In July 2014, we suspended enrollment in the phase 3 clinical trial for our TX-002HR drug candidate and in October 2014 we stopped the trial and are considering whether to update the phase 3 protocol based on discussions with the FDA. We intendhave currently suspended further development of this drug candidate to clinically test three of thoseprioritize our leading drug candidates. However, weWe have no current plans to conduct clinical trials for our TX-003HR drug candidate. Drug development is a necessarily uncertain undertaking. We may not be able to complete the development of theseour drug candidates, the results of the clinical trials may not be sufficient to support an NDA for any of them,our drug candidates, and even if we believe the results of our clinical trials are sufficient to support any NDA that we submit, the FDA may disagree and may not approve our NDA. In addition, even if the FDA approves one or more of our NDAs, it may do so with restrictions on the intended uses that may make commercialization of the product or products financially untenable. The failure to commercialize or obtain necessary approval for any one or more of these products wouldcould substantially harm our prospects and our business.

We may not be able to complete the development and commercialization of our hormone therapy drug candidates if we fail to obtain additional financing.

We need substantial amounts of cash to complete the clinical development and commercialization of our hormone therapy drug candidates. Our existing cash and cash equivalents willmay not be sufficient to fund these requirements. In addition, changing circumstances may cause us to consume funds significantly faster than we currently anticipate, and we may need to spend more money than currently expected because of circumstances beyond our control.on these programs. We do not currently have any committed external source of funds. We willmay attempt to raise additional capital from the issuance of equity or debt securities, collaborations with third parties, licensing of rights to theseour products, or other means, or a combination of any of the foregoing. Securing additional financing will require a substantial amount of time and attention from our management and may divert a disproportionate amount of their attention away from our day-to-day activities, which may adversely affect our ability to conduct our day-to-day operations. In addition, we cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all. If we are unable to raise additional capital when required or on acceptable terms, we may be required to take one or more of the following actions:

Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our existing stockholders will be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect the rights of our existing stockholders. If we raise additional funds through collaborations, strategic alliances, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs, or proposed products or grant licenses on terms that may not be favorable to us.

If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we will be prevented from pursuing discovery, development, and commercialization efforts, and our ability to generate revenue and achieve or sustain profitability will be substantially harmed.

harmed

We have no experience as a company in bringing a drug to regulatory approval.

approval

We have never obtained regulatory approval for, or commercialized, a drug. It is possible that the FDA may refuse to accept any or all of our planned NDAs for substantive review or may conclude, after review of our data, that our applications are insufficient to obtain regulatory approval of any of our hormone therapy drug candidates. We have begun to conduct validation and scale up of the manufacturing processes for TX-001HR, our proposed combination estradiol and progesterone drug candidate, and TX-004HR, our proposed applicator-free vaginal estradiol softgel drug candidate. The FDA may also require that we conduct additional clinical or manufacturing validation studies, which may be costly and time-consuming, and submit that data before it will reconsider our applications. Depending on the extent of these or any other FDA required studies, approval of any NDA that we submit may be significantly delayed, possibly for years, or may require us to expend more resources than we have available or can secure. Any delay or inability in obtaining regulatory approvals would delay or prevent us from commercializing our hormone therapy drug candidates, generating revenue from these proposed products, and achieving and sustaining profitability. It is also possible that additional studies, if performed and completed, may not be considered sufficient by the FDA to approve any NDA we submit. If any of these outcomes occur, we may be forced to abandon our planned NDAs for one or more of our hormone therapy drug candidates, which would materially adversely affect our business and could potentially cause us to cease operations.operations

We have recently completed our phase 3 clinical trials of TX-001HR for the treatment of moderate to severe VMS due to menopause in post-menopausal women with an intact uterus and TX-004HR for the treatment of moderate to severe dyspareunia in postmenopausal women with VVA. Although we have discussed our clinical development plans for each drug candidate with the FDA, the agency may ultimately determine that our phase 3 clinical trials for one or both candidates are not sufficient for regulatory approval. If we are required to conduct additional clinical trials or non-clinical studies, our development of TX-001HR or TX-004HR, as applicable, will be more time-consuming and costly than we presently anticipate, which could have a material adverse effect on our business, results of operations and financial condition.

On December 5, 2016, we announced positive top-line results from the REPLENISH Trial, our phase 3 clinical trial to evaluate the safety and efficacy of TX-001HR, an investigational bio-identical hormone therapy combination of 17ß-estradiol and progesterone in a single, oral softgel, for the treatment of moderate to severe VMS due to menopause in post-menopausal women with an intact uterus.  The REPLENISH Trial evaluated four doses of TX-001HR and placebo in 1,835 post-menopausal women between 40 and 65 years old. The doses studied were: 17ß-estradiol 1 mg/progesterone 100 mg; 17ß-estradiol 0.5 mg/progesterone 100 mg; 17ß-estradiol 0.5 mg/progesterone 50 mg; and 17ß-estradiol 0.25 mg/progesterone 50 mg (n = 424).  The REPLENISH Trial results demonstrated that TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5 mg/progesterone 100 mg both achieved all four of the co-primary efficacy endpoints and the primary safety endpoint and demonstrated a statistically significant and clinically meaningful reduction from baseline in both the frequency and severity of hot flashes compared to placebo.  TX-001HR estradiol 0.5 mg/progesterone 50 mg and TX-001HR estradiol 0.25 mg/progesterone 50 mg were not statistically significant at all of the co-primary efficacy endpoints; the estradiol 0.25 mg/progesterone 50 mg dose was included in the clinical trial as a non-effective dose to meet the recommendation of the FDA guidance to identify the lowest effective dose. The incidence of consensus endometrial hyperplasia or malignancy was 0 percent across all four TX-001HR doses, meeting the recommendations established by the FDA’s draft guidance.  Based on the results of the REPLENISH Trial, we currently intend to seek regulatory approval for the estradiol 1 mg/progesterone 100 mg and estradiol 0.5 mg/progesterone 100 mg doses of TX-001HR for the treatment of moderate to severe VMS due to menopause in post-menopausal women with an intact uterus in the U.S

On December 7, 2015, we announced positive top-line results from the REJOICE Trial, our phase 3 clinical trial to evaluate the safety and efficacy of three doses—25 mcg, 10 mcg and 4 mcg (compared to placebo)—of TX-004HR for the treatment of moderate to severe dyspareunia in postmenopausal women with VVA. Both the 25 mcg dose and the 10 mcg dose of TX-004HR demonstrated highly statistically significant results at the p < 0.0001 level compared to placebo across all four co-primary efficacy endpoints. The 4 mcg dose of TX-004HR also demonstrated highly statistically significant results at the p < 0.0001 level compared to placebo for the endpoints of vaginal superficial cells, vaginal parabasal cells, and vaginal pH; the change from baseline compared to placebo in the severity of dyspareunia was statistically significant at the p = 0.0149 level.  On July 7, 2016, we submitted an NDA for all three doses of TX-004HR that were evaluated in the REJOICE Trial.  As discussed below, where an NDA is supported by a single clinical trial, as is the case with TX-004HR, the FDA has taken the position initially that the results of our trial would have to achieve statistical significance at the 0.01 level or better. Statistical significance at the 0.0149 level may not be sufficient to satisfy this requirement.  If the FDA continues to maintain this position, we may have to either conduct an additional trial or eliminate the 4 mcg dose formulation from the TX-004HR NDA.  The elimination of this low dose from our product line could adversely affect our sales of TX-004HR, if approved. 

We cannot assure you that the FDA will approve all or any doses of TX-001HR or TX-004HR for commercialization. The FDA may not agree with one or more aspects of our clinical trial designs, including the duration of the trials, clinical endpoints, controls, dose ranges, collection of safety data, level of statistical significance, or adequacy of our non-clinical studies. In addition, to date we have only analyzed the top line data of the REPLENISH Trial; further safety and efficacy analyses of the trial data are ongoing. If the further analyses suggest the data are not as positive as we currently believe them to be, we may need to conduct additional clinical or non-clinical trials or studies, which could result in delays in approval or could prevent approval of TX-001HR

Our TX-001HR or TX-004HR hormone therapy drug candidates are currently undergoing stability testing.  The FDA will review the period of time that our drug candidates are stable, which will dictate the amount of time post-manufacturing that the products may be used by patients, if approved. If our hormone therapy drug candidates fail to remain stable or the period of time that they remain stable is too short, it could limit the commercial viability of our products, which could materially adversely impact our business, results of operations and financial condition.

In addition, prior to approval of an NDA, the FDA may audit one or more of the sites where the applicable phase 3 clinical trial was conducted to ensure the integrity of the data, inspect our clinical records in our corporate offices, and will inspect the facilities of our third party contract manufacturers where the applicable drug candidate will be manufactured commercially, if approved and where the drug was manufactured for clinical trials. If one or more site audits reveals anomalies, or if the manufacturing facilities do not pass inspection, full consideration of the NDA by the FDA could be delayed, or the FDA may require us to undertake further clinical or non-clinical trials or could require our contract manufacturers to improve or change their processes, any of which would delay or prevent commercialization of the applicable drug candidate and could materially adversely impact our business, results of operations and financial condition.

Clinical trials involve aare lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.results.

Three hormone therapy drug candidates are currently in various stages of clinical testing. We have recently begun phase 3 clinical trial of our estradiol and progesterone combination and our progesterone alone drug candidates. ClinicClinical trials are expensive, can take many years to complete and have highly uncertain outcomes. For example, we suspended enrollment in and subsequently stopped the SPRY trial for our progesterone alone drug candidate in order to update the phase 3 protocol based on discussions with the FDA. Failure can occur at any time during the clinical trial process as a result of inadequate performance of a drug, inadequate adherence by patients or investigators to clinical trial protocols, or other factors. New drugs in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through earlier clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials as a result of a lack of efficacy or adverse safety profiles, despite promising results in earlier trials. Our future clinical trials may not be successful or may be more expensive or time-consuming than we currently expect. Prior to approving a new drug, the FDA generally requires that the safety and efficacy of the drug be demonstrated in two adequate and well-controlled clinical trials. In some situations the FDA approves drugs on the basis of a single well-controlled clinical trial. We believe we may be required to conduct only a single phase 3 clinical trial of each of TX-001HR, our proposed combination estradiol and progesterone drug candidate, TX-002HR, our progesterone alone drug candidate, and TX-004HR, our applicator-free vaginal estradiol softgel drug candidate. However, in connection with our TX-004HR drug candidate, the FDA has previously indicated to us that in order to approve the drug based on a single trial, the trial would need to show statistical significance at the 0.01 level or lower for each endpoint, and that a trial that is merely statistically significant at a higher numerical level may not provide sufficient evidence to support an NDA filing or approval of a drug candidate where the NDA relies on a single clinical trial. If clinical trials for any of our hormone therapy drug candidates fail to demonstrate safety or efficacy to the satisfaction of the FDA, the FDA will not approve that drug and we would not be able to commercialize it, which willcould have a material adverse effect on our business, financial condition, results of operations, and prospects

Our dependence upon third parties for the manufacture and supply of our existing women’s health care products and our hormone therapy drug candidates may cause delays in, or prevent us from, successfully developing, commercializing, and marketing our products. 

We do not currently have, nor do we plan to build, the infrastructure or capability to internally manufacture our existing women’s health care products or our hormone therapy drug candidates. We have relied, and will continue to rely, on third parties to manufacture these products in accordance with our specifications and in compliance with applicable regulatory requirements.  We have entered into long-term supply agreements with Catalent for the commercial supply of our TX-001HR and TX-004HR hormone therapy drug candidates. Under the terms of the agreements, we will be obligated to purchase certain minimum annual amounts of each product once we commence commercial sales of such product following regulatory approval of Catalent as a manufacturer of the product.  We depend on Lang, a full-service, private label and corporate brand manufacturer, to supply approximately 98% of our vitaMedMD and BocaGreen products.  We do not have long-term contracts for the commercial supply of our existing women’s health care products, however, in certain circumstances, including our failure to satisfy our production forecasts to Lang, we may be obligated to reimburse Lang for the costs of excess raw materials purchased by Lang that it cannot use in another product category that it then sells. 

Regulatory requirements could pose barriers to the manufacture of our existing women’s health care products and our hormone therapy drug candidates. Our third-party manufacturers are required to comply with cGMP regulations. As a result, the facilities used by any of our current or future manufacturers must be approved by the FDA. Holders of NDAs, or other forms of FDA approvals or clearances, or those distributing a regulated product under their own name, are responsible for manufacturing even though that manufacturing is conducted by a third-party CMO. All of our existing products are, and our hormone therapy drug candidates, if approved, will be manufactured by CMOs. These CMOs are required by the terms of our contracts to manufacture our products in compliance with the applicable regulatory requirements. The CMO that will manufacture our hormone therapy drug candidates, if approved, has previously been inspected by the FDA and received Form 483 observations with respect to its softgel manufacturing plant that will be used for the manufacture of the commercial supply of TX-001HR and TX-004HR, if approved.  We anticipate that as part of the PAI of our NDA for TX-004HR, the FDA may inspect Catalent’s manufacturing facilities that would be used to manufacture the product. If this inspection results in Form 483 observations, the approval of our NDA could be delayed significantly. The CMO that manufactured the hormone therapy drug candidates used in our recently completed phase 3 clinical trials for TX-001HR and TX-004HR was recently inspected by the FDA, which issued it a Form FDA-483 listing various observations, some of which pertained to the clinical supply of our TX-001HR and TX-004HR drug candidates. The CMO has submitted its written response to the Form 483 observations to the FDA, however, neither we nor the CMO has been informed by the FDA as to whether the CMO’s response addresses and remediates these observations in a manner satisfactory to the FDA. If this CMO is not able to address and remediate the FDA’s observations pertaining to the clinical supply of our TX-001HR and TX-004HR drug candidates in a manner satisfactory to the FDA, it could have a material adverse effect on the FDA’s review of our NDA for TX-004HR or the timing of our anticipated submission of an NDA for TX-001HR.

If our manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA and any applicable foreign regulatory authority, they will not be able to secure the applicable approval for their manufacturing facilities. If these facilities are not approved for the commercial manufacture of our existing products or our hormone therapy drug candidates, we may need to find alternative manufacturing facilities, which would result in disruptions of our sales and significant delays of up to several years in obtaining approval for our hormone therapy drug candidates. In addition, our manufacturers will be subject to ongoing periodic unannounced inspections by the FDA and corresponding state and foreign agencies for compliance with cGMPs and similar regulatory requirements. Failure by any of our manufacturers to comply with applicable cGMP regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspensions or withdrawals of approvals, operating restrictions, interruptions in supply, recalls, withdrawals, issuance of safety alerts, and criminal prosecutions, any of which could have a material adverse impact on our business, financial condition, results of operations, and prospects. Finally, we also could experience manufacturing delays if our CMOs give greater priority to the supply of other products over our products and proposed products or otherwise do not satisfactorily perform according to the terms of their agreements with us. 

We also do not have long-term contracts for the supply of the API used in hormone therapy drug candidates.  If any supplier of the API or other products used in our hormone therapy drug candidates experiences any significant difficulties in its respective manufacturing processes, does not comply with the terms of the agreement between us, or does not devote sufficient time, energy, and care to providing our manufacturing needs, we could experience significant interruptions in the supply of our hormone therapy drug candidates, which could impair our ability to supply our hormone therapy drug candidates at the levels required for commercialization and prevent or delay their successful commercialization

Delays in clinical trials are common for many reasons, and any such delays could result in increased costs to us and jeopardize or delay our ability to obtain regulatory approval and commence product sales as currently contemplated.

We may experience delays in clinical trials for our hormone therapy drug candidates. Our planned clinical trials might not begin on time; may be interrupted, delayed, suspended, or terminated once commenced; might need to be redesigned; might not enroll a sufficient number of patients; or might not be completed on schedule, if at all. Clinical trials can be delayed for a variety of reasons, including the following: